Schizophrenia - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

SCHIZOPHRENIA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES...

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SCHIZOPHRENIA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Schizophrenia: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83638-8 1. Schizophrenia-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on schizophrenia. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON SCHIZOPHRENIA ....................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Schizophrenia ................................................................................ 8 E-Journals: PubMed Central ..................................................................................................... 135 The National Library of Medicine: PubMed .............................................................................. 142 CHAPTER 2. NUTRITION AND SCHIZOPHRENIA ........................................................................... 273 Overview.................................................................................................................................... 273 Finding Nutrition Studies on Schizophrenia............................................................................. 273 Federal Resources on Nutrition ................................................................................................. 281 Additional Web Resources ......................................................................................................... 281 CHAPTER 3. ALTERNATIVE MEDICINE AND SCHIZOPHRENIA ..................................................... 283 Overview.................................................................................................................................... 283 National Center for Complementary and Alternative Medicine................................................ 283 Additional Web Resources ......................................................................................................... 312 General References ..................................................................................................................... 316 CHAPTER 4. DISSERTATIONS ON SCHIZOPHRENIA ....................................................................... 317 Overview.................................................................................................................................... 317 Dissertations on Schizophrenia.................................................................................................. 317 Keeping Current ........................................................................................................................ 333 CHAPTER 5. CLINICAL TRIALS AND SCHIZOPHRENIA.................................................................. 335 Overview.................................................................................................................................... 335 Recent Trials on Schizophrenia.................................................................................................. 335 Keeping Current on Clinical Trials ........................................................................................... 354 CHAPTER 6. PATENTS ON SCHIZOPHRENIA .................................................................................. 357 Overview.................................................................................................................................... 357 Patents on Schizophrenia........................................................................................................... 357 Patent Applications on Schizophrenia ....................................................................................... 388 Keeping Current ........................................................................................................................ 403 CHAPTER 7. BOOKS ON SCHIZOPHRENIA ..................................................................................... 405 Overview.................................................................................................................................... 405 Book Summaries: Federal Agencies............................................................................................ 405 Book Summaries: Online Booksellers......................................................................................... 408 The National Library of Medicine Book Index ........................................................................... 434 Chapters on Schizophrenia......................................................................................................... 436 Directories.................................................................................................................................. 440 CHAPTER 8. MULTIMEDIA ON SCHIZOPHRENIA........................................................................... 441 Overview.................................................................................................................................... 441 Bibliography: Multimedia on Schizophrenia ............................................................................. 441 CHAPTER 9. PERIODICALS AND NEWS ON SCHIZOPHRENIA........................................................ 445 Overview.................................................................................................................................... 445 News Services and Press Releases.............................................................................................. 445 Newsletter Articles .................................................................................................................... 450 Academic Periodicals covering Schizophrenia ........................................................................... 450 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 453 Overview.................................................................................................................................... 453 U.S. Pharmacopeia..................................................................................................................... 453 Commercial Databases ............................................................................................................... 455 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 459 Overview.................................................................................................................................... 459

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NIH Guidelines.......................................................................................................................... 459 NIH Databases........................................................................................................................... 461 Other Commercial Databases..................................................................................................... 463 The Genome Project and Schizophrenia..................................................................................... 463 APPENDIX B. PATIENT RESOURCES ............................................................................................... 469 Overview.................................................................................................................................... 469 Patient Guideline Sources.......................................................................................................... 469 Associations and Schizophrenia................................................................................................. 474 Finding Associations.................................................................................................................. 478 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 481 Overview.................................................................................................................................... 481 Preparation................................................................................................................................. 481 Finding a Local Medical Library................................................................................................ 481 Medical Libraries in the U.S. and Canada ................................................................................. 481 ONLINE GLOSSARIES................................................................................................................ 487 Online Dictionary Directories ................................................................................................... 489 SCHIZOPHRENIA DICTIONARY ............................................................................................ 491 INDEX .............................................................................................................................................. 575

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with schizophrenia is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about schizophrenia, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to schizophrenia, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on schizophrenia. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to schizophrenia, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on schizophrenia. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON SCHIZOPHRENIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on schizophrenia.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and schizophrenia, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “schizophrenia” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Dental Care for the Psychiatric Patient: Chronic Schizophrenia Source: Journal of Canadian Dental Association. 58(11): 912-920. November 1992. Contact: Available from Canadian Dental Association. 1815 Alta Vista Drive, Ottawa, Ontario, Canada K1G 3Y6. (800) 267-6354 or (613) 523-1770; Fax (613) 523-7736; http://www.cda-adc.ca/. Summary: Due to a recent shift from a primarily institution-based treatment regimen to a more community-oriented approach, the general dental practitioner can expect to see an increasing number of patients with various psychiatric and behavioral disorders, many of whom present with significant dental pathology. In this article, the author provides an overview of the oral health findings and the management protocols for those individuals with chronic schizophrenia. The author familiarizes the practicing

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dentist with the main psychopathological features of this disorder as well as with the specific oral health care requirements and management protocols for these patients. The author notes that the management of these patients may require consultation between the dentist and the psychiatrist/physician, enabling the dentist to more fully understand not only the specific psychopathology of the disease, but also the treatment that these patients are receiving for their disorder. 2 tables. 42 references. (AA-M). •

Olfactory Dysfunction in Schizophrenia: A Qualitative and Quantitative Review Source: Neuropsychopharmacology. 21(3): 325-340. September 1999. Contact: Available from Elsevier Science, Inc. P.O. Box 7247-7682, Philadelphia, PA 19170-7682. Summary: Olfactory dysfunction in patients with schizophrenia has been a topic of increasing interest, with deficits in odor identification, detection threshold sensitivity, discrimination, and memory being reported. Despite increasing knowledge, controversy has existed about possible differential deficits among olfactory tests as well as the influences of gender, smoking, and medication status on olfactory measures. This article reports on a meta analytic (qualitative and quantitative) review of the English language literature on olfaction (smell) in schizophrenia. Moderator variables such as gender, medication status, and smoking history were also examined. Results indicated that substantial olfactory deficits, across all domains, are observed in patients with schizophrenia. No differential deficits were observed across domains of odor identification, detection threshold sensitivity, discrimination, and memory. The influences of gender, medication status, and smoking on effect sizes were not significant across studies. This supports the hypothesis of primary dysfunction in the olfactory system that is regulated by brain regions where structural and functional abnormalities have also been reported in neuroimaging studies. 1 figure. 2 tables. 113 references.

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Psychopathology, Medical Management and Dental Implications of Schizophrenia Source: JADA. Journal of the American Dental Association. 133(5): 603-610. May 2002. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: Schizophrenia is a psychiatric illness characterized by thought disturbances, bizarre behaviors, and cognitive impairments that may diminish a person's abilities in the areas of social relations, school or work, and self-care. Advanced dental disease is seen frequently in patients with schizophrenia for several reasons: the disease impairs these patients' ability to plan and perform oral hygiene procedures; some of the antipsychotic medications they take have adverse orofacial effects such as xerostomia (dry mouth); and these patients may have limited access to treatment due to lack of financial resources and to an inadequate number of dentists comfortable in providing care to this population. This article outlines the psychopathology, medical management, and dental implications of schizophrenia. The author notes that the recent introduction of more effective medications has permitted the majority of patients to receive their psychiatric care from community-based providers rather than in the hospital. Consequently, dentists in the private sector also are being called on more frequently to care for this patient population. To effectively provide treatment to patients with schizophrenia, dentists must be familiar with the disease process so that they can communicate effectively with the patient, the treating psychiatrist, and family members who serve as caregivers. In addition, dental treatment may need to be modified because of the patient's impaired ability to think logically, the local and systemic effects of

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psychiatric medications, and adverse interactions between these drugs and medications used in dentistry. 1 figures. 2 tables. 59 references. •

Schizophrenia Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 88(5): 526-528. November 1999. Contact: Available from Mosby, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-3318. (800) 453-4351 or (314) 453-4351. Website: www.mosby.com. Summary: This article familiarizes oral health care professionals with schizophrenia, a diagnostic category that includes a variety of mental illnesses with the following common features: early onset (usually in one's 20s or 30s), cognitive impairment, disorders of thought, and affective abnormalities. The author reviews the diagnostic features, etiology, and management of schizophrenia, along with considerations for the dental professional. Clinical manifestations of schizophrenia include disordered speech, hallucinations, delusions, disorders of balance and proprioception, and visual disturbances, including disorders of eye movement, prolonged staring, paroxysms of rapid blinking, and deviation of the eyes. Treatment of schizophrenia consists of the use of antipsychotic drugs and psychosocial therapy. The dental professional must be aware of the general diagnostic and treatment issues related to schizophrenia so that proper referral can be facilitated; know the effects of vasoconstrictors when local anesthetics are used; and be aware of and possibly treat the side effects of the drugs used to manage schizophrenia. The hematologic problems may manifest as unusual bleeding during surgical procedures, chronic oral ulcers, and recurrent oral candidiasis. Neuroleptic drugs may interact with epinephrine to cause severe hypertension and the use of atropine may result in an enhanced anticholinergic effect; thus, the use of epinephrine and atropine must be limited. In addition, the neuroleptic drugs often cause xerostomia and may occasionally cause dysphagia. 3 tables. 5 references.

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Oral Health Care for the Patient with Schizophrenia Source: SCD. Special Care in Dentistry. 11(5): 179-183. September-October 1991. Summary: This article outlines strategies for the oral health care of patients with schizophrenia. The authors note that conceptualizing the disorder as consisting of positive and negative symptoms has led to improved treatment modalities. Medications used in managing the positive symptoms have numerous adverse systemic and orofacial effects that must be recognized by the dentist. Dental treatment strategies for the identification and management of these side effects are described. Negative symptoms are responsible for chronicity of the disorder and frequently impede rehabilitation. These symptoms are potentially devastating to oral health, as they impair a patient's desire and ability to achieve preventive oral hygiene. The authors outline treatment strategies to improve compliance for oral hygiene. A medication, clozapine, that is specifically indicated for patients with treatment-resistant disease, has recently been approved for use in the U.S. The authors conclude by reviewing the adverse systemic and orofacial effects of this medication and its influence on dental management. 62 references. (AA-M).

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Dental Management of Child and Adolescent Patients with Schizophrenia Source: Journal of Dentistry for Children. 60(4-5): 281-287. July-October 1993.

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Summary: This article provides guidelines for the dental management of child and adolescent patients with schizophrenia, a chronic psychiatric disorder in which thought disturbances and severely disordered behavior lessen an individual's ability to conduct self care and to interact effectively with others. Topics include preschizophrenic behavioral patterns in infants, toddlers, preschoolers, and school-age children; the typical course of schizophrenia; and the medical management of schizophrenia, including orofacial findings. The authors conclude with a discussion of dental management considerations. The authors emphasize the importance of collaboration with a psychiatrist in the management of a patient can alleviate much of the doubt and anxiety associated with providing dental care to these individuals. 2 tables. 38 references. •

Lipreading in Prelingually Deaf and Hearing Patients with Schizophrenia Source: Journal of Nervous and Mental Disease. 186(4): 247-249. April 1998. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201. (800) 638-6423 or (410) 528-8555. Fax (410) 361-8048. Summary: This article reports on a research study that extends the investigation of speechreading skills to samples of prelingually deaf and hearing patients with schizophrenia and two psychiatric but nonpsychotic control groups. The study included four samples, with 25 subjects each: prelingually deaf schizophrenic (DS) patients, hearing schizophrenic (HS) patients, prelingually deaf (DP), and hearing (HP) psychiatric patients without psychotic episodes in their past history. To measure the speechreading performance, the authors administered a word recognition test of 15 videotaped words. In the speechreading tasks, the deaf subjects proved, as expected, to be experts. Their scores were higher than those of the hearing subjects. Both schizophrenic groups scored lower than their respective nonpsychotic control groups with the same hearing status. Analysis of variance revealed significant main effects of both hearing status and schizophrenia. The authors conclude that the ability to lipread may be affected by schizophrenia, but with much less impact than hypothesized. Speechreading requires high levels of attention and information processing and the researchers expected schizophrenia to have a greater impact on this skill than they found. They note that the relative impairment of speechreading skills that may be attributed to schizophrenia seems to be equal in quantitative terms in deaf and hearing patients. 2 tables. 11 references.

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Factors Which Influence the Oral Conditions of Chronic Schizophrenia Patients Source: SCD. Special Care in Dentistry. 16(2): 84-86. March-April 1996. Summary: This article reports on a study in which the oral health status of 249 individuals with chronic schizophrenia was evaluated by means of the Oral Hygiene Index (OHI-S) and Decayed, Missing, and Filled Teeth (DMFT) scores. The patients were subdivided as to chronicity of illness and venue of psychiatric treatment. Subjects included 158 inpatients with greater than 10 years' hospitalization, 34 inpatients with less than 10 years' hospitalization, and 57 outpatients. The results demonstrated that inpatients had greater amounts of dental disease than outpatients. The extent of dental disease among inpatients as measured by both the OHI-S and DMFT scores was directly related to the intensity of schizophrenia, magnitude of negative schizophrenia symptoms, and length of hospitalization. DMFT scores were directly related to EDC (equivalent dose of chloropromazine) value. 5 tables. 26 references. (AA-M).

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Olfactory Identification Deficits in Schizophrenia: Correlation with Duration of Illness Source: American Journal of Psychiatry. 154(7): 1016-1018. July 1997. Contact: Available from American Psychiatric Association. 1400 K Street, NW, Washington, DC 20005. (202) 682-6158. Summary: This article reports on a study that examined the relationship between deficits in olfactory identification (ability to identify smells) and duration of illness in young and elderly patients with schizophrenia. The olfactory identification performance of 38 patients with schizophrenia and 40 normal subjects was compared by using the University of Pennsylvania Smell Identification Test. The schizophrenic patients demonstrated olfactory deficits relative to the comparison group, and the elderly schizophrenic patients displayed a greater magnitude of olfactory deficit than the younger patients. Independent of normal aging effects and cognitive deficit, patients with schizophrenia showed a strong relationship between olfactory identification scores and duration of illness, which suggests that olfactory abilities decline progressively over the course of the disorder. The authors conclude that, in contrast to other neuropsychological measures that have been reported to be stable over the course of illness, olfactory identification abilities deteriorate steadily in patients with schizophrenia, even for those with relatively recent onset. 1 figure. 11 references. (AA).

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Senile Degeneration and Cognitive Impairment in Chronic Schizophrenia Source: American Journal of Psychiatry. 155(11): 1536-1543. November 1998. Summary: This journal article describes a study that investigated the role of Alzheimer's disease (AD) senile degenerative abnormalities in the cognitive impairment of chronic schizophrenia. Researchers reviewed medical records to establish psychiatric diagnoses and cognitive status of deceased psychiatric patients with schizophrenia, mood disorders, dementia, and other related diagnoses. The comparison group included deceased individuals with no neurological or psychiatric disease. Neuritic senile plaques and neurofibrillary tangles were identified and counted. Data demonstrated that 68 percent of the subjects with schizophrenia had definite cognitive impairment and only 8 percent satisfied neuropathological criteria for AD; definite cognitive impairment was associated with higher levels of plaques and tangles among the schizophrenia subjects without AD; and the schizophrenia subjects without definite cognitive impairment had fewer plaques and tangles than the unimpaired nonpsychiatric subjects. The authors formulated three primary conclusions: most cases of cognitive impairment in schizophrenia could not be attributed to AD; an association of mild AD-type pathology with definite cognitive impairment was unique to schizophrenia; and enhanced sensitivity to the effects of aging on the brain may be a manifestation of diminished cognitive reserve in schizophrenia. 3 figures, 3 tables, 63 references. (AA-M).

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Meta-Analysis of Postmortem Studies of Alzheimer's Disease-Like Neuropathology in Schizophrenia Source: American Journal of Psychiatry. 154(6): 861-863. June 1997. Summary: This journal article presents a meta-analysis of available data concerning the presence of Alzheimer's disease (AD)-like neuropathology in patients with schizophrenia, who presumably were exposed to long term treatment with neuroleptics. The analysis included data from seven published studies and one unpublished source that reported the presence or absence of AD-like neuropathology in the postmortem

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brains of patients with schizophrenia, healthy comparison cases, and comparison cases with affective disorders. The analysis revealed similar rates of AD-like changes in the patients with schizophrenia and comparison cases, both including those with affective disorders and excluding these cases. None of the comparisons in individual studies indicated a significantly higher rate of AD-like neuropathology in the brains of schizophrenia patients, but the rates varied somewhat across studies. The authors conclude that these data do not support the hypothesis that AD-like changes now are more prevalent in schizophrenia than in other idiopathic psychiatric disorders or in normal comparison cases. Moreover, these data do not support the hypotheses that ADlike neuropathological changes have increased since the 1950's or that cerebral plaques and neurofibrillary tangles are more common in schizophrenia in association with neuroleptic treatment. 2 tables, 18 references.

Federally Funded Research on Schizophrenia The U.S. Government supports a variety of research studies relating to schizophrenia. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to schizophrenia. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore schizophrenia. The following is typical of the type of information found when searching the CRISP database for schizophrenia: •

Project Title: A NEUROBEHAVIORAL FAMILY STUDY OF SCHIZOPHRENIA Principal Investigator & Institution: Almasy, Laura A. Associate Scientist; Southwest Foundation for Biomedical Res San Antonio, TX 782450549 Timing: Fiscal Year 2001; Project Start 24-JUL-2001; Project End 30-JUN-2006 Summary: Complex genetic mechanisms underlie susceptibility to schizophrenia. The goal of this proposed collaborative R01 project, submitted as part of the Clinical Studies of Mental Disorders (CSMD) program, is to combine genetic and neurobiologic paradigms enabling detection and localization of genes that modulate susceptibility to schizophrenia and related phenotypes. As part of a major collaborative effort between the University of Pennsylvania (UPENN, Dr. R. Gur, P.I.), the University of Pittsburgh (UPITT, Dr. V. Nimgaonkar, P.I.) And the Southwest Foundation for Biomedical Research (SFBR, Dr. L. Almasy, Dr. J. Blangero, P.Is.), we propose to shift the focus on the genetic basis of schizophrenia to the detailed dissection of correlated endophenotypes. We anticipate that these continuously distributed phenotypes related to brain function will serve as reliably measured risk factors and indicators of

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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schizophrenia liability in a way that is similar to the multiple risk factors that are routinely assessed as indicators of chronic common diseases (e.g., the relationship of cholesterol measures to risk of atherosclerosis). It is likely that neurocognitive endophenotypes are more proximal functions of gene action than schizophrenia itself and therefore any contributing genetic loci should be substantially easier to localize and characterize. A combined sample of 50 multiplex multigenerational families with about 1000 members will be ascertained at the UPENN and the UPITT. Comprehensive diagnostic assessment will include the DIGS, the FIGS and scales for dimensionalizing symptoms. DSM-IV diagnoses will be made by consensus best-estimate procedures. Quantitative neurocognitive measures will be obtained using efficient computerized testing that produces a neurocognitive profile of endophenotypic markers leading to characterization of brain function. SFBR will provide the expertise in genetics of complex traits and carry out the molecular and statistical genetic analyses. Using highly polymorphic genetic markers spaced at approximately 10 cM intervals, we will localize quantitative trait loci (QTLs) influencing phenotypic variation in te neurocognitive endophenotypes employing a novel oligogenic linkage analysis method. Additionally, multivariate linkage analysis will localize pleiotropic genes that jointly influence endophenotypic variation and schizophrenia liability. All collected data will become part of the NIMH-sponsored archival database for schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A NEUROBEHAVIORAL FAMILY STUDY OF SCHIZOPHRENIA Principal Investigator & Institution: Nimgaonkar, Vishwajit L. Professor of Psychiatry and Human Geneti; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 24-JUL-2001; Project End 30-JUN-2006 Summary: (Applicant's Abstract): Complex genetic mechanisms underlie susceptibility to schizophrenia. The goal of this proposed collaborative ROl project submitted as part of the Clinical Studies of Mental Disorders (CSMD) program, is to combine genetic and neurobiologic paradigms enabling detection and localization of genes that modulate susceptibility to schizophrenia and related phenotypes. As part of a major collaborative effort between the University of Pennsylvania (UPENN, Dr. R. Gur, P.I.), the University of Pittsburgh (UPITT, Dr. V. L. Nimgaonkar, P.I.) and the Southwest Foundation for Biomedical Research (SFBR, Dr. L. Almasy, Dr. J. Blangero. P.Is.), we propose to shift the focus on the genetic basis of schizophrenia to the detailed dissection of correlated endophenotypes. We anticipate that these continuously distributed phenotypes related to brain function will serve as reliably measured risk factors and indicators of schizophrenia liability in a way that is similar to the multiple risk factors that are routinely assessed as indicators of chronic common diseases (e.g., the relationship of cholesterol measures to risk of atherosclerosis). It is likely that neurocognitive endophenotypes are more proximal functions of gene action than schizophrenia itself and therefore any contributing genetic loci should be substantially easier to localize and characterize. A combined sample of 50 multiplex multigenerational families with about 1000 members will be ascertained at the UPENN and the UPITT. Comprehensive diagnostic assessment will include the DIGS, the FIGS and scales for dimensionalizing symptoms. DSM-IV diagnoses will be made by consensus best-estimate procedures. Quantitative neurocognitive measures will be obtained using efficient computerized testing that produces a neurocognitive profile of endophenotypic markers leading to characterization of brain function. SFBR will provide the expertise in genetics of complex traits and carry out the molecular and statistical genetic analyses. Using highly

10 Schizophrenia

polymorphic genetic markers spaced at approximately 10 cM intervals, we will localize quantitative trait loci (QTLs) influencing phenotypic variation in the neurocognitive endophenotypes employing a novel oligogenic linkage analysis method. Additionally, multivariate linkage analysis will localize pleiotropic genes that jointly influence endophenotypic variation and schizophrenia liability. All collected data will become part of the NIMH-sponsored archival database for schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADDRESSING CHALLENGES IN SCHIZOPHRENIA RESEARCH Principal Investigator & Institution: Stroup, Thomas Scott. Psychiatry; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2003; Project Start 11-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This K23 Mentored Patient-Oriented Research Career Development Award will enable the candidate to develop the skills and experience necessary to become an independent investigator and scholar in interventions research for schizophrenia. The candidate is making a transition from health services to interventions research in order to address directly problems he has confronted as a clinician. The primary focus of work will be medication adherence. The overarching hypothesis is that medication non-adherence is a multifactorial barrier to good outcomes that is surmountable with specific interventions, or combinations of interventions, that address the underlying causes. An additional focus is on the decision-making capacity of persons with schizophrenia, which has important implications for medication adherence and for human subjects protections. The career objectives are to: 1) Improve understanding of the theory, concepts, and methodology related to design and analysis methods for clinical trials, 2) Gain additional exposure to issues and theoretical underpinnings of human subjects protections in vulnerable populations, with an emphasis on decision-making capacity, 3) Establish credibility as an investigator in the area of medication adherence and decision-making capacity, 4) Design and pilot test a novel clinical effectiveness trial addressing medication adherence and outcomes in a group of schizophrenic patients at high risk of non-adherence. Supervised research with experienced mentors is the main component of the career development plan. Coursework, tutorials, and workshops will be the mechanism to further develop methodologic skills and to develop expertise in treatment adherence and decision-making capacity. Two research projects will be pursued. Project 1 will use data collected in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial to conduct a novel longitudinal evaluation of medication adherence, awareness of illness, and decision-making capacity. Project 2 will establish the feasibility of a longitudinal effectiveness trial examining an intervention to improve medication adherence and outcomes in schizophrenia. This pilot study will build upon what is learned in Project 1 and will guide the design and provide preliminary data for a subsequent R01 application. At the end of the career development period, the applicant will have the skills and experience needed to lead studies of interventions designed to improve treatment adherence. The applicant's career will focus on designing and testing interventions to improve outcomes of persons who are severely affected by schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AFFECTIVE DYSFUNCTION IN SCHIZOPHERNIA Principal Investigator & Institution: Gur, Ruben C. Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104

Studies 11

Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from applicant's abstract) The goal of the proposed research is to examine emotion processing in schizophrenia through convergence of neurobehavioral, structural and functional neuroimaging methods. Affective dysfunction has been recognized as a major deficit in schizophrenia. Advances in neuroscience provide unprecedented tools to probe the neurobiology of emotional processing in healthy people and determine with increased precision the mechanism responsible for dysfunction in people with schizophrenia. This has implications for understanding the presentation, course and treatment response of individuals with schizophrenia. The proposed line of investigation will assess emotion processing applying 3-D stimuli of facial expressions of emotions. This neurobehavioral domain will be related to neurocognitive processes and to clinical measures that assess symptoms and function, with special emphasis on affective state. Brain behavior relations will be established by concurrent neuroanatomic evaluations with magnetic resonance imaging (MRI) and with more specific neurobehavioral probes using functional MRI (fMRI). The anatomic studies permit volumetric measures of fronto-temporal structures implicated in the regulation of emotion. The neurobehavioral tasks developed to dissect emotion and cognitive processing will be applied as neurobehavioral probes during online measurements of brain activity with fMRI. This will afford an evaluation of brain systems that are recruited in healthy people during task performance, relative to people with schizophrenia who manifest deficit on such tasks. The application of a genetic strategy by studying family members of affected probands with the neurobehavioral paradigms will permit the integration of two powerful research strategies in schizophrenia, genetics and behavioral neuroscience, needed to assess genetic vulnerability. The longitudinal design will allow assessment of the stability of the neurobehavioral measures and their relation, at intake, to course of illness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGING PARENTS WITH A MENTALLY ILL ADULT CHILD AT HOME Principal Investigator & Institution: Greenberg, Jan S. Waisman Ctr/Mr & Human Devlmt; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001; Project Start 01-MAR-1999; Project End 29-FEB-2004 Summary: This is a revised application that seeks support for a study on the mental health of aging parents who have an adult child with schizophrenia. The aging parents in these families face the dual challenge of continuing responsibility for an adult son or daughter with schizophrenia at the same time that they must deal with the manifestations of their own aging. The proposed study builds upon our research during the past 10 years on aging caregiving mothers of adult children with mental illness, and our comparative work contrasting these mothers with aging mothers of adults with mental retardation. We propose to conduct a three-wave longitudinal study of 300 aging families of adults with schizophrenia who have lived with their mother, age 60-85, for at least the past five years. The study will address the following questions, all within the context of Pearlin's stress process model: (1) What are the factors that contribute to positive and negative psychological well-being in mothers with an adult child who has schizophrenia? To what extent do mothers and fathers differ in the factors that affect their psychological well- being? (2) What are the antecedents to and consequences of the transition from parental to non-parental care? (3) How are the experiences of parents of an adult with schizophrenia similar to and different from those of aging parents of adults with mental retardation? The research involves multiple sets of comparisons

12 Schizophrenia

driven by a single theoretical model to test the generalizability of the stress process in different caregiving contexts. This study will be the first large scale multiwave longitudinal study of aging parents of adults with schizophrenia and will thus provide new insights about the stress and coping process and implications for mental health policy development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AMPAKINES IN SCHIZOPHRENIA Principal Investigator & Institution: Johnson, Steven A. Senior Scientist; Cortex Pharmaceuticals, Inc. 15231 Barranca Pkwy Irvine, CA 92618 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-AUG-2003 Summary: (Adapted From the Applicant's Abstract) Currently available antipsychotics effectively control positive symptoms (hallucinations, delusions), but persistent negative symptoms (withdrawal, apathy) and cognitive deficits are little affected and can be quite disabling in most patients with schizophrenia. Recently, a new class of orallybioavailable molecule that specifically enhances AMPA-type glutamate receptor activity has been developed. AMPAKINES facilitate acquisition and retention of memory in rodents and humans, and synergistically interact with modern antipsychotics. We recently completed an exploratory safety trial of the AMPAKINE CX516 added to clozapine in 19 treatment-resistant patients. CX516 was well tolerated and produced consistent improvements in negative symptoms, attention, and memory. We now propose to conduct a larger, placebo-controlled trial of CX516 added to olanzapine in patients with schizophrenia. The primary hypothesis is that CX516 will improve negative symptoms, attention, and verbal memory. Secondary aims are: 1) to asses the safety and tolerability of CX516 compared to placebo in olanzapine-treated patients; 2) to assess CX516 effects on positive symptoms, anxiety, depressive symptoms, executive function, and verbal fluency; and 3) to assess effects on extrapyramidal symptoms, including parkinsonism, akathisia and tardive dyskinesia. Positive effects on clinical (negative, positive, extrapyramidal) and neuropsychological (cognition, memory, attention) symptoms in a larger trial will strongly suggest that AMPAKINES may be useful for treatment of schizophrenia. PROPOSED COMMERCIAL APPLICATION: This research may lead to the development of a new, improved class of antipsychotic drug for schizophrenia. These new drugs have the potential to treat the diverse symptoms of this complex disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AN SCHIZOPHRENIA

ASSOCIATION

STUDY

OF

NEUROGENIN

1

AND

Principal Investigator & Institution: Fanous, Ayman H. Psychiatry; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2002; Project Start 06-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant) Schizophrenia is a leading public health problem worldwide. Discovering genes that confer susceptibility to it is an important priority, as this may lead to the development of effective modalities of prevention and treatment. Although data from family, twin, and adoption studies suggest a genetic basis to schizophrenia, and several chromosomal regions have been linked to it, cloning susceptibility genes has been elusive. A specific and overarching pathophysiology of the disease has also been elusive, but evidence from neuroimaging and neuropathological studies converges to suggest that abnormal neurodevelopment may be a cause. In recent

Studies 13

years, the biological events underlying neurodevelopment have begun to be uncovered, and several molecules that are involved in this process have been identified. One of these is neurogenini, which is involved in neuronal determination, specification of the molecular phenotype of neurons, and regional patterning of the cerebral cortex and thalamus. The gene for neurogenini is located on chromosome 5q, which has been implicated in several linkage studies of schizophrenia, including the Irish Study of High Density Schizophrenia Families (ISHDSF), which we propose to study. It is located very close to some of the most highly linked markers in this region. We propose to perform an association study of neurogenin1 and schizophrenia. As there are no known sequence variants, we propose to sequence this gene in 25 schizophrenics from the ISHDSF. We then intend to test any variants that are discovered for association with the disease. To do this, we plan to genotype all triads consisting of two parents and one affected offspring in the ISHDSF, supplemented by an additional triad collection currently underway in Ireland. We will use the transmission disequilibrium test, which determines Wan allele is transmitted to an affected offspring more often that expected by chance, to test for association and linkage. We also propose to test whether any of the variants modifies any of the clinical features of the disease. To do this, we plan to regress symptom scores on three factors as well as individual symptoms onto the transmission status of the allele, using logistic regression. If there are resources left over, we plan to genotype 400 normal controls and perform a case-control analysis using a chi-squared test to confirm any suggestive findings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AN SCHIZOPHRENIA

INVESTIGATION

OF

OLIGODENDROGLIA

IN

Principal Investigator & Institution: Hof, Patrick R. Professor; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Demyelinating diseases have long been known to be associated with behavioral disturbances. The expression levels of several myelin-related genes are consistently and substantially lower in brains obtained from schizophrenic patients than in control cases. Diffusion tensor imaging (DTI), an in vivo magnetic resonance imaging technique which assesses the coherence of white matter tracts, reveals a marked decrease in anisotropy in schizophrenic patients, indicating changes in the directionality and alignment of axons. Magnetic transfer imaging (MTI) further demonstrates reduction in myelin content in schizophrenia. An explanation for the decreased expression of myelin-related genes in schizophrenia and for the fact that these genes differentiate control from schizophrenic cases is that oligodendroglial cells are dysfunctional in schizophrenia. We propose a thorough quantitative analysis of oligodendroglial pathology in cortical and subcortical regions in brains obtained from schizophrenic patients, and a characterization of the possible repercussions of such disruption of specific axonal pathways on the morphology and function of neocortical neuron populations in genetically modified mouse models in which myelin-related genes have been knocked out. We will use rigorous stereologic analyses to assess possible changes in the numbers of oligodendrocytes in the cerebral cortex or the thalamus in schizophrenia. The 3-dimensional, spatial distribution of oligodendrocytes in these pathways may be consequently modified and may offer a quantitative neuropathological correlate of the changes in myelination. We will estimate this parameter using stereologic tessellation algorithms and relate these analyses to in vivo data obtained by DTI and MTI in other components of this Center. Finally, disruption of

14 Schizophrenia

myelination resulting from knocking out specific myelin-related genes in mice will likely affect the organization of axonal pathways furnishing inputs to the neocortex. We will measure the degree of complexity of the dendritic arborization in reconstructed pyramidal neurons from such mice models. Changes in spine density, volume, and morphology, as well as ultrastructural changes in myelination will be quantified in these mice to assess how these parameters are modified by the myelination deficits. The human cases and the animal models studied within the context of this program offer an opportunity to analyze oligodendroglial changes that have a clinical impact and to determine the morphologic characteristics of the circuits whose alteration Ieads to the cortical and subcortical dysfunction that possibly underlies the pathogenesis of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIDEPRESSANT SCHIZOPHRENIA

AUGMENTATION

OF

LATE

LIFE

Principal Investigator & Institution: Kasckow, John W. Psychiatry; University of Cincinnati 2624 Clifton Ave Cincinnati, OH 45221 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: Depressive symptoms in schizophrenia, while highly prevalent, often chronic, and disabling, remain relatively understudied. Antidepressants are commonly used in clinical practice to treat a variety of symptoms in patients with schizophrenia. Although some literature describes the treatment of syndromal depression in primarily young adults with schizophrenia, comparatively little research is available to guide the treatment of subsyndromal depressive symptoms in this population, especially in middle-aged and older adults with schizophrenia. Older people with schizophrenia differ from their younger counterparts in several important ways, such as having greater physical comorbidity, cognitive impairment, and a higher risk of side effects. This study will evaluate the efficacy and safety of antidepressant (citalopram) versus placebo augmentation of atypical antipsychotics to treat subsyndromal, residual depressive symptoms in middle-aged and older patients with schizophrenia. This collaborative, two-site (University of California, San Diego and University of Cincinnati), five-year study hypothesizes that citalopram augmentation of antipsychotic medication will be more effective than augmentation with placebo at reducing depressive symptoms and enhancing functioning and quality of life. We propose to enroll a total of 240 outpatients with schizophrenia, who are 55 years or older and have a Hamilton Depression Rating Scale 17-item score of ten or greater, into a randomized, double-blind, flexible-dose, placebo-controlled study. After stabilization for at least four weeks on an atypical antipsychotic agent (either risperidone or olanzapine), patients who have residual depressive symptoms (HAM-D score of ten or greater) will be randomized to one of the following interventions: atypical antipsychotic (risperidone or olanzapine) plus citalopram; or atypical antipsychotic (risperidone or olanzapine) plus placebo. The double-blind treatment period will be three months with a follow-up assessment three months later. Depressive symptoms and side effects will be assessed weekly for the first month, biweekly for the second month, and again at the end of the third month. In addition, we will evaluate cognitive, motor and daily functioning, quality of life, and medication adherence throughout the study. Unique to this proposal, we will use performance-based outcome measures to assess real-world functional capacities. By providing empirical evidence to guide treatment of depressive symptoms in patients with schizophrenia, the study could have significant public health

Studies 15

implications for the reduction of disability and the enhancement of quality of life in this patient population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIPSYCHOTIC HYPOFUNCTION

ACTIONS

IN

MODELS

OF

NMDA

Principal Investigator & Institution: Duncan, Gary E. Research Associate Professor; Psychiatry; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2003; Project Start 10-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Clinical studies have demonstrated that NMDA receptor antagonists induce positive, negative and cognitive schizophrenic-like symptoms in healthy subjects and precipitate psychotic reactions in patients with schizophrenia. These data, and the resulting NMDA receptor hypofunction hypothesis of schizophrenia, provide a compelling rationale for characterizing neurobiological correlates in models of reduced NMDA receptor function. The present proposal will assess behavioral and brain metabolic phenotypes in a genetic model of reduced NMDA receptor function-the NMDA R1 (NR1) subunit deficient mouse. The NR1 subunit is a component of all NMDA receptors and reduced expression of this subunit will therefore result in a chronic state of NMDA receptor hypofunction. It is hypothesized that the behavioral and brain metabolic phenotypes associated with the NR1 deficient mouse model will mimic certain phenotypes observed in schizophrenic patients. Specifically, it is hypothesized that the NR1 deficient mice will exhibit reduced brain metabolism in prefrontal and limbic regions, and exhibit alterations in sensory processing (prepulse inhibition and startle habituation). If these hypotheses are correct, the mouse models could represent an approach to explore potential preventative strategies for schizophrenia. The proposed work also will test the hypothesis that administration of typical and atypical antipsychotic drugs will have different effects on the alterations in behavior and regional brain metabolic activity observed in the genetic model of reduced NMDA receptor function In addition to the heuristic value of the work for understanding differential effects of typical and atypical antipsychotic drugs, the proposed autoradiographic studies are analogous to human PET studies of brain metabolism and blood flow, and therefore offer an important potential translational opportunity to relate results found in rodents to humans. The proposed work will not only contribute to the understanding of neurobiological actions of atypical antipsychotic drugs, but also will provide paradigms in which novel pharmacological strategies could be explored for the treatment of schizophrenia. In addition, characterizing neurobiological actions of antipsychotic drugs in the genetic model of NMDA receptor hypofunction could help delineate neurochemical dysfunction in these models, and by inference, potential pathophysiological processes in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIPSYCHOTIC TREATMENT RESPONSE Principal Investigator & Institution: Miller, Del D. Psychiatry; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001; Project Start 01-MAY-2000; Project End 30-APR-2005 Summary: (Adapted from the Applicant's Abstract): In this application for a Mentored Patient-Oriented Research Career Development Award, Del D. Miller will obtain expertise in clinical trials methodology with the intent of studying the biological aspects

16 Schizophrenia

of antipsychotic response with the goal of improving outcome in persons suffering from schizophrenia. Despite the use of newer atypical agents, many patients with schizophrenia continue to suffer from chronic symptoms and never return to baseline functioning. Dr. Miller will examine plasma concentrations and the presence of mutations of genes that code for neurotransmitter receptors to determine their roles in the clinical response of treatment-refractory persons with schizophrenia receiving clozapine. The candidate proposes a training and research program using the resources of a preventive medicine department devoted to training clinical investigators in the intricacies of treatment trials, a psychiatry department with a long history of research, and a Mental Health Clinical Research Center devoted to the neurobiology of schizophrenia. While Dr. Miller has training in schizophrenia research, he requires additional training in the design of large scale clinical investigations to study the role of biological factors on antipsychotic response. This training will be integrated with a research project seeking: 1) To examine the influence of receptor of polymorphism of the genes that code for neurotransmitter receptors and transporters predicts response to treatment with clozapine 2) To determine whether the combination of clozapine plasma concentrations and presence or absence of genetic polymorphism of neurotransmitter receptors and transporters allows for prediction of response to treatment with clozapine and 3) To develop a model for understanding the relationship between these biological factors and known predictors of clinical outcome. These findings will lead to a therapeutic model for guiding clinicians in choosing treatments for persons with schizophrenia. This award would provide the candidate with the necessary background for further studies of factors influencing antipsychotic response and may yield important algorithms for the pharmacological treatment of schizophrenia. This award will also serve as a mechanism by which the candidate can establish professional collaborative relationships with his mentors and provide him with the background for ongoing research leading to an independent research career. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AUDITORY SCHIZOPHRENIA

CORTEX:

REGIONAL

PATHOLOGY

IN

Principal Investigator & Institution: Sweet, Robert A. Associate Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Reduced gray matter volume of the auditory cortex located on the supenor temporal gyrus (S I U) is the structural brain imaging abnormality most consistently identified in the cerebral cortex of subjects with schizophrenia. Functional studies of audition similarly indicate that subjects with schizophrenia have impairments in the precision of auditory sensory memory that localize to this region. Recently, we identified that among the contributors to reduced gray matter volume in the STG of subjects with schizophrenia was reduced pyramidal cell somal volume in deep layer 3 of auditory association cortex (BA42). In this R2 I application, we propose a series of initial studies to develop a body of data necessary for the proper interpretation of the current findings and upon which future studies of auditory cortex pathophysiology in subjects with schizophrenia will be built. Specifically we will test the following hypotheses: 1) Chemoarchitectonic criteria reliably parcellate human auditory cortex into regions corresponding to the core, lateral belt and parabelt regions delineated in non-human primates. 2) Auditory lateral belt and parabelt, but not core, cortex volumes are reduced in subjects with schizophrenia. 3) Reduced deep layer 3 pyramidal cell mean somal volume in subjects with

Studies 17

schizophrenia results from a shift to smaller size of all cells and not from a change in cell number. The planned studies are novel in that they will be the first to examine changes in volume of a chemo- or cytoarchitectonically defined region in subjects with schizophrenia, and in their rigorous application of stereo logic techniques to the determination of somal volumes and absolute numbers of pyramidal cells in subjects with schizophrenia. Successful completion of these studies will: 1) Enhance the interpretation of current and future findings by placing them in the context of the rich electrophysiologic and connectional data present in monkey through delineation of human analogues of core, lateral belt and parabelt; 2) Identify a pathologic target on which to focus future investigations by determining which chemoarchitectonic regions demonstrate reduced gray matter volume; and 3) Provide a basis for the generation of specific mechanistic hypotheses by clarifying whether cell volume or number is altered. Finally, it is anticipated that the generation of mechanistic hypotheses in future studies of auditory cortex in subjects with schizophrenia will be enhanced by the applicant's ongoing, complementary studies of the neurobiology of psychosis in Alzheimer disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AUDITORY HALLUCINATIONS IN SCHIZOPHRENIA: ERPS & FMRI Principal Investigator & Institution: Ford, Judith M. Associate Professor; Psychiatry and Behavioral Sci; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-MAR-2006 Summary: Corollary discharge (CD), originally described in the visual system but also documented in the auditory system may provide a mechanism for distinguishing selfgenerated from externally-generated percepts. Within the auditory system, corollary discharges from frontal lobes where speech is generated prepare the auditory cortex in the temporal lobe for recognizing that what is heard was self-generated. Thus, failure of CD has been posited to underlie certain positive symptoms of schizophrenia, including auditory hallucinations. This hypothesis is consistent with circuit-based models of brain dysfunction in schizophrenia that suggest disrupted connectivity between frontal and temporal lobes. While theoretically compelling, the role of corollary discharge in discriminating between self and externally generated speech, and its failure in schizophrenia, are not easily amenable to measurement. However, our recent studies using event related potential (ERP) responses, functional magnetic resonance imaging (fMRI) measures of regional brain activation, and measures of electroencephalographic (EEG) coherence between frontal and temporal lobes are all consistent with the hypothesis. In this competitive renewal, we will test patients with schizophrenia and matched healthy controls in a series of studies designed to: Extend earlier observations with new ERP and fMRI experiments that enhance our understanding of normal CD operation and refine neurobiologic observations of CD deficits in schizophrenia (Specific Aim 1); Relate diffusion tensor imaging (DTI) measures of microstructural integrity of white matter tracts connecting frontal and temporal lobes to ERP and fMRI indices of CD dysfunction (Specific Aim 2); Determine whether CD failure reflects state or trait features of hallucinatory behavior in schizophrenia by assessing ERP and EEG coherence measures before and after hallucinating schizophrenic patients undergo a course of repetitive trancranial magnetic stimulation (rTMS) treatment (Specific Aim 3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

18 Schizophrenia

•

Project Title: BEHAVIORAL SCHIZOPHRENIA

GENETICS--MODELS/MECHANISMS

OF

Principal Investigator & Institution: Kilts, Clinton D. Professor and Vice-Chair of Research; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2001; Project Start 15-SEP-1995; Project End 31-JAN-2003 Summary: (Verbatim from the Applicant's Abstract) The complex syndrome of schizophrenia has been related theoretically and empirically to an elementary dysfunction in stimulus filtering/selective attention and the control of behavior by context. Using artificial selection pressure on a behavioral phenotype (Latent Inhibition of LI) that reflects these key psychophysiological constructs of schizophrenia, we have generated a novel animal (rat) behavioral model of enduring cognitive behavioral deficits associated with schizophrenia, and their pharmacological corollaries. This application for renewed funding is a plan for model testing focusing on the neural system, pharmacologic, and neurotransmitter correlates of schizophrenia. Hypotheses to be tested include that selection for low LI phenotype results in a sensitive and specific analogue of the pharmacotherapy of schizophrenia; that selection-induced deficits in LI is a developmentally delayed and enduring trait; that selection for deficits in LI is associated with hemispherically lateralized alterations in limbic-striatal networks and of intrinsic dopamine (DA) and serotonin neuronal populations; and that selection for deficits in LI is related to alterations in brain neurotensin (NT) mechanisms and their response to antipsychotic drugs. Hypothesis testing will involve the following specific aims: Specific aim #1 would develop a third replicate of LI selection and characterize behaviorally the response of LI to artificial selection. Behavioral testing would define the age dependence of the response to selection and further evaluate deficits in the prepulse inhibition (PPI) of an acoustic startle response as a genetically correlated trait. Specific aim #2 would define the impact of a genetically selected deficit in LI on the effects of antipsychotic drugs on stimulus filtering ability. The effects on LI of typical and atypical antipsychotics, nonantipsychotics, and DA receptor agonists would be compared in the Low, High, and Control lines. Specific aim #3 would elucidate3 the neural pathway and neurotransmitter correlates of LI selection to explore the mechanisms of schizophrenia and antipsychotic drug action. Mitochondrial markers of synaptic activity and in vivo microdialysis estimates of DA and serotonergic neuronal activity would define the neural correlates of disrupted stimulus processing and the restorative effects of antipsychotic drugs. Specific aim #4 would determine the role of altered brain NI mechanisms in disrupted stimulus processing and the differential effects of antipsychotic drugs on disrupted versus normal stimulus filtering. Line differences in NT gene and peptide expression would be defined. The shorter term goals of this plan are to use behavioral genetic techniques to define the mechanisms of differential stimulus processing and the deficit state and genetic determinants of antipsychotic drug effects on this operation, with the longer term objective of developing a unique genetic model of the pharmacology and mechanisms of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOLOGICAL RESEARCH IN SCHIZOPHRENIA Principal Investigator & Institution: Holzman, Philip S. Esther & Sidney Rabb Professor; Mc Lean Hospital (Belmont, Ma) Belmont, MA 02478 Timing: Fiscal Year 2001; Project Start 01-AUG-1977; Project End 31-DEC-2002

Studies 19

Summary: Certain physiological and cognitive traits occur much more frequently among the first degree relatives of schizophrenic patients than they do in the general population. These traits are not clinically harmful, but they are very useful scientifically, both as probes into the pathophysiology os schizophrenia, and as supplementary phenotypes in linkage analysis. The objective of this Program Project is to discover such traits, and to use them to increase our understanding of the pathophysiology and genetics of schizophrenia. Eye tracking disorder and impaired spatial working memory are example of traits that aggregate in the first degree relatives of schizophrenic patients. Since they are frequently found in relatives who do not express any schizophrenia-like pathology, they cannot be secondary effects of schizophrenia, but are related in a unknown way to the biological processes underlying the disease. In this Program Project, eye tracking disorder, spatial working memory, cognitive interference, dysmorphology, and event-related potentials are studied in the relatives of schizophrenic patients, after thorough clinical assessment, both in the psychophysiology laboratory and through fMRI imaging. Traits that run in the families of to schizophrenic patients have genetic importance as well. The search for genetic markers linked schizophrenia has been hindered by the low rate at which the illness recurs in the families of schizophrenic patients. These co-segregating traits are generally much more common among family members, making them useful as genetic indicators. The sample drawn from the McLean Hospital, where the Program Project is based, but investigators form other Harvard institutions also contribute to the measurements and analyses, including the Vision Sciences Laboratory in the Department of Psychology, the Statistics Department of the Faculty of Arts and Science, the Eunice Kennedy Shrive Center for Mental Retardation, and the Molecular Neurogenetics Unit at the Massachusetts General Hospital. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OUTCOMES

BIOSOCIAL

FACTORS

AND

REHABILITATION

SERVICE

Principal Investigator & Institution: Brekke, John S. Professor; None; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001; Project Start 25-SEP-1998; Project End 31-JUL-2003 Summary: (Applicant's abstract): This is a request for an NIMH Independent Scientist Award (ISA). It will enable the applicant to develop a research career plan which focuses on the use of prospective studies to: 1) increase the understanding of the relationships between biological factors and psychosocial functioning in schizophrenia: 2) to generate knowledge that integrates social and biological factors in a psychosocial rehabilitation framework that can be used to improve community-based rehabilitation service outcomes for individuals with schizophrenia. This research program builds on an ROl held by the applicant, as well as other studies on rehabilitative and prospective functional outcomes in schizophrenia. Seven specific career goals are outlined. These goals will be met through research activities and collaborations with senior scientists, classroom and technical training, writing of joint grant applications and participation in new scientific meetings. Plans for mentoring and participating in advanced scientific education are aimed at furthering the integration of biological factors into a more complete biosocial model of rehabilitation in schizophrenia. Blending biological factors with psychosocial rehabilitation models in schizophrenia will require the integration of a variety of theoretical and empirical themes in schizophrenia research. This application will use data from existing and planned studies on the effectiveness of communitybased rehabilitative interventions, the etiology of schizophrenia, and on the relationship

20 Schizophrenia

between biological factors and psychosocial functioning. It will also incorporate recent notions about the remediation of cognitive and psychophysiological deficits in schizophrenia. Stress-vulnerability models will be used as a guiding heuristic for this research development program. An Independent Scientist Award at this stage of the applicant's career will provide release from teaching and administrative responsibilities, and will provide the time and resources needed to capitalize on a superior network of senior investigators who will provide outstanding collaborative and training opportunities in this area. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN ACTIVITY AND LANGUAGE COMPREHENSION IN PSYCHOSIS Principal Investigator & Institution: Salisbury, Dean F. Assistant Professor; Mc Lean Hospital (Belmont, Ma) Belmont, MA 02478 Timing: Fiscal Year 2001; Project Start 20-JUL-2001; Project End 30-JUN-2005 Summary: (provided by applicant) Thought disorder is a cardinal symptom of schizophrenia, and is inferred through abnormal language. The underlying cognitive abnormality that causes thought disorder is unknown. The broad aim of this proposal is to understand the neurophysiological basis of thought disorder in schizophrenia and psychotic mania. We will test a model of semantic over-activation and verbal Working memory dysfunction in schizophrenia, contrasted with an executive attention abnormality in mania. We will measure language comprehension, reaction times, and the activity of the brain via event-related potentials, and correlate these measures with clinical measures of symptoms and neuropsychological measures of working memory performance. One possible dysfunction is an abnormality in semantic memory activation (hyperpriming) whereby associated by contextually inappropriate concepts crowd the mind of schizophrenia patients. Paradoxically, schizophrenia patients outperform controls on speeded lexical decision tasks, with faster reaction times. However, at slower speeds, the performance of patients falls off sharply. The neural substrates of this hyperpriming and of the later drop off in performance are unknown. We test a two-factor model of schizophrenic thought disorder with both an initial automatic excitatory abnormality and a later abnormality in the controlled utilization of context stored in verbal working memory by having subjects process sentences, word pairs, and word triplets for semantic relatedness. The stimuli will include homographs as the primary probe of associative derangement. Homographs are words with multiple meanings, and occupy places in more than one unrelated semantic network. For example, board may mean plank or committee. Schizophrenia patients appear to display a semantic bias towards strong associates and networks such that they tend to select the dominant homograph meaning (board means plank) even in the face of context that mandates accessing the subordinate meaning (board means committee). We propose to examine language processing while varying networks strength (dominant versus subordinate meanings), while varying associative strength (strongly versus weakly associated words), in the face of strongly biasing context followed by weak associates, and in the face of weakly biasing context followed by strong associates. These different manipulations will be presented under fast (250 msec) and slow (1.25 sec) rates, to more heavily stress the semantic activation system and the verbal working memory system respectively. The use of ERPs allows for direct measures of stimulus processing, and provides some information about putative sources of brain dysfunction (when informed from previous direct recordings). These studies have the potential to help clarify the nature of cognitive dysfunction in schizophrenia and in psychotic mania.

Studies 21

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN ERPS AND COGNITIVE DEMAND IN SCHIZOPHRENIA Principal Investigator & Institution: Bruder, Gerard E. Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001; Project Start 01-AUG-1994; Project End 28-FEB-2003 Summary: (Adapted from applicant's abstract): Schizophrenic patients have shown a reduction in amplitude of the P3 brain ERP to tones, which was maximal over left temporal lobe sites. In the initial project period, the investigator replicated this finding in a dichotic complex tone task and found reduced N2 amplitude and asymmetry in schizophrenic patients in a dichotic syllable task. This suggests that left hemisphere dysfunction in schizophrenia for verbal processing occurs as early as 200 ms after stimulus onset. N2 abnormalities in schizophrenic patients were present in both auditory and visual tasks, whereas P3 abnormalities appear to be modality specific. The investigator proposes to conduct four studies to determine the task and patient characteristics necessary for producing these ERP abnormalities and to further resolve their neurophysiologic mechanisms. Study 1 will record ERPs in a large sample of schizophrenic patients (n=120) and normal controls (n=40) on verbal and nonverbal binaural oddball tasks, and will assess the influence of response mode (silent counting, right hand or left hand). These large samples will enable the investigator to examine the relation of ERP abnormalities in schizophrenia to symptom features, outcome of treatment with neuroleptics, familial history of schizophrenia, and neuroimaging measures. Study 2 will develop and apply new verbal and nonverbal tasks that incorporate advantages of dichotic listening procedures, but utilize a simple oddball paradigm. Study 3 compares ERPs of schizophrenic patients and controls in auditory and visual continuous word recognition tasks, which are thought to reflect left medial temporal lobe function. Study 4 continues the investigator's study of visuospatial processing in schizophrenia using a revised paradigm designed to disentangle effects of selective attention and later cognitive processing. Patients will be tested while off medication and again after six weeks of treatment with haloperidol or an atypical neuroleptic (clozapine or risperidone). A more long range clinical goal is to contribute toward the development of tests that could predict response to treatment with conventional or atypical neuroleptic medications for schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BRAIN IMAGING IN THE MAJOR PSYCHOSES Principal Investigator & Institution: Andreasen, Nancy C. Professor; Psychiatry; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001; Project Start 01-SEP-1985; Project End 31-MAR-2004 Summary: (adapted from applicants abstract): Basic Aims: To achieve an increasingly fine resolution of the components of the cognitive processes that are disordered in schizophrenia (e.g., attention, memory, language); to relate them to the symptomatic manifestations of the disorder; to identify their neural substrates; to further refine a unifying concept of schizophrenia that will facilitate more basic research targeted toward identification of its cellular, molecular, and developmental mechanisms. Basic Hypothesis: Schizophrenia is characterized by a fundamental cognitive deficit, referred to as "cognitive dysmetria." This deficit is due to an underlying dysfunction of the neural circuits that provide interconnections and ongoing feedback between prefrontal cortex and the cerebellum, linked through the thalamus. In the healthy brain, these

22 Schizophrenia

circuits facilitate the fluid coordination of mental functions--planning, initiation, timing, and monitoring of behavior. Patients with schizophrenia display impairments in both cognitive and motor behavior that reflect a dysfunction in this circuitry. The presence of this fundamental cognitive deficit leads to the very frequently observed phenomenon that patients with schizophrenia display a 'generalized deficit' on most cognitive tasks. It also explains the fact that schizophrenia is a polythetic disorder, that patients present with a diversity of symptoms, and that these symptoms cover the broad range of human cognitive, perceptual, emotional, and motor functions. Basic Methods: This hypothesis will be tested through convergent measures, using the techniques of MR imaging, PET imaging, experimental cognitive psychology, clinical psychopathology, and assessments of motor function. Interrelated experiments are proposed that permit the use of PET to dissect the components of cognitive operations and define their functional circuitry, complemented by the use of MR to localize these components anatomically and to determine whether they have gross anatomical substrates. During the five-year period of the grant, a total of 200 patients and controls will be studied. We have developed innovative MR sequences to measure the cerebellum and thalamic nuclei. We will also apply innovative image analysis techniques, either locally developed or obtained from experienced consultants, including neural nets, flat maps, and high dimensional transformations. These will be used to measure cortical surface anatomy and the volume of substructures such as caudate or hippocampus. Ten different groups of PET experiments will be completed, which are grouped into three general categories: motor rhythms and perception of time intervals, memory and temporal computation, and attention and executive function and temporal computation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN MIDLINE MALFORMATION IN SCHIZOPHRENIA Principal Investigator & Institution: Deutsch, Curtis K. Research Scientist; Psychiatry; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, MA 01655 Timing: Fiscal Year 2001; Project Start 05-JUL-2000; Project End 30-JUN-2004 Summary: (Verbatim from the Applicant's Abstract): The impetus for this project is an embryological model of brain maldevelopment deriving from our craniofacial dysmorphology studies of schizophrenia. In both an initial study and a recent replication, we have found excessive frontonasal-maxillary junctural dysmorphology among schizophrenic patients and their relatives. How might these findings relate to brain dysmorphogenesis? Because the brain and face arise from shared embryonic origins, genetic deviations or environmental insults during embryogenesis can manifest themselves both in the brain and craniofacial formations. Thus, delineating a region of craniofacial dysmorphology may circumscribe brain regions where development has gone awry. Embryologic fate-maps predict that the frontonasal-maxillary junctural region implicated in schizophrenia corresponds to the interface of the diencephalon and mesencephalon. Based on our craniofacial findings, we predicted that brain maldevelopment in schizophrenia might arise at this interface. Our preliminary studies of schizophrenia have borne out this prediction, revealing a marked deviation of the anterior-posterior brain midline above the diencephalic-mesencephalic border. Notably, the brain midline deviation and frontonasal-maxillary junctural dysmorphology are significantly correlated within subjects, further corroborating this model. We have also observed marked brain midline deviations among siblings of these probands which if confirmed, raises the possibility that these forms of dysmorphology are tapping a pathogenic process that is transmissible. In this project, we propose to: (1) determine the

Studies 23

extent to which the brain midline, imaged by magnetic resonance, is deviant in schizophrenia and (2) establish the specificity of these findings to schizophrenia, employing a contrast group with bipolar affective disorder. (3) Further, we will ascertain whether midline deviation is over-represented among non-psychotic siblings of schizophrenic probands, and determine if these deviation scores are positively correlated with thought disorder and other clinical variables among probands and their siblings. (4) Finally, we will document the degree to which brain and face dysmorphology coheres within subjects, as predicted by the embryological model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN PHOSPHOLIPID COMPOSITION IN SCHIZOPHRENIA Principal Investigator & Institution: Komoroski, Richard A. Professor; Radiology; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, AR 72205 Timing: Fiscal Year 2002; Project Start 06-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Studies of erythrocytes and platelets have suggested that schizophrenia arises from cell membrane abnormalities due to changes in phospholipid (PL) metabolism and composition in the brain. A hypothesis of schizophrenia based on cell membrane abnormalities can potentially explain a range of findings, and is consistent with abnormalities in multiple neurotransmitter systems and neurodevelopment. Examination of PL precursors and degradation products by in vivo 31P nuclear magnetic resonance (NMR) suggests alterations in brain PL metabolism in schizophrenia. A limitation of these in vivo NMR studies is that PLs are not observed directly because they are solid-like. For the 31 P in vivo NMR results to support strongly the membrane hypothesis of schizophrenia, changes in PL precursors and degradation products must be linked with actual changes in PL composition in the brain. In preliminary studies in our lab using 31P in vitro NMR, elevated phosphatidylinositol, elevated phosphatidylcholine with one saturated and one unsaturated side chain, and a trend toward increased total PLs, were found in extracts of postmortem schizophrenic brain (frontal cortex) relative to control. These results support the notion that PL abnormalities occur in the brain in schizophrenia. It is hypothesized that the PL compositions in frontal and temporal cortices (but not occipital cortex), regions implicated in schizophrenia, are different in schizophrenics than in controls. It is also hypothesized that, in the cases where in vivo 31 P NMR detects changes in PL precursors and/or degradation products, changes in PL composition are also occurring. It is proposed to measure both the PL composition (organic solvent extract and bile-salt solubilization) and PL precursors and degradation products (perchloric acid extract) in left frontal, temporal and occipital cortices of the same individuals (20 schizophrenics, 20 controls, and 10 psychiatric controls) using 31 P in vitro NMR. This study will shed light on the sometimes conflicting results of previous PL studies both on peripheral tissue and in vivo. It will also potentially provide support and clarification for several aspects of the membrane hypothesis of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BUILDING SCHIZOPHRENIA

A

MOUSE

MODEL

WITH

RELEVANCE

TO

Principal Investigator & Institution: Fish, Kenneth N.; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2006

24 Schizophrenia

Summary: (provided by applicant): The career development and research program described in this proposal supports the application for a Mentored Research Scientist Development Award for Dr. Kenneth N. Fish, and is intended to provide the candidate with the background knowledge, research experience, and research management skills that will prepare him for an independent research career in schizophrenia. Training will take place at the Harold L. Dorris Neurological Research Center in the Department of Neuropharmacology (Dr. Floyd E. Bloom, Chair) of the Scripps Research Institute, under the direct supervision of Dr. Tamas Bartfai. Dr. Bartfai is highly qualified to serve as Preceptor for the Candidate, because of his experience with the methodologies to be used, his active research program in depression and schizophrenia, and his commitment to the development of junior research scientists. The Department of Neuropharmacology emphasizes a multi-disciplinary approach to problems of mental disorders. Thus, this is an ideal environment for the Candidate to materialize his goal of developing a multidisciplinary research approach to the neurobiology of schizophrenia. The overall objective of the research plan is to perform a thorough analysis of the reeler and scrambler mice to define test parameters that will be used to study new mouse models and to determine their applicability as models to study schizophrenia. Tests will include a morphological analysis of the neocortex, cerebellum, and hippocampus using three-dimensional reconstruction with NeuroZoom, immunocytochemical analysis of DA, GLU, and GABA expression, quantitative behavioral measurements [prepulse inhibition (PPI) of the startle response], and their responsiveness to clinically effective antipsychotics (haloperidol, risperidone, and clozapine). In addition, to further characterize the reeler phenotype we will generate a transgenic mouse in which reelin expression is temporally regulated and generate a mouse model that has a conditional block of reelin function to induce specific changes in brain morphology that are required to alter prepulse inhibition and/or induce ataxia. These studies will advance our understanding of how neurodevelopmental abnormalities relate to behavioral changes and will assist in the development of new antipsychotic drugs with relevance to schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CAMP/PKA SCHIZOPHRENIA

SIGNALING

&

ENDOPHENOTYPES

OF

Principal Investigator & Institution: Druhan, Jonathan P.; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Recent evidence suggests that disturbances in intracellular signaling may underlie some of the cognitive and neurobehavioral dysfunctions observed in schizophrenia. Studies in humans suggest that the cyclic AMP/protein kinase A (cAMP/PKA) signaling pathway is upregulated within the central nervous systems of schizophrenic patients. Our preliminary studies indicate that transgenic mice overexpressing a constitutively active form of the signaling protein Gs(Gs-*) in forebrain neurons exhibit deficits in two neurobehavioral processes known to be disrupted in schizophrenics, inhibitory gating and explicit learning. Studies in this proposal will examine the effects of increased cAMP/PKA signaling on inhibitory gating and learning in mice to determine whether signaling disturbances could contribute to these endophenotypes of schizophrenia. Studies in Aim 1 will test transgenic mice that overexpress constituents of the cAMP/PKA signaling pathway (i.e. Gs-*, the catalytic subunits of PKA, or a nuclear target of PKA, CREB) in animal models of inhibitory gating and learning to determine whether such mice show deficits in these

Studies 25

paradigms (prepulse inhibition, P20/N40 gating, and Morris water maze). Offspring of Gs-* mice crossbred with mice having reduced PKA or CREB activity also will be tested in these behavioral paradigms to determine whether reductions in PKA or CREB can normalize the behavioral deficits produced by the overexpression of Gs-*. Studies in Aim 2 will measure inhibitory gating and learning after localized stimulation of cAMP/PKA activity in forebrain regions of wild-type mice, or after localized inhibition of cAMP/PKA in forebrain regions of Gs-* mice, to determine whether localized pharmacological manipulation of cAMP/PKA activity modifies gating and learning processes. Studies in Aim 3 will determine whether drugs effective at treating symptoms of schizophrenia will normalize gating and learning deficits in mice with upregulated cAMP/PKA activity. These studies will provide important new information about the role that intracellular signaling in cAMP/PKA pathways plays in the expression of gating and learning endophenotypes of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CANNABINOIDS AND CORTICAL-CEREBELLAR FUNCTION Principal Investigator & Institution: Patel, Sachin; Pharmacology and Toxicology; Medical College of Wisconsin Po Box26509 Milwaukee, WI 532264801 Timing: Fiscal Year 2002; Project Start 01-JUL-2002 Summary: (provided by applicant): Cannabis intoxication is known to produce psychotic symptoms such as delusions, and disorganized thoughts resembling schizophrenia. In addition, epidemiological data supports a correlation between cannabis use and subsequent development and/or exacerbation of schizophrenia in humans. Schizophrenia is known to inhibit the activity of prefrontal-thalamic-cerebellar network in humans, and has led to the cognitive dysmetria hypothesis of schizophrenia. This posits that a primary dysfunction in the prefrontal-thalamic-cerebellar network underlies the broad range of schizophrenic symptomatology. We will utilize functional magnetic resonance imaging, Fos immunohistochemistry and mass spectroscopy to explore the biological mechanisms by which cannabinoids may inhibit prefrontalthalamic-cerebellar networks in animals with the aim of further understanding the biological basis for the high correlation between cannabis use and schizophrenia. In addition, we plan to evaluate the role of the endogenous cannabinergic system in the regulation of the prefrontal-thalamic-cerebellar network. We hope that successful completion of these studies will provide enhanced understanding of both the endocannabinoid system and its possible contribution to the pathophysiology of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHARACTERIZATION OF PRODROMAL SCHIZOPHRENIA Principal Investigator & Institution: Cornblatt, Barbara A. Professor; Long Island Jewish Medical Center 270-05 76Th Ave New Hyde Park, NY 11040 Timing: Fiscal Year 2001; Project Start 01-MAY-2000; Project End 30-APR-2005 Summary: The prodromal phase of schizophrenia is considered to begin with early subtle changes in behavior and continue until the onset of psychosis. The proposed study is designed to prospectively characterize the prodromal phase of schizophrenia and determine the accuracy with which prodromal symptoms predict schizophrenia. This information, which is not currently available, is essential for establishing effective intervention programs. From a research perspective, since not all individuals displaying putative prodromal symptoms will actually develop schizophrenia, such subjects

26 Schizophrenia

constitute a new type of population at risk for schizophrenia, referred to here as clinical high risk (CHR). One hundred and twenty CHR patients, 60 normal controls and 60 psychiatric controls diagnosed with attention deficit hyperactivity disorder (included to evaluate specificity), will participate in the proposed five year study. All subjects will be between the ages of 14-21 years. High risk patients will be divided into two groups of 60 patients each: the CHR group, that will consist of patients characterized by social deficits, increasing school difficulties, and odd behaviors; and the CHR+P group, consisting of CHR patients who have also begun to display a range of attenuated positive symptoms. All high-risk patients will be recruited from the Recognition and Prevention of Psychological Problems (RAPP) Clinic. It has been operational for approximately a year and a half under the direction of the investigator and provides treatment to adolescents and young adults considered to be in the prodromal phases of schizophrenia. All study participants will be assessed at base and during regular follow ups, on clinical and neurocognitive characteristics thought most likely to define the prodrome, according to the literature and the pilot work already completed in the RAPP clinic. A number of clinicians and researchers have recently proposed that if treatment were to begin during the prodrome, progression to psychosis might be prevented or, at minimum, delayed and severity reduced. However, the prodrome is currently a retrospective concept that has not as yet been prospectively validated. The overall goal of this project is to assess and prospectively follow adolescents in all four subject groups to establish the sensitivity, specificity and predictive validity of the selected prodromal characteristics. This is expected to provide an evidential base that will lead to a variety of phase-specific interventions throughout the prodrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CITALOPRAM AUGMENTATION IN OLDER SCHIZOPHRENIA PATIENTS Principal Investigator & Institution: Zisook, Sidney; Professor & Director; Veterans Medical Research Fdn/San Diego Foundation of San Diego San Diego, CA 92161 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: Depressive symptoms in schizophrenia, while highly prevalent, often chronic, and disabling, remain relatively understudied. Antidepressants are commonly used in clinical practice to treat a variety of symptoms in patients with schizophrenia. Although some literature describes the treatment of syndromal depression in primarily young adults with schizophrenia, comparatively little research is available to guide the treatment of subsyndromal depressive symptoms in this population, especially in middle-aged and older adults with schizophrenia. Older people with schizophrenia differ from their younger counterparts in several important ways, such as having greater physical comorbidity, cognitive impairment, and a higher risk of side effects. This study will evaluate the efficacy and safety of antidepressant (citalopram) versus placebo augmentation of atypical antipsychotics to treat subsyndromal, residual depressive symptoms in middle-aged and older patients with schizophrenia. This collaborative, two-site (University of California, San Diego and University of Cincinnati), five-year study hypothesizes that citalopram augmentation of antipsychotic medication will be more effective than augmentation with placebo at reducing depressive symptoms and enhancing functioning and quality of life. We propose to enroll a total of 240 outpatients with schizophrenia, who are 55 years or older and have a Hamilton Depression Rating Scale 17-item score of ten or greater, into a randomized, double-blind, flexible-dose, placebo-controlled study. After stabilization for at least four weeks on an atypical antipsychotic agent (either risperidone or olanzapine), patients

Studies 27

who have residual depressive symptoms (HAM-D score of ten or greater) will be randomized to one of the following interventions: atypical antipsychotic (risperidone or olanzapine) plus citalopram; or atypical antipsychotic (risperidone or olanzapine) plus placebo. The double-blind treatment period will be three months with a follow-up assessment three months later. Depressive symptoms and side effects will be assessed weekly for the first month, biweekly for the second month, and again at the end of the third month. In addition, we will evaluate cognitive, motor and daily functioning, quality of life, and medication adherence throughout the study. Unique to this proposal, we will use performance-based outcome measures to assess real-world functional capacities. By providing empirical evidence to guide treatment of depressive symptoms in patients with schizophrenia, the study could have significant public health implications for the reduction of disability and the enhancement of quality of life in this patient population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNATURES

CLASSIFYING

SCHIZOPHRENIA:LEUKOCYTE

MULTIGENE

Principal Investigator & Institution: Clelland, James D.; Nathan S. Kline Institute for Psych Res Psychiatric Research Orangeburg, NY 10962 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): This proposal is designed to produce data for development of a biological classification of schizophrenic patients, based on highdensity microarray measurement of transcribed white blood cell (leukocyte) RNA. In a recently completed NIMH B-start grant, the PI has utilized global gene expression analysis of peripheral leukocytes as a classification medium for schizophrenia. The preliminary study results were striking; hierarchical clustering of the gene expression data from seven schizophrenic patients and five controls, resulted in classification of all the samples into their correct group (schizophrenic patients or healthy controls). This exciting result has led to the present proposal with the following Specific Aims: (1) a. To collect peripheral blood leukocytes from twenty neuroleptic-naive schizophrenics, twelve neuroleptic-treated schizophrenics, and fourteen healthy control subjects over the two-year period of the project, and b. To employ Affymetrix GeneChip mieroarray technology to measure global gene expression in the leukocyte samples. (2) The leukocyte gene expression datasets collected during the preliminary study and the proposal, resulting in a final analysis of 58 subjects, will be combined and analyzed by hierarchical clustering and discriminate analyses to identify and validate multi-gene fingerprints that differentiate schizophrenic subjects from healthy controls. The current proposed study, which incorporates the collection of samples from neurolepfic-naive schizophrenic patients, is designed to avoid the potential confounding factor of neuroleptic-medication induced gene expression changes. We are optimistic that completion of this proposed exploratory study will lead to the creation of a multigene expression signature that can classify leukocyte samples into schizophrenic patient or control groups and that can be used to predict the class of unknown samples. If the validity of our approach is demonstrated in this exploratory study, our longer-term aims for this research are to increase the scope of this work by: 1. Increasing the number of subjects in our schizophrenic dataset to the level of acceptable statistical power and also duplicating this dataset for other psychiatric disorders including bipolar disorder, schizoaffective disorder and major depression. This will allow us to test these classification signatures and thus attempt biological diagnosis of psychiatric disorders and possible biological subtypes of those disorders. These biological signatures may, in

28 Schizophrenia

turn, stimulate the development of targeted novel medications. 2. Perform a follow-up study recruiting families with members at increased risk of developing schizophrenia. These families will allow us to test whether gene expression patterns that classify schizophrenia are present in premorbid subjects and whether it is possible to predict risk of illness, and thus provide early treatment that might mitigate the course of the disorder. The public health benefits of a biological classification of schizophrenia are potentially large, especially if predictive testing in the premorbid stage is possible, raising the possibility of targeted preventative treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: APPROACHES

CLINICAL

TRIALS

IN

SCHIZOPHRENIA--MOLECULAR

Principal Investigator & Institution: Malhotra, Anil K. Chief of Mol. Psychiatry; Long Island Jewish Medical Center 270-05 76Th Ave New Hyde Park, NY 11040 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: This application for a Mentored Patient-oriented Career Development Award (K23) is to support the development of the candidate into a independent investigator capable of conducting large scale clinical trials in psychiatry that address issues of treatment efficacy and effectiveness in addition to serving as the clinical basis for pharmacogenetic studies. The development plan has four major goals: 1) Gain expertise in the design of a clinical trial in schizophrenia, 2) Participate in the execution of a clinical trial, 3) Utilize statistical methodology to analyze clinical trials studies, and 4) Conduct pharmacogenetic analyses of clinical trials data. To accomplish these aims, three major career development activities are proposed: 1) A didactic program to prepare the candidate to independently design, conduct, and analyze clinical trials, 2) Participation in a large clinical trial comparing new antipsychotic medications in patients experiencing their first episode of schizophrenia. This will involve the candidate's participation in the clinical trial as an investigator and will provide the opportunity to develop a pharmacogenetic protocol and, 3) The design, conduct and analysis of a pilot study of the effects of adding the serotonin re-uptake inhibitor, sertraline, to the antipsychotic treatment regimen of schizophrenia patients with treatment-refractory hallucinations. The research plan incorporates two studies. The first is a pharmacogenetic assessment of response to the antipsychotic agents olanzapine and risperidone. This study involves determination of genotype at specific candidate loci within the dopamine and Serotonin receptor systems and case-control and family-based association analysis between these loci and clinical phenotypes of treatment response, drug-induced weight gain and drug-induced extra pyramidal symptoms. The second study is a clinical trial examining sertraline augmentation in schizophrenia patients with hallucinations. The basis of this study is evidence from clinical trials research as well as molecular genetics. This represents an initial effort to utilize the two distinct methodologies to enhance the treatment of schizophrenia. The career development activities and completion of the research studies described in this application are expected to provide the candidate with the knowledge and research experience to develop into an independent investigator with the expertise to conduct high quality clinical trials that incorporate pharmacogenetics into psychiatry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLOZAPINE TREATMENT OF SCHIZOPHRENIC PATIENTS Principal Investigator & Institution: Buchanan, Robert W. Professor; Psychiatry; University of Maryland Balt Prof School Baltimore, MD 21201

Studies 29

Timing: Fiscal Year 2002; Project Start 01-APR-1990; Project End 31-DEC-2006 Summary: This is a submission of a competitive renewal application, MH 45074: "Clozapine Treatment of Schizophrenic Outpatients". Over the last ten years, the new generation antipsychotics clozapine, risperidone, olanzapine, quetiapine, and ziprasidone have been approved and introduced for the treatment of schizophrenia. Of these agents, only clozapine has been shown to have superior efficacy to conventional antipsychotics, and is FDA approved for treatment-resistant patients with schizophrenia. However, up to 50 percent of patients adequately treated with clozapine will fail to respond, and will continue to exhibit clinically significant residual positive and negative symptoms and cognitive impairments. These patients represent a major therapeutic challenge and raise the question: What treatment options are available for these patients? The major emerging treatment trend is to use a second antipsychotic medication. This clinical practice has become relatively widespread, but there is little empirical evidence to support the validity of this approach. We will conduct a 16-week randomized, parallel group, double-blind comparison of adjunctive risperidone and placebo in clozapine-treated patients with schizophrenia to address two primary aims: is adjunctive risperidone superior to placebo for the treatment of persistent positive symptoms and cognitive impairments in clozapine-treated patients with schizophrenia, and three secondary aims: is adjunctive risperidone superior to placebo for the treatment of persistent negative symptoms and functional impairments, and is adjunctive risperidone associated with increased incidence of side effects as compared to placebo in clozapine-treated patients with schizophrenia. We will perform biweekly positive and negative symptom and side effect assessments, and baseline and end of study neuropsychological and functional assessments. The study will provide new information on the clinical utility of adjunctive risperidone in treatment-resistant patients who fail to adequately respond to clozapine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLOZAPINE, CANNABIS AND FIRST EPISODE SCHIZOPHRENIA Principal Investigator & Institution: Green, Alan I. Psychiatry; Harvard University (Medical School) Medical School Campus Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 11-MAY-2001; Project End 30-APR-2004 Summary: (provided by applicant): Accumulating evidence suggests that early intervention (particularly with novel antipsychotics) may improve the long-term course of schizophrenia. While clinicians are routinely using novel antipsychotic drugs for patients within the first episode of schizophrenia, and large-scale investigations of novel antipsychotics in first episode patients are underway, the novel drug clozapine (CLOZ) is not used clinically or in most research studies in patients because of Its side effects and the practical difficulties with its use. The notion behind our proposed research, however, is that CLOZ may be relatively safe and particularly helpful for first episode patients who are comorbid for cannabis use disorder (CUD). These comorbid patients, comprising approximately 50% of first episode patients, have a poor outcome, especially when cannabis use continues over time. A number of lines of evidence provide support for a study of CLOZ in this population: (a) preliminary data suggest that CLOZ (but not risperidone [RISP] -or olanzapine) decreases substance use in patients with schizophrenia; (b) preliminary data suggest that CLOZ (but not RISP or olanzapine) is more efficacious for first episode patients than typical antipsychotics; (c) preliminary data suggest that CLOZ decreases suicide rates in chronic schizophrenia; and (d) established data indicate CLOZ's unique efficacy in poor-outcome patients. The PI's recently published neurobiologic formulation to help explain the beneficial effects of

30 Schizophrenia

CLOZ on comorbid substance use provides further support for this application. In this revised application (under 'Pilot Effectiveness Trials for Mental Health'), the PI and colleagues begin a line of investigation to study the comparative effects of CLOZ and RISP in patients within their first episode of schizophrenia who are comorbid for CUD. The overarching hypothesis is that CLOZ (compared to RISP) will decrease cannabis and other substance use and will also improve the outcome of these patients. The clinical implication of this hypothesis is that CLOZ may have a clear therapeutic advantage for such patients (and may even be lifesaving) and may well be the drug of choice for them. In this pilot application, we will gather short- and long term preliminary efficacy data (and effect sizes), and further assess the risks and benefits of CLOZ in this population, to provide the basis for a large-scale effectiveness trial to compare the effects of treatment with CLOZ or RISP on cannabis and other substance use, global functioning, clinical symptoms, quality of life, and neurocognitive functioning, as well as on cost effectiveness of treatment in first episode patients with schizophrenia who are comorbid for CUD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITIVE NEUROSCIENCE OF SCHIZOPHRENIA Principal Investigator & Institution: Carter, Cameron S. Associate Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 30-JUN-2006 Summary: (provided by applicant) This is an application for an Independent Scientist Award (K02) from an applicant who is currently supported by a Mentored Scientist Award for Clinicians (K08), which ends 4/01 During the period of the KO8 the applicant has made significant progress in pursuing his training goals, which were to increase his expertise in basic cognitive neuroscience and to develop expertise in conducting functional imaging studies of impaired cognition in schizophrenia. In addition to accomplishing a significant level of productivity in these two areas, the applicant has also made the transition from advanced trainee to independent scientist during the period of the K08. The goals of the present application are 1) to develop new expertise in the use of ERP, and in the integration of ERP and fMRI, into multimodal imaging studies of human executive functions, 2) to build upon the applicants current expertise in the analysis of event-related fMRI data related to impaired cognition In schizophrenia and 3) to develop further expertise in cognitive modeling to facilitate the design and interpretation of future multimodal functional brain imaging studies of impaired cognition in schizophrenia. These goals will be pursued through a combination of course work and intensive consultation with world experts in the fields of ERP, fMRl and cognitive modeling. They will also be pursued in a series of experiments using fMRI and ERP both alone and in combination, to test hypotheses related to the neural basis of normal executive functions, as well as the neural basis of impaired executive functions in schizophrenia. Successful funding of this award will ensure that the applicant is freed up from clinical, teaching and administrative responsibilities for the next five years so that he can spend at least 80 percent of his time on research and on the further development of his research expertise. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMPONENTS SCHIZOPHRENIA

OF

WORKING

MEMORY

DEFICIT

IN

Principal Investigator & Institution: Park, Sohee; Psychology; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917

Studies 31

Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-MAY-2003 Summary: (Adapted from applicant's abstract): The major goal of this project is to analyze the neurocognitive components of working memory deficits in schizophrenia. The three proposed studies are designed to specify parameters of the prefrontal working memory systems and to characterize their possible links to the expression of the symptoms of schizophrenia. The investigator's global hypothesis is that an inability to regulate behavior by prefrontal working memory systems may demarcate cardinal features of schizophrenia. Growing evidence supports this view but the role of working memory in clinical symptoms is unclear, because of the functional heterogeneity of the frontal lobes, multiplicIty of the working memory systems and diffuse definitions of symptoms. The roles of the dorsolateral prefrontal and ventral/orbitofrontal systems in schizophrenia will be probed, using a series of specific experiments designed to assess dissociation and integration of the multiple working memory systems. Spatial working memory is mediated by a neural circuitry including the dorsolateral prefrontal cortex, whereas visual (nonspatial) and olfactory working memory systems are associated with the integrity of the ventral/orbitofrontal system. There are 3 studies, consisting of 3 experiments each. Study 1 is focused on examining spatial, visual (nonspatial) and olfactory working memory systems separately in schizophrenia patients in order to determine which systems are consistently impaired independent of fluctuating symptoms versus which systems are linked to the symptoms. Young siblings of schizophrenia patients will be tested to see if they show similar patterns of deficit. Study 2 is concerned with determining how these anatomically and psychologically separable working memory systems are dissociated, coordinated or inhibited to guide action by a control mechanism (the "central executive"). In Study 3, the integrity of the connections between orbitofrontal and dorsolateral prefrontal systems will be examined by inspecting the roles of affect, arousal and reward on working memory. Ultimately, all the components of working memory and subdivisions of frontal systems must be integrated in an organism with intact personality and self-regulating behaviors. The key to understanding cognitive deficits and symptoms of schizophrenia may be found in the patterns of dissociation and integration of these multiple systems, in response to specific task demands. In summary, this project will enable the investigator to further identity and elucidate neurocognitive components of schizophrenia and thus contribute towards our understanding of the complex interplay between cortical functions, cognitive deficits and clinical syndromes in men and women with schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--BRAIN IMAGING Principal Investigator & Institution: Jernigan, Terry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001 Summary: Little is known about the brain abnormalities associated with schizophrenia and related psychoses in late life. In the proposed research, we will use morphometric and qualitative analyses of magnetic resonance images (MRI) to examine qualitative and quantitative brain structural features that underlie late-life psychosis. The research will be guided by the following questions: (1) Are brain abnormalities different in quality or number in the various late-onset psychoses? In older schizophrenia patients: (2) Do brain abnormalities differ with age-of-onset? (3) How do brain abnormalities in older schizophrenia patients relate to clinical, psychosocial, or treatment outcomes? (4) How do the patterns of brain morphology in schizophrenia patients relate to impairments in executive function, information processing, and sensory gating? (5) Is there evidence for

32 Schizophrenia

abnormalities in thalamo-cortical circuits that may be associated with schizophrenic symptomatology? Our working model is that schizophrenic symptomatology may be a result of dysfunction in the cortical-subcortical circuitry. This dysfunction may be due to problems in the functional balance between basal ganglia, thalamic, and cortical function, leading to dysfunction in cortical- subcortical circuits. Particular abnormalities in the relations among these structures may bear relationships to the particular clinical, neuropsychological and psychophysiological features exhibited by individual patients. Thus, the variety of brain abnormalities may be linked to the heterogeneous nature of symptomatology of schizophrenia and other psychoses in late life. Our findings thus far suggest that there may be specific brain morphometric differences between early-onset and late-onset forms of schizophrenia, particularly in the thalamus and in ventricle size. In the next funding period we will study larger numbers of subjects with varied ages of onset so that we can examine morphometric differences in greater detail. We will also attempt to understand the heterogeneity of behavioral disturbance in schizophrenia on the basis of brain morphology. In addition, we will formulate specific hypotheses that can be tested using functional imaging methods now in use (e.g., SPECT) or under development within our facilities (e.g., functional MRI). We will attempt to study all subjects from the Center. Subjects will receive MRI examinations, and all MRIs will be rated quantitatively for abnormalities. In addition, we will study a subset of schizophrenia and normal comparison subjects using quantitative MR image analytic methods that measure volumes of many cortical and subcortical brain regions. MRI measures will be related to age-of-onset, clinical features (including outcomes), and neuropsychological and psychophysiological function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--DIAGNOSIS AND TREATMENT RESEARCH CORE Principal Investigator & Institution: Amador, Xavier F. National Director; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001 Summary: The DTRC has three main aims: recruitment, diagnosis/assessment and treatment. Each specific aim has both center-wide and core-specific goals as follows: 1.) Recruitment. To ensure adequate and efficient subject flow for the MHCRC's studies we plan to centralize our existing recruitment efforts. We will recruit a broad range of patients with schizophrenia and related disorders including first-episode patients, chronic patients in acute exacerbation, stable outpatients, chronic inpatients in state facilities, patients with significant co-morbidities, and the homeless. In addition, we will continue to recruit controls from the Normal CONTROLS Unit at the New York State Psychiatric Institute (NYSPI) and to provide the proposed MHCRC with updated diagnoses on this sample. 2.) Diagnosis/Assessment. We will rigorously diagnose and characterize patients participating in the MHCRC's research protocols and broadly sample schizophrenia-related conditions across multiple domains of psychopathology (e.g. trait-related symptoms, course of illness, and neuro-cognitive variables). Corespecific research will build on our previous work studying unawareness deficits and suicidal behavior ion schizophrenia. 3.) Treatment. To provide high quality treatment to patients admitted to either inpatient site-the Schizophrenia Research Unit at Creedmoor (SRU- C) and the Schizophrenia Research Unit at NYSPI (SRU-P)- and the Outpatient Research and Rehabilitation Program (ORR). Core-specific treatment research will focus especially on the use of atypical antipsychotics with refractory patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies 33

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Project Title: CORE--GENOMICS AND NEUROBIOLOGY RESEARCH CORE Principal Investigator & Institution: Gilliam, T Conrad. Borne Professor of Genetics and Developm; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001 Summary: The GNRC unites three groups studying the neurobiology and pathophysiology of schizophrenia with a core of scientists in the Columbia Genome Center (CGC) working on "genomic" strategies to identify schizophrenia-related genes. These GNRC has two major objectives. The first goal is to elucidate the neurobiological underpinnings of schizophrenia, including neurochemical abnormalities (in synaptic proteins and MAP2), and neuroimmunological abnormalities (relating to the immunogenicity of an abnormal chaperonin, hsp60). The key genes, proteins, proteinprotein interactions, and regulatory mechanisms generated by these and other studies then provide the template for the first of two computational genomic "search engines". The first engine is designed to elaborate biochemical and regulatory pathways by predicting novel protein-protein interactions based upon systematic phylogenetic homology searchers. By matching human genes and proteins with their orthologues in lower, well-characterized organisms, new patterns of interaction can be predicted. These new "protein networks" thereby form a database of likely target genes for schizophreniarelated DNA alterations. The second goal of the GNRC is to combine molecular and computational strategies to systematically identify and characterize all genes in a given large schizophrenia-linked chromosomal region. A second "search engine" will collect all genes and predicted genes from such regions and characterize their phylogenetic homology relationships. Simultaneously, we will use established high throughout technologies to sequence large segments of the linked regions and analyze for predicted protein coding regions. Together, these strategies will yield a new set of gene and protein sequences that form a positional candidate gene database. Next, the proteininteraction and positional candidate search engines will cross- analyze to predict high priority candidate genes. In the final phase of the proposal we will develop a strategy to DNA sequence multiple candidate genes in a collection of patient and control DNA samples. In this way we will generate a public database of schizophrenia-related DNA alterations that will lay the foundation for a DNA microchip assay for large samples. A significant feature of this "genomic" search strategy is that it bypasses the necessity of detecting shared chromosomal segments, the basis of all current genetic search strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--NEURODEVELOPMENTAL AND GENETIC EPIDEMIOLOGY RESEARCH CORE Principal Investigator & Institution: Susser, Ezra S. Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001 Summary: The NGERC seeks to advance research on the antecedents of neurodevelopmental schizophrenia, i.e., on the origins and early manifestations of neurodevelopmental disturbance in this disorder. We will use data from life course cohorts that have been followed from early life and are now either in the age of risk for schizophrenia. Drawing on the resources and infrastructure of the MHCRC, we propose to extend the uses of the data for each of three types of life course cohorts: populationbased birth cohorts, genetic high-risk cohorts, and epigenetic high-risk cohorts. Population-based birth cohorts are unselected for any specific etiology, whereas a

34 Schizophrenia

genetic high-risk cohort is selected so as to be enriched for genetic etiology, and an epigenetic high-risk cohort is selected so as to be enriched for an environmental factor which can impact on genetically programmed neurodevelopment (e.g., prenatal brain insult). The specific aims are to investigate antecedents of neurodevelopmental schizophrenia in: 1. a collaborative study that combines data across four birth cohorts. This study includes the large Oakland Child Health and Development Study birth cohort together with three cohorts derived from the multi-site National Collaborative Perinatal Project. Each cohort was based on births during 1959-1966, was followed from the prenatal period into childhood or later, and is currently being followed up for schizophrenia by Co- investigators in this proposal. Taken alone each cohort has limited statistical power, especially for rare exposures. By contrast, the combined sample of approximately 30,000 live births provide adequate power for a comprehensive investigation. Using the infrastructure of the MHCRC, we will be able to create a combined database, conduct collaborative research, and make this database a resource for other schizophrenia researchers. 2. a cohort enriched for genetic etiology. In the New York High-Risk Project, of L. Erlenhmeyer-Kimling of the NGERC, 324 offspring of schizophrenic, affectively ill, and normal parents have been followed into midadulthood. The present study undertakes to extend the data analysis to focus on early manifestations of neurodevelopmental disturbance in schizophrenia. 3. a cohort enriched for epigenetic etiology. in the Rubella Birth Defects Evaluation Project, 70 individuals exposed to rubella during gestation have been followed into adulthood and have been shown to have a greatly increased risk of schizophrenia. The present study will extend the collection and uses of family history and brain imaging data. While the other Cores of the MCHRC are essential to all three aims, this Core in turn is designed to contribute to each of the other Cores, not only by providing unique data, but also by fostering interdisciplinary research that is jointly conceived and conducted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--NEUROPSYCHOLOGY Principal Investigator & Institution: Heaton, Robert K. Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001 Summary: Although a considerable amount of neuropsychological research has been conducted in schizophrenia, relatively little is known about the cognitive functions associated with schizophrenia and other psychoses in later life. During the initial funding period of the CRC, we began to characterize the neuropsychological patterns of individuals with psychosis in late life and to differentiate the cognitive profiles of these patients from those of their younger counterparts and of patients with other diseases associated with aging. Our findings thus far have suggested that the level and pattern of neuropsychological performance in older patients with schizophrenia are generally quite similar in both early-onset and late- onset groups (and very different from patients with early Alzheimer's disease). Nevertheless, some qualitative differences do exist among cohorts of patients with schizophrenia: (a) performances on semantic memory and episodic memory tasks vary with age-of-onset; (b) the pattern of learning and memory impairments in schizophrenia is heterogeneous among schizophrenia patients (viz., 50% have a "subcortical" profile, 15% have a "cortical" profile, and 35% have "normal" learning and memory); (c) the overall level of neuropsychological impairment in older patients with schizophrenia is worse in patients with tardive dyskinesia; and (d) the specific cognitive abilities of attention and learning are more impaired in patients with tardive dyskinesia. In addition, we have found that the level of neuropsychological

Studies 35

impairment in patients with late life psychoses remains stable over a 3-year period, and that psychosis patients with a diagnosis of unipolar depression are neuropsychologically more similar to patients with a diagnosis of schizophrenia than to patients with unipolar depression who are not psychotic. During the CRC renewal period, the Neuropsychology Core proposes to address several additional aspects of the neuropsychology of schizophrenia by pursuing the following scientific objectives: (a) further elucidating the specific nature of memory impairments across the full spectrum of late life psychosis, and relating memory findings to clinical characteristics, psychophysiological performances, and neuroimaging measures of frontostriatal and temporolimbic volumes; (b) increasing the generalizability of our findings regarding the current illness severity, by adding schizophrenia patients at the extremes of this dimension (i.e., institutionalized and remitted patients); (c) examining the effects of neuropsychological impairment on functional outcome of schizophrenic disorders in older age groups; and (d) further establishing the reliability and stability of neuropsychological deficits over longer time periods, and their relative independence from changes in symptom status and treatment effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORTICAL BASIC OF SCHIZOPHRENIA SENSORY GATING DEFICIT Principal Investigator & Institution: Canive, Jose M. Assistant Professor; Biomedical Research Institute of New Mex of New Mexico Albuquerque, NM 87108 Timing: Fiscal Year 2002; Project Start 05-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Deficits in sensory gating are believed to be involved in a variety of clinical symptoms and disrupted cognitive functions in patients with schizophrenia. The psychological and biological mechanisms of normal and impaired gating, and why some novel antipsychotic medications improve gating while conventional antipsychotics do not, are not well understood. Progress toward understanding neural mechanisms involved in gating can contribute to theory about schizophrenia and to its treatment. A prominent research paradigm for studying gating deficits in schizophrenia involves presentation of a pair of clicks and noninvasive measurement of the P50 component of the associated event-related brain potential. P50 amplitude to the second click is normally reduced substantially from that to the first click, but patients (and some of their family members) commonly show less reduction, i.e. have impaired gating. The proposed project will address three pressing issues surrounding this well-established finding. (1) What are the neural generators of P50? Are they confined to bilateral superior temporal gyrus? (2) How are those generators affected by antipsychotic medication, is the effect equal across the generators, and is the effect different for conventional vs. novel antipsychotics? (3) Is the gating deficit specific to auditory stimuli, or is it cross modal as the literature assumes? This application presents extensive pilot data addressing all three of these issues in hopes of furthering our understanding of impaired sensory gating in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORTICAL CIRCUITRY AND COGNITION IN SCHIZOPHRENIA Principal Investigator & Institution: Lewis, David A. Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2003; Project Start 01-APR-1990; Project End 30-JUN-2008

36 Schizophrenia

Summary: (provided by applicant): Based on our findings during the current period of funding, this renewal application for a Conte Center for the Neuroscience of Mental Disorders posits that understanding the neurobiology of schizophrenia requires a focus on the abnormalities in cognitive processing that are present in this disorder, on the components of the dorsolateral prefrontal cortex (DLPFC) and its extrinsic connections that are likely to mediate these processes, and on the developmental events that may make these neural systems vulnerable in schizophrenia. In particular, deciphering the cascade of pathophysiological events that produces the clinical features of schizophrenia depends upon investigations that examine 1) the normal molecular, structural and functional features of DLPFC circuitry, 2) the effects of alterations in one component of the system on other elements of the circuitry, and 3) the normal development of this circuitry and the impact of genetic factors on these developmental trajectories. Moreover, the success of such an endeavor depends upon the creative blending of clinical and basic studies, each of which is guided by and informs a common central hypothesis. Consequently, in the seven integrated programs of research proposed by Center investigators, we will test complementary aspects of the following central hypothesis: Certain critical disturbances in the regulation of cognition in schizophrenia reflect functional abnormalities both in the intrinsic circuitry of the DLPFC and in its interconnections with other cortical and subcortical regions. These functional disturbances arise during postnatal development as a consequence of alterations in the molecular signals and structural elements that determine synaptic efficacy in the affected circuits. The convergent tests of this hypothesis will be conducted in a highly interactive scientific environment that integrates the basic and clinical research activities of multiple investigators from the University of Pittsburgh, in concert with faculty at the adjacent Carnegie Mellon University and with accomplished senior scientists at Princeton and Vanderbilt Universities. Collectively, our Center represents a broad array of expertise that spans molecular, developmental, systems, cognitive and clinical neuroscience. Our extensive interactions enable us to conduct a translational research program in schizophrenia that effectively transfers information from the clinic to the laboratory and back to the clinic in a truly bidirectional fashion. PROJECT 1: Dysfunction of DLPFC Pyramidal Neurons in Schizophrenia: Morphology and Mechanisms Drs. David A Lewis/ RA Sweet/ K Mirnics/ LS Krimer/ PR Levitt/ CR Olson (provided by applicant): The central hypothesis of our Center focuses on critical disturbances in the regulation of cognition and behavior in schizophrenia that reflect functional abnormalities in the intrinsic circuitry of the dorsolateral prefrontal cortex (DLPFC) and in its interconnections with other brain regions. These functional disturbances are hypothesized to arise during postnatal development as a consequence of alterations in the molecular signals and structural elements that determine synaptic efficacy in the affected neural circuits. These alterations include somatodendritic morphological abnormalities, such as smaller somal volumes, decreased dendritic arbor size and complexity, and reduced dendritic spine density, of pyramidal neurons, the principal excitatory projection neurons of the neocortex. Furthermore, these somatodendritic abnormalities in schizophrenia may be specific to, or at least present to a greater degree in, a subset of pyramidal neurons. Because a neuron's dendritic arbor is a major determinant of its functional circuit properties, pyramidal neuron somatodendritic abnormalities, in concert with related synaptic disturbances, may be central to DLPFC-mediated cognitive dysfunction in schizophrenia. Consequently, knowledge of the specific subsets of pyramidal neurons that are affected in schizophrenia is essential for determining both the potential causes of these abnormalities and their contributions to disturbed DLPFC information processing. Thus, using an integration of experiments in postmortem human brain specimens and in nonhuman primates, the studies proposed in this project are designed to determine 1)

Studies 37

the laminar location(s) of the DLPFC pyramidal neurons that exhibit somatodendritic abnormalities in schizophrenia; 2) the molecular phenotypes of pyramidal neurons that furnish different types of extrinsic projections in monkey DLPFC; 3) the somatodendritic integrity of molecularly-identified subpopulations of DLPFC pyramidal neurons in schizophrenia; and 4) the molecular mechanisms that may contribute to developmental somatodendritic changes in monkey DLFPC pyramidal neurons. These investigations have a number of conceptual and technical links with other Center projects and depend upon support provided by all of the proposed cores. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORTICO-STRIATAL SUBSTRATES OF DEFICIENT STARTLE GATING Principal Investigator & Institution: Swerdlow, Neal R. Professor; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 15-JAN-1997; Project End 31-DEC-2005 Summary: The first three years of the project included studies to understand how experimental manipulations of the hippocampus or medial prefrontal cortex (MPFC) in rats produce deficits in basic gating and habituation functions that are linked to schizophrenia. Both prepulse inhibition (PPI) and habituation of startle responses have been used to demonstrate gating and habituation deficits in schizophrenia patients and in rats with altered cortico-striatal circuitry. The ventral hippocampus (VH) and MPFC appear to modulate startle inhibitory processes via connections with the nucleus accumbens (NAC). Rats with VH or MPFC lesions exhibit an enhanced sensitivity to the PPI-disruptive effects of dopamine (DA) agonists. This proposal seeks continued support to test specific hypotheses about neural circuitry that is implicated in the pathophysiology of schizophrenia, and to understand the role of this circuitry in schizophrenia-linked gating deficits. Aim 1 will assess the importance of VH lesions (excitotoxic and electrolytic) versus NAC de-efferentation in the development of the enhanced DA-mediated loss of sensorimotor gating, using septal undercuts to interrupt the rostral fornix. To enhance our understanding of the neurochemical basis for the effects VH lesions on PPI, studies will also assess changes in the PPI-disruptive effects of NMDA antagonists and 5HT agonists after VH lesions, and the PPI-restorative effects of antipsychotics. Aim 2 will assess the neural basis for VH lesion effects on PPI, by measuring changes in PPI after DA infusions into NAC subregions. Studies will also test the hypothesis that the effects of VH lesions on PPI are accompanied by changes in DAergic substrates in the MPFC or orbital cortex. Aim 3 will examine the ability of glutamatergic manipulations of the NAC, or transection of the VH-NAC projection, to reverse the PPI-disruptive effects of intra-VH infusion of NMDA. Aim 4 will assess the enhanced DA-mediated loss of PPI after cell or ablative lesions of the MPFC, across post-lesion intervals and via DA receptor subtype-specific agonists, and with measures of forebrain DA receptors. Aim 5 will examine MPFC lesion-induced changes in PPI after infusion of DA agonist into NAC subregions. Aim 6 will test the ability of manipulations of the NAC or ventral tegmentum to reverse the PPI-disruptive effects of MPFC 6-OHDA lesions or intra-MPFC infusion of DA antagonists. In total, these studies will systematically characterize cortico-striatal circuitry regulating critical inhibitory functions that are deficient in schizophrenia. Specific circuit mechanisms responsible for DA-mediated gating deficits after VH or MPFC lesions - revealed by these studies - will continue to be the basis for innovative models of the pathophysiology of schizophrenia and related disorders, and for prospective strategies for novel drug development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

38 Schizophrenia

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Project Title: COURSE SCHIZOPHRENIA

OF

FUNCTIONAL

DEFICITS

IN

LATE-LIFE

Principal Investigator & Institution: Harvey, Philip D. Professor; Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): This is a collaborative study of the course and antecedents of functional decline in geriatric patients with schizophrenia. Functional (i.e., social, occupational, self-care, and independent living) impairment is one of the primary factors that influences both quality of life and societal cost of schizophrenia, with some evidence suggesting that some older patients with schizophrenia experience functional decline in later life. While in other illnesses such as dementia and head trauma it is clear that cognitive decline is an antecedent to functional decline, evidence regarding the correlates of functional status in schizophrenia is largely cross-sectional. The present study adopts a longitudinal approach to determine if the cross-sectional relationships between cognitive and functional deficits are the result of cognitive decline being an antecedent of functional decline. The results of previous studies regarding cognitive and functional decline are contradictory, with the Mt. Sinai group studying older and sicker patients finding decline and the UCSD group finding no evidence of decline in similar time periods. In order to determine if these discrepancies are due to differences in subject samples or the methods employed, the Mt. Sinai group will employ both their previous methods and those of the UCSD group in this study. Samples of healthy controls and ambulatory older schizophrenia patients who vary in their lifetime history of course of illness will be followed for 5 years and examined with performance-based measures of functional skills, assessments of cognitive functioning, and clinical symptom ratings. Sophisticated data analytic techniques will be employed to determine the course of functional changes, their temporal relationships with changes in cognitive and functional status, and their association with lifetime illness history. Findings from this study will clarify the course of functional status in schizophrenia and the timing of cognitive and functional changes. The results will also inform research on the biological basis of functional change in schizophrenia, as well as research on treatment of the illness. In a much-neglected area, the study of schizophrenia in late life, this research will focus on an aspect of the illness (the course of functional status) that has been studied for 100 years, but is still not well understood. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CREATIVITY AND LIABILITY FOR SCHIZOPHRENIA Principal Investigator & Institution: Kinney, Dennis K.; Mc Lean Hospital (Belmont, Ma) Belmont, MA 02478 Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 28-FEB-2004 Summary: The study's broad, long-term objectives are to advance understanding of the relation of creativity to variables that are associated with liability for schizophrenia. The specific aims are to test hypotheses about the relation of creativity to liability for schizophrenia. The study will test: (a) whether previous reports of higher creativity in the relatives of schizophrenics and in individuals with multiple schizotypal signals can be confirmed with more rigorous methods, including new and larger samples, current diagnostic criteria, more sensitive measures of schizotypal features, and reliable measures of creativity shown in real-life activities. The study will also test (b) whether individuals with multiple schizotypal signals will similarly score significantly higher than controls on tests of creative thinking. The research design involves (a) samples of

Studies 39

70 schizophrenic probands, (b) 110 of their adult siblings, and (c) 110 normal controls. The sibling and control samples will be matched for age, gender, and ethnicity, and each group will be diagnosed using DSM-IV criteria and research interviews (SCID), supplemented by data from chart reviews and family informants. Schizotypal features will be assessed using the Structured Interview for Schizotypy and the Perceptual Aberration-Magical Thinking Scale. Subjects' creativity will be assessed, while blind to diagnostic data, using measures of real-life avocational and vocational creativity (the Lifetime Creativity Scales) as well as of creative thinking (the Torrance Tests of Creative Thinking). Rapid advances in the ability to detect genes for schizophrenia make it increasing important to know whether such genes may also be associated with beneficial behavioral traits. Knowledge that genes which increase risk for schizophrenia are also associated with creativity-enhancing traits would have important health implications for individuals and social decisions about how to apply new genetic knowledge. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CULTURAL CONCEPTS OF SUFFERING, AND SCHIZOPHRENIA Principal Investigator & Institution: Adler, Sarah E. Anthropology; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2002; Project Start 13-MAR-2002; Project End 31-OCT-2004 Summary: (provided by applicant): This research focuses on how suffering is culturally constructed and how these constructions affect the ways in which schizophrenia is experienced and coped with. The objective of this study is to explore how Buddhist notions of suffering influence health-seeking behavior for schizophrenia in Burma. This study has three specific aims: 1) Identify specific sources and interpretations of suffering among Burmese Buddhists; 2) Examine the relationship between cultural concepts of suffering and specific features of mental illness, specifically (a) the subjective experience of schizophrenia from the diverse perspectives of healers, patients, and patient's family members; and (b) social and clinical beliefs about mental illness; 3) Determine the influence cultural concepts of suffering have on health-seeking behavior for schizophrenia. These aims will be addressed through ethnographic observations, structured and semi-structured interviews with healers involved with mental health care, in- and outpatients with schizophrenia seeking treatment at the Yangon Psychiatric Hospital in Rangoon, Burma, and patient's family members or caregivers. This study will advance understanding of the relationship between religion and severe mental illness experience, and the role of suffering in shaping illness course and outcome, health beliefs, and health care utilization patterns. Given that suffering is a common and pervasive feature of illness experience, its study stands to shed light into several areas important to anthropology, medicine, and psychology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEFICITS OF EMOTION AND ATTENTION IN SCHIZOPHRENIA Principal Investigator & Institution: Germans, Marja K. Psychology & Human Development; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001; Project Start 27-SEP-2001 Summary: Empirical research has indicated that schizophrenia patients are characterized by deficits in both attentional and emotional processes. However, there has been little theoretical work or empirical research examining the nature of the putative relations between these deficits. The primary goal of the proposed research is to posit and examine relations between deficits of attention and emotional responding in

40 Schizophrenia

schizophrenia patients. Based on the extant literature on emotion- attention relations in nonpatients, as well as known deficits of emotion and attention in schizophrenia patients, several hypotheses are developed to guide the proposed research. First, based on previous research on attention in schizophrenia, schizophrenia patients are hypothesized to be impaired in their ability to utilize task relelvant information to direct attention to a target stimulus. Second, based on previous research on emotion and emotional deficits in schizophrenia, it is hypothesized that schizophrenia patients are impaired in the ability to maintain emotion-related motivational states over time. Third, it is proposed that the direction of attention and the maintenance of motivational state tap top-down influences common to emotional and attentional processes. These hypotheses will be tested in the proposed research by employing two tasks measuring modulation of the startle eyeblink, a non-verbal, psychophysiological measure of attention and emotional responding, in schizophrenia patient and matched control participants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENTAL SCHIZOPHRENIA

INSULT

AND

BRAIN

ANOMALY

IN

Principal Investigator & Institution: Brown, Alan S. Psychiatry; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 15-MAR-2001; Project End 28-FEB-2004 Summary: (Adapted from applicant's abstract) This study will investigate the relation of early developmental insult (EDI) to adult brain disturbance among cases of schizophrenia and schizophrenia spectrum disorder (SSD). The study represents a collaborative effort between epidemiologists and clinical neuroscientists, in which advanced neuroimaging and neuropsychological approaches are brought to bear on a large birth cohort with extensive early developmental exposure data. The proposal study builds upon two unique investigations, the Child Health and Development Study (CHDS) and one of its extensions, the Prenatal Determinants of Schizophrenia (PDS) Study. The CHDS was based on a cohort of 19,044 live births during 1959-1966 in the Oakland Hospital of the Kaiser Foundation Health Plan (KFHP). Using cases already diagnosed in the PDS study, and cases to be diagnosed in the present study, we expect that 100-11O cases and 100-110 matched controls will be assessed for all the proposed adult brain disturbances. Specifically, the applicants aim to: 1) Compare case of SSD with matched controls from the PDS study with respect to adult brain disturbances indicative of early development insult. The applicants hypothesize that associations will be demonstrated between SSD and adult brain disturbances in the following dimensions: neuroanatomical, neurochemical, and neuropsychological; 2) Examine, among cases of SSD, associations between EDI and adult brain disturbances; and 3) For those adult brain disturbances that show a relation to ED! in Aim 2, the applicants will then examine evidence for whether familial liability to SSD contributes to EDI, leading to the above adult brain abnormalities in SSD cases. This study has several notable strengths, which include: extensive prospectively collected data on EDT and prenatal sera for analysis of additional early developmental exposures; research-based diagnoses; good control of bias; a representative sample of control subjects; more refined and extensive brain measures; good statistical power; and the ability to analyze causal pathways. Important implications of this study are to provide evidence of pathogenic mechanisms by which ED! might lead to SSD, lend validation for the neurodevelopment hypothesis of schizophrenia, and elucidate underpinnings of the diverse brain disturbances found in patients with SSD.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DOPAMINE AND GABA IMAGING IN SCHIZOPHRENIA Principal Investigator & Institution: Kegeles, Lawrence S. Psychiatry; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 05-DEC-1999; Project End 30-NOV-2004 Summary: This MCSDA application requests support for a career development and associated research plan to study the integrity of GABAergic transmission and its modulation of dopaminergic function in schizophrenia, and to relate these neurochemical indices to measures of psychopathology and cognition. The chemical imaging modalities of magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) permit study in vivo of neurochemistry. The best-established theory of neurochemical disturbance in schizophrenia involves altered dopamine (DA) neurotransmission. Receptor studies to date have focused mainly on the D2 subclass of DA receptors and demonstrated excess dopaminergic function in the striatum. It has been hypothesized that the dopaminergic overactivity at the level of the striatum may be due to a GABAergic deficiency. A growing body of neuropathological evidence points toward abnormalities in frontal cortical gamma- aminobutyric acid (GABA) local circuit neurons. Moreover, the frontal neurochemical imbalances may contribute to the negative symptoms of attentional and working memory deficits. The proposed project involves PET neuroimaging of DA function and MRS measurement of GABA concentration, and studying the relation between these measures and both psychopathology and cognition. The short-term goals of the project include development of MRS methods specific for GABA measurement, and preclinical evaluation and validation of these methods by comparison with PET studies in conjunction with a GABAergic pharmacological challenge. Human studies will begin with a Phase I PET investigation of GABA/DA interactions using the same pharmacological challenge in healthy volunteers. In the final three years of the award period, a clinical study will make use of both the MRS and D2 DA PET receptor approaches to test the hypothesis that the dopaminergic response to a GABAergic challenge is diminished in the striatum in schizophrenia. This research plan is intended to build on the candidate s prior work with D2 receptor investigations of striatal function and its modulation by pharmacological challenges. The career development activities proposed are aimed at building on the candidate s previous fellowship training with neuroreceptor imaging, MRS, and pharmacological challenges to develop the skills needed to execute a program targeting the DA and GABA abnormalities in schizophrenia, their potential interactions, and their potential relation to neurobehavioral measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DOPAMINERGIC PSYCHOPATHOLOGY

DIATHESIS

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SCHIZOPHRENIC

Principal Investigator & Institution: Amin, Farooq; Assistant Professor; Psychiatry and Behavioral Scis; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: Non-psychotic relatives of schizophrenic probands often manifest attenuated psychopathology of this illness including negative symptoms that are hypothesized to be due to decreased brain dopamine (DA) function. We now have systematic evidence suggesting that plasma homovanillic acid (pHVA), an indicator of brain DA activity, is

42 Schizophrenia

reduced in such relatives in relation to the characteristic negative symptoms that indicate a genetic diathesis to schizophrenia. These pHVA findings are not due to peripheral factors suggesting that they may reflect brain DA activity. These data suggest that the reduced DA activity (assessed by pHVA measures), presumably reflecting a genetic diathesis to schizophrenia, is detectable in non-psychotic relatives. This putative low-DA trait can be used as a biological phenotype in genetic studies to ultimately locate and identify gene(s) underlying the DA dysfunction in schizophrenia. However, before considering such work, the low-DA phenotype needs to be better established. The proposed work is designed to address this current crucial limitation. When using pHVA measures as a phenotype in genetic studies, the well-known limitation of pHVA (inability to localize abnormality in the brain) is no longer an issue, because brain localization is not required in a genetic approach. This instrument is highly stable and suitable for large samples needed for genetic studies. In pilot data, it identified DAaffected relatives with high specificity and sensitivity. In the proposed work, two pHVA measures (i.e., decreased pHVA and decreased morning pHVA decline) suggested by the previous data would be further tested in 90 non-psychotic relatives (from multiplex families with schizophrenia) and 90 normal comparison subjects (without a family history of schizophrenia) in a four-year study. On study days, pHVA will be measured and negative symptoms blindly assessed. Whether the two proposed pHVA measures distinguish relatives from normal subjects under optimized conditions (cross-sectionally and longitudinally) will be determined. The relationship of negative symptoms with pHVA will be further established. Using these two pHVA measures, a method to classify relatives as DA-affected or unaffected will be developed with high sensitivity and specificity. Stability of pHVA measures and of the classification will also be established. Once the low-DA phenotype has been established, the door will be open to many important genetic, high risk, and biological possibilities. For example, it would set the stage to employ genetic studies to ultimately locate and identify the gene(s) responsible for the DA dysfunction in schizophrenia. Also, identification of relatives with the DA phenotype at an early age may be very useful in developing preventive strategies even before DA-related gene(s) are identified. This is particularly relevant since many successful interventions affecting DA function are already available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DYNAMIC ASSESSMENT OF COGNITION IN SCHIZOPHRENIA Principal Investigator & Institution: Brown, Catana; Occupational Therapy; University of Kansas Medical Center Msn 1039 Kansas City, KS 66160 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Understanding the factors associated with functional deficits experienced by people with schizophrenia is essential for identifying interventions that can support independent living for these individuals. One promising line of work has examined the cognitive factors that may interfere with successful functional outcomes (Green, 1996). Despite this accumulating evidence that cognitive deficits in schizophrenia are related to functional outcome, findings have been shown to have limited utility in rehabilitative interventions. Green and colleagues (2000) have suggested that rather than focusing only on specific cognitive processes, research in this area should examine the broader concept of learning potential, which may be an important factor in the acquisition and performance of life skills. Broadly defined, learning potential is the ability to attain cognitive skills and to employ those skills in the appropriate situations to solve some problem (Sternberg & Grigorenko, 2002). Learning potential is measured with dynamic assessment methods, which combine mediated

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instruction with test administration. The extent to which an individual can take advantage of the instruction to improve performance is taken as an index of learning potential. A number of authors have argued that learning potential is a better indicator of cognitive ability than scores on static performance tests (Campione & Brown, 1987; Hamers & Sitjsma, 1995; Sternberg & Grigorenko, 2002, Tzuriel, 2000). In the proposed project, individuals with schizophrenia will be evaluated in terms of static cognitive ability, their learning potential and their functional skill ability in the domain of grocery shopping. Analyses will determine whether learning potential predicts functional skill performance over and above the prediction based on static cognitive measures alone. We will also determine whether different domains of learning potential predict different specific aspects of grocery shopping. The immediate goal of this work is to better understand the relation between domains of learning potential and functional outcome; the long term goal is to use this information to produce rehabilitative interventions that better support successful community living for people with schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EARLY BRAIN DEVELOPMENT IN HIGH RISK CHILDREN Principal Investigator & Institution: Gilmore, John H. Professor; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Despite the widespread belief that schizophrenia is a disorder of abnormal early brain development and numerous theories to that effect, there is little direct evidence to support this idea. This is in part due to the fact that until recently, the clinical study of human fetal and neonatal brain development was limited by a lack of appropriate tools with which to carry out such studies. Ultrasound and magnetic resonance imaging (MRI) are ideal techniques for the study of brain development in the human fetus, neonate, and child. Using ultrasound, it is possible to image the developing lateral cerebral ventricles in utero. Using high resolution MRI, it is possible to examine brain structure and its development from the neonatal period through childhood and into the period of risk for the onset of schizophrenia. The primary hypothesis of this research program is that abnormalities of brain structure and development, reflected in ventricle size and shape, along with abnormalities in total brain volume and white matter integrity in fetal and neonatal brain, are markers of abnormal development of thalamo-limbic-cortical circuits, associated abnormal GABA interneuron development, and ultimate susceptibility to schizophrenia. This will be the first study to use ultrasound to prospectively study prenatal and neonatal brain development in the offspring of women with schizophrenia. It will also prospectively study the development of fetuses with mild enlargement of the lateral ventricles, a structural abnormality that is hypothesized to represent an endophenotype of risk for schizophrenia. Subjects will have 2D ultrasounds in the second and third trimesters, and a 3D ultrasound and an MRI at 2 weeks after birth. Early childhood development will be followed prospectively at ages 1 and 2 years with the Mullen Scales of Early Learning and an assessment of working memory and attention, neurocognitive processes in which GABA interneurons play an important role. The identification of the timing of ventricle enlargement will provide a focus for studies of neurodevelopmental mechanisms that underlie schizophrenia. Understanding the causes of early abnormalities of ventricle structure will provide important information about genetic and environmental risk factors in schizophrenia. Finally, the study of lateral ventricle development will allow the early identification of children at high risk for

44 Schizophrenia

schizophrenia and other neurodevelopmental disorders, ultimately making early intervention possible to prevent or mitigate this risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ELECTROPHYSIOLOGY SCHIZOPHRENIA

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Principal Investigator & Institution: Freedman, Robert; Medical Director; Psychiatry; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 01-APR-1984; Project End 30-APR-2005 Summary: adapted from applicant's abstract):The fundamental discovery of this project is the identification of the alpha7-nicotinic acetylcholine receptor as a strong candidate gene for an inherited physiological dysfunction in schizophrenia. The scientific work of the past 10 year-funding period has led to: (1) discovery of the alpha7-nicotinic receptor's neurobiological role in an inhibitory deficit associated with schizophrenia, (2) the first genetic linkage of the inhibitory deficit, as well as schizophrenia itself, to the chromosome 15q14 locus of the alpha7-nicotinic receptor gene, (3) the first evidence for decreased expression of this receptor in the hippocampus of schizophrenics, (4) the first description of the complex genomic structure of the human alpha7-nicotinic receptor gene, and (5) the first evidence for co-dominant inheritance of inhibitory deficits in childhood-on set schizophrenia. This renewal application seeks to replicate the current findings of linkage of an inhibitory neurophysiological deficit (Aims 1 and 2), and then extend the findings to a broader phenotype based on neuropsychological evaluation of probands and their relatives who do or do not carry genetic risk (Aim 3) and to a broader range of illnesses that have been associated with the alpha7-nicotinic receptor locus, viz. childhood-onset schizophrenia and bipolar disorder (Aims 4 and 5). The initial study used a neurobiological phenotype, i.e., the P50 inhibitory deficit, to find genetic linkage; in the replication, this new genetic information will now be used, first to improve precision, and then to broaden the description of this phenotype. Schizophrenia and bipolar disorder are complex illnesses with multiple genetic and non-genetic elements. The goal of this project is elucidate one of these elements as they are discovered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENVIRONMENTAL-PERSONAL TREATMENT OF SCHIZOPHRENIA Principal Investigator & Institution: Hogarty, Gerard E. Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2002; Project Start 01-APR-1978; Project End 30-JUN-2004 Summary: Schizophrenia has resisted traditional forms of social and vocational rehabilitation. While behavioral cognitive interventions have recently shown effects on resistant symptoms or selected aspects of neurocognition and problem solving ability, there has been little evidence of broad generalization to community life. In contrast, Cognitive Enhancement Therapy (CET), a developmental approach to facilitating social cognitive capacities, is demonstrating extensive effects on social cognition, social and vocational adjustment, neuropsychological performance and residual symptoms. This proposal first seeks to undertake and publish extensive analyses of the two year outcomes among 121 patients randomized to CET or Enriched Supportive Therapy. Second, we propose to complete and publish a provocative third year, post-treatment assessment that indicates a maintenance of effects. Third, we shall prepare training

Studies 45

materials for dissemination to the public sector. Post-hoc analyses have suggested a therapeutic potential of our recently tested Personal Therapy (PT) for schizophrenia patients who abuse alcohol and/or cannabis, and selected CET principles appear uniquely relevant to the cognitive deficits of this population. Thus, a fourth objective is to develop a modified CET/PT intervention targeted toward the cognitive deficits and the dysregulating temperament of these patients. Improved efficacy might ultimately result by addressing the shared pathoetiologies of schizophrenia and substance use disorder in a single treatment. In order to determine the feasibility, relevance, acceptance and preliminary evidence of efficacy for the new intervention, a progressive series of treatment development pilot studies are proposed that will include 30 schizophrenia patients with a substance use disorder involving alcohol and/or cannabis. These pilot studies continue the process that has historically characterized this program's mission to first develop and later test novel interventions that respond to the needs of underserved schizophrenia patients. If successful, a Treatment Manual will be made available to researchers interested in testing the new approach. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXAMINATION OF THE LIMBIC CORTEX IN SCHIZOPHRENIA Principal Investigator & Institution: Tamminga, Carol A. Professor; Psychiatry; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2003 Summary: (provided by applicant) This application seeks to identify and characterize the nature and localization of anatomic and chemical abnormalities in the limbic cortex of schizophrenic (hippocampus, entorhinal cortex, and anterior cingulate) contributing to the pathophysiology of the disease. Several laboratories have generated data suggesting limbic pathology in schizophrenia; our own in vivo imaging and postmortem studies (see Prelim Data) suggest a limbic focus as well. Recently, data from Csernansky et al, have suggested that pathology in the hippocampus is not homogeneous, but is localized within that structure to the lateral head of the hippocampus and the medial aspect of the body (subiculum); this might explain the variability of outcomes reported across studies in postmortem analyses, because few studies control for hippocampal axis. To answer this question, we have paired anatomic and neurochemical measures within the hippocampus, entorhinal cortex, and anterior cingulate from anterior to posterior extent, quantifying markers of neuronal structure and transmission, which may be abnormal in schizophrenic limbic cortex. The hypothesis driving this work is based on our in vivo imaging data from patient studies and our animal model work, which are extensively in agreement with the published literature. We have raised the speculative hypothesis that positive symptoms in schizophrenia are associated with reduced glutamatergic activity at the NMDA receptor in the hippocampus. The resulting reduction in the activity of the glutamatergic hippocampal efferent signal to its projection fields, including entorhinal cortex, anterior thalamus, and anterior cingulate may underlie the generation of psychotic symptoms in schizophrenia. 24 postmortem schizophrenia brains with paired EC, hippocampi and cingulates will be compared to the same structures in 24 matched healthy and 12 matched psychotic control brains. We will study neuronal number, synaptic and dendritic density, along with neurochemical measures of the glutamate, and GABA, systems along the A-P- extent of these structures. We postulate that only certain regions of hippocampus will be affected (lateral head and medial body), and that the neurochemical abnormalities in these regions will colocalize with neuronal number and/or synaptic and dendritic changes, and that related regions of hippo, EC, and ACC

46 Schizophrenia

will be affected. These data will have implications for understanding the mechanisms of the illness and for directing future new drug discovery for schizophrenia therapeutics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPLORATION OF KCC2: ROLE IN SCHIZOPHRENIA Principal Investigator & Institution: Yu, Baojian; Pharmacology and Toxicology; University of Texas Medical Br Galveston 301 University Blvd Galveston, TX 77555 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): This is an exploratory/development grant (R21) proposal in response to NIMH RFA#PA-00-073. The K-CI Co-Transporter (KCC2) is neuronal specific and widely distributed in the central nervous system. KCC2 serves a dual function in neurons: the maintenance of low intracellular chloride ([CI]i) and the buffering of external potassium ([K]o) concentrations in the brain. Functionally, KCC2 is coupled with GABAA receptors whose activation allows anions (predominantly CI-) to flow into neurons, producing GABA's principal synaptic function - inhibition. Whether GABAA receptor activation leads to inhibition or excitation depends upon the value of its reversal potential (EGABAA). The reversal potential value is primarily determined by an electrochemical gradient of the CI across the membrane; KCC2 plays a pivotal role in regulating neuronal [Cl]i homeostasis. Thus, KCC2 regulates the physiological functions of GABAA receptors, namely, synaptic inhibition in normal adult CNS neurons, while also synaptic excitation in normal developing or neonatal neurons, and possibly - in a maladaptive manner - in disease affected neurons. The GABAergic system, the main inhibitory system in the brain, is reported to malfunction in schizophrenia (SCZ). SCZ is a complex mental disorder characterized by a debilitating disturbance of cognitive function and behavior that may result from a dysfunction of multiple CNS neurotransmission systems including the GABAergic system. However, the expression and function of the KCC2 transporter have not been studied in schizophrenic brains or in animal models of schizophrenia. We propose to explore the role of KCC2 in a chronic phencyclidine (c-PCP) rat model of schizophrenia. The experiments will test the hypothesis that in rats treated chronically with PCP, KCC2 is functionally down-regulated and/or its expression is altered in neurons of the medial prefrontal cortex (mPFC). The mPFC has long been implicated in the pathogenesis of schizophrenia. The specific aims are threefold: namely, 1) compare the synaptic physiology of GABAA receptors in the prefrontal cortex of normal and c-PCP rats; 2) determine the value of GABAA receptor reversal potentials (EGABAA), for GABAA receptors at synaptic and non-synaptic sites in normal and c-PCP rats, respectively; and, 3) determine the levels of protein expression of KCC2 while investigating its pharmacological manipulation with an antagonist, furosemide, in normal and c-PCP rats. Results from the proposed study may provide an impetus to consider a novel pathogenesis for schizophrenia, while at the same time providing a basis for a more effective pharmacotherapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FAMILIAL PSYCHIATRIC DIS & ATTENTION IN SCHIZOPHRENIA Principal Investigator & Institution: Asarnow, Robert F. Professor; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 15-AUG-1989; Project End 30-JUN-2005 Summary: (Adapted from the Applicant's Abstract): This project addresses two major bottlenecks to progress in detecting susceptibility genes for schizophrenia: 1) the

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probable genetic heterogeneity of the schizophrenia disorders and 2) uncertainty over the boundaries of the schizophrenia phenotype. This project was stimulated by the hypothesis that early (childhood) onset schizophrenia is associated with increased genetic loading for this disorder. The proposed project will replicate and extend important findings from the first phase of this project indicating that there is a significantly increased familial aggregation of schizophrenia, schizophrenia spectrum personality disorders, and certain neurocognitive impairments in families of probands with childhood-onset schizophrenia compared to families of community control and adult-onset schizophrenia probands. The long-term stability and predictive validity of schizophrenia spectrum diagnoses and neurocognitive impairments detected during adolescence in the siblings of probands with childhood-onset schizophrenia will be determined. Hypotheses about the role obstetric complications play in triggering an early onset of schizophrenia and about the relation between history of obstetric complications and impaired functioning of the hippocampal/temporal lobes will be tested. The hypothesis that relatives of probands with childhood-onset schizophrenia who have neurocognitive impairments will show subtle signs of formal thought disorder impaired discourse and impairments in working memory will also be tested. The proposed project will test a number of genetic models of the familial transmission of putative measures of the extended schizophrenia phenotype, including analyses to examine the evidence for a single vulnerability factor versus two familial vulnerability factors (one influencing mainly neurocognitive measures and the other mainly schizophrenia spectrum diagnosis. Whether chromosomal regions found in prior research to be associated with susceptibility to schizophrenia are associated with susceptibility to childhood-onset schizophrenia and potentially associated phenotypes (including neurocognitive impairments) will be determined. These specific aims will be addressed by rediagnosing all previously studied (N = 50) probands and relatives with childhood-onset schizophrenia to confirm their original diagnoses, enrolling an additional 90 new families of probands with childhood-onset schizophrenia and 60 families of probands of community controls, and capitalizing on data from 120 families of adult-onset schizophrenia probands which has already been collected. We will conduct a genetic linkage analysis to determine whether putative susceptibility genes identified in prior research are associated with the presence of schizophrenia spectrum disorders and/or neurocognitive impairments in families of probands with childhoodonset schizophrenia. DNA will be retained for use in future linkage, linkage disequilibrium, association and other studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FAMILY-GENETIC SCHIZOPHRENIA

STUDY

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Principal Investigator & Institution: Myles-Worsley, Marina; Research Associate Professor of Psychiat; Psychiatry; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-MAR-2006 Summary: (Applicant's abstract): This is an application for competitive continuation of our research on the genetic etiology of schizophrenia in Palau, a geographic and ethnic isolate in Micronesia that is not inbred. The completion of the epidemiological phase of our Palau study has laid the foundation for the proposed prospective study of high-risk (HR) offspring in the large multiplex schizophrenia families that have now been identified. We plan to study not only all 14-18 year-old adolescent offspring of affected parents (approximately 100) but also the adolescent offspring of unaffected parents who

48 Schizophrenia

are possible carriers of a genetic liability for psychotic illness (approximately 200). These 300 HR adolescents will be compared to 100 14-18 year olds who are identified as behaviorally but not genetically at risk (adolescents with no close affected relatives who have been referred for substance abuse counseling, psychosocial counseling, or psychiatric treatment) and 100 normal adolescent controls. All subjects will be comprehensively assessed with a battery of clinical/psychosocial and neuropsychological measures plus two neurophysiological endophenotypes for schizophrenia and followed up longitudinally for the development of psychopathology in order to accomplish three specific aims. 1. Describe the genetic epidemiology of schizophrenia in HR offspring within multiplex families. 2. Develop and test etiological models that describe how genetic liability, environmental factors, and individual traits interact to cause schizophrenia spectrum psychopathology. 3. Describe the phenomenology of schizophrenia in its developmental stages to facilitate early detection and intervention. Our proposed study has a number of unique characteristics that will greatly enhance the information it generates. Compared to prior studies of HR offspring, we will be able to sample a broader range of relationships to schizophrenic patients and a broader range of parental clinical phenotypes that can transmit schizophrenia spectrum psychopathology. Also, a unique component of our study design is the comparison of genetically HR subjects with a group of behaviorally, but not genetically, HR subjects, which may help to disentangle environmental precursors of schizophrenia from genetic liability. Furthermore, our study proposes to fill existing gaps in the assessment of MR offspring by adding several measures including two promising endophenotypes for schizophrenia, saccadic ocular motor dysfunction and P50 sensory gating deficits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FMRI AND TMS STUDIES OF WORKING MEMORY IN SCHIZOPHRENIA Principal Investigator & Institution: Manoach, Dara S. Assistant Professor; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2001; Project Start 10-DEC-1999; Project End 30-NOV-2004 Summary: This is an application for a NIMH Mentored Patient-Oriented Research Career Development Award (K-23) entitled, fMRI and TMS of Working Memory in Schizophrenia. Working memory (WM) deficits are a persistent, disabling and treatment-resistant feature of schizophrenia that are associated with dorsolateral prefrontal cortex (DLPFC) dysfunction. However, the responsible neural circuitry and the exact contribution of the DLPFC are unknown. The candidate aims to elucidate the neural basis and nature of WM deficits in schizophrenia. This work will clarify the function of the DLPFC and other components of WM neural circiutry and contribute to the development of more focused interventions to improve WM and the behaviors that rely on it. The DLPFC is a large and functionally heterogeneous area. Event- related functional magnetic resonance imaging (fMRI) on a 3.0 Tesla system and high resolution cortical flat mapping will be used to identify DLPFC subregions associated with each temporally separated behavioral subcomponent of WM performance in normal and schizophrenia subjects. Using a stereotactic mapping system, transcranial magnetic stimulation (TMS) will be applied to these DLPFC subregions, identified in each subject with fMRI, to produce reversible functional disruption with millisecond accuracy during WM performance. This will establish whether a region is necessary for WM, and the timing of its contribution. Together, these complementary methods yield more precise information about the location, timing and contribution of regional brain activity

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to WM than was previously available. The two WM paradigms employed in these paired fMRI/TMS studies will test the hypothesis that schizophrenia subjects fail to automate WM performance as reflected in aberrant recruitment of frontostriatal neural circuitry, a failure to show the normal lateralization of DLPFC function in response to task demands, and an increased sensitivity of DLPFC function to WM load. The training program supplements the candidate s strengths in experimental psycholpathology and neuropsychology and capitalizes on the rich, diverse neuroscience community in the Boston area. It provides didactic instruction and expert mentorship in advanced statistics, event-related fMRI, cortical flat mapping, TMS and models of brain function relevant to schizophrenia. The integrated training and research program will allow the candidate to master complex and sophisticated tools and to establish herself as an independent investigator of the neurobiology of cognitive deficits and symptoms in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FMRI OF CHOLINERGIC DYSFUNCTION IN SCHIZOPHRENIA Principal Investigator & Institution: Tregellas, Jason R. Pharmacology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2002; Project Start 01-AUG-2002 Summary: (provided by applicant): Abnormalities in smooth pursuit eye movements and deficits in auditory sensory gating are two of the best characterized physiological endophenotypes associated with schizophrenia. Transient normalization of both of these sensory deficits by smoking, in addition to evidence from epidemiology, animal models, genetics, molecular biology and post-mortem binding studies, suggests involvement of nicotinic cholinergic receptors in the disease. The functional effect of this putative cholinergic dysfunction on mental processes in individuals with schizophrenia, however, remains unknown. This first aim of this study proposes the use of functional magnetic resonance imaging (fMRl) to characterize the functional neuroanatomy associated with smooth pursuit eye movements in patients with schizophrenia and age-matched healthy controls to determine if failure to properly execute this task in patients with schizophrenia is associated with a detectable, abnormal pattern of neuronal activation. The second aim of his study is to use fMRI to detect differences in functional neuroanatomy between control and patients with schizophrenia are due to nicotinic cholinergic receptor dysfunction by examining taskspecific (smooth pursuit eye movement) changes in neuronal activity associated with administration of nicotine to controls and patients with schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FMRI STUDIES IN ADOLESCENTS AT-RISK FOR SCHIZOPHRENIA Principal Investigator & Institution: Diwadkar, Vaibhav A. Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2003; Project Start 20-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The aim of this career development proposal is to allow the applicant to acquire the skills necessary to characterize neurodevelopmental abnormalities associated with adolescents at risk for schizophrenia. Schizophrenia is a highly debilitating and complex disorder marked by severe abnormalities in cognitive function, particularly working memory. The illness may be mediated by neurodevelopmental abnormalities and by genetic factors. Studies of neurodevelopment in adolescent first-degree relatives who are at significantly elevated risk for developing

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the illness promise to help better elucidate the premorbid diatheses of the illness. This proposal will use fMRI to investigate working memory abnormalities in adolescent firstdegree relatives of schizophrenia patients. The use of fMRI will facilitate an understanding of alterations in the functional neuroarchitecture of these subjects and fill a lacuna in the present understanding of the precursors of the illness. The analysis of the fMRI data will focus on identifying regions of aberrant activation, as well as probing functional disconnections between regions of the brain. Relationships between aberrant fMRI activation and structural alterations in the brain will also be explored. During the course of this award, the applicant will obtain training in: 1) understanding developmental neuroscience during the period of adolescence, 2) the use of fMRI for the study of adolescent high-risk populations 3) understanding of the clinical issues associated with schizophrenia, particularly its premorbid and prodromal phases, 4) understanding of statistical, ethical and epidemiological issues associated with the field neuropsychiatric research. By the conclusion of the award, the applicant expects to emerge as an expert on the application of neuroimaging to the study of the neurobiological precursors of schizophrenia. The proposal's focus promises to provide better insights into the developmental neurobiology of the illness and the contributions of development and genetics. The data will help the applicant develop larger projects during the concluding years of the award period that may help in the development of psychosocial and psychopharmacologic interventions in adolescents at risk for schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL ANALYSIS OF 22Q11 SCHIZ. SUSCEPTIBILITY GENES Principal Investigator & Institution: Karayiorgou, Maria; Associate Professor; Lab of Human Neurogenetics; Rockefeller University New York, NY 100216399 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Microdeletions of the 22q11 locus are the only known genetic lesions that increase an individual's risk for schizophrenia to a striking 25-31 times over the general population risk, a level comparable to the risk of an individual born to two schizophrenic parents. These microdeletions are present among adult schizophrenics and cases of severe childhood onset schizophrenia at rates significantly higher than in the general population. Based on our results from an extensive, detailed association analysis of all individual genes from the 22q11 locus, we propose here to use gene targeting and chromosomal engineering approaches to generate 3 mouse models that will help us understand the biological basis of the increased schizophrenia risk associated with this region. Specifically, we propose to disrupt a 250 Kb subregion that we believe carries most, if not all the genetic elements responsible for the striking increase for schizophrenia risk associated with this locus. We also propose to generate general or conditional deletions of two individual genes from this locus which, according to our genetic studies in patients, may account for a large part of the disease risk attributed to this region. We propose to examine the strains of mice that we will generate for behavioral phenotypes that may serve as models of schizophrenia-related endophenotypes (components of pathophysiological processes mediating between predisposing genes and clinical diagnosis). Furthermore, and because gray matter loss is the most consistent feature in brains of schizophrenic patients, we will address the possibility of generic or spatially restricted neuron or neuropil loss in the brains of the mutant mice using a battery of sophisticated histochemical and imaging approaches. Finally, we will use oligonucleotide microarrays

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to address the nature of the molecular and physiological targets affected in the brain by the disruption of individual genes or clusters of genes. Analysis of expression patterns in the brains of mice that carry well-defined genetic deficits associated with schizophrenia in humans will provide a more accurate and reproducible profiling of gene expression associated with the disease. This comprehensive approach, in conjunction with our ongoing genetic and neurocognitive studies in patients, will provide important insights into the biological processes underlying the increased schizophrenia risk associated with this region. Furthermore, the engineered mouse strains will also facilitate the identification of novel and more specific compounds with neuroleptic properties. The design of such compounds can be directed by the knowledge of individual genes from the deleted region that contribute to schizophrenia susceptibility. This will be an unprecedented situation in schizophrenia genetics and pharmacotherapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL DISABILITY AMONG OLDER SCHIZOPHRENIA PATIENTS Principal Investigator & Institution: Palmer, Barton W. Assistant Adjunct Professor; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 01-FEB-1997; Project End 31-JAN-2003 Summary: (Adapted from applicant's abstract): The objective of this 5 year academic award is to develop Dr. Barton W. Palmer's expertise in functional disabilities among older schizophrenia patients, and to set the foundation for a research career focused on this topic. The plan of this award will develop Dr. Palmer's skills and knowledge in the following areas: 1)methodological issues in the assessments of functional disabilities in older schizophrenia patients, 2) the nature of functional impairments associated with schizophrenia in late-life, 3) factors contributing to functional impairment among these patients. The plan will also foster further development of Dr. Palmer's general skills in research methodology as applied to issues in geriatric psychiatry. These goals will be achieved through a structured training plan, including relevant coursework, and through consultation with leading experts in the fields of functional disabilities, schizophrenia, geriatric psychiatry, and clinical research methodology. In addition, the plan includes a pilot research project designed to provide a preliminary investigation into the nature of functional impairments among older institutionalized and community dwelling schizophrenia patients. These activities will help Dr. Palmer evolve as a clinical investigator in geriatric psychiatry, and additionally provide the foundation for a long term research program focused on functional impairment among elderly schizophrenia patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONAL IMAGING RESEARCH IN SCHIZOPHRENIA TESTBED Principal Investigator & Institution: Holmes, Edward W. Dean; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2002; Project Start 01-MAR-1974; Project End 30-NOV-2004 Summary: (provided by applicant): Functional brain imaging has the potential to advance the diagnosis and treatment of major neuropsychiatric illness as well as contribute to the understanding of its causes. This potential has remained unfulfilled

52 Schizophrenia

because of technological impediments that can be surmounted by construction of infrastructure to facilitate sharing of data such as federated databases and information discovery tools based on knowledge engineering approaches. This Functional Imaging Research in Schizophrenia Testbed (FIRST) BIRN proposal, in response to the NCRR "Biomedical Imaging Research Network" RFA, focuses upon the development and validation of a common fMRI protocol for a large-scale multi-center study of schizophrenia. The proposal is crystallized around a high-speed broadband network supporting a federated database, specifically developed for the pooling and sharing of data across sites to facilitate large scale hypothesis testing and intelligent data mining to address complex scientific problems. There are two major goals. The first goal is technological - development of a distributed network infrastructure that will support the creation of a federated database consisting of large-sample fMRI datasets contributed by the eleven institutions at ten centers. To meet this goal, the consortium will assess the major sources of variation in fMRI studies conducted across centers, including instrumentation, calibration, acquisition protocols, challenge tasks, and analysis methods, and develop methods that support the analysis of a combined data set. The second major goal is clinical -applying the technology developed in this proposal to study specific regional brain dysfunction, as well as changes in brain function in the progression and treatment of schizophrenia. In addition, this proposal specifically intends to capture the added value of each center's unique approach to the study of schizophrenia in their currently funded projects. These independent projects use diverse fMRI cognitive activation tasks and study unique patient populations. In this proposal, a common consortium fMRI protocol will be standardized, calibrated, and validated to enhance sharing of data across sites and populations. The infrastructure and federated database developed in this proposal will provide access to and sharing of stored MRI images, clinical findings, and behavioral data relevant to the study of schizophrenia. The technology and infrastructure developed by this proposal, using advances in information engineering and broadband networking, will create a federated database focused on sharing data and intelligent database querying to address the proposal hypotheses and generate new knowledge. The technological developments supported by this proposal will accelerate progress in understanding and treating schizophrenia and be immediately applicable to other disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL SCHIZOPHRENIA

MAGNETIC

RESONANCE

STUDIES

IN

Principal Investigator & Institution: Mcdowell, Jennifer E. Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 10-AUG-2001; Project End 16-AUG-2002 Summary: (provided by applicant) The long-term career goal of the primary investigator is to advance the knowledge ot schizophrenia-related functional neuropathology by establishing and directing a brain imaging laboratory. The short-term goal is to develop an expertise in the design, execution, and analysis of functional magnetic resonance imaging (fMRI) studies using a series of saccadic tasks. The realization of these goals will occur through a combination of intensive training and the completion of a systematic research plan over the course of the proposed funding period. Training in functional neuroimaging will occur within the UCSD functional neuroimaging group and during yearly 2-week training sessions at the NIMH. Training in neuroanatomy and neuropsychology will be completed within the UCSD neuroscience community. The research plan utilizes the P.I.'s existing studies on the saccadic performance of

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schizophrenia patients and their relatives as a foundation for generating and testing hypotheses of basal ganglia-thalamocortical circuitry dysfunction associated with schizophrenia. Schizophrenia patients perform normally on refixation saccade tasks, but demonstrate characteristic abnormalities on antisaccade and ocular motor delayed response tasks. A similar pattern of performance is observed among biological relatives of the patients, suggesting that this phenotype may be associated with the liability for developing schizophrenia. The pattern of saccadic performance is consistent with pathology of prefrontal cortex and its associated cortical and/or subcortical circuitry. This hypothesis may be tested using saccadic tasks as behavioral probes during fMRI to measure BOLD (blood oxygenation level dependent) signal change while subjects are engaged in ongoing behavioral and cognitive activity. Three specific aims are proposed; 1) evaluate the patterns of neural activation associated with refixation saccade performance in schizophrenia and normal subjects, 2) to test hypotheses of differing patterns of frontal activation between schizophrenia and normal groups during tasks that ostensibly require prefrontally-mediated inhibition (antisaccade and delayed response tasks), and 3) to test hypotheses of prefrontal cortex dysfunction among the biological relatives of schizophrenia patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL SCHIZOPHRENIA

SKILLS

TRAINING

FOR

LATE

LIFE

Principal Investigator & Institution: Patterson, Thomas L. Associate Professor; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Despite improved pharmacological treatments for schizophrenia, patients continue to have difficulties functioning in the real world (e.g., medication management, communicating needs, establishing social networks, managing finances). These difficulties are likely compounded as persons with schizophrenia age (e.g., physical limitations, cognitive impairment), thus, making it more difficult to live in the community. As the proportion of older persons in the U. S. virtually explodes, so too will the proportion of older persons with schizophrenia, creating a drain on mental health and social service systems ill-equipped to serve them. There is a current paucity of studies on the effectiveness of rehabilitation programs for schizophrenia patients and none has been designed and tested with older patients. Thus, there is a clear need to develop effective rehabilitation programs sensitive to the deficits of older persons with schizophrenia. Psychosocial interventions which efficiently promote better symptom management, medication management, every day living skills, and psychosocial functioning are of particular importance in that they may reduce the chance that older patients with schizophrenia require hospitalization and long-term care while minimizing burden on health care systems. The goal of the proposed project is to test the efficacy of a skills training protocol, entitled Functional Adaptation Skills Training (FAST), designed to enhance daily functioning of older patients with schizophrenia. We will enroll 200 community dwelling patients over age 60 into a randomized, pretest, multiple posttest control group design study. Subjects will enroll in one of two timeequivalent interventions: Experimental treatment, a 24-session group intervention designed for older adults targeting 6 functional skill domains (i.e., financial management, social skills, communication skills, transportation, organization and planning, and medication management); or psychosocial placebo (a friendly support group). Treatment will be followed by six one-monthly maintenance sessions.

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Assessments are conducted at 6-, 12-, and 18-months post-baseline. A unique feature of the proposed study is the use of performance-based outcome measures which reduce problems associated with lack of insight common in schizophrenia. Data will allow us to determine short-term effects of our intervention, effectiveness of maintenance sessions, and post-intervention duration of treatment effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GATING OF INFORMATION FLOW WITHIN THE NUCLEUS ACCUMBENS Principal Investigator & Institution: Grace, Anthony A. Professor; Neuroscience; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2002; Project Start 15-AUG-1997; Project End 31-JUL-2007 Summary: (provided by applicant): This proposal represents a competing continuation of a grant to investigate the basic science aspects of schizophrenia as it relates to limbic system function. Pharmacological evidence has implicated the dopamine (DA) system in schizophrenia; however, there is little evidence for a direct pathology within the DA system itself. Instead, evidence has amassed to suggest a primary deficit within limbic cortical structures, each of which supplies a glutamatergic input that overlaps with the DA system within the nucleus accumbens (NAc). Three regions in particular have been associated with several aspects of schizophrenia, including the prefrontal cortex, the hippocampus subiculum and the basolateral amygdala. In the previous proposal, we examined how each of these systems provides synaptic influences in the NAc. In the current proposal, we will extend this to examine, using in vivo intracellular recording methods, how tonic activation of these afferent systems affects the state of the neurons in the NAc, and moreover how these activity patterns are modulated by selective DA drugs administered locally via reverse dialysis. We will also investigate how the NAc system in turn modulates the FA system, and how these systems are altered in a developmental disruption model of schizophrenia. This will be done according to the following four specific aims: 1) Examine how tonic activation of NAc neuron afferents affects baseline activity and response of NAc neurons to afferent stimulation, 2) Examine the DA receptor subtypes involved in modulating afferent interactions within the NAc, 3) Examine how the NAc system modulates the activity of DA neurons in the ventral tegmental area and how this correlates with DA release, and 4) Examine the effects of developmental neurotoxic disruptions on the integration of information flow within the NAc and its projections to the ventral tegmental area, and how this differs in prepubertal vs postpubertal rats. In this way, we hope to extend our knowledge of cortical-subcortical interactions in modulating the state of NAc neurons, how this state is regulated in an interactive manner by the DA system, and how developmental disruptions lead to a reorganization of limbic systems during development in a manner that may contribute to the pathophysiology of schizophrenia in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC EPIDEMIOLOGY OF SCHIZOPHRENIA IN IRELAND Principal Investigator & Institution: Kendler, Kenneth S. Professor; Psychiatry; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2001; Project Start 01-DEC-1986; Project End 31-MAR-2003 Summary: Family, twin and adoption studies provide strong evidence that genetic factors play a major role in the etiology of schizophrenia. While evidence has begun to accumulate for replicated linkage for schizophrenia to several chromosomal regions,

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efforts to identify the location of susceptibility loci for schizophrenia have previously proven unsuccessful. This may in part be true because prior studies of linkage disequilibrium (LD) were small in size, utilized a case control vs. a family based method, were ethnically and clinically heterogeneous and were conducted in large outbred populations where LD may exist over only very short genetic distances. One of the studies that has contributed to these advances is the Irish Study of High Density Schizophrenia Families (ISHDSF), the original phase of which ascertained and studied, in Ireland and Northern Ireland, 265 multiplex schizophrenia families containing 1,408 individuals with detailed clinical information and DNA. In this third and final submission of this competitive renewal, we seek support to critically extend the ISHDSF by collecting 500 proband-parent triads for family-based association studies. We will select triads with a positive family history of psychosis to reduce the rate of "phenocopies", interview parents for their personal and family history of schizophrenia and schizophrenia spectrum illness so as to weight transmissions on the basis of the probability that they contain a susceptibility allele and sample all living and available relatives with schizophrenia or chronic schizoaffective disorder so as to weight, in those triad-families, those that are more likely to be segregating a susceptibility allele in a given chromosomal region. With support for the genotyping and statistical analysis of this new sample, we seek to address two critical questions: 1. Can we replicate, by means of linkage disequilibrium, previously obtained evidence for linkage in the 4 putative susceptibility regions found in the ISHDSF to date (6p24-22, 8p22-21, 5q21-31 and 10p15-p11) and new regions that may emerge as we complete our genome scan? 2. Can we, by applying dense marker maps to our triad sample, obtain fine localization of schizophrenia susceptibility loci in these and other potential candidate regions? High genetic and cultural homogeneity, large family size, low rates of drug abuse, high levels of linkage disequilibrium demonstrated over genetic distances of 0.5 to 1.0 centiMorgans and a cooperative, stable population make Ireland ideal for linkage disequilibrium studies of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC LINKAGE OF SCHIZOPHRENIA AND RELATED STUDIES Principal Investigator & Institution: Levinson, Douglas F. Associate Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 30-JUL-2001; Project End 30-JUN-2006 Summary: This is a revision of a competing renewal application for a Midcareer Investigator Award which was funded as an Independent Scientist Award (K02) in 1995, with this renewal requested under the K24 mechanism for patient related research. The research theme has been collaborative studies in the genetics of schizophrenia and (more recently) major mood disorders. The applicant is a psychiatrist who has pursued a career of research in the recruitment and clinical assessment of families for these studies, the application of advances in statistical genetics to the design of clinical studies, and the organization and coordination of large collaborations to collect new samples and to carry out multicenter linkage studies of existing samples. The applicant has moved to an institution with an outstanding research and research training environment. Career award support is needed to provide sufficient protected time to focus on the proposed program of patient- oriented research and active involvement in mentoring of beginning research trainees. The current award period has included completion of a genome scan of schizophrenia; organization of a series of linkage studies of schizophrenia candidate regions in very large multicenter samples; creation and initial testing of a new dimensional rating scale for psychotic disorders; pilot data

56 Schizophrenia

collection of mood disorders in an inbred population; work on computer simulation studies; initiation of two large pedigree collections, one of major depression (as coordinator of a six-site collaboration) and one of schizophrenia (as PI of one of nine sites); and mentoring activities. The protected time made possible by the proposed award will permit development of a new research focus on dimensional approaches to measuring psychopathology in psychotic disorders, organization of new large collaborations based on advances in the field, career development activities to enhance knowledge of molecular and statistical genetics, and participation as a teacher and mentor in a funded Clinical Scholars Research Program for psychiatry residents in a four-year research training track. Other activities will include the funded multicenter pedigree collections and genome scans of major depression and schizophrenia; completing a previous schizophrenia genome scan project; collaborative efforts to identify specific susceptibility genes; coordinating a funded project to continue multicenter linkage and association studies of schizophrenia; and completion of the isolated population mood disorders data collection and development of related population simulation software and genetic analysis strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC VULNERABILITY FOR SCHIZOPHRENIA Principal Investigator & Institution: Dionisio, Daphne P. Psychology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 10-JAN-2002; Project End 09-OCT-2005 Summary: As nearly 1% of the U.S. population is affected by schizophrenia and the country's annual expense related to the mental disorder is over 70 billion dollars, the disorder remains a pressing concern. Although genetic linkage studies initially appeared promising, they have yielded inconsistent results in the search for the location of major genes predisposing for schizophrenia. It is believed that this is due to in large part to the partial penetrance of the affected genes and a clinical diagnosis of the disorder that only identifies a fraction of the relevant population (i.e. only those who display full symptom expression). To increase the strength of genetic linkage studies, investigators have begun to study individuals with genetic liability for schizophrenia rather than those who manifest full symptom expression. The present fellowship applicant is principally interested in examining markers (e.g. eye movement dysfunction) that show promise for identifying genetic risk. Also, it is important to identify and study the affected biological relatives of schizophrenia patients who share the genetic diathesis. By examining relatives for vulnerability markers, it may be possible to identify relatives with genetic liability for the disorder and families that may be most informative for genetic linkage studies. Some such vulnerability markers suggest deficits related to reduced integrity of prefrontal cortical brain areas in relatives of schizophrenia patients. Further investigation of these genetic liability indicators may yield insights into the neuropathology of the schizophrenia diathesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETICS OF ENDOPHENOTYPES AND SCHIZOPHRENIA Principal Investigator & Institution: Goldstein, Jill M. Director; Psychiatry; Harvard University (Medical School) Medical School Campus Boston, MA 02115 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 29-FEB-2008 Summary: (provided by applicant): Neurobiological deficits that serve as informative endophenotype markers have been demonstrated in schizophrenia by a number of

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different paradigms. Neurophysiological deficits are prominent in P50 event related suppression, prepulse inhibition (PPI) of the startle response, and the antisaccade (AS) task for eye movement dysfunction. Neurocognitive deficits in schizophrenia are revealed by poor performance on the CPT, verbal memory, and tests of working memory. Each of these deficits has also been demonstrated in clinically unaffected relatives of schizophrenia patients, which is evidence that they may reflect part of the heritable risk for the illness. This conclusion is reinforced by findings of deficits in nonpsychotic, unmedicated schizophrenia patients, and schizotypal patients. The null hypothesis is that all 6 deficits reflect a single, common underlying heritable dysfunction in all schizophrenia patients. A test of that hypothesis requires measurement of all of these deficits in the same group of schizophrenia patient probands and their relatives. If they are all manifestations of the same genetic dysfunction (although perhaps expressed in different brain areas), then a multivariate analysis would show that they all contribute to a single dimension in both relatives and schizophrenia patients. An alternative hypothesis is that only one or a small subset of deficits is present in each family, which is consistent with the heterogeneity found in current genetic linkage studies. In that case, the multivariate analysis would show the different measures or subsets of them loading onto different dimensions. Schizophrenia itself is likely to be the result of multiple deficits in any individual. Therefore, the analysis is performed in the same cohort of schizophrenia patient probands and their relatives to take advantage of Mendel's second law, which holds that genetically independent deficits segregate independently. Hence, although schizophrenia patient probands themselves have multiple deficits, if the deficits are caused by different genetic factors, then they will segregate to different groups of relatives. This 7 site collaborative RO1 project will gather a combined total of 420 pedigrees (1680 subjects) and 525 normal subjects over 5 years (each site will contribute 1/7th of these totals). Findings of heritable deficits in specific measures will be used to guide the next generation of studies of the genetics of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLUTAMATE AND PREFRONTAL CORTEX FUNCTION Principal Investigator & Institution: Moghaddam, Bita; Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 10-JUL-1999; Project End 30-JUN-2004 Summary: A plethora of evidence has implicated the improper functioning of the prefrontal cortex in the pathophysiology of schizophrenia. While numerous findings have described a role for monoaminergic and cholinergic projections to the prefrontal cortex in the cognitive functions associated with this region, the extent of the involvement of the most prevalent prefrontal cortex afferents, namely those projections that contain glutamate as their neurotransmitter, in mnemonic, attentional, and other associative functions of the prefrontal cortex has not been well characterized. Considering that a number of recent findings are suggestive of glutamatergic abnormalities in schizophrenia, it is imperative that more be learned about the role of glutamate receptors in cognitive functions that are relevant to schizophrenic symptomatology. The research proposed in this request for an Independent Scientist Award (K02) involves characterizing the contribution of glutamate receptors in regulating those associative functions of the prefrontal cortex that are relevant to the pathophysiology of schizophrenia. This award will allow the applicant to devote maximal effort to the above research objectives which entails receiving appropriate training in order to establish in her laboratory behavioral paradigms that have direct

58 Schizophrenia

relevance to different aspects of the cognitive dysfunctions associated with schizophrenia and that are analogous to clinical tests at which patients with schizophrenia show an impairment. Considering that the present mode of therapy for schizophrenia, i.e., treatment with antidopaminergic drugs, does not effectively treat cognitive deficits associated with this disorder, an understanding of the neurochemical basis of associative functions of the prefrontal cortex will help in the development of novel pharmacotherapeutic strategies for the treatment of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLUTAMATE SCHIZOPHRENIA

RECEPTOR

SUBUNIT

FUNCTION

AND

Principal Investigator & Institution: Lindahl, Josette; Psychiatry; University of South Dakota 414 E Clark St Vermillion, SD 57069 Timing: Fiscal Year 2002; Project Start 21-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Schizophrenia is a debilitating neurodevelopmental illness that honors no racial or ethnic boundaries. Initial research into its etiology has focused on hyperdopaminergic activity based on clinical observations that dopamine blocking drugs diminish positive psychotic symptoms. Recent findings have implicated the role of glutamate receptors in schizophrenia. These studies propose that reduced NMDA receptor function stimulates abnormally high glutamate release within the synapse, which subsequently leads to unregulated excitation, disinhibition of inhibitory pathways, and neuronal degeneration. Such impaired glutamatergic neurotransmission is potentially associated with the abnormal cognitive, behavioral and memory functions characteristic of schizophrenia. The NMDA receptor hypofunction theory of schizophrenia guides two hypotheses proposed in this research: (1) Glutamate receptor dysfunction in schizophrenia is dependent on alterations in NMDA and AMPA receptor subunit composition in specific brain regions; and (2) Atypical neuroleptics reduce schizophrenic symptoms through cellular mechanisms that either restore NMDA function or circumvent NMDA dysfunction. The primary objective of our research is to contribute to a fundamental understanding of schizophrenia and it's underlying physiological mechanisms. We will contribute to this knowledge base by examining three aims that test these hypotheses. AIM 1: To localize NMDA and AMPA glutamate receptor subunits by immunocytochemistry and light microscopy in normal rat brains and PCP-psychosis induced rat brains. AIM 2: To elucidate the effects of atypical neuroleptics on relative NMDA and AMPA receptor subunit composition in normal rat, PCP-psychosis induced rat, normal neuroleptic treated rat and neuroleptic treated, PCP-psychosis induced rat brains. AIM 3: To examine potential physiological mechanisms of action that may underlie the effects of atypical neuroleptics on NMDA and AMPA-mediated glutamatergic neurotransmission in normal, normal neuroleptic treated, PCP-psychosis induced and PCP-psychosis induced neuroleptic treated rat brains. While the overall scientific goal of this K08 application is to elucidate the role of glutamate receptors in schizophrenia's pathophysiology, the long-term intent of this proposal is to establish my career as a clinical scientist with the potential to develop as an independent researcher. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GLUTAMATE SYNAPSE ABNORMALITIES IN SCHIZOPHRENIC CORTEX Principal Investigator & Institution: Meador-Woodruff, James H. Professor/Senior Research Scientist/Asso; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-JUL-1995; Project End 28-FEB-2006 Summary: (Adapted from applicant's abstract)This project is designed to examine the expression of proteins associated with glutamate neurotransmission in the prefrontal and cingulate cortex of autopsy-obtained brain tissue from schizophrenic patients and matched controls. Converging evidence indicates that there are abnormalities of glutamatergic neurotransmission in specific brain regions in schizophrenia. While pharmacological evidence suggests involvement of the NMDA receptor in this illness, other studies and theoretical considerations suggest that other molecules associated with glutamatergic transmission may be abnormal in schizophrenia. The investigators hypothesize that there are abnormalities in the expression of the genes associated with the glutamate synapse in the limbic neocortex in schizophrenia. Accordingly, this project will examine the expression of these molecules in postmortem brain samples from schizophrenics and controls. The investigators propose to examine the proteins associated with the glutamate synapse in a comprehensive fashion, by (1) examining the expression of receptors, transporters, and anchoring proteins critical for glutamatergic neurotransmission; and (2) determining their expression at multiple levels of gene expression and organization, by determining the expression of the mRNAs encoding each, as well as protein levels, and higher order levels of protein organization as reflected by specific binding sites. While some evidence has accumulated to support the concept of a disturbance in glutamatergic transmission in schizophrenia, most previous studies have been limited in scope, often focusing on a single molecule in a discrete region of the brain. The investigators propose to conduct a comprehensive examination of the glutamate synapse in schizophrenia, by examining the expression of each molecule at multiple levels of molecular genetic organization. Further, the investigators will do this in the same brains, allowing meaningful comparisons within a given brain. At the conclusion of this set of experiments, the investigators will have a clearer understanding of the molecular genetic expression of the proteins associated with the glutamate synapse in schizophrenia at multiple levels of gene expression. Examination of the expression of these proteins critical for neurotransmission at the limbic cortical glutamate synapse may highlight abnormalities which can be more profitably targeted for novel treatment of this disabling illness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GLYCINE-KETAMINE INTERACTIONS IN HEALTHY SUBJECTS Principal Investigator & Institution: D'souza, Deepak C. Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 06-JUL-2000; Project End 30-JUN-2003 Summary: (Adapted from applicant's abstract): Background: Based on the NMDA deficit hypothesis of schizophrenia, it has been proposed that facilitation of NMDA receptor function may have therapeutic potential in schizophrenia. Agonists of the strychnine-insensitive NMDA receptor glycine site offer a safe method to facilitate NMDA receptor function. Clinical trials with glycine added to neuroleptics show promise in the treatment of negative symptoms and cognitive deficits associated with schizophrenia. However, there are limitations to the interpretation of clinical trials.

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Further, clinical trials do not offer insight into the mechanism of action of glycine' therapeutic efficacy. The noncompetitive NMDA receptor antagonist ketamine, induces symptoms in healthy individuals resembling several aspects of schizophrenia. Preclinical studies suggest that glycine site agonists reverse the effects of noncompetitive NMDA receptor antagonists. The ketamine paradigm offers a safe, feasible and clearly interpretable method to clarify the therapeutic potential of glycine and provide insight into the mechanistic underpinnings of its clinical efficacy. Aims: Does glycine pretreatment reduce ketamine-induced: 1) the perceptual alterations, 2) negative symptoms and 3) amnestic effects in healthy subjects. A secondary exploratory aim is to determine whether the effects of glycine are dose-related. Methods: Healthy subjects (n = 42) will complete 6 test days during which they will be administered intravenous glycine (0.1 g/kg), (0.2 g/kg) or placebo (normal saline) pretreatment followed by ketamine or placebo in a randomized, double-blind, counterbalanced order. Behavioral ratings for perceptual alterations (Clinician Administered Dissociative Symptom Scale), negative and positive symptoms of psychosis (Brief Psychiatric Rating Scale), recall (Hopkins Verbal Learning Test) and working memory will be administered. Ketamine levels will also be measured. Behavioral measures and drug levels will be subjected to a repeated measures analysis of variance (RMANOVA) with within subject factors of ketamine (ketamine vs. placebo), glycine (glycine vs. placebo), and time. Cognitive measures (HVLT, working memory) that are administered only once per test day, the RMANOVA performed on these data will just include within subjects factors of ketamine and glycine. Relevant covariates including age, weight, baseline WAIS-R scores, education level, drug levels will be included into the analyses. Pilot Data: Ketamine induces a schizophrenia-like syndrome in healthy humans that includes perceptual alterations, negative symptoms and amnestic effects have previously been reported. The central bioavailability and dose-related effects of intravenous glycine in healthy subjects will also be studied. Pilot data (n=12) towards this proposal suggests that glycine reduces ketamine-induced perceptual alterations, negative symptoms and impairments on recall without worsening positive symptoms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GOLGI STUDIES OF SCHIZOPHRENIA Principal Investigator & Institution: Dwork, Andrew J. Associate Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant) In a previous study, we found a profound loss of spines on the apical dendrites of pyramidal neurons in the left subiculum of individuals with schizophrenia, with no overlap between subjects with schizophrenia and those without psychiatric illness. In addition, there was a significant reduction in the apical dertdritic arbors of these cells, but not in their basilar dendritic arbors, nor in the dendritic arbors of pyramidal neurons in the adjacent neocortex. Since completing that study, we have improved our technique for rapid Golgi staining, so that it is now applicable to tissue from the pre-neuroleptic era, that has been in lormalin for over 50 years. Furthermore, the number of Golgi-impregnated neurons is now sufficient to permit random sampling of neurons for evaluation. Similar findings by other researchers who examined other regions of the brain, and our own data showing abnormalities of subicular MAP2, supporting diminished cognitive reserve, and documenting the longitudinal course of cognitive and clinical deterioration, all support the notion of decreased synaptic connectivity as a substrate for schizophrenia. We now propose to employ improved Golgi staining to study 5 groups of 20 individuals in order:

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(1) To evaluate the replicability of our previous finding. (2) To determine whether similar abnormalities are present in archived brains from schizophrenia patients who died before the introduction of neuroleptic drugs. It is possible that these drugs induce the loss of spines, that they protect against it, or that they do neither. (3) To determine whether similar abnormalities are present in the brains of young schizoprhenia subjects, which will help to determine whether the loss of spines is more likely a cause or a result of schizophrenia, and whether it is progressive. (4) To evaluate prefrontal cortex, primary visual cortex, and additional areas of hippocampus, in order to determine whether spine loss in schizoprhenia is localized or generalized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIPPOCAMPAL GENE EXPRESSION IN SCHIZOPHRENIA Principal Investigator & Institution: Benes, Francine M. Professor of Psychiatry (Neuroscience); Mc Lean Hospital (Belmont, Ma) Belmont, MA 02478 Timing: Fiscal Year 2001; Project Start 16-SEP-2000; Project End 31-AUG-2003 Summary: (Applicant's abstract): This is a request for an R21 entitled "Hippocampal Gene Expression in Schizophrenia" in response to the RFA MH-00-002 "Gene Expression in the Nervous System". We propose to study the expression of genes in the hippocampus of normal subjects and patients with schizophrenia using a combination of gene array technology and in-situ hybridization. This research project is integrated into our ongoing study of abnormal circuitry in the hippocampus in schizophrenia. Specifically, we will test the hypothesis that an abnormality of GABAergic neurons will result in an abnormal expression of genes in subsets of hippocampal neurons. We will study two groups of schizophrenic patients, those with (T+) and without (T-) a history of treatment with neuroleptic drugs within 6 months prior to death. Both the schizophrenic and the normal control groups will be comprised of an equal number of male and female subjects. Gene array technology will be used to screen a large number of candidate genes and ESTs. Initial studies will make control vs. control comparisons to determine the amount of variation in gene expression in the normal population. This information will be used to determine the threshold at which differential expression between schizophrenics and controls can be considered significant. Brain tissue samples of several subjects will be pooled in each group to achieve a higher signal-to-noise ratio in the between-group comparisons. Genes of interest for further studies will be defined as having a) a markedly different expression in schizophrenia, b) a known function in the central nervous system and altered expression in schizophrenia, and c) differential expression in the (T-), but not (T+) schizophrenia groups. Genes of interest will then be studied with in situ hybridization in intact human brain tissue to confirm differential expression in schizophrenia and to study the subregional and cellular localization. Overall, gene profiling as outlined in this research proposal will be a powerful tool to gain information about molecular abnormalities in the hippocampus of schizophrenic subjects. The new gene array technology will be fully integrated into an existing research program to study the molecular, cellular, and systems aspects of hippocampal dysfunction in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HSP60 ABNORMALITIES IN SCHIZOPHRENIA Principal Investigator & Institution: Sadiq, Saud A.; St. Luke's-Roosevelt Inst for Hlth Scis Health Sciences New York, NY 10019 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003

62 Schizophrenia

Summary: (adapted from applicant's abstract): This application proposes to investigate abnormalities in human heat shock protein 60 (HSP60) in schizophrenia. This is potentially important as abnormalities of hsp60 in schizophrenia may impair cellular responses to stress; the biological role of normal hsp60 is to protect cells from oxidant injury and other forms of stress. This proposal is based on findings that 27% (16/59) of patients with schizophrenia had high-titer serum IgG antibodies to recombinant human hsp60 compared to 0% (0/81) of disease controls and 3% (2/66) of normal subjects. Also, in cerebrospinal fluid (CSF) anti-hsp60 antibodies were found in 53% (8/15) of patients with schizophrenia compared to 6% of disease controls, and 0% (0/6) normal subjects. Additional data suggests that this aberrant immune response may arise as a result of a genetic alternation of brain hsp60 in schizophrenia; the site of a cDNA sequence abnormalities in brain hsp60 coincides with the location of a 11-me peptide epitope of hsp60 targeted by the anti-hsp 60 antibodies. The specific aims are (1) are anti-hsp60 antibodies present in drug-naive patients with schizophrenia; (2) can serum antibody findings be replicated in a new patient population and are CSF anti-hsp60 antibodies more specifically associated with schizophrenia; (3) Is there a unique clinical profile or specific clinical features associated with anti-hsp60 antibody-positive patients with schizophrenia; (4) what is the molecular basis of the abnormal response to hsp60; and (50 does epitope localization of the anti-hsp60 antibodies correlate with more specific clinical or biological abnormalities in patients with schizophrenia. All antibody testing with be by Western blotting. Antibody-positive and negative patients with schizophrenia will be compared using several clinical measures grouped under three domains: demographic and historical, current clinical symptoms and neuropsychological performance. Molecular studies will involve genomic and cDNA cloning of hsp60 from peripheral and brain tissue. Epitope mapping will be done by ELISA using overlapping peptides spanning the entire normal human hsp60 sequence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IDENTIFYING SCHIZOPHRENIA

&

CHARACTERIZING

PRODROMAL

Principal Investigator & Institution: Lencz, Todd E.; North Shore-Long Island Jewish Res Inst Jewish Research Institute Manhasset, NY 11030 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): This revised application for a Mentored Research Scientist Development Award (K01) presents a plan for the candidate to pursue training and research in the assessment of the schizophrenia prodrome. The goals of the training and research plan are integrated around the hypothesis that attenuated negative symptoms represent a critical domain of risk for schizophrenia that is dissociable from attenuated positive symptoms at both the phenotypic and endophenotypic level. Research will utilize self-report questionnaire measures and functional magnetic resonance imaging (fMRI), with the candidate developing skills in the training program to become an independent investigator operating at the cutting edge of research in the development of schizophrenia spectrum disorders. The training plan would increase the candidate's skills in two domains necessary for state-of-the art research in subjects at risk for schizophrenia: 1) clinical assessment of psychosis and sub-psychotic states, including phenomenology, developmental issues in psychopathology, and psychometrics; and 2) functional neuroimaging assessment, including neurophysiology, neurodevelopment, and fMRI task design and statistical analysis. Additionally, the candidate will be trained in ethical issues of research involving adolescent subjects who may be at risk for severe mental illness. For each domain, there are local lead advisors

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who will provide regular supervision of the candidate's training and research progress, as well as consultation with and visits to leading laboratories relevant to prodromal research. The candidate will be closely supervised by the overall mentor, Dr. Barbara Cornblatt, Director of the Division of High Risk Studies at The Zucker Hillside Hospital. The research plan consists of a study integrating the two assessment domains above. Research will be conducted with adolescent subjects entering the Hillside Recognition and Prevention (RAP) Program, a federally funded study of risk for schizophrenia. Preliminary research in the RAP Program has led to a hypothesized neurodevelopmental model of the prodrome, in which cognitive deficits (such as attentional impairment) and attenuated negative symptoms (such as social isolation) precede onset of attenuated positive symptoms and psychosis. This hypothesis will be tested by administering the schizotypal personality questionnaire (SPQ) to RAP patients and treatment-seeking comparison subjects. Confirmatory factor analysis will be performed to identify positive and negative symptoms domains, which may differentiate RAP subgroups from each other and from non-RAP patients. Neurofunctional correlates of these symptom domains will be examined using both newly-developed and previously designed fMRI tasks to test the hypothesis that attenuated negative symptoms are related to dysfunction of the ventral prefrontal cortex, and attenuated positive symptoms are related to dysfunction of dorsal prefrontal cortex. This study will provide the candidate with the knowledge and research experience necessary to apply for an R01 to expand upon this research from a neurodevelopmental perspective. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMAGING OF DOPAMINE FUNCTION IN SCHIZOPHRENIA Principal Investigator & Institution: Laruelle, Marc A. Associate Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2003; Project Start 01-APR-1996; Project End 31-JUL-2007 Summary: (provided by applicant): This application is a competitive renewal application (5 RO1 MH54192-07). The dopamine (DA) hypothesis of schizophrenia proposes that positive symptoms of the illness are associated with hyperactivity of DA transmission. Recently, several groups have demonstrated that binding competition between endogenous DA and D2 receptor ligands enables measurement of changes in DA concentration in the vicinity of D2 receptors with PET and SPECT. During the first cycle of this grant, we used this approach to study amphetamine-induced DA release with SPECT and [123I]IBZM in schizophrenia. We observed that this response was elevated in schizophrenia. During the second cycle of this grant, we studied baseline occupancy of D2 receptors in schizophrenia, again using SPECT and [123I]IBZM. We observed that this occupancy was elevated in schizophrenia and that elevated DA transmission was predictive of a good treatment response to antipsychotic medication. An important limitation of the work carried out so far is that, due to the limited spatial resolution of SPECT, DA transmission could be studied only at the level of the striatum as a whole. Using [llC]raclopride and high resolution PET, we recently demonstrated the reliability of measuring DA transmission within the limbic, associative and sensorimotor subdivisions of the striatum. Because of the apparent "mesolimbic" selectivity of new antipsychotic drugs, it is widely accepted that dysfunction of DA transmission in schizophrenia involves mesolimbic rather than nigrostriatal DA pathways. In preliminary data obtained with high resolution PET and [11C]raclopride, we made the surprising observation that DA transmission in schizophrenia is not elevated in the ventral striatum, as anticipated, but in the precommissural dorsal

64 Schizophrenia

caudate nucleus (preDCA), and that elevated preDCA DA transmission is related to antipsychotic efficacy. Given the low number (n = 8) of subjects with schizophrenia included in these preliminary data, this finding, which challenges common views about DA in schizophrenia, should be viewed with caution. Therefore, in the third cycle of this grant, we propose to study alterations of DA transmission in striatal subregions with PET and [11C]raclopride in 36 patients with schizophrenia and 36 controls. Given that the preDCA is the striatal subregion that modulates information processing in the dorsolateral prefrontal cortex (DLPFC), altered DA transmission in the preDCA might be involved in the DLPFC dysfunction observed in schizophrenia. This finding, if confirmed, might contribute to a better understanding of the pathophysiology of this illness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFORMED SCHIZOPHRENIA

CONSENT

AND

MEDICATION

STATUS

IN

Principal Investigator & Institution: Moser, David J. Psychiatry; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-AUG-2003 Summary: The degree to which individuals with schizophrenia are able to provide informed consent to participate in research is an important and highly controversial issue. Recent studies (including our own pilot investigation) suggest that individuals with schizophrenia, on average, may have relatively impaired decision-making ability, but that many are able to provide informed consent. Nonetheless, the issue remains complex and becomes even more so within the context of medication free schizophrenia research. There is clearly a need for scientifically rigorous and ethical medication-free schizophrenia research, but there exists the valid concern that individuals may be able to provide consent at the beginning of a given study that requires a medication taper and subsequently "lose" this capacity following discontinuation of medication. The proposed research will directly measure the degree to which informed consent capacity changes following discontinuation of antipsychotic medication and whether this change is related to worsening psychiatric symptoms, increasing cognitive impairment, or both. It will also be determined whether reduced informed consent capacity can be remediated. At the time of enrollment, subjects will already be scheduled to undergo a medication-free period on an inpatient schizophrenia research unit with 24-hour supervision, and all decisions regarding discontinuation and reinstatement of medication will be made independently of the proposed research project. Assessment of informed consent capacity (using a hypothetical drug study scenario), neuropsychological functioning and psychiatric symptoms will be administered before and at the end of a 14-day medication free period. Subjects who demonstrate significantly reduced decisional capacity at the end of the medication-free interval will participate in an educational intervention focused on remediating this capacity and will then be reassessed. We are unaware of any investigation that has directly addressed this important scientific and ethical question in the manner that we propose. Our findings will have significant implications for the continued development of ethical guidelines that provide adequate subject protection without placing undue restrictions on important scientific advance, and will also lay the foundation for larger studies of informed consent capacity in vulnerable populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERLEAVED PREFRONTAL TMS/FMRI IN SCHIZOPHRENIA Principal Investigator & Institution: Nahas, Ziad; Psychiatry and Behavioral Scis; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2005 Summary: (provided by applicant): Schizophrenia is associated with considerable morbidity and economic burdens. Knowledge about its pathophysiology is still incomplete. Some evidence exists that the brain's dorsolateral prefrontal cortex (DLPFC) may be dysfunctional in schizophrenia. Neuroimaging studies have reported both hypoactive and hyperactive DLPFC in subjects with schizophrenia involved in a cognitive task. These apparent contradictions may be due in part to the subjects' skill, performance and the difficulty of each task. Transcranial Magnetic Stimulation (TMS) is a non-invasive technique that employs a high magnetic field to activate neuron and a direct method of brain stimulation that does not depend on subject's compliance or effort. Our group at MUSC has pioneered the interleaved TMS/fMRI technology to get real-time images of brain activity with TMS. Here, we plan to use interleaved TMS/fMRI in schizophrenia subjects to investigate if DLPFC is truly hypoactive and characterize the Blood Oxygen Level Dependent (BOLD) response to TMS. We hypothesize that in subjects with schizophrenia and prominent negative symptoms (such amotivation and flat affect) will show a weaker rCBF response underneath the TMS coil as compared to matched healthy controls. Specific Methods: In this 3 year grant proposal, we plan enroll 15 schizophrenia males with prominent negative symptoms and neuroleptic free (for at least 2 weeks) and 15 healthy controls matched for age, handedness, parental education and smoking habits. They will be rated for psychosis, mood, extrapyramidal symptoms and cognition. They will undergo a high resolution structural scan to determine the location of left middle frontal gyrus (Brodmann Area 9) and to measure the distance ratio from skull to prefrontal cortex over skull to motor cortex. On a different day, they will undergo an interleaved TMS/fMRI session. We will stimulate intermittently over the left middle frontal gyrus at 1Hz and acquire 'in-the-moment BOLD fMRI scans. Each 21-second epoch of TMS will be preceded and followed by an equal length of no stimulation. TMS will be randomly delivered at 80%, 100% and 120% of motor threshold (intensity necessary to move the thumb). The intensity used will be adjusted relative to the degree of prefrontal atrophy if needed. Changes in rCBF will be the primary outcome measures. Conclusions: This study builds on the Prs preliminary work with interleaved prefrontal TMS/fMRI in healthy subjects and in one case of schizophrenia, as well as TMS research in negative symptoms of schizophrenia. It will assess whether TMS/fMRI is a feasible and safe method in this population. It will characterize the BOLD response to TMS (which is hypothesized to be weaker in schizophrenia subjects compared to controls). This is a necessary first step to better understand neuronal response to non-invasive stimulation in subjects with schizophrenia. In future work, results from this R2I grant will help investigating the functional connectivity of the DLPFC, the relation of TMS to complex cognitive and pharmacological probes and possibly add to the understanding of how to restore DLPFC function in patients with schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: JERUSALEM PERINATAL COHORT SCHIZOPHRENIA STUDY Principal Investigator & Institution: Malaspina, Dolores; Associate Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004

66 Schizophrenia

Summary: This is a resubmission of the Jerusalem Perinatal Cohort Schizophrenia Study. We plan to investigate the relations between prenatal exposures, obstetric complications, neonatal health, heredity and schizophrenia. The design has been improved over the prior submission by now including face-to-face interviews on 25 percent of cases, by including methods to address genetic influences and geneenvironment interactions, and by clarifying the sizes of subgroups with overlapping prenatal, obstetric and neonatal data. The study is based on 92,500 pregnancies in Jerusalem from 1966-74 on whom a wealth of prospective data was collected from early in gestation for the Jerusalem Perinatal Study. The cohorts are now at the age of risk for schizophrenia. The incidence of schizophrenia will be identified by cross-linking the cohort data to the Israeli Psychiatric Case Registry. About 800 cases with schizophrenia are anticipated. The strengths of the study include its extensive data sets on demographics, prenatal exposures, obstetric complications, and infant condition at birth, health data through childhood, and data on parental health, including reported mental illness and consanguinity. It has sufficient power to examine even rare exposures. The aims are to examine whether prenatal exposures (including infections, nutrition, hormones, maternal stress, smoking, anemia, vaginal bleeding, x-ray's, Rh incompatibility) and obstetric complications are associated with an increased incidence of schizophrenia. The approach is illustrated with plausible risk factors. Furthermore, we have data on possible confounding, mediating variables and effect modification. We will propose causal pathways that may underlie the observed associations. We will conduct twin and sibling studies to examine hereditary factors and models for gene environment interaction. We will lay the groundwork to add military induction neuropsychological data on these subjects and establish the feasibility of future brain imaging studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: K+ CHANNEL MODEL FOR TRINUCLEOTIDE-EXPANSION DISEASES Principal Investigator & Institution: Chandy, K George. Professor; Physiology and Biophysics; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001; Project Start 15-DEC-1998; Project End 30-NOV-2002 Summary: Several human hereditary neurological diseases are caused by expanded CAG repeats although the pathophysiological mechanism remains uncertain. Longer CAG alleles have also been reported to be over-represented in patients with bipolar disorder and schizophrenia, but the defective gene(s) remain unidentified. We isolated a human gene encoding a calcium-activated potassium channel (hSKCa3), found in neurons and containing a novel CAG repeat. Encoding a polyglutamine repeat near the amino terminus, this CAG repeat is highly polymorphic in normals, and long alleles are over-represented in schizophrenia and bipolar disorder. We now propose to combine the strengths of the four principal investigators in molecular biology, human genetics, neuroanatomy, biochemistry, and electrophysiology, to develop a detailed biophysical and pharmacological "fingerprint" of this channel. Using a chimeric strategy between hKCa3 and its "repeat-free" relative, hKCa4, coupled with site-specific mutagenesis, we will define functional domains within these proteins, and determine the effects of longer polyglutamine repeats on channel function. In-situ hybridization studies on human brains, from controls and patients with schizophrenia, will ascertain the neuronal distribution of hKCa3 in relation to neurotransmitter receptors and other channels, and potentially pinpoint key anatomical areas that might be implicated in schizophrenia. By defining the intron/exon organization of this gene, we will be able to initiate screening

Studies 67

studies to identify point mutations in hKCa3 that might be associated with schizophrenia. We will also define the precise location of this gene with respect to other genetic markers for schizophrenia. The identification of the native promoter for hKCa3 will set the stage for the generation of transgenic mice that over-express hKCa3 with long polyglutamine repeats in the relevant regions of the brain; such mice might exhibit altered behavior. These experiments provide the framework for understanding the role of polyglutamine repeats in a protein of known function. The long term goal of these studies is to understand the role of hKCa3 in the pathogenesis of schizophrenia, and to develop specific modulators of this channel for potential use in the therapy of this debilitating neuropsychiatric disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LANGUAGE PROCESSING IN SCHIZOPHRENIA Principal Investigator & Institution: Kuperberg, Gina R.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Adapted from applicant's abstract)This is a request for an NIMH Mentored Patient-Oriented Research Career Development Award (K-23) entitled 'The Cognitive Neuroscience of Language Processing in Schizophrenia'. A disorder of thought and language has long been considered a core feature of schizophrenia. The candidate will test the hypothesis that such language abnormalities arise from specific cognitive and neural deficits in processing meaning (semantics). To address this question, she aims to acquire training in three complementary methodologies. First, psycholinguistic paradigms will be used to define the specific nature of language processing deficits in schizophrenia at a cognitive level. Second, electrophysiological experiments will determine the timing 01 neurophysiological abnormalities during language processing in schizophrenia, by examining the latency and amplitude of the N400- an event related potential that is known to be sensitive to semantic context. Third, event-related fMRI studies will characterize the functional neuroanatomy of language processing deficits in schizophrenia, by examining activity within the temporal and the inferior frontal cortex (particularly on the left) regions that are known to mediate semantic processing. The use of these three methodologies to address the same fundamental questions will give insights into the cognitive and neural basis of language dysfunction in schizophrenia, in both spatial and temporal domains. Additional didactic instruction and expert mentorship, in cognitive neuroscience, psycholinguistics and advanced statistics, will provide the theoretical framework and the analytical tools to integrate across these three methodologies, both conceptually and quantitatively. This training and research program will advance the candidate to the stage when she can establish herself as an independent investigator of the cognitive neuroscience of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LANGUAGE SYSTEMS IN SCHIZOPHRENIA: BEHAVIORAL & ERP DATA Principal Investigator & Institution: Niznikiewicz, Margaret A. Psychiatry; Harvard University (Medical School) Medical School Campus Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 10-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant) The broad aim of this five year study is to advance our understanding of language dysfunction in schizophrenia spectrum disorder using event-related potential, event-related gamma, experimental neuropsychological and

68 Schizophrenia

clinical measures in three DSM-IV diagnosed clinical groups: chronic schizophrenia (CS), first episode schizophrenia (FES) and schizotypal personality disorder (SPD), and their matched normal controls. The use of the three clinical groups will afford studying both differences and similarities in language impairment across the schizophrenia spectrum. Similarities and differences in language processing in males and females in these three clinical groups will be studied as a secondary goal. In order to arrive at a comprehensive model of language dysfunction in the schizophrenia spectrum, we will use a heuristic model of language in which semantic organization includes three distinct but interacting components referred to as properties, processes, and content of semantic networks. Properties refer to connectivity weights among words, and to the size and the coherence of networks. Processes refer to activation, inhibition, and context use (both local and global). Network contents including words, numbers, and symbols will not be measured. We propose a gradual breakdown in language function with most impairment in CS>FES>SPD. We will test these hypotheses in a five-year study of three schizophrenia spectrum groups: 1) 30 patients with CS; 2) 30 patients with FES; and 3) 30 individuals with SPD, and 30 normal controls matched to each clinical group (n=90). Each control group will be matched for age, gender and parental SES to its respective clinical group and all subjects will be right handed, with English as their primary language. We will use ERP, event-related gamma, experimental neuropsychological, and clinicaldata (Thought Disorder Index TDI), to study language disorder in the three clinical groups. We thus predict over-activation in semantic networks as indexed by the N400, word-pair study at short stimulus onset asynchrony (SOA) in SPD, FES, and CS. The evidence of abnorma inhibitory/context utilization processes will be found in the N400, sentence and paragraph studies, with most severe impairment in CS>FES>SPD. The evidence of abnormal properties in semantic networks will be found in the neuropsychological study of word recall, in the N400, word-pair, short SOA study, and in the event-related gamma data, it FES and CS, but not in SPD. Correlational analyses among the four data sets will seek to characterize the relationships among the four domains of analysis.We predict that females will show less impairment than males on all these measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LATE ONSET SCHIZOPHRENIA--A NEUROPSYCHIATRIC STUDY Principal Investigator & Institution: Jeste, Dilip V. Professor & Chair; Veterans Medical Research Fdn/San Diego Foundation of San Diego San Diego, CA 92161 Timing: Fiscal Year 2001; Project Start 01-APR-1988; Project End 31-JAN-2003 Summary: Schizophrenia has traditionally been thought to be a disease with onset of symptoms during adolescence or early adulthood. Hence very little systematic research has been done on late-onset schizophrenia (LOS), especially in the USA. Over the past 9 years, we have studied rigorously diagnosed 241 middle-aged and elderly outpatients with schizophrenia and 143 normal comparison subjects. The age of onset of schizophrenia has ranged from 12 to 76. Our studies have shown several similarities between LOS and early-onset schizophrenia (EOS) in terms of positive symptoms, family history, course, neuroleptic responsiveness, and nonspecific neuropsychological and MRI abnormalities, suggesting that LOS is indeed a form of schizophrenia with neurodevelopmental origins. On the other hand, we have also found a number of critical differences in gender distribution, subtype characterization, negative symptoms, neuroleptic dose, and specific neuropsychological deficits as well as MRI abnormalities (e.g., larger thalamus). These differences suggest that LOS is likely to be a neurobiologically distinct subtype of schizophrenia. Our data from several different

Studies 69

domains support the notion that LOS is best defined as schizophrenia with onset of prodromal symptoms at or after age 40. We believe that we probably have the best-ever characterized sample of LOS patients along with appropriate comparison groups that we have been following longitudinally. We now propose to expand our sample by adding new subjects, as well as important comparison group of patients with late-onset delusional disorder (LODD). The study of LODD will help validate its diagnostic status, and also determine specificity of certain cognitive and MRI characteristics of LOS. Additionally, we will continue to follow the subjects in our current cohort. Some of our assessment methods will be modified so as to make them more sensitive (e.g., MRI quantitative analysis, outcome and functioning measures) to the new questions being asked. Our studies should have a major impact on the understanding of schizophrenia and aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIABILITY MARKERS FOR DEFICIT SCHIZOPHRENIA? Principal Investigator & Institution: Hong, L E. Psychiatry; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): The heterogeneity theory of schizophrenia is generally accepted but identification of subtypes, which is crucial for genetic research, has been difficult. Deficit syndrome schizophrenia has been proposed as a valid subtype and is characterized by patients who exhibit primary enduring negative symptoms. High concordance of deficit schizophrenia in families suggests a shared genetic and/or environmental etiology. This proposed study represents the first effort (to our knowledge) to systematically determine neurobiological markers for deficit schizophrenia by studying their non-psychotic family members. Non-ill relatives may carry smaller numbers of susceptibility genes that do not result in psychosis, but may result in abnormalities that can be detected by neurobiological tests such as eye movements. Identification of heritable cognitive and electrophysiological abnormalities in deficit syndrome will help demarcate the boundary of the disorder and provide alternative phenotypes in genetic studies. Neurobiological abnormalities identified only in deficit patients and their family members may be marking the liability of deficit schizophrenia. In our preliminary study with small sample sizes that examined components of the smooth pursuit eye movement response, we found that impaired smooth pursuit initiation was specifically associated with deficit probands and their relatives, whereas predictive smooth pursuit was equally impaired in patients with and without deficit schizophrenia and in their relatives. This supports the validity of our research approach. In this proposed study, we aim to determine whether pursuit initiation is impaired only in relatives of deficit probands by using a modified initiation task in which predictive factors are minimized. We will also include memory saccade task, antisaccade tasks, and a version of the CPT with degraded presentations. These tasks are chosen because they have shown evidence of association with schizophrenia or deficit syndrome. These tasks will be administered to 30 relatives of deficit probands, 30 relatives of nondeficit probands, and 30 normal controls. Testing in relatives rather than patients will serve to eliminate differences in secondary effects of psychosis and medications. We plan to use the preliminary data collected from this grant support to guide our full-scale search for phenotypic markers specifically associated with the liability for deficit schizophrenia and subsequent molecular genetic studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LINKAGE ANALYSIS METHODS IN SCHIZOPHRENIA Principal Investigator & Institution: Ott, Jurg; Professor and Head; Lab/Statistical Genetics; Rockefeller University New York, NY 100216399 Timing: Fiscal Year 2001; Project Start 01-MAY-1989; Project End 31-DEC-2002 Summary: The long-term goal is to provide new and improved analytical methods that will enable researchers to find gene markers genetically linked with the putative gene(s) for schizophrenia. This, in turn, will open the way to identifying the schizophrenia gene(s). Once such genes are found, there is hope that knowledge of their structure will lead to a deeper understanding of the disease etiology and, thus, to the possibility of ameliorating or curing schizophrenia. The specific aims consist of 1) developing and implementing chromosome-based computer simulation, 2) implementing exclusion mapping of schizophrenia under heterogeneity, 3) studying and implementing methods of allowing for biological variables in linkage analysis of schizophrenia, 4) adapting the LINKAGE programs for their use on parallel computers for more efficient linkage analysis, 5) to study the feasibility and power of nonparametric ad hoc statistics for major genes in schizophrenia families, and 7) to consult with and give advice to researchers collecting schizophrenia families and to apply the methods obtained to schizophrenia families (data collected through projects of other investigators). Computer programs and methods obtained through this work will be made freely available to researchers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MANAGEMENT FOR RISK OF RELAPSE IN SCHIZOPHRENIA Principal Investigator & Institution: Marder, Stephen R. None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 01-JUL-1986; Project End 31-JAN-2005 Summary: (Applicant's abstract): This is a competing renewal application for a research program that has focused on the development of innovative pharmacological and psychosocial treatment strategies for managing individuals with schizophrenia who are living in the community. The current proposal will extend the investigator's previous work into the arena of vocational activity and rehabilitation. The investigator's experience to date in enhancing psychosocial outcomes with social skills training led him to hypothesize that he can combine skills training with supported employment to improve social adjustment and quality of life. The investigator is also hypothesizing that skills training can improve the relatively poor job tenure of individuals with schizophrenia and schizoaffective disorder who participate in supported employment. The investigator will also study the long-term effectiveness and side effects of two new antipsychotic medications, olanzapine and risperidone, in patients participating in this program. Neurocognitive deficits in schizophrenia appear to be important factors that can interfere with functional outcome in schizophrenia. With this in mind, the investigator will study the relationship between a number of cognitive measures and social and vocational outcome. One hundred-sixty patients with schizophrenia or schizoaffective disorder who are living in the community will be randomly assigned to olanzapine or risperidone. After these patients have been stabilized in their drug condition they will participate in a program of Individual Placement and Support (IPS) as developed by Robert Drake who is the co-principal investigator on this grant. After patients are placed in a job they will be randomly assigned to continued IPS with or without Psychoeducational Skills Training (ST). The ST will consist of six months of skills training using both the Workplace Fundamentals Module and additional clinic

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and community-based skills training. The investigator will evaluate outcome during the next two years with measures of clinical psychopathology, medication side effects, functional outcomes, and quality of life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MARKERS SCHIZOPHRENIA

OF

OLFACTORY

NEUROTRANSMISSION

IN

Principal Investigator & Institution: Rioux, Lise; Neurobiology and Anatomy; Drexel University 3201 Arch Street Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Reduced expression of synaptic and plasticityrelated proteins in OB in schizophrenia suggests alterations in the synaptic machinery. Dysfunctional synapses between ORNs and target cells during development and throughout life may be responsible for the reduced OB volume and the olfactory deficits observed in schizophrenia. Understanding the mechanisms and consequences of this dysfunction is essential to the development of better treatment for schizophrenia. It is our hypothesis that in schizophrenia, synapses of the ORNs with their OB targets are hypofunctional. Hypoglutamatergic transmission at these synapses results in an impairment of long-term potentiation in the OB. While preliminary results suggest that this hypothesis is valid, it warrants further study. In aim 1, we will show evidence of hypoglutamatergic transmission at the synapses between ORNs and their OB targets in schizophrenia. These synapses are located in discreet spherical composites of pre- and post-synaptic elements called glomeruli. We will use quantitative radioimmunohistochemistry to test the hypothesis that there is a decreased expression of some subtypes of NMDA, AMPA or Group1 metabotropic glutamate receptors in OB glomeruli from individual with schizophrenia. We will also use a novel proteomic method, immunodetection amplified with T7 polymerase (IDAT) to investigate a shift in subunit composition away from NMDAR2 B subtype and toward gluR2 subtype. We expect glutamate receptors, in particular the NMDA receptors, to be down regulated in OB glomeruli in schizophrenia. Glutamatergic function is essential to the induction and maintenance of LTP. Several proteins, including syntaxin, brain-derived neurotrophic factor (BDNF), nitric oxyde synthetase (NOS) and activity-regulated cytoskeletonassociated protein (arc) are up-regulated following the induction of LTP and can serve as markers for that form of synaptic plasticity. We will look at the expression of these selected LTP markers in OB glomeruli with quantitative radioimmunohistochemistry. We will also use IDAT to examine the coordinate expression of glutamate receptors and LTP markers in the same glomeruli. We expect LTP markers to be down regulated in glomeruli in schizophrenia. We also expect a correlation between the expression of NMDA receptors and LTP markers. A correlation between glutamatergic function, LTP markers and schizophrenia will better define the role of these proteins in the olfactory deficits observed in schizophrenia. The effect of the antipsychotic on the expression of these proteins will also be investigated in mice chronically treated with haloperidol to discriminate between disease- and treatment related changes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MATERNAL/FETAL SCHIZOPHRENIA

GENOTYPE

INCOMPATIBILITY

IN

Principal Investigator & Institution: Sinsheimer, Janet S. Associate Professor; Human Genetics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024

72 Schizophrenia

Timing: Fiscal Year 2002; Project Start 02-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): It is highly likely that some non-Mendelian mechanism involving environmental and genetic factors gives rise to schizophrenia. Current research is providing compelling evidence that one environmental factor, which acts prenatally to increase susceptibility to this disorder, arises from a maternal/fetal genotype incompatibility. Because it is genetic in origin, a maternal/fetal genotype incompatibility is one cause of an adverse environment that can be precisely studied, even years after the adverse environment was present, and thus may provide a useful research approach for identifying prenatal environmental factors that interact with susceptibility genes to cause this disorder. We propose a family-based genetic study to test hypotheses about the role of maternal/fetal genotype incompatibility in schizophrenia.This research integrates the study of genes and environment in an innovative manner and provides the first gene-based test of this highly plausible nonMendelian mechanism in schizophrenia susceptibility. The research will require the development of some new statistical model specifications -- essential because current research methods are unlikely to detect, or may lead to incorrect inferences about, such an underlying non-Mendelian mechanism. This exploratory study develops the necessary substrate for this area of research using four existing data sets containing more than 2200 individuals with 900 affecteds, comprising at least 300 independent mother, father, affected child trios with diagnoses and DNA, in order to identify promising incompatibilities that would launch a future large-scale data collection effort and detailed hypothesis testing. The study will accomplish: (1) genotyping of plausible incompatibility loci (i.e., HLA, ABO, RHD) in samples with existing genotyping for putative schizophrenia susceptibility loci; (2) development of a maternal/fetal genotype test using new specifications of the gamete competition model and trio comparison model that can decompose incompatibility effects from linkage effects; and, (3) hypothesis testing about, (a) the direct effect of maternal/fetal genotype incompatibility on susceptibility to schizophrenia, (b) the cumulative effect of maternal/fetal genotype incompatibilities, and (c) the interaction of the maternal/fetal genotype incompatibility with a putative schizophrenia susceptibility locus on chromosome lq. This proposal is important because it could lead to a concrete research model in which the essential genetic and environmental elements involved in the etiology of schizophrenia could be studied precisely. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF CONTEXT PROCESSING IN SCHIZOPHRENIA Principal Investigator & Institution: Cohen, Jonathan D. Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 30-SEP-1991; Project End 31-MAY-2004 Summary: (Applicant's Abstract): This is a revision of 2 R01 MH47073-06, and is a proposal for continuation of work begun under a FIRST Award (5 R29 MH47073-05) to the P.I. The primary goal of this study is to test our theory concerning a disturbance in the processing of context in schizophrenia, and its relationship to prefrontal cortex (PFC) function. In previous work, we constructed neural network models of normal performance in a set of cognitive tasks in which schizophrenics were known to exhibit deficits. This resulted in a specific hypothesis concerning the function of PFC, and its involvement in schizophrenia: that PFC is responsible for the processing of context information, and that a disturbance in this mechanism is responsible for a number of the cognitive deficits observed in schizophrenia. Under the FIRST Award, we conducted behavioral experiments designed to test predictions made by this theory. In this study,

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and two others that we have recently completed, we observed a highly selective pattern of schizophrenic deficits in conditions sensitive to the processing of context, that provide strong preliminary support for our hypothesis. At the same time, our findings have raised a number of important new questions, that we address in the specific aims of this project. First, we propose a set of behavioral studies, that will test new predictions made by our current generation of computer simulation models. Second, we will test each subject three times, permitting a more sensitive assessment of the relationship between cognitive deficits and clinical symptoms. Third, we will test unmedicated, as well as medicated patients, to more carefully assess the influence that medications have on predicted deficits. Finally, we will conduct a neuroimaging experiment in a subset of subjects, using fMRI to study activation of PFC during performance of one of our cognitive tasks (AX-CPT). This will provide a more direct test of our hypothesis concerning the function of PFC, and its involvement in schizophrenia. Thus, this project will use a set of carefully constructed, theoretically motivated cognitive tasks to test specific predictions concerning the cognitive deficits in schizophrenia and, in a subcomponent, the relationship of PFC function to these deficits. We have already begun to demonstrate that our theory successfully predicts how tasks can be made more sensitive and specific to schizophrenic deficits. Positive results would represent a significant advance in our theoretical and empirical work, providing the groundwork for the development of powerful new behavioral and functional imaging tools for use in the diagnosis, assessment, and treatment of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEMBRANE SCHIZOPHRENIA

DEFICIT

&

ITS

TREATMENT

IN

EARLY

Principal Investigator & Institution: Reddy, Ravinder D. Associate Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant) Schizophrenia is a major public health concern. Almost 40 percent of patients with schizophrenia have poor outcome despite the best current treatment efforts, indicating a need for new therapeutic approaches. This Mentored Clinical Scientist Development Award (SDA) application describes a training and research program aimed at clarifying the role of membrane deficits in schizophrenia, a novel and promising area of research with significant potential for a new hypothesis-driven therapeutic approach to improving outcome. There is accumulating and consistent evidence that membrane deficits, particularly reductions in polyunsaturated fatty acids (PUFA) are seen in schizophrenia and that reversal of these deficits by essential fatty acid supplementation have positive clinical effects. If this area of research is found to have pathophysiological relevance for schizophrenia, then PUFA supplementation strategies may be useful adjuncts to current empirically derived treatments. However, a number of questions must be addressed before this area of research can gain wider acceptance. Therefore, careful and systematic assessment of the notion that membrane deficits are relevant to schizophrenia is needed; this can be achieved by developing and testing heuristic models and establishing clinical parameters by, which to assess therapeutic efficacy of essential fatty acid supplementation. Because of Dr. Reddy?s clinical experience with schizophrenia, his previous research on membrane biochemistry, he is ideally positioned to further the research in this emerging area. Moreover, the mentorship in separate but overlapping areas of expertise that is central to this SDA is available at his institution. In addition to

74 Schizophrenia

the structured training plan that includes course work, tutorials and supervision, Dr. Reddy will conduct related studies that will, (I) examine the clinical and biological effects of repairing putative membrane deficits by conducting an open-label adjunctive treatment trial with an omega-3 fatty acid in 40 early-course schizophrenic patients; (2) examine whether PTJFA levels in red blood cells (RBC) parallel central phospholipid metabolism as determined by 31P magnetic resonance spectroscopy; and, (3) examine in a rat model whether RBC PUFA levels parallel brain PUFA levels, a critical issue in determining whether RBC PUFA levels can serve as surrogate for brain PUFA levels. By completing these training and research goals, Dr. Reddy will be ready to independently engage in the future development and application of interventions targeting membrane deficits in schizophrenia. Further, the training will provide versatility and flexibility in applying his expertise to other neuropsychiatric disorders where membrane deficits may play a role, and being able to evaluate emerging treatments focused on membrane repair. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MHCRC IN SCHIZOPHRENIA STUDIES Principal Investigator & Institution: Gorman, Jack M. Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-DEC-2002 Summary: OVERALL (Adapted from Applicant's Abstract): We are proposing the creation of a Mental Health Clinical Research Center (MHCRC) in Schizophrenia Studies to replace our current Developing Clinical Research Center (DCRC). This section serves as an introduction to the MHCRC proposal. Our DCRC has now been in place for three and one half years. In that time we have focused our attention on our original aim,. To examine the contributions of genetic and epigenetic (or environmental risk) factors in schizophrenia etiology. We have also met another of our original goals and established a significant neuroimaging component to our Center. Finally, we have established strengths in diagnosis, phenomenology, neuroimmunology, neuropathology, and molecular biology. We now believe that we are now in an excellent position to link neuroimaging and neurobiological research to genetics and epidemiology of schizophrenia. In this way, we hope to make systematic observations that establish both likely etiological factors occurring from prenatal life and their specific relationship to biological abnormalities in adults who develop schizophrenia. The proposed MHCRC will have five cores: 1) Administrative, Biostatistical and Data Management; 2) Diagnosis and Treatment Research Core (DIRC); 3) Neurodevelopmental and Genetic Epidemiology Research Core (NGRC); 4) Brain Imaging Research Core (BIRC); and 5) Genomics and Neurobiology Research Core (GNRC). Each core will be responsible for supporting critical Center-wide needs and for conducting Core-specific research. Many of these functions require MHCRC support including the provision of standardized research-quality diagnoses and assessments that can be used across projects; the ability to maintain patients in a medication-free state and to recruit medication-naive subjects; the maintenance of several large birth cohorts; and the provision of state-of-the-art neuroimaging and laboratory facilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR CHARACTERIZATION OF HUMAN GLUTAMATE CARBOXYPEPTIDASE II Principal Investigator & Institution: Coyle, Joseph T. Professor and Chairman; Harvard University (Medical School) Medical School Campus Boston, MA 02115

Studies 75

Timing: Fiscal Year 2001 Summary: Rationale: Glutamate Carboxypeptidase II (GCPII; EC 3.4.17.21) was identified as an enzyme that catalyzes in brain the hydrolysis of N-acetyl- aspartylglutamate (NAAG) to acetyl-aspartate (NAA) and glutamate with 200 nM Km for NAAG. Given the role of NAAG as an endogenous antagonist at NMDA receptors and an agonist at mGluR3 receptors in brain reduced GCPII activity would be predicted to attenuate NMDA receptor. Since the dissociative anaesthetics, phenylcyclidine and ketamine, produce the symptoms of schizophrenia by antagonizing the NMDA receptor, NAAG could serve as endogenous psychotogen. Indeed, post-mortem neurochemical studies indicated significant reductions in the activity of GCPII in temporal, cortex, hippocampus and frontal cortex in schizophrenics (Tsai et al., 1995). Consistent with this post-mortem finding, several studies have independently demonstrated by MR spectroscopy reductions in the levels of NAA, the product of GCPII activity, in temporal cortex and frontal cortex in schizophrenia, the very regions shown to have reduced GCPII activity. Folate reduction and its surrogate elevated homocysteine, have been shown to be common in schizophrenia. Studies of enzymatic activity and, more recently, molecular cloning have demonstrated that GCPII accounts for folypoly- gamma-glutamate carboxy peptidase activity in the small intestine in humans, which is responsible for effective absorption of folate. While we have demonstrated that the GCPII protein expressed in human cerebellum is identical to that of jejunal peptidase as cell as the cell surface marker for metastatic prostate cerebellum is identical to that of jejunal peptidase as well as the cell surface marker for metastatic prostate cancer, Prostate Specific Membrane antigen (PSM) a complete characterization of human brain GCPII, possible allelic variants and the nature of the loss of activity in schizophrenia needs to be performed in order to understand more fully its possible role in schizophrenia and how that may related to reported impairments in folate absorption in schizophrenia. Specific Aim 1. Identify common allelic variants of GCPII targeting both normal subjects and patients suffering from schizophrenia studied in Project VI. Specific Aim 2. Carry out Northern blots, in situ hybridization, Western blots and immunocytochemical studies to define the expression for the GCPII in selected regions of control and schizophrenic brains as previously described in rat brain (Berger et al., 1999). Specific Aim 3. Measure the levels of NAA, NAAG, glutamate and aspartate in temporal cortex, hippocampus, frontal cortex and other regions in post-mortem brain studies from individuals suffering from schizophrenia and suitable controls. Through microdissection, we will distinguish between gray matter and white matter as NAA is present in axons. Levels of glycine, D-serine and folates will also be measured. Potential alterations in amino acid levels and folate levels will be correlated with the expression GCPII in these samples. Specific Aim 4. Develop a conditional knock-out of GCPII to determine its effects on behavior and hippocampal neurophysiology in Project III. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETICS OF SCHIZOPHRENIA Principal Investigator & Institution: Black, Donald W. Professor; Psychiatry; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: (Adapted from investigator's abstract) Susceptibility to schizophrenia appears to be transmitted in part through a complex genetic mechanism involving interaction of multiple genes, each of relatively small effect. Detection of such loci through genetic linkage studies is likely to require a very large sample of multiply affected pedigrees. In response to RFA MH-99-005, nine investigators propose a

76 Schizophrenia

Collaborative Study of Mental Disorders to collect in three years a sample of 517 affected sibling pairs (ASPs) with DSM-IV schizophrenia, to complete a genome scan of these pedigrees for multipoint ASP analysis to detect susceptibility loci, and to share biological materials, genotypes and blinded clinical data with the scientific community through an NIMH-sponsored mechanism. Each site will recruit families in a large geographic area, using an opportunistic ascertainment strategy and efficient assessment procedures to maximize the number of ASPs collected. Subjects suspected of having schizophrenia will be assessed with the Diagnostic Interview for Genetic Studies supplemented by information from the Family interview for Genetic studies and medical records. Diagnoses will be made by consensus best-estimate procedures. Interviewer training and quality assurance monitoring of protocol adherence will be provided for all sites. Blood specimens will be obtained from all individuals with psychotic disorders plus their parents and (when both parents are not available) up to two additional siblings to provide genetic phase information. Permanent cell lines will be created and DNA extracted at the NIMH-sponsored Center for Genetic Studies. All clinical data will be merged regularly into a central study database, and blinded data transmitted to the Center for Genetic Studies. At the end of the four-year project period, biological materials and blinded pedigree and clinical data will be made available to scientific community for genetic studies of schizophrenia and related disorders. In year 4, a genome scan will be undertaken at CIDR (if approved) or at the University of Chicago. Affected subjects and relatives needed for phase information will be genotyped using the latest screening map, currently the Weber Version 9 Linkage Mapping Set, containing 387 microsatellite markers at approximately 10 cM spacing. The primary statistical approach will be multipoint analysis of allele sharing in affected individuals, with DSM-IV schizophrenia defined as affected. Secondary analyses will also be carried out. Power analyses suggest that this study would have excellent power to detect loci associated with lambda sibs of 1.4, and moderate power for a value of 1.3, i.e., loci with relatively small etiologic effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETICS OF SCHIZOPHRENIA Principal Investigator & Institution: Mowry, Bryan J.; University of Queensland Cumbrae Stewart Building Brisbane, Queensland, 4072 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Susceptibility to schizophrenia appears to be transmitted in part through a complex genetic mechanism involving interaction of multiple genes, each of relatively small effect. Detection of such loci through genetic linkage studies is likely to require a very large sample of multiply affected pedigrees. In response to RFA MH-010-98, nine investigators propose a Collaborative Study of Mental Disorders to collect in three years a sample of 500 affected sibling pairs (ASPs) with DSM-IV schizophrenia, to complete a genome scan of these pedigrees for multipoint ASP analysis to detect susceptibility loci, and to share biological materials, genotypes and blinded clinical data with the scientific community through an NIMH-sponsored mechanism. Each site will recruit families in a large geographic area, using an opportunistic ascertainment strategy and efficient assessment procedures to maximize the number of ASPs collected. Subjects suspected of having schizophrenia will be assessed with the Diagnostic Interview for Genetic Studies supplemented by information from the Family Interview for Genetic Studies and medical records. Diagnoses will be made by consensus best-estimate procedures. Interviewer training and quality assurance monitoring of protocol adherence will be provided for all sites. Blood specimens will be obtained from all individuals with

Studies 77

psychotic disorders plus their parents and (when both parents are not available) up to two additional siblings to provide genetic phase information. Permanent cell lines will be created and DNA extracted at the NIMH-sponsored Center for Genetic Studies. All clinical data will be merged regularly into a central study database, and blinded data transmitted to the Center for Genetic Studies. At the end of the four-year project period, biological materials and blinded pedigree and clinical data will be made available to the scientific community for genetic studies of schizophrenia and related disorders. In year 4, a genome scan will be undertaken at CIDR (if approved) or at the University of Chicago. Affected subjects and relatives needed for phase information will be genotyped using the latest screening map, currently the Weber 9.0 map containing 383 microsatellite markers at approximately 10 cM spacing. The primary statistical approach will be multipoint analysis of allele sharing in affected individuals, with subjects with DSM-IV schizophrenia defined as affected. Secondary analyses will also be carried out. Power analyses suggest that this study would have excellent power to detect loci associated with lsibs of 1.4, and moderate power for a value of 1.3, i.e., loci with relatively small etiologic effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MONOAMINERGIC MODULATION OF PREFRONTAL CORTEX Principal Investigator & Institution: Surmeier, D James. Professor and Chairman; Physiology; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the Investigator's Abstract) Disordered dopamine signaling has long been known to be a critical factor in the etiology of schizophrenia. This view is based upon several key observations. Foremost among them is the ability of neuroleptics that antagonize DA receptors to alleviate the positive symptoms of schizophrenia. However, in recent years, the exclusive involvement of DA in schizophrenia has been questioned. In part, the clinical effectiveness of atypical neuroleptics like clozapine has motivated this new line of thought. The ability of atypical neuroleptics to antagonize both DA receptors and serotonin receptors is generally thought to be critical to their efficacy. Although there is evidence for altercations in neuronal function at several levels of the neuroaxis in schizophrenia, most experimental evidence points to the prefrontal cortex. It is the central hypothesis of this proposal that the cognitive deficits observed in schizophrenics and their close relatives are a direct consequence of altered DA and 5-HT signaling within the prefrontal cortex. This disruption may have a common cellular locus-that is, interactions between these two monoamines at the single cell level may be responsible for the pathophysiology in schizophrenia. However, at present there are fundamental gaps in our understanding of how DA and 5-HT regulate neural activity in the PFC. To begin to fill these gaps, we propose to apply a combination of electrophysiological, anatomical, pharmacological and molecular techniques to achieve four specific aims. Our initial aim is to use single cell RT-PCR techniques and retrograde labeling to identify the DA and 5HT receptors expressed by PFC pyramidal neurons participating in circuits thought to be affected in schizophrenia. Next, the impact of D1/D5 DA receptors on voltagedependent Na and Ca channels will be determined in retrogradely identified PFC pyramidal neurons using a combination of RT-PCT, voltage-clamp and fluorometry. In parallel, the modulatory effects of 5-HT-2 receptors on these same channel populations will be determined using a similar combination of techniques. Lastly, the nature of the interaction between these two schizophrenia linked signaling pathways in the modulation of Na and Ca channels will be determined. It is our thesis that these two

78 Schizophrenia

pathways synergistically interact in ways critical to the disease process. Achieving these specific aims will provide the molecular and cellular framework necessary to begin building an accurate, integrative model of PFC function and dysfunction in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MORBIDITY IN SCHIZOPHRENIA--A FOCUS ON DIABETES Principal Investigator & Institution: Dixon, Lisa B. Professor; Psychiatry; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Persons with schizophrenic disorders have significantly higher mortality rates than persons in the general population. It is likely that modifiable patient behaviors and health care delivery system characteristics contribute to this phenomenon. Identification of such modifiable patient and health care system factors may be critical to improving the health status and longevity of persons with schizophrenia. Due to the complexity of this issue, we selected a "tracer" condition strategy, focusing on a single medical disease, diabetes, as a prototypical serious, chronic medical problem from which lessons may generalize to other disorders. Diabetes is a highly prevalent chronic medical disorder which requires active self-care and which may serve as a prototype disorder to understand problems that persons with schizophrenia and other severe mental illnesses have in obtaining and making use of adequate medical care. Using the health beliefs model as a conceptual framework, this study will compare 100 persons with schizophrenia who have diabetes to 100 persons with major depression and to 100 persons without serious and persistent mental illness who suffer from diabetes on: 1) diabetes-specific health behaviors (e.g., compliance), health outcomes (control of blood sugar), and quality of diabetes care received; 2) potential mediating variables, hypothesized to differ between schizophrenics and nonschizophrenics, including diabetes health beliefs and illness knowledge. Additional analyses will compare the schizophrenia sample to published norms on diabetesspecific measures. We will also examine whether system characteristics (e.g., integration of physical care and psychiatric care) and clinical characteristics (e.g., social skills and symptoms) account for poorer outcomes among persons with schizophrenia and major depression. Patients with schizophrenia and major depression will be drawn from a variety of mental health centers in the Baltimore area. A matched sample will be drawn from a University of Maryland Family Practice Clinic. Patients will receive a single assessment and chart review. This proposal thus focuses on diabetes and schizophrenia, although our underlying assumption is that our findings will contribute to our understanding of management and outcomes of other medical illnesses in persons with schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOTION PERCEPTION IN SCHIZOPHRENIA Principal Investigator & Institution: Thaker, Gunvant K. Research Associate Professor; Psychiatry; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-APR-2008 Summary: (provided by applicant): Identifying disease-related genetic effects is a major focus in schizophrenia research. Efforts have been multifaceted with the ultimate goal being to describe a causal path from specific genetic variants to changes in neuronal functioning to behavioral deficits to functional impairments. The schizophrenia

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diagnosis likely reflects a heterogeneous combination of several such causal paths, and is therefore characterized by a varying collection of phenotypes each associated with specific neurocognitive deficits reflecting the effects of a small number of gene(s). Nonspecific genetic and environmental modifiers also likely play an etiologic role. Based on this complex etiologic model, schizophrenia researchers have advocated the use of more elemental phenotypes. Notable examples include COMT and prefrontal dysfunction and nicotinic receptors and sensory gating deficits. Studies suggest that smooth pursuit eye movement (SPEM) abnormalities also mark a schizophrenia-related phenotype. However, in contrast to prefrontal and sensory gating deficits, we know little about the specific cognitive processes and associated neural substrates underlying these abnormalities. We have been focused in recent years on addressing this critical issue. Progress to date has been aided by our efforts to incorporate neurophysiological findings in human and non-human primate studies of motion perception and oculomotor functioning, which have shown that SPEM response can be parsed into component processes with distinct neuronal substrates. SPEM broadly involves: (a) the processing of retinal motion information (i.e., the movement of a target image on the retina); (b) the initiation of an oculomotor response based primarily on this retinal information; (c) the processing and integration of extraretinal motion signals generated by movement of the eyes; and (d) the maintenance of pursuit based on a combination of predictive eye movements guided by extraretinal signals and corrective eye movements guided by retinal velocity and position error signals. SPEM deficits in schizophrenia could be the result of a problem with one or more of these components. We propose to use a number of recently developed experimental techniques to characterize specific aspects of motion perception and oculomotor functionoing in 30 schizophrenia patients, 30 biological relatives who exhibit schizophrenia spectrum personality (SSP) symptoms, and 60 community subjects (30 of who exhibit SSP symptoms in the absence of family history for psychotic illness). Results will enhance the application of the SPEM phenotype in studies of schizophrenia by providing measures that reflect specific processing deficit(s). In this way, the phenotype can be used more effectively in imaging and drug probe studies to identify brain regions and receptor systems of interest. A refined phenotype is also likely to be more proximal to the effects of genes, and therefore better suited for alternative phenotype approaches in molecular genetic analyses. Finally, knowledge of the biological mechanisms underlying the SPEM phenotype will enhance studies of the functional significance of any candidate genes that are identified. The proposed project is a collaborative effort--involving clinical scientists studying schizophrenia pathophysiology and basic scientists studying motion perception and eye movements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOTION PROCESSING SYSTEM IN SCHIZOPHRENIA Principal Investigator & Institution: Chen, Yue; Assistant Professor; Mc Lean Hospital (Belmont, Ma) Belmont, MA 02478 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2003 Summary: (Adapted from applicant's abstract) The investigators focus on the visual motion processing system was initially motivated by the finding that many schizophrenic patients and their biological relatives have impaired smooth pursuit, but other kinds of eye movements are normal. The selectiveness of eye tracking dysfunction suggested possible involvement of the cortical motion processing systems in schizophrenia. The investigators recent studies have shown that motion processing is indeed compromised in schizophrenia. In this application, the investigators propose to

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extend the study of motion processing systematically and parametrically in relation to schizophrenia. The goals are to assess motion processing and its roles at different levels of visual, cognitive and motor processing. In a series of studies, we propose to examine various aspects of motion processing, including velocity discrimination, both detection of and smooth pursuit responses to coherent motion, and perceptual grouping of motion-based signals for object recognition in schizophrenia patients. The motionrelated visual, cognitive and oculomotor tasks serve as probes into the neural activities of the motion-sensitive brain areas, such as Middle Temporal Area and Medial Superior Temporal Area, as well as the brain areas that use motion| information (such as those in the parietal lobe). The results of these studies will generate a systematic characterization of the functional properties of the motion processing system as well as the parietal system in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOTOR/COGNITIVE ASYMMETRY IN OLDER PSYCHOTIC PATIENTS Principal Investigator & Institution: Lohr, James B. Associate Professor in Residence; Veterans Medical Research Fdn/San Diego Foundation of San Diego San Diego, CA 92161 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-MAY-2003 Summary: (Applicant's abstract): There have been a growing number of reports associating schizophrenia with lateralized pathology in the brain, in most cases implicating dysfunction in the left hemisphere. Studies reporting hemispheric asymmetries in schizophrenia have utilized diverse methodologies, including magnetic resonance imaging, positron emission tomography, neuropathology and chemopathology, motor assessments, event-related potentials, and neuropsychological assessments. There is a smaller body of literature regarding lateralized pathology in bipolar disorder, which suggests that there may be greater right than left hemisphere involvement in this condition. Because findings related to hemispheric asymmetry are among the most commonly reported psychobiological findings in schizophrenia with localizing value, we considered that laterality assessments may be associated with psychopathological symptoms and illness outcome (quality of life) as well. Further, because some investigators have theorized that schizophrenia and bipolar illness may in fact be closely related, we considered that measures of laterality may also shed light on the relationship of these two conditions, with schizophrenia being associated with greater left hemisphere impairment, and bipolar disorder with greater right hemisphere impairment. We have recently completed studies of upper extremity motor instability which support this idea. In the current proposal we plan to assess patients with schizophrenia, bipolar disorder, and healthy comparison subjects to determine if these groups differ from each other on measures of lateralized function over a six month interval. Measures include L and R motor, sensory, and cognitive function (hand force instability and rigidity, dichotic listening, Warrington Recognition Memory Test Posner Test, verbal and figural fluency Consonant-Vowel-Consonant Test, Chair Identification Test), and brain function (functional MRI). We also plan to determine if these same measures relate to the positive psychotic symptoms, manic symptoms, and illness outcome as reflected in a measure of quality of life (Quality of Well Being Scale). The longitudinal nature of the study allows us to address important trait and state issues. We hope these studies will provide insights into the localization of pathology in schizophrenia and bipolar disorder, as well as their relationship to each other. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NALTREXONE SCHIZOPHRENIA

TREATMENT

OF

ALCOHOL

ABUSE

IN

Principal Investigator & Institution: Batki, Steven L. Professor and Director of Research; Psychiatry and Behavioral Scis; Upstate Medical University Research Administration Syracuse, NY 13210 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): The long-term goal of the proposed project is to improve the treatment of alcohol abuse and dependence in patients with schizophrenia and schizoaffective disorder. Alcohol use disorders are common among patients with severe mental illness. It is estimated that there may be as many as 750,000 individuals in the United States with comorbid schizophrenia and alcohol disorders. Alcohol disorder comorbidity requires treatment because it is associated with adverse consequences such as increased rates of hospitalization. Yet, to date, there are no reports of controlled trials testing the efficacy of pharmacological treatments for alcohol abuse or dependence in this population. Naltrexone pharmacotherapy is an effective treatment for alcohol dependence, but it has not been systematically applied to the care of patients with schizophrenia. The specific aims of this study are: To test the efficacy of naltrexone in reducing alcohol use among individuals with schizophrenia and schizoaffective disorder who also have alcohol abuse or dependence. We will test hypothesis 1: Naltrexone will be more effective than placebo in reducing alcohol use. Our primary outcome measure will be the number of drinking days over the course of the treatment trial. To test naltrexone's efficacy in reducing psychiatric symptom severity and medical utilization by reducing alcohol use. We will test hypothesis 2: Patients responding to naltrexone by reducing alcohol use will also show reductions in severity of psychiatric symptoms and utilization of inpatient and emergency psychiatric services. To determine the relationship between a) changes in alcohol use, and b) psychiatric symptom severity and inpatient and emergency service utilization. We will test hypothesis 3: Severity of psychiatric symptoms and amount of service utilization will correlate positively with alcohol use. The proposed research will study a cohort of 150 subjects in a double-blind, randomized, placebo-controlled trial of naltrexone using three times per week directly observed administration of medication. The study will be 6 months in duration, consisting of a 12-week course of naltrexone or placebo plus 3 monthly follow-up interviews after discontinuation of medication. Voucher incentives contingent on attendance will be provided to all subjects to ensure attendance for medication administration. Weekly motivational enhancement counseling sessions will also be provided to all subjects. Study outcomes will consist of self-report and biological measures of alcohol use as well as measures of psychiatric symptom severity and medical service utilization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEGATIVE SYMPTOMS OF SCHIZOPHRENIA: ANIMAL MODELS Principal Investigator & Institution: Markou, Athina; Associate Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000 Timing: Fiscal Year 2002; Project Start 19-APR-2002; Project End 31-MAR-2007 Summary: Schizophrenia is a mental illness that results in tremendous human suffering and monetary costs to society. Understanding the neuropathologies mediating schizophrenia through the use of animal models will lead to better treatments. One realistic approach to model development is to model specific psychological constructs that are affected by the disorder of interest. Accordingly, this application focuses on

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continuing the development and validation of two distinct rat models of a cluster of schizophrenia symptoms called negative symptoms. It is hypothesized that the negative symptoms reflect deficits in reward and motivational processes that are operationally defined as elevations in brain reward thresholds induced by manipulations (phencylidine withdrawal and amphetamine withdrawal) that induce behavioral and neurobiological abnormalities relevant to the negative symptoms of schizophrenia. These drug withdrawal models of the negative symptoms should not be confused with models acute effects of these drugs hypothesized to reflect the positive symptoms of schizophrenia. SPEC. AIMS: Specific Aims 1 and 2 will continue to explore whether decreases in brain reward function associated with either phencyclinde or amphetamine withdrawal are valid models of the negative symptoms by testing whether these reward deficits are reversed by atypical, but not typical, antipsychotics. This prediction is based on clinical data that typical antipsychotics are ineffective against negative symptoms, while atypical show some therapeutic efficacy against these symptoms. Preliminary data support the above predictions. Specific Aims 3 & 4 will investigate the neurobiology of these reward deficits, and the neurobiology of the reversal of these deficits by pharmacological treatments. Aim 3 will test whether selective antagonists for the 5-HT2 and alpha2 adrenergic receptors will reverse the reward deficits in the models. These antagonists were selected based on a theoretical rationale indicating a role of the neurotransmitter systems probed by these antagonists in the negative symptoms, and the receptor profile of atypical antipsychotics. Aim 4 will use the models developed and the oligonucleotide microarray technology to explore gene expression changes associated with reward deficits, and gene expression changes associated with the reversal of the reward deficits. Follow-up studies will validate the results provided by microarrays. These studies will provide rat models of the negative symptoms that have been dificult to model, and will explore the neurobiology of these symptoms using behavioral, pharmacological and molecular biological techniques. Such studies will lead to better treatments for schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEOCORTICAL SCHIZOPHRENIA

TRANSCRIPTOME

CHANGES

IN

Principal Investigator & Institution: Mirnics, Karoly; Assistant Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Schizophrenia is a complex disorder that is characterized by multiple functional and anatomical changes across the neocortex. Dysfunction of the prefrontal cortex (PFC) in schizophrenia has been associated with deficits of working memory, while functional changes in the superior temporal gyrus (STG) have been related to psychosis. In addition, a functional disconnection between the PFC and STG may contribute to the cognitive symptoms of schizophrenia. Although changes in the expression of individual genes have been reported in both STG and PFC, the transcriptome differences across these regions and the relationship between them remain mostly unknown. The presentation of schizophrenia across genders has been associated with differences in age of onset, symptomathology, premorbid history, neuroimaging findings, drug responsiveness and brain structure. Functional and structural studies suggest that gender differences are present in the STG and PFC of subjects with schizophrenia. However, we do not know if these gender differences reflect (or are reflected by) differences in the underlying transcriptomes. This application is focused around two critical questions: 1) Is there a schizophrenia-related

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expression profile within and across different brain regions and 2) Are schizophreniarelated expression changes different across genders? In this context, we propose to test seven specific hypotheses using 3 specific aims: Aim 1. Compare gene expression pattern in 12 MALE subjects with schizophrenia and matched controls across the prefrontal (PFC) and superior temporal (STG) cortices. Aim 2. Compare gene expression pattern in 12 FEMALE subjects with schizophrenia and matched controls across the prefrontal (PFC) and superior temporal (STG) cortices. Aims 1 and 2 will share the same methodology, and compare the transcriptomes: A) Using whole genome HG_U133A and B Affymetrix microarrays. B) Using custom-made, high-sensitivity polymer cDNA microarrays. These cDNA polymer arrays, involving our proprietary probes (patent application in progress) will allow us an improved and targeted assessment of many transcripts that are too sparse to be detected by the currently available microarrays. Aim 3. Verify and localize the microarray-uncovered gene expression changes to cell types A) at transcript level using in situ hybridization and B) at protein level using immunohistochemistry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURAL SCHIZOPHRENIA

CORRELATES

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SOURCE

MONITORING

IN

Principal Investigator & Institution: Weiss, Anthony P.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): This is an application for an NIMH Mentored Patient-Oriented Research Career Development Award (K-23), entitled "Neural Correlates of Source Monitoring in Schizophrenia." The candidate's interest is in understanding the neural basis for the aberrant memory processes seen in schizophrenia, with an eventual goal of examining the role of these faulty cognitive processes in the production of hallucinations and delusions. In addition to the proposed research described below, the candidate seeks training in functional neuroimaging acquisition and analysis, the cognitive psychology of abnormal memory, and the conduct of ethical clinical research. The proposed research plan, didactic courses, and tutorial instruction from mentors and advisors will serve to foster the candidate's development into an independent clinical researcher in the functional neuroimaging of schizophrenia. Schizophrenia is associated with a particular type of memory disturbance, with intact old/new recognition (i.e., deciding whether an event had occurred previously), but impaired recollection of the contextual details of an experienced event. With limited contextual memory, these patients show deficits in source monitoring, the ability to specify the origin of recollected events. Thus, they may recognize an event as familiar, but have difficulty determining whether the recollected event was actually witnessed, or simply imagined. Although old/new recognition and source monitoring rely on similar neural regions, namely the hippocampus and prefrontal cortex (PFC), source monitoring requires greater activity in these regions. Intact old/new recognition with aberrant source monitoring, as seen in schizophrenia, may therefore indicate that the hippocampaI-PFC network is functioning, but is unable to up-regulate its activity in the face of greater cognitive demands. The proposed experiments will test this hypothesis by using the complimentary approaches of functional MRI and magnetoencephalography to examine both the spatial extent and time-course of neural activity during old/new recognition and source monitoring performance in schizophrenia. In addition to providing greater insight into the pathophysiology of schizophrenia, it is hoped that the proposed experiments will lead

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to objective biological markers for psychiatric illness states, a critical step in developing and monitoring novel treatment interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURAL NETWORK MODELS OF LANGUAGE Principal Investigator & Institution: Hoffman, Ralph E. Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Schizophrenia is characterized by alterations of language and inferential processes. In spite of extensive research, core mechanisms of these disturbances remain uncertain. The overall objective of this RO1 proposal is to use DISCERN, a neural network simulation of natural language processing (Miikkulainen & Dyer 1991; Miikkulainen 1993, 1998), to investigate the mechanism(s) of language-based disturbances in schizophrenia. DISCERN learns stories, utilizes inferential processes, replies to questions, and produces coherent, multi-sentence narrative paraphrases of episodic memories. To enhance applicability of DISCERN as a model of human narrative language production, a larger corpus of stories will be learned that incorporates emotion-coding and self-reference. Simulations will be conducted to determine if disrupted function in different neural modules of DISCERN can produce three core language-based illness manifestations of schizophrenia -- (I) positive thought disorder (such as derailment and illogicality), (II) negative thought disorder (reduced language outputs), and (III) delusions of the idee fixe type. DISCERN will be used to compare and contrast effects of excessive noise versus reduced network connectivity when applied to semantic and working memory modules. Both types of "lesions" have been postulated to play an important role in the pathophysiology of schizophrenia. Noise-induced lesions are predicted to produce word selection errors and curtail language output -- but not to produce positive thought disorder or delusions. In contrast, connectivity loss, when applied to story processing modules, is predicted to simulate all three disturbances, i.e., derailment and curtailment of language outputs as well as production of "fixed" narratives that simulate delusions. A parallel, pilot study of normal subjects and patients with schizophrenia will assess narrative recall of episodic memory. These behavioral data will be used to test and refine models of normal and schizophrenic language production. These findings will significantly advance our understanding of illness mechanisms in schizophrenia and direct future research aimed at developing more selective treatments that reverse these abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROBIOLOGIC SCHIZOPHRENIA

MECHANISMS

OF

DRUG

ABUSE

IN

Principal Investigator & Institution: Scheller-Gilkey, Geraldine; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2001; Project Start 15-JUL-1998; Project End 30-JUN-2003 Summary: (Adapted from applicant's abstract): This proposal for a Mentored Research Scientist Development Award is designed to provide the candidate with training in the neurobiological sciences. The long-term goal is to establish the candidate as an independent investigator in the area of substance abuse and schizophrenia. The extremely high rate of co-morbidity of substance abuse and schizophrenia presents a serious problem in delivery of public mental health care to the chronically mentally ill. The candidate's preliminary studies on outpatients attending a community mental

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health clinic indicate that concurrent substance abuse is not only a common occurrence in schizophrenia patients (55 percent) but is also a major contributor to acute exacerbations as manifested by re-hospitalization. The candidate hypothesizes that these disorders share a common neurobiologic substrate involving the hypothalamicpituitary-adrenal (HPA) axis and mesolimbic dopamine (DA) pathways. Specifically, it is the candidate's belief that in schizophrenia patients who become substance abusers, increases in stress hormones (corticosteroids) lead to increased mesolimbic DA activity, accompanied by an increase in psychotic symptoms, drug craving and sensitivity to drugs of abuse, enhancing the potential for addiction. To test this hypothesis, the following specific aims are proposed Aim 1: To characterize clinical features (including stress, depression and social support) of subjects with co-morbid substance abuse and schizophrenia as distinguished from subjects with schizophrenia or substance abuse alone, and healthy age-, sex- and race-matched controls. Aim 2: To characterize baseline neuroendocrine function (plasma ACTH, cortisol, and homovanillic acid (HVA)) in the four matched groups of subjects. Aim 3: To test the hypothesis that substance abusers will exhibit an increased dopaminergic response to cortisol administration with subsequently increased DA activity in mesolimbic pathways as assessed by plasma HVA, the Positive and Negative Symptom Scale, and Craving Indices. This research project, taken together with the training component of the proposal and the resources of Emory University, will help develop the candidate's skills as a researcher and will allow the candidate to make significant contributions to our understanding and treatment of co-morbid substance abuse and schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROBIOLOGY OF CANNABIS BEHAVIORAL EFFECTS Principal Investigator & Institution: D'souza, D C. Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 15-MAR-2001; Project End 29-FEB-2004 Summary: (Adapted from Applicant's Abstract): Comorbid cannabis abuse has a significant negative impact on the course and treatment of schizophrenia. Comorbid cannabis abuse is highly prevalent in schizophrenia and schizophrenics prefer cannabis to other illicit drugs. There are no pharmacological studies characterizing the effects of cannabis in schizophrenics. The existing literature is limited by its exclusive reliance on naturalistic, retrospective self-report studies. These studies suggest that cannabis may reduce certain symptoms associated with schizophrenia at the expense of worsening others. Studying the effects of cannabis on the symptoms of schizophrenia is the first step in understanding the problem of cannabis abuse and schizophrenia. Cannabis continues to be a public health problem in the general population. While an association between cannabis use and psychosis in "healthy" individuals has been reported, the magnitude of cannabis' psychogenic effects has not been adequately studied using standardized assessments. This investigation proposes to answer the following questions: 1. Does THC have anxiolytic and euphoric effects in schizophrenia? 2. Is there altered cannabinoid sensitivity in schizophrenia: does THC increase psychosis and cognitive deficits in schizophrenics, is THC psychogenic in controls and finally, are schizophrenics more vulnerable to the effects of THC? Study subjects will be stable schizophrenics with previous cannabis exposure and matched controls. They will be tested under three conditions: placebo, 2.5 and 5mg THC delivered IV. Primary outcome measures are: PANSS, Visual Analogue Scale for Mood Disorders, CADSS (perceptual alteration scale) and tests sensitive to frontal and temporal cortical function. Secondary

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measures include measures of drug liking, movement rating scales and long term follow-up assessment of cannabis use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROBIOLOGY SCHIZOPHRENIA

OF

SELECTIVE

ATTENTION

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Principal Investigator & Institution: Belger, Aysenil; Psychiatry; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 06-APR-2001; Project End 31-MAR-2006 Summary: (Applicant's abstract) Schizophrenia is associated with a fundamental deficit in selectivity that operates at all levels of information processing from basic sensory to higher order semantic processing. However the neurobiological bases of these deficits and their modulation through the course of the disease has not been established. We propose a series of studies that assess information selection deficits in schizophrenia within the framework of a multistage model, comprising an initial stage of sensory filtering or gating, a subsequent stage of sensory discrimination and memory processing, and a final stage of response selection. Parallel experiments will examine the functional and structural substrates of attention deficits in schizophrenia, using converging evidence from behavioral, electrophysiological (ERP) and functional Magnetic Resonance Imaging (fMRI) techniques. Electrophysiological (event-related potential, or ERP) studies will compare ERPs evoked in sensory gating, automatic and voluntary attention allocation, and response selection tasks in groups of schizophrenic patients and healthy controls. These studies will document ERP abnormalities at each level of processing previously observed in schizophrenic patients by the PI and her colleagues. Functional magnetic resonance imaging (functional MRI, or fMRI) studies will then be conducted using the same tasks and patterns of activation will be compared in healthy and schizophrenic subjects. Event-related fMRI analysis will be used to isolate activations evoked by task relevant and irrelevant stimuli. Group differences in activation patterns will be used to identify critical brain regions engaged at these levels of stimulus and response selection. The clinical objective of the proposed studies is to relate selective attention deficits in schizophrenia to symptomatology and chronicity of this illness. Information from these studies will further our understanding of the functional and structural basis of distractibility and information processing deficits in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROCHEMICAL SCHIZOPHRENICS

CONTROL

OF

MEMORY

IN

AGING

Principal Investigator & Institution: Newcomer, John W. Associate Professor; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 30-APR-2003 Summary: This Independent Scientist Award (K02) application proposes an integrated research eve development plan and project that includes funded experiments to further investigate glucose- and insulin- induced improvements in memory performance in aging patients with schizophrenia (RO1 MH53363), and extends this to include the investigation of N-methyl-D-aspartate (NMDA) glutamate receptor regulation of memory performance. Impairment in memory performance in schizophrenia predicts poor functional outcomes with more costly care requirements. There are currently no specific treatments for such impairment and the neurobiology that could guide

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treatment development remains incompletely understood. The candidate's prior research has combined the perspectives of cognitive neuroscience and neuroendocrinology into a focus on the cognitive effects of neurohormones that regulate intraneuronal energy availability, producing evidence of memory impairment by glucocorticoids and clinically significant improvements using both glucose and insulin, supporting immediate aims to define the dose-response relationships of glucose and insulin to memory performance in older patients with schizophrenia. Glucose and insulin can regulate NMDA glutamate receptor-related functions, including long-term potentiation (LTP). These reports, recent evidence for NMDA glutamate receptor hypofunction (NRH) in schizophrenia, and the importance of LTP for the study of memory, have motivated the development of-a model of memory impairment, in schizophrenia using ketamine-induced NRH in healthy humans. This KO2 Award will provide specific additional training needed to extend this by testing a rational series of pharmacological strategies to reverse memory impairment induced by NRH, including insulin, a muscarinic cholinergic receptor antagonist, a GABAa receptor facilitator, an alpha 2 adrenergic receptor agonist, a serotonergic receptor ligand, and a novel antipsychotic. All experiments utilize within subjects, placebo controlled, randomized study designs, to test the effects of treatments on cognitive performance. The goals and development activities described m this application are facilitated by the candidate's access to extensive resources including appropriate experts in preclinical and clinical cognitive neuroscience. This Award will facilitate the long-term public health goal of characterizing those fundamental neurochemical regulators of memory performance most likely to lead to therapies to treat and/or prevent cognitive impairment in aging patients with schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROCOGNITIVE BOUNDARIES OF THE SCHIZOPHRENIA SPECTRUM Principal Investigator & Institution: Condray, Ruth; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 01-MAY-1993; Project End 30-JUN-2003 Summary: (Applicant's abstract): Disturbances in language function were among the first clinical observations reported for individuals described as schizophrenic, with selected aspects accorded preeminent theoretical status. Currently, language disturbances are among the constellation of hallmark symptoms that are diagnostic of the schizophrenia disorder. However, the linguistic conditions and psychological functions that contribute to schizophrenics' language dysfunction are not well understood and require elucidation. The focus of this revised application remains directed to the development of a theory that will explain the language processing disturbances of schizophrenia. The meaning embodied in discourse (i.e., connected language) is generally assumed to be realized through multiple layers of linguistic structures. Our model of language dysfunction in schizophrenia proposes that schizophrenic individuals are characterized by capacity limitations that influence their ability to use fully the contextual information that is conveyed through semantic and syntactic linguistic conventions. These capacity limitations exist at multiple levels, and produce dysfunctions that range from the processing of single words in small, discrete units of semantic context (lexical identification), to the processing of the logical relationships expressed in complex sentence structures. In the FIRST award project, schizophrenics showed a reduction in their ERP sensitivity to semantic context during lexical identification (ERP priming), which was only marginally improved during

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pharmacological treatment. A major finding was that the source of patients' compromised ERP priming was in their response to semantically associated contexts. Functions that were correlated with the accuracy of sentence comprehension included a sensitivity to word frequency information during lexical identification as well as a capacity to hold or maintain information while the semantic and syntactic parsing is accomplished. In contrast, sensitivity to type of semantic context during lexical identification (ERP priming) was not correlated with comprehension accuracy. The specific aims of the current proposal are: (1) To increase the specification of our model of language processing disturbance in schizophrenia, we will test hypotheses about the linguistic conditions and psychological functions that produce disruptions in schizophrenics' language processing. (2) To compare language processing between schizophrenic patients, family members of schizophrenic probands, and normal controls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURODEVELOPMENTAL INSULTS AND SCHIZOPHRENIA Principal Investigator & Institution: Poland, Russell E. Professor and Director of Research; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, CA 90048 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2003 Summary: (adapted from applicant's abstract): The overall objective of the proposed research plan is a test of the neurodevelopmental hypothesis of schizophrenia. Diverse evidence suggests that schizophrenia has a neurodevelopmental component of unknown etiology in which injury to the brain occurs during early development. Epidemiologic studies indicate that human offspring exposed to developmental insults such as nutritional deficiencies, viral infection, obstetric complications, and stress are at higher risk for subsequent development of schizophrenia. Brain pathology which might be linked to the neurodevelopmental insults includes abnormal biochemistry as measured by proton (1H) magnetic resonance spectroscopy (MRS). The investigator proposes to link these biochemical abnormalities with the early life stress diathesis of schizophrenia by assessing whether the MRS findings in schizophrenia can be reproduced by early developmental insults in rats. The general design of the proposal includes the use of in vitro 1H MRS to characterize the effects of perinatal stress on the brain regional concentration of N-acetyl-aspartate (NAA) and myoinositol (MI). Behavioral, neuroendocrine, and neurochemical characteristics of perinatal stress would also be defined. Determinations would be conducted at 4 developmental time-points spanning 30-360 days of age and in 8 brain regions. In experiment I, the investigator proposes a characterization of the effects of prenatal stress in the form of repeated daily physical restraint of pregnant dams. Pups born from stressed or non-stressed moms will be cross-fostered at birth and reared by prenatally stressed or normal moms to yield four experimental groups. Experiment II would characterize the effect of postnatal stress in the form of maternal deprivation. Four experimental groups would be used to characterize the interaction of the prenatal stressor with the postnatal stress resulting from rearing by stressed versus non-stressed moms and maternally deprived versus normally reared animals. The investigator provides preliminary evidence that adult male offspring subjected to stress perinatally demonstrate decreased NAA in the left frontal cortex. The proposal would determine when during development this NAA change appears and if it is progressive in nature. The relationship among NAA concentration, and behavioral, neuroendocrine, and neurochemical measures of stress response would also be determined. The results of the proposed studies should provide

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basic information on potential links between the neurodevelopmental abnormalities and anomalies in adult neurochemistry defined by 1H MRS in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROIMAGING SCHIZOPHRENIA

OF

HIPPOCAMPAL

FUNCTION

IN

Principal Investigator & Institution: Heckers, Stephan; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 30-JUN-2004 Summary: This is a request for an NIMH Mentored Patient-Oriented Research Career Development Award (K-23) entitled "Neuroimaging of Hippocampal Function in Schizophrenia". The candidate's interest is the study of hippocampal function in the human brain with a special emphasis on schizophrenia. Several lines of evidence have implicated abnormalities of the hippocampus in schizophrenia. The candidate proposes to test the hypothesis of memory associated hippocampal deficits in schizophrenia with functional neuroimaging experiments. The candidate's previous training was in neuroanatomy and clinical psychiatry, and includes initial training in positron emission tomography (PET) technology. The proposed project will provide more advanced training in PET as well as training in (1) the application of structural and functional magnetic resonance imaging (fMRI), (2) the cognitive neuroscience of memory, (3) the statistical aspects of comparing psychiatric patients and control subjects, and (4) the neurobiology of schizophrenia. The research project designed to achieve these goals integrates four experimental approaches to study hippocampal function in schizophrenia. First, established PET activation paradigms will be used to assess hippocampal function during memory retrieval in schizophrenic patients and control subjects. Second, fMRI will be used to study hippocampal activating during memory processes in schizophrenic patients and control subjects. Third, the pattern of hippocampal activation will be correlated with the structural organization of the brain using morphometric analyses. Fourth, psychological experiments will be developed to study memory and conscious recollection in schizophrenia. This integrated program, providing training in neuroimaging technologies, cognitive neuroscience, and statistical analyses, will foster the candidate's development into an independent investigator in the fields of schizophrenia research and neuropsychiatry. The research conducted will advance our understanding of hippocampal function in the human brain and elucidate the neuropsychology and neurobiology of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROMORPHOMETRY SCHIZOPHRENIA

IN

SIBLINGS

AT

RISK

FOR

Principal Investigator & Institution: Csernansky, John G. Gregory B. Couch Professor; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2004 Summary: Variation in the morphology of specific brain structures in schizophrenia may be attributable to genetic factors, environmental factors, or their interaction. Thus, neuroimaging studies of sibling pairs that vary in clinical, neuromorphological and genetic factors provide a powerful approach to evaluating brain structure abnormalities associated with the pathogenesis of schizophrenia. If specific genes underlie neurodevelopmental errors that are involved in the pathogenesis of schizophrenia, such genes could be discovered by examining the degree to which they segregate with brain

90 Schizophrenia

structure abnormalities observed in schizophrenia subjects are the result of environmental factors or gene-environment interactions, controlling for such variability should facilitate efforts to detect other disease- related genes. Recently, we have developed tools for high dimensional brain mapping (HDBM) that permit the detailed analysis of brain structure volumes and shapes. We have used HDBM to compare the structure of the hippocampus in schizophrenia subjects and matched controls, and in these studies, shape deformities of the hippocampus were found to powerfully discriminate between groups. Thus, HDBM should be an ideal method for discovering neuromorphological abnormalities in non-psychotic siblings of schizophrenia, whom one would expect to show very subtle disturbances. The specific aims of this Project are: Aim 1. To collect high resolution magnetic resonance (MR) scans from sixty schizophrenia probands, their non-psychotic siblings sill within the age of risk for developing the disorder, and from matched controls; Aim 2. To develop a database of neuromorphometric variables for each subject, including metrics for gray matter volume, thickness (for cortical surfaces), and shape, and for anisotropy; Aim 3. To test the hypothesis that non-psychotic siblings of schizophrenia probands are discriminated from both schizophrenia subjects and healthy controls using neuromorphometric metrics. It is hypothesized that non-psychotic siblings will demonstrate brain structure abnormalities intermediate between the other two groups; Aim 4. To examine relationships between gray and white matter metrics with related brain regions; and Aim 5. To begin the collection of longitudinal data, with the ultimate goal of predicting the onset of schizophrenia in the non-psychotic siblings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROPHYSIOLOGICAL SCHIZOPHRENIA

NMDA

DYSFUNCTION

IN

Principal Investigator & Institution: Javitt, Daniel C. Director; Psychiatry; New York University School of Medicine 550 1St Ave New York, NY 10016 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-DEC-2001 Summary: (Adapted from applicant's abstract): Phencyclidine (PCP) induces a psychotic state that closely resembles schizophrenia by blocking neurotransmission at the NMDA-type glutamate receptor. The ability of NMDA antagonists to induce schizophrenia-like symptoms indicates that endogenous NMDA receptor dysfunction or dysregulation may contribute substantially to the pathophysiology of schizophrenia. This K02 award will enable the candidate to pursue investigations directed to the continued development of the PCP/NMDA model of schizophrenia. Specific projects will include: 1) characterization of neurophysiological and neurocognitive dysfunction in schizophrenia relative to the predictions of the PCP/NMDA model, 2) investigation of mechanisms underlying neurophysiological and neurocognitive dysfunction in schizophrenia using multichannel intracortical recordings in monkeys, 3) determination of the effects of NMDA augmenting agents on negative symptoms and cognitive functioning in schizophrenia, and 4) development of novel, clinically relevant NMDA augmentation strategies. Neurophysiological studies will focus on impaired generation of mismatch negativity (MMN) and other cognitive event-related potential (ERP) in schizophrenia. Treatment studies will focus on the clinical use of glycine and characterization of preclinical effects of glycine precursors and/or reuptake inhibitors on rodent behavior and free extracellular glycine levels. The research will build upon studies currently supported by NIH research and career development awards to the candidate. Over the past several years, the candidate has acquired expertise in PCP/NMDA neuropharmacology and in the application neurophysiological methods to

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the analysis of brain dysfunction in schizophrenia, and has gained experience in clinical psychopharmacology research in schizophrenia. This award will permit the candidate to develop further expertise in neurophysiology and psychopharmacology and to obtain exposure and experience in the use of structural and functional neuroimaging in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROPHYSIOLOGICAL STUDIES OF SCHIZOPHRENIA Principal Investigator & Institution: Mccarley, Robert W. Professor; Psychiatry; Harvard University (Medical School) Medical School Campus Boston, MA 02115 Timing: Fiscal Year 2003; Project Start 01-APR-1986; Project End 31-JUL-2007 Summary: (provided by applicant): This study of schizophrenia has as its main goal to advance our knowledge of the neurophysiology of schizophrenia by evaluating functional abnormalities in event-related potentials (ERPs) that span both early and late stages of processing, by integrating this information with the structural MRI anatomy, and by integrating both with the clinical features of this disorder. Recently the aim of describing the course of the disorder has become prominent, as we have moved into a prospective longitudinal study of first episode subjects. In fact one of the more exciting preliminary findings is the apparent post onset progression of schizophrenia, which is very rapid in the first 1.5 years after initial hospitalization, but much slower in chronic patients. Unifying our approach is a cellular-based model, and it, as well as our preliminary data, has led to an increasing focus on early-stage brain processing, especially auditory, as experiments in early processing appear to be especially amenable to correlation with anatomy and with documentation of progression of the disorder. We will also evaluate what is specific to schizophrenic vs. manic psychosis in ERP, MRI and longitudinal measures. We plan to examine the following measures. 1) Gamma Band (40Hz) frequency abnormalities in both steady state and evoked paradigms. 2) The auditory Mismatch Negativity (MMN, 100-200 ms), which our preliminary data suggest is normal at first hospitalization for schizophrenia and then subsequently becomes abnormal, pari passu, with grey matter volume loss in Heschl's gyrus. 3) The N170 facerelated potential, which our preliminary data indicate to be abnormal in chronic schizophrenia. 4) The auditory P300. 5) The N400 to word pairs abnormalities and their MRI correlates in reduced fusiform and inferior middle temporal gyri gray matter in schizophrenia. MRI measures, including gray-white segmentation, will include all temporal lobe gyri and subdivisions, and medial temporal lobe structures. Subjects in this longitudinal study will be male and female individuals with first episode (first hospitalization) schizophrenia, affective (manic) psychosis and with chronic schizophrenia and will be evaluated for interrelationships among the physiologic, anatomic and clinical features, as well as progression of abnormalities. All groups will have appropriate matched controls. Should our prediction of very rapid progression of ERP and MRI abnormalities in the months following initial hospitalization for schizophrenia be confirmed, it would immediately form a scientific foundation and moral impetus for studies of the possible preventive effects of medication and psychosocial treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROSTEROIDS AND SCHIZOPHRENIA Principal Investigator & Institution: Marx, Christine E. Psychiatry; Duke University Durham, NC 27706

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Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (Adapted from applicant's abstract) My career goal is to become an academic psychiatrist and independent investigator in the areas of schizophrenia focusing on its neurobiology and therapeutics, applying molecular mechanism-based research to prospective clinical studies. Specifically, I propose to investigate the importance of neurosteroids in schizophrenia. Neurosteroids are differentially expressed in males and females, modulate GABAA and NMDA receptors, regulate neuronal cytoarchitecture, demonstrate neuroprotective effects, play a role in neurodevelopment, and possess memory-enhancing effects. Neurosteroids are therefore logical candidates of investigation to elucidate schizophrenia pathophysiology, since they are potential modulators of schizophrenia gender differences, GABAergic and glutamatergic dysregulation, neurodevelopmental insults associated with increased schizophrenia risk, cytoarchitectural abnormalities in postmortem specimens from patients with schizophrenia, and cognitive disturbances in the disorder. The laboratory has demonstrated that neurosteroids protect embryonic cerebral cortical neurons against anoxia, a neurodevelopmental insult associated with increased schizophrenia risk. We have also demonstrated that acute olanzapine and clozapine administration alters cerebral cortical neurosteroids in rodents. The investigators hypothesize that neurosteroids are important modulators of schizophrenia pathophysiology (including the pronounced gender differences of the disorder) and antipsychotic drug action. We also propose that compounds affecting neurosteroid expression or neurosteroids themselves may be developed as novel therapeutic agents in the treatment of schizophrenia. To test this hypothesis, three investigational strategies are proposed: 1.) A preclinical study examining the effects of antipsychotics on cerebral cortical and serum neurosteroid levels in rodents, 2.) A postmortem study determining neurosteroid levels in parietal cortex and posterior cingulate specimens provided by the Stanley Foundation from patients with schizophrenia compared to control subjects, and 3.) A clinical study examining neurosteroid levels in subjects with schizophrenia from two UNC clinical trials (Dr. Lieberman, PI) to determine if serum or CSF neurosteroid alterations are correlated with antipsychotic efficacy, neurocognitive changes, and/or structural changes on MRI. Results from these preliminary investigations will inform the design of future prospective clinical studies to confirm initial findings and target neurosteroids as therapeutic agents in schizophrenia. To achieve these goals, the candidate will receive training through formal coursework in neuropharmacology, clinical trials design, drug development, and biostatistics. She will also learn highly sensitive and specific gas chromatography mass spectrometry (GC/MS) and other stateof-the-art neurosteroid detection methods. The mentorship of Drs. Jeffrey Lieberman and Leslie Morrow will be critical to the overarching goal of this proposal, the successful translation of exciting preclinical neurosteroid findings to prospective clinical studies examining neurosteroids in schizophrenia pathophysiology and therapeutics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROSTEROIDS: RELEVANCE TO CORTICAL DEVELOPMENT Principal Investigator & Institution: Grobin, a C. Psychiatry; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The field of schizophrenia research needs innovative research programs that utilize basic neuroscience approaches and translate their findings into clinically meaningful goals. The goal of this proposal is to develop a pharmacologist with a background in industrial chemistry into an independent

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investigator of the neurobiology of schizophrenia. The broad-based training environment at UNC, including exposure to a talented multidisciplinary faculty and interaction with a critical mass of research fellows of diverse backgrounds is ideal for such translational endeavors and career development. The candidate will develop comprehensive knowledge of developmental neurobiology, assimilate current schizophrenia literature and acquire necessary research skills through didactic training, tutorials and original research. The research project proposes to investigate generally the role of neurosteroid influences on brain development and specifically if their response to stress could alter prefronal cortical neurodevelopment in a permanent manner that affects brain function and behavior in the adult. It is widely believed that schizophrenia is an environmentally modulated, genetically mediated neurodevelopmental disorder. Non-specific stress is the developmental factor most closely associated with increased schizophrenia vulnerability. Neurosteroids, including 3alpha-hydroxy-5alphapregnane-20-one (allopregnanolone or 3alpha,5 alpha-THP) and 3alpha,21- dihydroxy5alpha-pregnane-20-one (THDOC) are rapidly induced after stress stimulus in adults and neonates. Furthermore, allopregnanolone and THDOC are potent modulators of GABAA receptors and likely to regulate cortical development. Finally, aberrant cortical development is thought to underlie altered indices of GABAergic neurotransmission present in post-mortem brain tissue of schizophrenics. To test the hypothesis that GABAergic neurosteroid levels play a role in normal cortical development, neurosteroid levels will be altered during the first week of rodent life and cortical morphology, cytoarchitecture and sensory gating measured 80 days later. Preliminary data suggest that neonatal administration of allopreganolone produces long-lasting changes in prefrontal cortex interneuron cell localization and prepulse inhibition that resemble the loss of neural matter and sensory-gating deficits evident in schizophrenics. These studies could represent a model of the role of neurosteroid on stress in brain development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEW TREATMENT AND MECHANISMS IN SCHIZOPHRENIA Principal Investigator & Institution: Goff, Donald C. Director; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 30-JUN-2006 Summary: Candidate: Dr. Goff completed postgraduate training in 1985 and started the Schizophrenia Program of the Massachusetts General Hospital (MGH) with an NIMH "Faculty Scholar Award in Schizophrenia" in 1988. He has focused on augmentation trials for negative symptoms, and over the past five years has conducted a series of studies examining glutamatergic agents and glutamatergic activity of atypical antipsychotics. Dr. Goff has also established a group of ten young investigators working collaboratively to translate recent advances in the neurosciences to the study and treatment of schizophrenia. Environment: Dr. Goo's group has ample space and access to schizophrenia subjects at the Freedom Trail Clinic of the Lindemann Mental Health Center and to a collaborative network of mental health clinics that he has established for recruitment of research subjects in the greater Boston area. He works closely with the MGH Neuroimaging group, the MGH Biostatistics Center, the MGH Amino Acid Laboratory and collaborates with the Transcranial Magnetic Stimulation Research Group at the Beth Israel Hospital and the Brain Imaging Center at McLean Hospital. Dr. Goff is principal investigator for the clinical trials section of the NIMH-funded Neurosciences Center for the Study of Glutamate in Schizophrenia under the leadership of Dr. Joseph Coyle. Dr. Goff has full institutional commitment from Dr. Jerrold

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Rosenbaum (interim Chief of Psychiatry, MGH) ensuring protected time and resources to accomplish research and mentoring goals. Research: Dr. Goo's research plan involves continuation of his study of glutamatergic agents in schizophrenia and of the role of glutamatergic activity in the therapeutic action of atypical antipsychotics. He will devote the period of the career development award to completing on-going RO1-funded controlled trials of NMDA receptor agonists, initiating trials of new glutamatergic agents (D-serine and an Ampakine) and developing expertise with new research tools and developing collaborations to apply to his research, including neuroimaging, spectroscopy, transcranial magnetic stimulation and genetics. He will also continue his mentoring activities as he guides the career development of ten junior faculty researchers in his group as well as residents and research fellows working on research projects under his direction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NICOTINE AND SMOKING CESSATION IN SCHIZOPHRENIA Principal Investigator & Institution: Evins, Anne E.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Applicant's Abstract) This proposal focuses on providing the candidate with the expertise needed to bridge several disciplines in the study of pharmacologic and behavioral interventions in the treatment of nicotine addiction in schizophrenia. Nearly 90 percent of patients with schizophrenia smoke cigarettes compared to less than 25 percent of the general U.S. adult population. Compounded by the problem that patients with schizophrenia are less likely to receive adequate routine and preventative medical care, heavy smoking represents a significant and neglected public health problem for people with schizophrenia. In pilot trials, the candidate found bupropion SR to be safe and effective for smoking reduction and cessation in patients with schizophrenia while improving negative and depressive symptoms and preventing weight gain and exacerbation of psychosis. In the proposed study, 60 subjects with schizophrenia who smoke greater than 10 cigarettes per day and wish to quit smoking will be randomized, in double blind fashion, to receive either bupropion SR or placebo for twelve weeks, combined with a nine week cognitive behavioral Quit Smoking Group Therapy Program modified by the candidate for patients with schizophrenia. The primary outcome measure is 7-day point prevalence of greater than or equal to 50 percent smoking reduction at the end of 12 weeks treatment that is biochemically confirmed. Secondary outcome measures are 7-day point prevalence tobacco abstinence at the end of the 3 month treatment and 3 month follow up phases, sustained tobacco abstinence or reduction, change in psychiatric symptoms, cognitive functioning, weight, side effects and health related quality of life. Career Development Plan: The candidate will build upon her experience conducting treatment trials for negative symptoms of schizophrenia. With consultation from individuals with the appropriate expertise, the candidate will design, implement and interpret pharmacologic intervention trials for smoking cessation in schizophrenia, study of cognitive behavioral therapy interventions in patients with the dual diagnoses of addiction and major mental illness, study of harm reduction strategies in patients with schizophrenia unable to attain abstinence, and studies of the effect of nicotinic agents on attention and memory in schizophrenia that will lay the foundation for future independent investigation by the candidate in these areas. The mentored investigative work will take place at the Massachusetts General Hospital and will complement an intensive training program of coursework at the

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Massachusetts General Hospital and the Harvard School of Public Health on methodology, epidemiology, statistics, and responsible conduct of research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NMDA SCHIZOPHRENIA

ANTAGONIST-INDUCED

NEUROTOXICITY

IN

Principal Investigator & Institution: Shim, Seong S. Psychiatry; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2004 Summary: (provided by applicant) Non-competitive and competitive N-methyl-Daspartate receptor (NMDAR) antagonists have the ability to induce schizophrenia-like psychosis as shown in the phencyclidine (PCP) model of schizophrenia. However, the mechanism by which NMDAR antagonists produce schizophrenia-like psychosis is not well understood. The systemic administrations of non-competitive and competitive NMDAR antagonists also induce neuronal injury in limbic forebrain including the hippocampus. Several lines of evidence suggest that this NMDAR antagonist-induced neurotoxicity may be closely associated with NMDAR antagonist-induced psychosis. Evidence from human studies indicates that hippocampal disturbances may play a central role in the pathophysiology of schizophrenia. Since NMDAR antagonists induce schizophrenia-like psychosis, and produce neurotoxicity in the hippocampus, the best documented locus of pathology in schizophrenia, this study on the mechanisms by which NMDAR antagonists induce neurotoxicity in the hippocampus may provide a significant contribution toward understanding the pathophysiology of schizophrenia. In this proposal, I will examine the neurotoxic consequences of in vivoexposure to PCP and the preventive action of s-amino butyric acid (GABA) agonists in the hippocampus to investigate the mechanism by which NMDAR antagonists induce neurotoxicity with the three specific aims; 1) assess morphological injury induced by the administration of PCP and the preventive action of GABAergic agonists, 2) assess electrophysiological impairment induced by the administration of PCP and the preventive action of GABA agonists, and 3) assess changes in glutamate and GABA release induced by the administration of PCP and the preventive action of GABAergic agonists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NMDA-BASED TREATMENT OF SCHIZOPHRENIA Principal Investigator & Institution: Klitenick, Mark A.; Glytech, Inc. 138 Aster Dr New Hyde Park, NY 11040 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 15-FEB-2003 Summary: (provided by applicant): Schizophrenia is a major mental disorder with estimated prevalence of 1 percent of the population. Current treatment approaches for schizophrenia rely on the use of dopamine antagonists (antipsychotics). These drugs have only partial effectiveness in a large percentage of patients, especially in the treatment of negative and cognitive symptoms. This project will explore alternative treatment strategies for schizophrenia based upon the PCP model of the disorder. PCP (phencyclidine, "angel dust") induces symptoms that closely resemble those of schizophrenia, by blocking neurotransmission mediated at N-methyl-D-aspartate (NMDA) type glutamate receptors. Several dietary amion acids, including glycine and D-serine, potentiate activation of NMDA receptors in vitro and reverse behavioral effects of PCP in vivo. In small scale clinical trials, glycine and D-serine have been shown to be effective in the treatment of persistent symptoms of schizophrenia. This

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project will focus on development of commercializable formulations of glycine and Dserine. Both products fall within the scope of Federal medical foods legislation. The specific aims are to explore feasibility of glycine and D-serine development as medical foods for dietary management of schizophrenia. In the case of D-serine, preclinical toxicology would be required. In successful, this project will lead to development of new treatment approaches for schizophrenia. PROPOSED COMMERCIAL APPLICATIONS: This project will permit commercialization of a diet-based treatment approach for schizophrenia Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NR3 EXPRESSION IN HUMAN BRAIN Principal Investigator & Institution: Mueller, Helena T. Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 28-SEP-2001 Summary: Adapted from applicant?s abstract): The goal of this project is to study the expression of the NR3 subunit of the NMDA receptor (NMDAR) in human fetal and adult schizophrenic brain. NMDAR?s play an important role in many normal and pathological processes in the brain. The NMDAR is a multimeric complex comprised of 4 or 5 subunits (NR1, NR2A-D and NR3) derived from six different genes. Since subunit composition can alter the pharmacological and physiological properties of the NMDAR, differential expression of these various subunits may reflect an important level of NMDAR regulation. Pharmacological studies suggest NMDAR dysfunction plays a role in schizophrenia and changes in NMDAR subunit expression have been reported in schizophrenia, supporting this hypothesis, although the NR3 subunit has not been studied in this illness. Prenatal insults to the brain during the second trimester of pregnancy have been linked to schizophrenia, suggesting a neurodevelopmental component may play a role in the etiology of schizophrenia. Studies in rodent suggest that the NR3 subunit is expressed at a time in development that may be relevant in schizophrenia. Further, electrophysiological studies demonstrate that incorporation of the NR3 subunit into a functional NMDAR can decrease NMDAR current, consistent with the glutamate hypothesis of schizophrenia involving decreased NMDAR activity. Thus, we hypothesize that the NR3 subunit may be important in the etiology and/or pathophysiology of schizophrenia. Since the human NR3 subunit has not been investigated, these studies are designed to 1) examine NR3 mRNA expression and protein levels in fetal and adult human brain, and 2) test the hypothesis that NR3 expression is altered in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OCULAR MOTOR AND NEUROANATOMIC STUDIES OF SCHIZOPHRENIA Principal Investigator & Institution: Clementz, Brett A. Professor; Psychology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 01-SEP-1993; Project End 30-NOV-2003 Summary: Ocular motor performance provides a powerful behavioral means for studying what is specifically different about the functioning of schizophrenia subjects' brains, and for evaluating functional deviations that are correlated with predisposition for developing this illness. Identifying and refining schizophrenia-specific ocular motor abnormalities will serve at least two important functions. First, the ocular motor system is well understood both functionally and neuroanatomically. Dysfunction in particular

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parts of its neural control system result in characteristic patterns of ocular motor response. By presenting subjects with the appropriate set of tasks and monitoring their performance, hypotheses about the location of neuropathology can be tested. Ocular motor measurement, therefore, can aid the investigation of schizophrenia's neuropathology. Second, schizophrenia patients' clinically normal biological relatives seem to have the same pattern of ocular motor abnormalities as the patients themselves. These findings suggest that some aspect of ocular motor system dysfunction is assessing a component of brain functioning closely associated with a neurobiological predisposition for this illness. Further research on this phenomenon, therefore, could lead to the development of highly sensitive indicators of clinically unaffected gene carriers. A research programme appropriate for these undertakings requires collecting data on ocular motor performance across a range of tasks, a strategy we have used with considerable success. It is remarkable to think that studies of schizophrenia subjects' behavioral performance can provide consistent and theoretically meaningful neurologically localizing information. This is exactly the conclusion that could be drawn with data from some additional clarifying studies. Research conducted with this grant will allow us to (1) rule out the possibility that schizophrenia subjects have a primary dysfunction of their smooth pursuit systems, (2) provide data inconsistent with the thesis that schizophrenia subjects have dysfunction of either posterior parietal cortex ocular motor-related regions or frontal eye fields, and (3) corroborate the hypothesis that the ocular motor abnormalities observed among schizophrenia subjects are a consequence of dysfunction in dorsolateral prefrontal cortex and/or its related subcortical circuitry. These data will be critically important for the success and efficiency of future functional neuroimaging and genetic linkage studies, because research with these important, but expensive, technologies will be suboptimal if they are based on the wrong behavioral measures. In this regard, it will be especially important to refine stimulus conditions to the point where measurement error is reduced as much as is practically feasible, a goal toward which we will aspire with our proposed research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OCULOMOTOR SCHIZOPHRENIA

&

SPATIAL

COGNITION

DEFICITS

IN

Principal Investigator & Institution: Sweeney, John A. Professor; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Verbatim from the Applicant's Abstract) Abnormalities of eye movement control and spatial cognition are well-established deficits in schizophrenia. However, the regional disturbances in brain function causing these deficits are not yet known. This application proposes a series of integrated behavioral and fMRI studies designed to identify causes of pursuit eye movement and spatial working memory deficits in schizophrenia. We will determine whether there are intrinsic functional disturbances in extrastriate regions that process visual motion information (Area MT) using both optic flow and motion aftereffect paradigms. We will parametrically manipulate attentional enhancements during pursuit tracking to clarify the causes of what appears to be a reduced influence of extra retinal signals on the control of pursuit eye movements in schizophrenia. We will use an oculomotor delayed response (ODR) task to study spatial working memory impairments in schizophrenia. We will parametrically manipulate the rate of "distractor" information presented during the delay period of this prototypic spatial working memory task in order to model changes in dorsal brain regions of interest across a range of processing load conditions. Fifty schizophrenic patients will

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be recruited, 25 first episode antipsychotic-naive patients and 25 unmedicated chronic patients. In addition to matched healthy subjects, 50 patients with non-bipolar depression will be recruited as a clinical comparison group. Depressed patients are of interest because our group and others have demonstrated relevant disturbances of eye movement control and spatial cognition in this disorder. Subjects will be restudied after 3 months, during which all patients will receive controlled treatment, in order to assess the extent of normalization of brain function associated with treatment and clinical recovery. The results of these studies will clarify the neurobiological basis of one of the most robust and promising biological markers of risk for schizophrenia, and of working memory disturbances known to be a prominent component of the neuropsychological profile of the disorder. Findings will also clarify the diagnostic specificity of regional brain disturbances causing these abnormalities, and the impact of known effective treatments upon them. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OLFACTION: A NOVEL MOUSE MODEL OF SCHIZOPHRENIA Principal Investigator & Institution: Kanes, Stephen J. Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 19-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Introduction: This proposal seeks a period of supervised scientific training to enable Stephen J. Kanes M.D., Ph.D. to develop into an independent physician-scientist. The candidate completed graduate training in both Medicine and Molecular and Cellular Pharmacology at SUNY-Stony Brook followed by post-graduate clinical and research training at Yale University. During the proposed period of additional training, the candidate plans to develop the necessary skills to use animal models to investigate the neurobiology, pharmacology and genetics underlying inbred mouse strain differences in olfactory abilities and olfactoryguided behaviors. Background: Schizophrenia patients and their first-degree relatives have decreased olfactory detection threshold, identification, discrimination and memory. These are accompanied by specific neuropathological findings in the olfactory epithelium and bulb. Because both patients and unaffected relatives share these abnormalities, it is likely that the olfactory deficit is under genetic control and that this deficit may share some genetic risk factors with schizophrenia. Identifying these genes may provide important insights into the causes of schizophrenia itself. Inbred mice provide the ideal model system to begin exploring the genetic underpinnings of variation in olfactory structure and function. Research Project: The experiments proposed will examine the differences among 10 inbred mouse strains in olfactory-guided behaviors, olfactory bulb anatomy and the role of dopaminergic neurotransmission on olfaction. This battery will then be used in the evaluation of olfactory-guided behavior and olfactory bulb structure in D1, D2, D3 and D4 dopamine receptor knockout mice. Environment: The candidate will train in a structured environment that includes high-quality basic science and clinical research facilities. Senior mentoring will be geared towards facilitating methodological approaches to combine clinical observations with pre-clinical studies of olfaction. The primary training sites at the University of Pennsylvania will be in the Center for Neurobiology and Behavior under the supervision of Maja Bucan, Ph.D. and the Schizophrenia Research Center under the supervision of Raquel E. Gur, M.D., Ph.D. Research Career Development: In addition to the proposed research project, the candidate will participate in weekly lab meetings and attend seminars addressing scientific and ethical issues involved in animal and human research. A steering committee will meet with the candidate on a regular basis to supervise his progress.

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Data collected will serve as the basis for future quantitative trait locus analysis, targeted and random mutagenesis as well as anatomic and pharmacological investigation. These studies have the potential to provide new and important insights into the pathogenesis and treatment of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OLFACTORY SCHIZOPHRENI

ERPS

&

FRONTO-LIMBIC

PATHOLOGY

IN

Principal Investigator & Institution: Turetsky, Bruce I. Associate Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract) There is growing evidence to suggest that schizophrenia is a neurobehavioral disorder that affects fronto-temporal areas of the brain. A relatively neglected, but in many ways ideal, probe of the frontolimbic system is olfaction. Olfactory processing is mediated by limbic structures implicated in the pathophysiology of schizophrenia. The olfactory system is unique in that only one synapse lies between peripheral receptors and sensory cortex, providing one of the most direct links between the brain and environment. Patients with schizophrenia have significant olfactory deficits. Unlike the relatively static pattern of cognitive deficits seen over the course of illness, though, olfactory abilities appear to decline in linear fashion, independent of normal aging and gender effects. However, family studies have also demonstrated marked deficits in olfactory identification in unaffected first-degree relatives of schizophrenic probands. It would seem, therefore, that olfactory brain regions are affected by genetically-mediated developmental, as well as neurodegenerative processes. In this project, we will investigate the physiological and anatomical correlates of olfactory dysfunction, longitudinally, in patients, siblings and controls. We will build on prior psychophysical work to include the integrated assessment of psychophysical, psychophysiological and volumetric measures of olfactory structure and function. We will study 40 patients with schizophrenia, 40otherwise healthy siblings and 40 unrelated controls. Physiological data will be acquired using a unique and previously unavailable assessment tool, unilateral olfactory eventrelated potentials (ERPs), with high density electrode arrays and current source and dipole localization analytic methods. Psychophysical olfactory test data and volumetric MRI measurements of olfactory cortical regions and the olfactory bulbs and tracts will also be obtained. All testing will be repeated after a two-year interval, to assess any differential decline in olfactory abilities in the patietns, attributed to their disease state. The relationship of these olfactory measures to clinical, cognitive and affective symptoms will be investigated. Given the relevance of the neural substrate, we anticipate that a comprehensive assessment of olfactory integrity will illuminate important aspects of the neuropathology of schizophrenia and could be especially helpful in distinguishing developmental from degenerative aspects of the disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OLFACTORY FUNCTION IN SCHIZOPHRENIA: A LIFESPAN ANALYSIS Principal Investigator & Institution: Moberg, Paul J. Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2002; Project Start 07-DEC-2001; Project End 30-NOV-2006

100 Schizophrenia

Summary: (provided by applicant) There is growing evidence to suggest that schizophrenia is a neurobehavioral disorder that affects fronto-temporal areas of the brain. A relatively neglected, but in many ways ideal, probe of the fronto-limbic system is olfaction. Olfactory processing is mediated by limbic structures implicated in the pathophysiology of schizophrenia. Patients with schizophrenia have significant olfactory deficits, which occur at the first onset of illness. Unlike the relatively static pattern of cognitive deficits seen over the course of illness, though, olfactory abilities appear to decline in a linear fashion, independent of normal aging and gender effects. Family studies, however, have also demonstrated significant deficits in olfactory identification in unaffected first-degree relatives of schizophrenic probands. It would seem, therefore, that olfactory brain regions are affected by genetically-mediated developmental, as well as neurodegenerative processes. Unfortunately, little is known about the developmental course, scope and laterality of olfactory processing deficits in schizophrenia, how these deficits interact, and the manner in which they are moderated by age and gender. In this project, we will investigate the psychophysical correlates of olfactory dysfunction and decline, cross-sectionally, in patients with schizophrenia and healthy controls. A reliable and well-validated psychophysical battery assessing the domains of odor identification, detection threshold sensitivity, memory and intensity/hedonics will be given so differential deficits/decline can be detected. All olfactory measures will be administered unilaterally so laterality effects can be detailed. Neuropsychological and emotional measures will be obtained to investigate interactions with olfactory functions as well as assess whether any decline over the lifespan is specific to olfaction. These measures will be investigated in men and women with schizophrenia (n=96) and healthy controls (n=96) age 18-57, with a sufficient number of individuals in each decade band to yield a cross-sectional estimate of developmental trajectory. In order to assess whether any declines in olfactory function are due to antipsychotic use, cumulative antipsychotic burden will be assessed across decade bands and acute effects will be assessed in a subsample of 48 neuroleptic-naive and previously-medicated patients in a pre- post-medication design using a standard medication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ONLINE SCHIZOPHRENIA

FAMILY

SUPPORT

AND

EDUCATION

FOR

Principal Investigator & Institution: Glynn, Shirley M. Clinical Research Psychologist; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2004 Summary: (Provided by applicant): Participation in family psychoeducational programs for schizophrenia has been found to reduce patient relapse rates and reduce relative distress. Nevertheless, participation rates are often low, reflecting both family impediments to attending sessions (e.g. transportation difficulties, time constraints, sensitivity to stigma) and limited professional dissemination of the interventions. To address these difficulties, we are proposing a test of a novel intervention -- a private, secure educational internet website with family-to-family chat capabilities, streaming video mini-lectures on the management of schizophrenia, written materials on topics pertinent to key issues in schizophrenia management, professionally facilitated online discussions of the material, and additional resource links. Recent technological advancements in video conferencing, online communication, and streaming audio/visual presentations, which are increasingly easy to use and gaining widespread

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acceptance among mental health professionals, make the test of this intervention feasible. Equally important, the widespread growth of Internet access makes a test of such an intervention particularly timely. In this developmental project, we propose a randomized trial of 72 relatives of outpatients with schizophrenia to 18 months of customary care alone, or 18 months of customary care with access to the website for the first year. We hypothesize that participation in the website will reduce patient symptom exacerbations by increasing family knowledge of illness management, and reduce family burden by increasing perceived social support. This project involves an extension of our 15 years of work in psychosocial family interventions for schizophrenia into a new dissemination/communication medium. We intend our end product to be a set of empirically-validated low-cost materials which has the potential to be exported to multiple sites, used by families unable to attend face-to-face meetings, and adaptable to other psychiatric disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHENOTYPE DEFINITION IN FAMILIAL SCHIZOPHRENIA Principal Investigator & Institution: Brzustowicz, Linda M. Associate Professor; None; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, NJ 08901 Timing: Fiscal Year 2001; Project Start 01-FEB-1997; Project End 31-JAN-2002 Summary: (Adapted from applicant's abstract): This is a revised application for a Mentored Clinical Scientist Development Award. The purpose of this application is to acquire a theoretical statistical background and training in particular multivariate techniques, to be used to examine psychiatric symptom data in the members of families with a high rate of schizophrenia, to develop alternative classifications of affection status for use in genetic linkage studies. Support through this award would enable the applicant to develop a unique area of expertise within the field of psychiatric genetics, contributing to the long-term career goal of research independence. The contribution of genetic factors to the etiology of schizophrenia is well accepted. Multiple family studies have demonstrated elevated rates of schizophrenia and other psychiatric disorders within the families of schizophrenic probands. Numerous unsuccessful gene linkage studies of schizophrenia have been conducted, using traditional clinical diagnoses to define affection status. One possible factor contributing to these difficulties is that current clinical diagnoses do not accurately correspond to the patterns of symptoms seen in individuals from families with a high rate of schizophrenia. Analysis of the transmission patterns of individual symptom data, not only the overall diagnosis, may lead to a more useful definition of affection status for linkage studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHYSIOLOGY OF VISUAL DYSFUNCTION IN SCHIZOPHRENIA Principal Investigator & Institution: Schroeder, Charles E. Professor; Nathan S. Kline Institute for Psych Res Psychiatric Research Orangeburg, NY 10962 Timing: Fiscal Year 2001; Project Start 01-MAY-2000; Project End 30-APR-2003 Summary: This project will investigate the biological basis of early visual information processing dysfunction in patients with schizophrenia. The visual backward masking (VBM) paradigm has revealed characteristic visual processing deficits in patients with schizophrenia. In schizophrenia, visual targets require longer processing time to "escape" the effects of a subsequent mask stimulus, indicating dysfunction at a basic level of visual processing. This deficit correlates strongly with the severity of persistent negative symptoms in medicated patients. Human visual processing is conducted

102 Schizophrenia

through parallel Parvocellular (P) and Magnocellular (M) pathways. Visual processing deficits in schizophrenia may, therefore, reflect isolated dysfunction in either the M or P system, or a dysfunctional interaction of these systems. We have formed an IRPG group to define neural mechanisms of early visual processing deficits in schizophrenia. There are two projects with interlocking roles. Experiments in humans (this application) will use both behavioral and visual evoked potential (VEP) measures to evaluate the integrity of the M and P pathways in schizophrenia and to define the isolated or interactive roles of the M and P systems in VBM. Experiments in monkeys (the accompanying IRPG application) will pursue direct brain electrical recordings in behaving monkeys in order to evaluate and refine he P- and M-specificity of the stimuli used in the human studies and to describe neural mechanisms of VBM at the level of specific cortical regions, neuronal populations, and cellular processes. Shared resource cores will support stimulus development and data analysis. The stimulus development shared resource will permit development of specific M and P stimuli and support collaborators with expertise in visual psychophysiology, electrophysiology and etiopathology. The data analysis shared resource will permit rapid and flexible application of closely coordinated analysis strategies to data from both species and support a collaborator with unique expertise in integrated human/monkey studies and in the proposed analyses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PLASTICITY SCHIZOPHRENIA

IN

STIMULUS

ENCODING

CIRCUITS

IN

Principal Investigator & Institution: Arnold, Steven E. Assistant Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Perception, attention, working memory, and explicit learning represent a continuum of information processing in which there are major deficits in schizophrenia. These deficits may reflect abnormalities in the molecular and/or physical architecture mediating activity-dependent neural plasticity and are likely to be especially prominent in highly plastic, nodal regions for information processing. One neural system which is known to play important roles in sensory gating phenomena, novelty detection and salience, and verbal and spatial learning is composed of the hippocampus, prefrontal cortex, and nucleus accumbens. At the cellular level early information processing events associated with sensory gating and novelty detection are electrophysiologically mediated, without long lasting molecular or structural changes. With learning of environmental stimuli, there are long lasting modifications of synaptic neurotransmission that are mediated by post-synaptic neuronal changes in gene expression, pre-synaptic axon terminal remodeling, increases in post synaptic densities and dendritic spines, and associated changes in the neuronal cytoskeleton. In turn, these changes modify earlier information processing events. Our central hypothesis is that selective cellular and molecular mechanisms that mediate sensory gating, learning and activity-dependent plasticity are abnormal in schizophrenia. This will be investigated in human postmortem tissues from wellcharacterized subjects with schizophrenia and matched, healthy controls as well as mice that have undergone genetic, behavioral and electrophysiological manipulations relevant to schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POPULATION BASED MAPPING OF SCHIZOPHRENIA GENES Principal Investigator & Institution: Escamilla, Michael A. Associate Professor; Psychiatry; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: (Adapted from the Investigator's Abstract): Linkage disequilibrium (LD) analysis has been shown to be an ideal method for mapping complex disease genes in isolated founder populations. This proposal is designed to collect a sample of patients with schizophrenia who are descended from the founder population of Costa Rica, with the goal of mapping and identifying schizophrenia predisposition genes in this country. The Costa Rican population is ideal for this study, because it is a large population descended over 20 generations from a small group of founders, and predisposition genes for bipolar affective disorder have already been mapped in this country. The investigators' sample consists of Costa Rican patients with multiple hospitalizations for acute schizophrenic episodes and with early age of onset. Diagnostic procedures include a blinded interview by a bilingual psychiatrist, using the DIGS (Diagnostic Interview for Genetic Studies), as well as a family history interview, semi-structured collection of medical records, and a best-estimate process. Genealogic workup is done for each proband to document birthplace of ancestors in the great-grandparents' generation. The initial goal of this study is to recruit 400 schizophrenic probands who meet the following criteria: 1) DSM-IV consensus diagnosis of schizophrenia; 2) two or more psychiatric hospitalizations; 3) ancestry from central valley of Costa Rica; and 4) age of onset prior to age 40. The investigators' hope is to collect information on several subtypes of schizophrenia, such as paranoid, undifferentiated and schizoaffective types. DNA samples will be collected from probands and parents, to allow for haplotype and linkage disequilibrium analyses. In the fifth year, a complete genome screen will be performed at 5 cM intervals, and ancestral haplotype recombination statistics will be used to map schizophrenic predisposition loci. Fine mapping at 1 cM density will be performed across schizophrenic candidate regions identified in this or other populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POPULATION GENETIC STUDIES Principal Investigator & Institution: O'donovan, Michael J. Senior Investigator; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The extensive literature on the epidemiology of schizophrenia has provided decisive support for a major contribution of genetic factors to the aetiology of this disorder. Moreover, several recent lines of evidence reviewed in the main body of the CCNMD application have strongly implicated abnormal myelination as a pathogenic processes underlying schizophrenia. From the above, we postulate that DNA sequence variation within genes encoding proteins involved in myelination alter the structure or expression of these proteins. In this application, we will to test this hypothesis. We will screen genes involved in myelination for DNA sequence variation affecting protein sequence and expression. Genes will be selected based upon the gene expression, neuropathology and neuroimaging studies which form other strands of this center application. We will also screen perigenic and intronic sequences that have been identified by our CCNMD colleagues using bio-informatic approaches as potential regulatory elements. We will test whether the identified

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variants are involved in susceptibility to schizophrenia by looking for association between these variants and schizophrenia in a large ethnically homogeneous large case control association sample of 860 UK Caucasians meeting DSM-IV criteria for schizophrenia and 860 UK Caucasian blood donor controls. All variants showing evidence for significant association in the full case control sample (p <0.001) will be genotyped in 230 UK Caucasian parent-proband trios to ensure the findings are not attributable to stratification. Non-synonymous polymorphisms showing association will be examined for effects on gene expression by our colleagues in this CCNMD (Buxbaum/Project 2) who will look for correlation between genotype gene expression correlation in mRNA extracted from postmortem brains. Additionally, polymorphisms in proximal 5 ? flanking regulatory elements showing evidence for association with schizophrenia will be tested in a reporter gene assay in 3 mammalian cell lines for evidence that the associated variant alters gene expression. Currently, even using advanced bioinformatics, it is not possible to directly identify all DNA sequences involved in regulating gene expression since the location of all such sequences cannot be known for any gene. To ensure comprehensive analysis of our hypothesis, all genes with polymorphisms in genomic sequence corresponding to mRNA will be screened indirectly for polymorphisms altering gene expression by measuring the relative expression levels of the alleles within RNA samples from heterozygous. The research is dedicated to the longer term goal of understanding the mechanisms of schizophrenia and identifying genetically valid subtypes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREFRONTAL D1 AND 5HT1A RECEPTORS IN SCHIZOPHRENIA Principal Investigator & Institution: Abi-Dargham, Anissa; Irving Associate Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 31-MAY-2003 Summary: Several lines of evidence suggest that negative symptoms and working memory impairment in schizophrenia are associated with a dysfunction of the dorsolateral prefrontal cortex (DLPFC). In addition, preclinical and clinical data support the hypothesis that alterations in prefrontal dopamine (DA) and serotonin (5-HT) function may underlie these deficits. Decreased binding of the D1 receptor PET radiotracer, [11C]SCH 23390, has been reported in the prefrontal cortex of male patients with schizophrenia, suggesting that schizophrenia may be associated with a deficiency in D1 receptors in the DLPFC (1). Furthermore, a relationship between this decreased binding and the severity of working memory impairment was observed. We now proposed to extend this important finding to patients of both genders and to first episode/drug naive patients, suing a higher resolution PET camera, a more specific D1 radiotracer, [11C]NNC-112, and a more extensive neuropsychological battery. Groups will include 40 chronic untreated patients, 20 first episode/drug naive patients, and 60 matched healthy controls. In postmortem studies, the most replicated neurochemical finding in the prefrontal cortex of patients with schizophrenia is an increase in serotonin 5- HT1A receptor density. This finding has been observed in 7 out of 7 postmortem studies. The significance of this finding for the pathophysiology of schizophrenia remains clinical symptomatology, and assess the role of previous treatment by including drug naive patients. The second goal of this application is to measure prefrontal 5-HT1A receptor density in the same group of patients with schizophrenia using the PET radiotracer, [11C]WAY- 100635. D1 and 5-HT1A receptor function play a critical role in the modulation of pyramidal cells activity in the DLPFC. Recent postmortem studies revealed that schizophrenia is associated with reduced

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arborization and D1 receptor and increased 5-HT1A receptor density. By measuring D1 and 5-HT1A in the same patients, we will test the hypothesis that both abnormalities coexist and reflect a common alteration in the neurodevelopment of the DLPFC. This study will lead to a better understanding of neurochemical abnormalities in schizophrenia, their relations to symptomatology, and their implications for treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROBING D2 RECEPTOR IN VIVO Principal Investigator & Institution: Hwang, Dah-Ren; Psychiatry; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 15-MAY-2001; Project End 30-APR-2004 Summary: (provided by applicant) The dopamine hypothesis of schizophrenia proposed that at least some of the symptoms of the illness are related to hyperactivity of dopamine transmission. This hypothesis was recently supported by three studies, which demonstrated that the amphetamine-induced reduction in [123I] IBZM or [11C] raclopride binding potential (BP) is elevated in patients with schizophrenia. However, the increased displacement of these D2 antagonists following amphetamine challenge in patients with schizophrenia could result from either a greater increase in synaptic dopamine concentration following amphetamine (i.e. presynaptic factors), from an increased affinity of D2 receptors for dopamine (i.e. postsynaptic factors), or from some combination of both factors. Furthermore, currently available data methods cannot tease apart the respective contributions of these factors, due to the lack of in vivo methods for measuring affinity of D2 receptors for agonists. The present application proposes to develop a probe needed to address this important issue, by developing a D2 receptor agonist as a new PET radiotracer. R-(-)-N-propyl-norapomorphine (NPA) has been chosen as the lead compound and there is preliminary data demonstrating the feasibility of labeling NPA with C-11, thus supporting the potential of [11C]NPA as a PET imaging agent. The radiolabeling procedure requires an innovative radiochemistry approach based on N-propionylation followed by reduction. This application proposes to improve the radiolabeling procedure, to characterize the in vivo binding of [11C]NPA both in rodents (to examine D2-D3 selectivity) and in baboons (to examine relative contribution of high and low agonist affinity sites to in vivo binding, vulnerability to endogenous dopamine, and vulnerability to D1-D2 interactions), and to determine the whole body dosimetry. The overall goal of this application is to develop and validate a method that will make it possible to characterize the pre- or post-synaptic nature of the dysregulation of dopamine transmission revealed by the amphetamine challenge in patients with schizophrenia. If this development is successful, clinical studies using the radiotracer will be proposed in the competitive renewal of this application. In addition to schizophrenia, this radiotracer will provide a useful tool for characterization of dopamine transmission at the D2 receptor in a variety of other conditions, such as ADHD, Parkinson's disease, and substance abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROCESS OF CHANGE IN DRUG ABUSE BY SCHIZOPHRENICS Principal Investigator & Institution: Bellack, Alan S. Professor; Psychiatry; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 20-APR-1999; Project End 31-MAR-2004 Summary: Substance abuse by individuals with schizophrenia has reached epidemic proportions, yet little is known about why they use substances or how they can be

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helped to decrease use. The most widely accepted conceptualization of their substance abuse treatment needs is adapted from Prochaska and DiClemente's Transtheoretical Model (TTM). This model has proven to be quite robust in explaining the process of change in a variety of less impaired substance abusing populations, and several instruments have proven to be reliable and valid for assessing central components of the model. However, the TTM assumes intentional behavior change and full participation in the process of change by the substance abuser. Schizophrenia is marked by a number of symptomatic, neurocognitive, and psychosocial characteristics that would make it difficult for many individuals to successfully perform these complex activities, thereby raising questions about the applicability of the model for this population. Notably, patients with schizophrenia have significant impairments in cognitive function, including attention, memory, and higher level "executive" abilities, that may limit their ability to analyze the pros and cons of substance use, retain a focus on goals for decreased use over time, and form realistic efficacy expectations based on past experience. The disorder also is frequently associated with avolition and anhedonia, which may interfere with the ability to sustain motivation to reduce use. The overall purpose of this project is to examine attitudes about substance use, motivation to reduce use, and the process of change among schizophrenia patients who meet DSM-IV criteria for current Cocaine Dependence or are in Early Remission. The specific focus is the validity of the TTM for this population, and the adequacy of the standard measures of stages and processes of change developed for less impaired groups. Four groups of subjects will be assessed at Baseline, 3-, 6-, 9-, and 12-months: 70 Schizophrenia patients with current Cocaine Dependence, 70 Schizophrenia patients who are in Early Remission from Cocaine, 70 patients with Major Depression and current Cocaine Dependence, and 70 patients with Major Depression who are in Early Remission from Cocaine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSPECTIVE SCHIZOPHRENIA

STUDIES

OF

THE

PATHOGENESIS

OF

Principal Investigator & Institution: Lieberman, Jeffrey A. Professor and Vice Chairman; Psychiatry; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The proposed UNC-CCNMD is a multidisciplinary organization comprised of scientists from the University of North Carolina, Duke, Harvard and the University of Washington directed by Dr. Jeffrey Lieberman, a research psychiatrist whose career has focused on the natural history and neurobiology of schizophrenia. The proposed center consists of 3 projects and 2 cores. The general aim of the UNC-CCNMD is to identify predictors of onset of schizophrenia and the underlying pathology in neurodevelopmental mechanisms that mediate disease vulnerability and expression. Although schizophrenia is believed to be a genetically mediated neurodevelopmental disorder, there is little clinical research demonstrating early abnormalities in brain structure and function and no definitive data identifying risk genes. Moreover, studies have neither identified causal neurobiologic mechanisms nor linked them to the natural history and clinical onset of the disease. Symptoms of schizophrenia emerge predominantly between the ages of 15 and 25 years. Thus, neurodevelopmental events in adolescence may be targets of pathogenic processes that contribute to disease vulnerability and expression. We hypothesize that schizophrenia vulnerability and expression arises from the consequences of dysconnectivity in

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thalamo-limbic-cortical circuits (TLC) due to disrupted differentiation of cortical GABA neurons and the cellular elements with which they modulate local cortical circuitry. These developmental anomalies in GABA interneurons confer vulnerability that when acted on by ontogenetic and environmental events during adolescence trigger dysfunction in TLC circuits and disease expression. 2 clinical and 2 preclinical projects will address this hypothesis. The clinical projects are prospective longitudinal studies of 2 unique high-risk populations enriched for the development of schizophrenia: adolescents and young adults with prodromal signs (Project 1) and fetuses and neonates of parents with schizophrenia (Project 2). The preclinical project involves a study of cell biological mechanisms of dendritic and axonal development in cortical GABA neurons as well as consequences of mutations in suspected vulnerability genes on this process (Project 3). Thus, the UNC-CCNMD is distinguished by its focus on behavioral and neurobiologic mechanisms that lead to the onset of the disease rather than clinical or pathologic correlates that emerge once it has been diagnosed. Our results will contribute to the identification of diagnostic methods and novel targets for intervention prior to the clinical deterioration that characterizes schizophrenia. In this way the Center will not only advance the neuroscience of schizophrenia but will have an immediate impact on the clinical care and treatment of persons who have and are at risk for schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PSYCHIATRISTS' ADOPTION OF SCHIZOPHRENIA GUIDELINES Principal Investigator & Institution: Steinwachs, Donald M. Professor and Chair; Health Policy and Management; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2002; Project Start 16-MAY-2002; Project End 30-APR-2005 Summary: There is substantial evidence that quality of care for schizophrenia falls short of evidence-based standards derived from the clinical research literature. Studies of nonadherence to guidelines for other conditions have found lack of knowledge, disagreement with the evidence, lack of confidence in ability to implement guidelines effectively, and perceived organizational barriers to their implementation. Reasons for the gap between practice and evidence are not known for schizophrenia. This study will address these issues through a survey of psychiatrists providing direct patient. The aims are: 1) To identify sources of information used by psychiatrists to learn about advances in diagnosis and treatment of psychiatric disorders, 2) To assess the extent of agreement with and adherence to evidence-based guidelines developed in the schizophrenia PORT project, 3) To examine characteristics of psychiatrists, their practices and the external environment associated with readiness to adopt evidence-based guidelines, and 4) To assess the willingness of psychiatrists to participate in educational opportunities to advance their knowledge about and ability to implement guidelines, and their preferences among alternative educational formats. The survey sample will be all psychiatrists in the state of Maryland who are providing direct patient care. Based on survey responses, psychiatrists will be classified by learning style (what methods and resources they are most likely to respond to), readiness to adopt guideline-based practices (following Prochaska and DiClemente's readiness to change model), and clinical interest in schizophrenia. Among those treating or having an interest in schizophrenia, willingness to participate in practice assessments will be determined, as will perceived need for practice tools to overcome barriers to implementation of guideline-based patient care. The findings of this research will be used to design educational intervention trials in Maryland to improve the care of patients with schizophrenia.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PSYCHOPHYSIOLOGY OF SCHIZOPHRENIA Principal Investigator & Institution: Dawson, Michael E. Psychology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001; Project Start 01-JUN-1993; Project End 31-MAY-2003 Summary: (adapted from applicant's abstract): The overall aims of this proposed Research Career Award (K02) are to provide time for the PI to: (1) engage in an interdisciplinary, multi-site program of research on the psychophysiology of schizophrenia and (2) gain additional knowledge and skills in order to better integrate cognitive science, clinical science and neuroscience. More specifically, electrodermal activity and prepulse inhibition (PPI) of the startle eyeblink reflex will be measured in four sets of research projects at three different sites to test predictions derived from a vulnerability-stress model of schizophrenia. The first project investigates whether changes in electrodermal activity can help in the prediction of symptomatic exacerbation/relapse in schizophrenia patients. The second project examines whether schizophrenia PPI deficits are due to dysfunctions in automatic processes, controlled processes, or both. The third project tests whether PPI impairments demonstrated in both passive and attentionally active paradigms also occur in unaffected siblings of schizophrenia patients. The fourth project explores whether abnormalities in brain structures are related to electrodermal and PPI anomalies in schizophrenia patients and schizotypal individuals. In addition to these four research projects, the K02 will permit the PI to receive formal and informal training in techniques and principles of clinical science and neuroscience. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PSYCHOTIC SCHIZOPHRENIA

SYMPTOMS

ON

VISUAL

LEARNING

IN

Principal Investigator & Institution: Holcomb, Henry H. Associate Professor; Psychiatry; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): Most, but not all, persons diagnosed with schizophrenia are able to learn when given systematic, repetitive exposure to a perceptual or motor task. In spite of their normal skill acquisition, persons with thought disorder or reality distortion might not be able to learn by using normal brain physiology. The behavioral and physiological impact of particular symptom profiles on perceptual learning has not been assessed in an experimental design explicitly created to generate similar performance across subjects of differing abilities. This proposal will use event related functional magnetic resonance imaging (fMRI) with normal healthy volunteers and persons with schizophrenia, to determine whether thought disorder (disorganization), or reality distortion (hallucinations plus delusions) specifically influence the physiological response to learning a visual / spatial recognition task. We expect thought disorder to have a significantly greater effect on a schizophrenic's neural activity patterns associated with learning, than reality distortion. Thought disorder is hypothesized to diminish hippocampal and frontal cortex response to training, especially during the encode phase of the trial. We will determine the dynamic roles of particular cortical systems in normal subjects before and after visual recognition training. We will then assess the relative impact of these two symptom profiles, in persons with schizophrenia learning a visual Delayed Match to Sample Task (DMST),

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on the changes found in these regions. We will obtain event related fMRI studies on 30 clinically stable, medicated persons with schizophrenia (15 with thought disorder and 15 with reality distortion) and 25 age and sex matched comparison subjects (normal volunteers) before (first fMRI) and after (second fMRI) visual skill training using a visual DMST. Clinical characteristics, thought disorder (TD) and reality distortion (RD), of the schizophrenic volunteers will be correlated with the physiological (especially encode components of the trial) and behavioral response to visual learning. A third fMRI study after 8 weeks of intensive visual training, will be done on all schizophrenic volunteers following the second study. SZ with predominantly RD may be able to use this extended training to further normalize their task-activated BOLD signal patterns but SZ with predominantly TD may not benefit. Our understanding of how symptom clusters contribute to abnormal physiological activity patterns associated with learning visual recognition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PUPILLARY SCHIZOPHRENIA

RESPONSES

AND

COGNITIVE

AGING

IN

Principal Investigator & Institution: Granholm, Eric L.; Veterans Medical Research Fdn/San Diego Foundation of San Diego San Diego, CA 92161 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: The broad goal of the project is to advance our understanding of the relationship between aging, cognitive impairment and pathophysiology in schizophrenia. Some, but not all, studies support the neurodegenerative hypothesis that the extent of age- related cognitive decline in schizophrenia is greater than the decline found in normal aging. Discrepant findings may be due to differences in the sensitivity of cognitive tasks used (traditional neuropsychological v. information processing or IP). Specific IP tasks are very sensitive to schizophrenia in younger patients, but aging effects on these tasks have not been studied in older schizophrenia patients. In addition, the findings from IP, brain imaging and psychophysiology studies suggest that the IP resources of patients with schizophrenia are easily overloaded, possibly due to abnormalities in thalamocortical- reticular brain circuits. Despite current interest in this resource-limitations hypothesis, few schizophrenia studies have attempted to directly measure processing resource overload. Pupillary responses recorded during cognitive tasks can be used to index the extent of resource allocation to the task, which is thought to be mediated by the thalamocortical-reticular circuits that may be involved in the pathophysiology of information overload in schizophrenia. METHODS: In crosssectional and longitudinal studies, a novel, innovative application of pupillography methods will be used to examine the relationship between aging and processing resource limitations indexed on well-studied IP tasks in 100 middle-age and older outpatients with schizophrenia and 100 age-comparable normal comparison participants. AIMS: To determine whether older patients with schizophrenia show the characteristic patterns of impairments found on well-studied IP tasks in younger patients, whether older patients with schizophrenia show abnormal resource limitations on pupillary response measures, and whether the extent of age- related decline on these measures is greater in older patients with schizophrenia than in nonpsychiatric participants. Abnormal age-related decline on these measures would suggest an abnormally accelerated depletion of processing resources with aging in schizophrenia in late life and would support the neurodegeneration hypothesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: QUANTITATIVE STRUCTURAL NEUROIMAGING IN PSYCHOSIS Principal Investigator & Institution: Pearlson, Godfrey D. Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 01-AUG-1988; Project End 30-JUN-2002 Summary: This competing renewal uses quantitative structural MRI to address several fundamental questions regarding the status of morphometric brain alterations in schizophrenia and bipolar affective disorder. The initial grant gathered samples of subjects with schizophrenia, and bipolar disorder as well as healthy control subjects. The current proposal focuses on six major inter-related questions spanning the origin and progression of the brain alterations, whether they are inherited, and their relation to symptom classes and to disease outcome. The major questions concern the following: 1. Which brain changes in schizophrenia are specific to the disorder, as opposed to shared with psychotic bipolar disorder. 2. Is there evidence of neuro-developmental brain changes in schizophrenia, and if so do these differ from those seen in psychotic bipolar disorder. 3. Are brain changes in schizophrenia progressive in some or all patients. 4. Are local brain alterations in schizophrenia related to clinical symptoms. 5. Do local brain alterations in schizophrenia predict social and occupational functioning 5 years later. 6. Do the types of brain changes seen in schizophrenia also occur in some or all of their siblings. There are several strengths to the application. Many of the patients and controls derive from large, well-characterized populations who are participants in ongoing, funded studies of the genetics of schizophrenia and bipolar disorder, or a longitudinal study of normal aging who have already been MRI scanned using identical parameters. These subjects' origin in existing studies helps ensure ease of tracking, subject retention and willingness to be re-MRI scanned. This latter is important as a proportion of patients will be re-scanned 5 years after their initial, existing MRI studies. The investigators have developed state-of-the-art software methods for MRI display and measurement and have expertise in sophisticated, reliable volumetric quantification of many brain regions, including complex cortical areas. This latter ability is important, as preliminary evidence suggests that these same brain regions are disproportionately affected by the disorder. Preliminary data gathered with our new MRI methods show feasibility, and will allow us to further study these cortical areas, providing supportive evidence for a hypothesis of particular reduction of volume in, and disruption of normal asymmetries within heteromodal association cortical gray matter regions in schizophrenia. The overall project will allow a systematic investigation of related multisystem neural deficits. The circumstances of the proposed project are exceptional, in that they offer an opportunity to address a series of important and wide-ranging questions regarding brain abnormalities in schizophrenia and bipolar disorder in an integrated manner. The combination of advantages referred to above will help us to provide answers to hypotheses ranging from the level of inherited abnormalities to that of disease outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF CNS SYNAPTIC TRANSMISSION BY MGLURS Principal Investigator & Institution: Gallagher, Joel P. Professor; Pharmacology and Toxicology; University of Texas Medical Br Galveston 301 University Blvd Galveston, TX 77555 Timing: Fiscal Year 2001; Project Start 01-MAR-1998; Project End 28-FEB-2004 Summary: (Adapted from applicant's abstract): Schizophrenia has been associated with at least two receptor complexes, namely, dopamine and GLU. Theories have been

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developed which invoke hypotheses supporting specific roles for these neurotransmitters in schizophrenia. The overall goal of this application is to investigate and characterize the cellular pharmacology of presynaptic and postsynaptic mGLURs at pharmacologically and electrically isolated native excitatory and inhibitory synapses, while determining their role in an animal model of the GLU-NMDA Receptor Hypofunction (NRF)-hypothesis of schizophrenia. Intracellular recordings from a brain slice preparation of the dorsolateral septal nucleus (DLSN) will be used to investigate the cellular actions of specific mGLUR agonists and antagonists for the three GROUPs of mGLURs (I, II, III). The specific aims of this application will determine: (1) the mechanisms by which an endogenous excitatory transmitter, GLU, regulates its own release via specific presynaptic mGLURs (autoreceptors); (2) how activation of mGLURs on gamma-aminobutyric acid (GABA)ergic terminals regulates the release of GABA via other types of presynaptic mGLURs (heteroreceptors); and (3) how activation of a postsynaptic mGLUR may potentiate the NMDA component of an excitatory synaptic terminal, a component suggested to be depressed in the NRF hypothesis of schizophrenia. Finally, mGLUR mechanisms in control animals will be compared with brains of animal models of schizophrenia from rats treated chronically with PCP, a drug known to induce behavioral changes similar to those seen in patients with schizophrenia. The DLSN slice preparation has been chosen to study since DLSN contains the relevant neuronal circuitry implicated in the GLU-NRF-hypothesis of schizophrenia as proposed by Coyle (Fig. 3) and the DLSN expresses multiple types of mGLURs. Furthermore, no comparable circuitry is available in a more reduced preparation. These experiments will enhance our understanding of the mechanisms of normal synaptic transmission and transmission in an animal model of schizophrenia. Together these data may provide evidence for the use of a novel group of drugs in the treatment of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REHABILITATION, SCHIZOPHRENIA

BRAIN

FUNCTION

AND

EARLY

Principal Investigator & Institution: Keshavan, Matcheri S. Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Therapeutic intervention early in the course of schizophrenia may positively influence the outcome of this illness. The Environmental and Personal Indicators of Course in Schizophrenia (EPICS) treatment program at WPIC has developed a disorder-relevant rehabilitation of cognitive deficits (CET) found to be highly effective in chronic schizophrenic outpatients. Improvements in these cognitive deficits may reflect improved structural and functional integrity of the PFC and related structures. The Center for the Neuroscience of Mental Disorders (CNMD) at WPIC prospectively investigates PFC function in first-episode schizophrenia using structural and functional MRI and MRS. In this study, CNMD and EPICS investigators collaboratively seek to determine the efficacy of CET in ameliorating specific cognitive, structural and functional brain abnormalities in early course schizophrenia. We predict that CET will be more effective than enriched supportive psychotherapy (EST) in differentially improving behavioral and neurobiological dysfunctions in schizophrenia that compromise "executive" cognitive functions, specifically the structural and functional integrity of the PFC. We also predict that a relatively preserved PFC integrity will be associated with a better response to CET. A series of early course schizophrenic patients, stabilized on an atypical antipsychotic will be randomized to CET or EST.

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Cognitive and functional outcomes will be assessed before, and following 1 and 2 years of psychosocial treatment and maintenance antipsychotic treatment. In a subset of these patients, an integrated neuroimaging study will be conducted before and one year after the CET or EST. If successful, the study will provide the first evidence of neurobiological remediation, and possible mechanisms and site(s) of action, for cognitive rehabilitation in early schizophrenia. An understanding of the cerebral correlates of improvement (or lack thereof) in cognition and behavior might guide development of future cognitive rehabilitation strategies for schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESEARCH ETHICS IN SCHIZOPHRENIA Principal Investigator & Institution: Carpenter, William T. Professor and Director; Psychiatry; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-MAY-2004 Summary: The goal of this research is to inform and influence the debate on the ethics of schizophrenia research with empirical data on the central question of informed consent and decisional capacity. Decisional capacity and quality of informed consent will be ascertained in 100 persons participating in schizophrenia research and compared to 100 normal subjects. Impairments will be related to clinical symptoms and cognitive variables in schizophrenia and cognitive variables in normal controls. An informed consent educational process will be tested in a RCT design to determine if observed impairments in schizophrenia subjects can be remediated. The effect of time (2 weeks) and medication status on decisional capacity and informed consent will be determined. Preliminary data are presented which support the following hypotheses: 1. Baseline decisional capacity is reduced in schizophrenia subjects; 2. Good quality informed consent can be obtained, even in schizophrenia subjects with low decisional capacity; 3. In schizophrenia subjects, symptoms are modestly related and cognitive impairments robustly related to decisional capacity; the relation of cognition to decisional capacity will be described in the normal subjects; 4. Decisional capacity will improve to normal levels following an educational informed consent process which addresses specific cognitive liability in contrast to the effect of skills training; and 5. Adequate informed consent will persevere over a 2 week period which includes a medication withdrawal period, and the effect of time and medication status on decisional capacity will be described. The proposed work will provide a major source of scientific data of relevance to the current debate on ethics of schizophrenia research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RISPERIDONE SCHIZOPHRENIA

TREATMENT

OF

ADOLESCENTS

WITH

Principal Investigator & Institution: Armenteros, Jorge L. Psychiatry and Behavioral Scis; University of Miami Box 016159 Miami, FL 33101 Timing: Fiscal Year 2001; Project Start 01-MAR-1998; Project End 28-FEB-2003 Summary: (Adapted from applicant's abstract): Schizophrenia in adolescents is an understudied area and data on its psychopharmacological treatment are scarce. The goal of this First Independent Research Support and Transition (FIRST) Award proposal is to contribute to the development of a rational foundation for the pharmacological treatment of schizophrenia in adolescents. A program for the evaluation of risperidone will be used as a model. Over a 42 month period a minimum of 70 adolescents who meet DSM IV criteria and who need inpatient hospitalization are expected to complete the

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study. The primary aims of the study in this population are (1) to assess the short efficacy of risperidone (2) to assess critically the short-term safety of risperidone. Secondary aims are to examine the relationship of risperidone plasma levels to clinical response and side effects, the relationship of serotonin-2 (5-HT2) binding in blood platelets to risperidone treatment response and the effect of risperidone on cognitive functioning. The importance of this research arises from the pressing need for data about the safety and efficacy of neuroleptics in adolescents with schizophrenia; current treatment of this disorder in adolescents is based largely on extrapolation from research on adults even though research with other medications suggests that the response of adolescents to psychotropics may differ from adults. A double blind, placebo controlled parallel groups design will be used. An initial one week washout will be followed by a one week placebo baseline during which placebo will be administered under singleblind conditions. Patients who meet clinical criteria will be randomly assigned to two independent treatment groups, risperidone or placebo, for a period of four weeks. Treatment response will be measured with the Positive and Negative Syndrome Scale for Schizophrenia as well as other widely used measures sensitive to medication effects. Side effects will be carefully monitored with standard instruments. Plasma levels of risperidone plus 9-OH-risperidone will be monitored throughout the treatment period and related to treatment response and side effects. Pre- and post-treatment serotonin platelet will be assessed and related to treatment response. The study will advance knowledge about the pharmacological treatment of schizophrenia in adolescents (1) it will replace clinical anecdote and case reports about this now widely used medication with systematic data regarding efficacy and safety relative to placebo (2) it will provide needed information about the relationship between plasma levels, treatment response and side-effects and serve as guide for minimal effective therapeutic dose in the future (3) it will explore 5-HT2 platelet binding as a predictor of treatment response to risperidone, which may permit the selection of patients most likely to respond (4) it will examine the effects of risperidone on cognitive function. The study will also provide the basis for other innovative grant proposals by the Principal Investigator to study questions relevant to the treatment of schizophrenia in adolescents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SCHIZOPHRENIA AND ACTIVATION DURING SELECTIVE ATTENDING Principal Investigator & Institution: Taylor, Stephan F. Assistant Professor; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-FEB-1997; Project End 31-JAN-2002 Summary: (Adapted from applicant's abstract): This proposal for a Mentored Clinical Scientist Development Award describes a plan to apply neurobehavioral probes and CBF activation to clinical schizophrenia research. The sponsor, Dr. Rajiv Tandon, will supervise the development of the candidate, Dr. Stephan Taylor. Dr. Tandon will directly train the candidate in clinical schizophrenia research and facilitate his training with Dr. Robert Koeppe, in PET techniques to measure CBF, and with Dr. Sylvan Kornblum, in the cognitive psychology of attention. The training will occur through regular laboratory interactions, during formal coursework through participation in the scientific meetings and during scheduled visits to the laboratories of Drs. Weinberger and Cohen. Knowledge of the mechanism of attentional impairment in schizophrenia may provide important information about the pathophysiology of schizophrenia, since attentional dysfunction may mark vulnerability or trait characteristics of the illness.

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Attentional dysfunction may occur because of localized abnormalities in central regions or systems which allocate selective attention, e.g., prefrontal cortex, or because of more widespread abnormalities, e.g., from a failure or cortical ontogenesis, which could affect the earliest levels of sensory processing. Preliminary functional neuroimaging data indicate an abnormally hyperactive response of the striate and extra-striate cortex to visual stimuli. Experiments analyzing the response to simple visual stimuli in the striate and extra-striate cortex, with and without attentional modulation, will follow-up preliminary results. This experimental design will aim to determine if attentional impairment in schizophrenia is associated with dysfunction at the level of the sensory cortex or with dysfunction in heteromodal association cortex (e.g., prefrontal cortex), or with abnormal activation in both types of cortex. The successful conclusion of the research plan will provide important clues about pathophysiological mechanisms of this severe and debilitating mental illness. As a result of the proposed training plan, Dr. Taylor should be able to independently pursue further questions that require cognitive psychological frameworks to interpret functional neuroimaging results in psychiatric populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SCHIZOPHRENIA AND IMMUNE ACTIVATION Principal Investigator & Institution: Rapaport, Mark H. Chairman; Veterans Medical Research Fdn/San Diego Foundation of San Diego San Diego, CA 92161 Timing: Fiscal Year 2001; Project Start 01-FEB-1997; Project End 31-JAN-2003 Summary: (Adapted from applicant's abstract): Schizophrenia is a common and costly disorder currently defined by descriptive criteria. This type of diagnostic nosology suggests that schizophrenia is most likely a syndrome caused by a variety of different pathophysiological mechanisms rather than a single disease. If schizophrenia is a heterogeneous syndrome, then the equivocal findings of most large etiopathophysiologic studies and the less than robust results of most treatment trials are understandable. The investigators believe that it is imperative to develop reliable and reproducible methods to categorize patients with schizophrenia into biologically relevant subtypes. This application investigates one biological finding, the association between increased serum soluble interleukin-2 receptors (SIL-2Rs) and schizophrenia. This research is an extension of the PI and others' work which has led us to hypothesize that increased serum SIL-2r in schizophrenia are caused by TH1 T-cell activation. TH1 cells are a subset of activated CD4+ helper T-cells which modulate macrophage activation and T-cell mediated immunity. TH1 cells preferentially release the cytokines interleukin-2 (IL-2) and interferon-gamma (INF-g), and IL-2 has been found to stimulate central nervous system dopamine release in animal models. The specific objectives of this application are: 1) to determine whether immune activation seen in a subgroup of schizophrenic patients is due to TH1 cell activation and to investigate the reproducibility of this finding in African-American and Hispanic-American patients; 2) to explore the relationship between this subgroups of patients, clinical measures of psychopathology, and the deficit syndrome model; 3) to determine if there are two forms of immune activation in schizophrenia - one being TH1 cell activation which occurs in a small group of patients and is relatively fixed, and the second, a general nonspecific activation which decreases with the resolution of the psychosis; and 4) to determine whether patients with TH1 activation are more likely to develop spontaneous dyskinesia. These findings would be important because they would allow us to biologically subtype a group of schizophrenic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SCHIZOPHRENIA RESEARCH TRAINING Principal Investigator & Institution: Rieder, Ronald O. Professor of Clinical Psychiatry; Psychiatry; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 01-AUG-1988; Project End 30-JUN-2005 Summary: The overall purpose of this training program is to increase the number of researchers is the area of schizophrenia who have the ability to apply modern techniques of clinical research and incorporate recent developments is neuroscience into their investigations. Training in the disciplines of psychopharmacology, brain imaging, genetics, neuropathology, neuropsychology, molecular neurobiology and epidemiology will be offered by participating faculty actively engaged is schizophrenia-related research. All members have federally-funded research projects. The training will develop research skills by supervised participation is ongoing research, but the trainee will be expected to construct and execute independent projects as well. Didactic work focuses on research design and statistics, and a weekly schizophrenia research seminar reviews current schizophrenia research in all areas. Trainees for the project will primarily be psychiatrists who have completed both their medical school training and 4 years of residency. These trainees have had considerable experience with the diagnosis and treatment of major psychiatric disorders, including schizophrenia, but are likely to lack specific research skills such as developing testable hypotheses, designing a feasible research study acceptable to institutional review boards, and the collection and analysis of standardized research data. In addition to these MD psychiatrists, we expect that we will recruit MD/PhD psychiatrists with a background in basic science research. PhD psychologists, MD neurologists, and PhD biologists with a special interest in schizophrenia. We will adapt the training to suit their background and interests. Eight stipends are requested to support 2 to 3 fellows per year, with most projected to receive some support for a third year of training. This program will be conducted at the New York State Psychiatric Institute (NYSPI), the Creedmoor Psychiatric Center (CPC) in Queens, NY, and the Columbia-Presbyterian campus of the New York Presbyterian Hospital (NYPH), by faculty members of Columbia University at these institutions. With a total of over fifty million dollars annually is federal grants, a research institute with 64 beds (including a 12 bed designated schizophrenia inpatient research unit funded by NYS at NYSPI), another 25 research beds at CPC similarly funded, an NIMH schizophrenia center grant, a Hughes Institute, and 5 other MHCRCs, there exists the research personnel and clinical facilities to continue to execute this proposed training program, which has had excellent success is its training efforts thus far. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SCHIZOPHRENIA SUSCEPTIBILITY GENES Principal Investigator & Institution: Pulver, Ann E. Associate Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Schizophrenia is a frequent and disabling disease of variable expression and unknown etiology, with the majority of cases having an onset before age 45. Both cognitive and emotional dysfunction is observed causing social and occupational impairment. There is convincing evidence that genetic susceptibility plays some role in determining who is affected. Like most common complex diseases, it is likely that mutations at several or many different loci are associated with susceptibility.Since 1983 our group has focused on the epidemiologic and genetic study of schizophrenia and other psychotic disorders. We have developed several clinical

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samples including multiplex pedigrees with schizophrenia. These families have been examined in a series of investigations including linkage studies that have provided evidence for schizophrenia susceptibility loci on chromosomes 8, 13 and 22. Other groups have supported these findings. Individuals in these families were last seen during the period 1989-1995. There are undoubtedly individuals in these families who have since developed schizophrenia.The long term objective of this research is to localize and characterize genes of importance to schizophrenia and to test the hypothesis that some genetically-determined susceptibility is associated with identifiable subgroups of the patients. This application requests support to update the clinical status of individuals in our large, already-established multiplex families, to replenish our supply of DNA from lymphoblastoid cell lines and to conduct state of the art analyses of previously obtained molecular data as well as the new data that will be generated during this grant period (i.e., linkage analysis, linkage disequilibrium studies, and haplotype relative risk studies, using highly polymorphic microsatellite markers and anonymous and candidate SNP's). No support is necessary for this molecular genetics laboratory work. For this initial grant period, laboratory efforts will focus on identifying a susceptibility gene on chromosome 8. Understanding the factors that contribute to schizophrenia may benefit affected individuals and their relatives, Identification of the genes involved may provide new targets for the development of medications to ameliorate these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SCHIZOPHRENIA--RELATED TRAITS Principal Investigator & Institution: Levy, Deborah L. Co-Director; Mc Lean Hospital (Belmont, Ma) Belmont, MA 02478 Timing: Fiscal Year 2001; Project Start 01-JUN-1992; Project End 31-JAN-2003 Summary: (adapted from applicant's abstract): Linkage studies of schizophrenia are hampered by low recurrence risk and a non-Mendelian mode of transmission. Although schizophrenia itself is not highly penetrant, traits that are associated with schizophrenia and that occur at a higher rate in relatives of schizophrenics could serve as useful pointers to the gene(s) for schizophrenia in linkage analysis. Prominent among these associated traits are eye tracking dysfunction, thought disorder, craniofacial dysmorphology, and clinical signs and symptoms associated with the schizophrenia spectrum. The investigators propose to maximize discrimination among genotypes by mapping these more prevalent associated quantitative traits, rather than relying on an all-or-none disease phenotype. Because this strategy bases affectedness on traits that have a higher genetic signal than schizophrenia, the investigators expect that it will increase the power of linkage analysis. The investigators will use both nonparametric and model-dependent methods to test for linkage in a sample comprising 160-208 sibling pair combinations. They will include recent modifications of the Haseman-Elston method as well as lod score analysis. They will use discriminant functions as quantitative phenotypes. They will scan the entire genome for evidence of linkage to individual quantitative phenotypes and combinations of quantitative phenotypes by typing highly informative multi-allele markers, using a map of 10 cM or less. Robust statistical methods for evaluating the results of genomic scans will be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SCHIZOPHRENIC COGNITION--A LONGITUDINAL STUDY Principal Investigator & Institution: Harrow, Martin; Professor; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612

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Timing: Fiscal Year 2001; Project Start 25-SEP-1986; Project End 31-MAR-2003 Summary: The goal of the overall research project is to further our knowledge about schizophrenia and other major psychoses by a prospective longitudinal investigation involving a 15 year followup of a large sample of patients previously studied prospectively at the acute phase and already followed up four times over a ten year period. The following hypotheses about functioning and adjustment over time in schizophrenia, and about the course of positive and negative symptoms, will be addressed. Hypothesis 1: Contrary to recent hypotheses, modern-day schizophrenics still have relatively poor outcomes. Schizophrenics are vulnerable to a sustained disorder and not just to intermittent episodes. Hypothesis 2: Psychosis persists or recurs over time in schizophrenia, and in schizoaffective disorders, but remits in other psychotic disorders. Hypothesis 3: Negative-deficit symptoms persist in schizophrenia, and they identify a subgroup of poor outcome schizophrenics. The research involves a multi-faceted prospective, longitudinal investigation of the course of positive symptoms, negative symptoms, and major components of psychosocial functioning and adjustment over time, using a battery of structured interviews, performance tests, thought disorder measures, and behavioral ratings. A large sample of young, nonchronic schizophrenic and schizoaffective disorders, bipolar affective disorders, unipolar psychotic depressives, and non-psychotic disorders are being assessed longitudinally. Patients have been evaluated at the acute phase, during partial recovery, and are being followed up at various phases during the posthospital period, for delusions, hallucinations, disordered thinking, and negative symptoms. They also are being assessed for neurotic and affective symptoms, rehospitalization, and social and work adjustment. The data are used to evaluate a number of theories about psychoses, thought disorder, negative symptoms, prognostic factors, and to assess the long-term clinical course and level of functioning and adjustment in modern-day schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SENSORY GATING IN SCHIZOPHRENIA: MULTIPLE MEASURES Principal Investigator & Institution: Patterson, Julie V. Neurology; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant) Debilitating deficits in attention, perception, and information processing are prominent features in individuals with schizophrenia.a number of theories suggest that schizophrenia is primarily a disease of disordered cognition, and that deficits in perception and attention are basic to the disorder and its symptoms. A central hypothesis, which has been proposed to account for these deficits is that schizophrenics cannot inhibit or 'gate' sensory input, leading to sensory inundation and an overload of information reaching consciousness. The two most commonly used physiological procedures to assess inhibitory mechanisms and test the gating hypothesis have been the auditory dual-click conditioning-testing (p50) and prepulse inhibition (PPI) of acoustic startle. Schizophrenics show less inhibition (or gating) in their p50 responses to the second stimulus and also have reduced amplitude to the first click. Similarly for PPI, schizophrenics have impaired inhibition of the acoustic startle response when it is preceded by a weaker auditory stimulus, compared to normal controls. These reports support hypotheses of neuronal hyperexcitability possibly related to a defect in inhibitory neuronal pathways, and are consistent with clinical observations of defective attention in schizophrenia. Schizophrenic patients have been characterized clinically by a constellation of positive, negative, and/or disorganized symptoms, but they also report perceptual abnormalities, which could be

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consistent with this kind of filtering deficit. Our laboratory has developed a structured clinical interview to record perceptual anomalies, which reflect sensory inundation and flooding by sensory stimuli. Self- reports of perceptual anomalies have face validity as behavioral exemplars of defective inhibitory mechanisms and sensory gating and would be expected to correlate with the physiological measures of sensory gating. No previous studies have assessed sensory gating as measured by p50and PPI and clinical reports of external sensory gating simultaneously and in the same subjects, and there is currently only one published report concurrently assessing p50 and PPI in human subjects. The purpose of this proposal is to test the meaning and significance of a sensory gating phenomenon in schizophrenia by assessing the correspondence among subjective assessments of perceptual anomalies using our structured clinical interview (siapa), and physiological measures (p50 and PPI) of sensory and sensorimotor inhibition, in normal controls and unmedicated individuals with schizophrenia, and to better characterize the sensory gating construct by relating these measures to neuropsychological function, and clinical measures including symptom profile, length of illness, chronicity, and insight. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOCIAL ANHEDONIA AND SCHIZOPHRENIA PRONENESS Principal Investigator & Institution: Blanchard, Jack J. Associate Professor; Psychology; University of Maryland College Pk Campus College Park, MD 20742 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 31-MAR-2006 Summary: The accurate identification of individuals prone to the development of schizophrenia is necessary for the study of environmental and biological factors that heighten or reduce the probability of developing this disorder. The detection of such vulnerable individuals would also help in prevention efforts. Unfortunately, prior research on the psychometric detection of schizophrenia-proneness has been limited in that what has been detected is more generally psychosis-proneness. Also, there are concerns that prior research is limited by the study of non-minority college students that are not representative of the general population. In this revised application it is proposed that social anhedonia may be a promising indicator of the latent liability for schizophrenia. The role of social anhedonia in the development of schizophrenia will be studied in a randomly ascertained community sample of 18 year-olds who will be selected independently of race, education, or socio-economic status. First, this study will examine the hypothesis that taxometrically identified socially anhedonic individuals are at risk for schizophrenia and schizophrenia-spectrum disorders. Subjects (social anhedonics and controls) will be assessed for schizophrenia and other Axis I disorders, schizophrenia-spectrum personality disorders, and psychotic-like experiences at a base assessment and again at a 3-year follow-up. Second, to understand the range of outcomes in at-risk individuals, other individual difference variables will be assessed that may potentiate the expression of schizophrenia and schizophrenia-spectrum disorders. It is hypothesized that, in vulnerable individuals, reduced social support, elevated trait negative affect, and attentional impairment at the base assessment will increase the probability of clinically diagnosable illnesses and generally poorer functioning at the follow-up assessment. Third, the proposed investigation will examine the hypothesized genetic risk for schizophrenia associated with social anhedonia by directly assessing schizophrenia-related diagnoses and characteristics in the biological parents of social anhedonics and controls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRIATAL AMPA RECEPTOR PATHOLOGY IN SCHIZOPHRENIA Principal Investigator & Institution: Noga, John T. Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2001; Project Start 15-JUL-1998; Project End 30-JUN-2003 Summary: (Adapted from applicant's abstract): Immediate Goals: 75 percent full-time support for five years for Dr. Noga to enhance his academic psychiatry career mentored by outstanding teachers and neuroscientists Dr. Michael Kuhar, (Chief of Neuroscience, Yerkes' Regional Primate Center at Emory) and Dr. Raymond Dingledine, (Chairman, Emory Department of Pharmacology). Their active research interests in and extensive knowledge of molecular aspects of receptor function are highly sought after by Dr. Noga in neuropsychiatric disease research. Dr. Noga will mature scientifically through an intensive and structured sequence of advanced neurobiology coursework and mentored laboratory experience designed to develop fully his potential to become an independent investigator of first-rank in the molecular aspects of neuropsychiatric diseases. This developmental plan will comprise 30 percent didactic and 70 percent research components around the theme of neuroreceptor theory and molecular biological methods, particularly for the continuing study of glutamatergic systems in human neuropsychiatric disease. The didactic portion includes formal coursework, neuroscience seminars, and professional scientific meetings enabling Dr. Noga to become fluent and well grounded in basic principles of molecular neuroscience. Research Project: 70 percent of the program comprises Dr. Noga's specific research focus on the complexity of striatal AMPA receptor pathology at the molecular and biochemical levels in schizophrenia. Drs. Noga, Kuhar, and Dingledine propose to extend and expand upon Dr. Noga's preliminary finding of increased AMPA receptor binding in caudate nucleus in schizophrenia using a new, larger sample of striatal tissue (n=31 schizophrenia; 31 normals, 22 bipolars 15 major depression, and 9 suicides) from the NIMH and Stanley Foundation brain banks. The null hypothesis is that AMPA receptor binding and gene expression are not different in schizophrenia compared with controls. Long-Term Goals: Dr. Noga desires to study etiopathologic and clinicopathologic correlations in neuropsychiatric diseases presenting with psychotic symptoms and cognitive impairment such as schizophrenia, Alzheimer's disease, vascular dementia, and Parkinson's disease in which glutamatergic systems have been increasingly implicated in pathological mechanisms and therapeutics. Dr. Noga's unifying theme in academic psychiatry is to understand further the neurobiological basis for psychotic and cognitive aspects of disorders such as schizophrenia and dementia syndromes, in order to alleviate further their enormous personal, societal, and public health costs. This theme is central to the focus of his developing clinical practice, teaching, and research in geriatric neuropsychiatry at Emory. Dr. Noga will grow from this intensive neuroscience educational and practical experience to become a first-rank clinician scientist able to organize independently the advanced study of molecular structure and function in neuropsychiatric diseases, especially as related to glutamatergic neurotransmission systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE, FUNCTION AND COGNITION IN SCHIZOPHRENIA Principal Investigator & Institution: Buckner, Randy L. Assistant Professor; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2004

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Summary: This proposal is designed to examine the relationships between structural brain abnormalities and both functional activation and cognitive deficits in schizophrenia. Anatomical abnormalities in regions such as the temporal cortex/hippocampus, the anterior cingulate (ACC), the prefrontal cortex (PFC), and the thalamus are a critical biological characteristic of schizophrenia. Many investigators have hypothesized that these structural abnormalities form the anatomical substrates of cognitive deficits in schizophrenia. Further, a growing functional imaging literature demonstrates that patients with schizophrenia exhibit activation disturbances in many of these same cortical regions during tasks that tap a range of cognitive processes, including working memory and long term memory encoding and recall. However, relatively little empirical evidence exists regarding the functional significance of brain structural abnormalities in schizophrenia. Thus, the goal of this project is to more clearly identify the relationship between particular brain structural characteristics and central functional activation and cognitive deficits in individuals with schizophrenia and those at risk for schizophrenia. To accomplish this goal, we will combine our cognitive challenge functional magnetic resonance imaging methods with state of the art structural imaging and high-dimensional brain mapping algorithms (Dr. Csernansky and Dr. Miller; Project 1). This will allow us to test the hypotheses that in schizophrenia: 1) deficits in both working memory and long term memory arise from a disturbance in a set of functionally and structurally interconnected brain regions that normally work together to support a range of cognitive processes; 2) structural disturbances in these regions are related to disturbances in the ability to functionally activate these areas during cognitive challenge; 2) deficits in these brain structures arise as a result of a neurodevelopmental process (Dr. Selemon, Project 3), and are thus present in individuals genetically at risk for schizophrenia (Dr. Clonninger, Project 1). The project outlined in this proposal has the potential to provide a unifying framework in which to understand the often seemingly bewildering array of cognitive and functional activation deficits that appear to be present in schizophrenia, and to understand the relationships of these disturbances to abnormalities present at the structural level. Success in this work would represent a significant advance in both our theoretical and empirical efforts, and could provide the groundwork for the development of powerful probes for detecting bio-behavioral and genetic risk markers for the development of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUICIDAL BEHAVIOR IN SCHIZOPHRENIA Principal Investigator & Institution: Harkavy Friedman, Jill M.; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 28-FEB-2003 Summary: (Adapted from applicant's abstract): Suicide is the leading cause of premature death in schizophrenia. Ten to fifteen percent of individuals with schizophrenia commit suicide and 3O-4O percent make suicide attempts. Suicidal behavior is devastating to the individual as well as the family and community. The goals of this study are: 1) to describe suicidal behavior in patients with schizophrenia; 2) to compare individuals with schizophrenia who have made a suicide attempt (high-risk group) with individuals with schizophrenia who are nonattempters (low-risk group) with respect to sex, race, clinical state, aggression, impulsivity depression, premorbid functioning demoralization, serotonin measures, family history of suicidal behavior and substance use; and 3) to collect baseline data for a prospective follow-up study in the future. These variables were selected because they have been found to be related to

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suicidal behavior in other patient groups and may be indicators of reduced ability to inhibit suicidal behavior. The variables were also selected because it is feasible to measure them in clinical settings making them accessible for clinical assessment and intervention studies. Information obtained from this study will be used to develop clinical interventions targeted to individuals with schizophrenia. No published study exists where all these major domains have been assessed simultaneously in a group of individuals with schizophrenia who are at high-risk for suicidal behavior in order to determine their relative contributions towards that behavior. This study will be the first phase in a future prospective study of suicidal behavior in schizophrenia. Participants will be inpatients on the Schizophrenia Research Units at the New York State Psychiatric Institute and Creedmoor Psychiatric Center. Standard structured interviews, observational rating scales and self-report measures will be administered to assess suicidal behavior, clinical state, aggression, impulsivity depression, premorbid adjustment, family history and substance use. Genetic and biochemical measures of serotonin are also obtained. Long-term objectives of this research are to identify variables that contribute to suicidal behavior in order to facilitate the development of assessments and interventions specific for individuals with schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THALAMIC PATHOLOGY IN NEUROPSYCHIATRIC DISORDERS Principal Investigator & Institution: Young, Keith A. Assistant Professor; Psychiatry and Behavioral Scis; Texas A&M University Health Science Ctr College Station, TX 77843 Timing: Fiscal Year 2001; Project Start 10-MAY-2000; Project End 30-APR-2004 Summary: (Adapted from applicant's abstract) Several lines of evidence suggest that the thalamus is abnormal in patients with neuropsychiatric disorders. In both schizophrenic and unipolar depressed patients, some structural MRI studies indicate a reduction in the volume of the thalamus. We have recently used stereological cell counting procedures to estimate total neuron number in 5 thalamic nuclei from postmortem schizophrenic and control brains. Our data indicate that numbers of neurons in MD, the anteroventral and anteromedial thalamic nuclei (AV/AM) and the laterodorsal thalamic nucleus (LD) are decreased by more than 20 percent in schizophrenics. In the same brains, neuron number is unaffected in the ventroanterior/ventrolateral nuclear complex (VA/VL) and the reticular (R) nucleus. These data are noteworthy because the MD, AV/AM and LD thalamus provide input to areas of the cortex where functional deficits are consistently observed not only in patients with schizophrenia but also in patients with affective disorders. Since neuron cell counts have never been performed in affective disorder cases, nor in many regions in the thalamus in schizophrenia, it is unclear whether: a) the MD and the anterior nuclei are the only regions in the thalamus that are abnormal in schizophrenia, and b) similar thalamic neuron number reductions are present in affective disorder patients. Using stereological cell counting methods, we propose to measure thalamic neuron number in 9 thalamic nuclei in postmortem brains from schizophrenics, bipolar and unipolar depressed subjects, and age-matched controls. There are two specific aims: Aim 1: Are thalamic neuron number abnormalities in schizophrenia confined to MD, AV/AM and LD nuclei? It is predicted that significant neuron number reductions will be observed in schizophrenics in thalamic nuclei that communicate with prefrontal and limbic cortical regions, specifically, the MD, LD and AV/AM. Aim 2: Are thalamic neuron number abnormalities that characterize schizophrenia also found in affective (mood) disorder patients? Based on observations that there are similar abnormalities in the the function of prefrontal and limbic cortex in both schizophrenia and affective

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disorder, it is predicted that significant neuron number reductions will be observed in the MD, LD and AV/AM of unipolar and bipolar subjects. The study will provide information about whether there are similar or different thalamic abnormalities in schizophrenia and affective disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE GENETICS OF ENDOPHENOTYPES AND SCHIZOPHRENIA Principal Investigator & Institution: Braff, David L. Professor; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2003; Project Start 04-APR-2003; Project End 29-FEB-2008 Summary: (provided by applicant): Neurobiological deficits that serve as informative endophenotype markers have been demonstrated in schizophrenia by a number of different paradigms. Neurophysiological deficits are prominent in P50 event related suppression, prepulse inhibition (PPI) of the startle response, and the antisaccade (AS) task for eye movement dysfunction. Neurocognitive deficits in schizophrenia are revealed by poor performance on the CPT, verbal memory, and tests of working memory. Each of these deficits has also been demonstrated in clinically unaffected relatives of schizophrenia patients, which is evidence that they may reflect part of the heritable risk for the illness. This conclusion is reinforced by findings of deficits in nonpsychotic, unmedicated schizophrenia patients, and schizotypal patients. The null hypothesis is that all 6 deficits reflect a single, common underlying heritable dysfunction in all schizophrenia patients. A test of that hypothesis requires measurement of all of these deficits in the same group of schizophrenia patient probands and their relatives. If they are all manifestations of the same genetic dysfunction (although perhaps expressed in different brain areas), then a multivariate analysis would show that they all contribute to a single dimension in both relatives and schizophrenia patients. An alternative hypothesis is that only one or a small subset of deficits is present in each family, which is consistent with the heterogeneity found in current genetic linkage studies. In that case, the multivariate analysis would show the different measures or subsets of them loading onto different dimensions. Schizophrenia itself is likely to be the result of multiple deficits in any individual. Therefore, the analysis is performed in the same cohort of schizophrenia patient probands and their relatives to take advantage of Mendel's second law, which holds that genetically independent deficits segregate independently. Hence, although schizophrenia patient probands themselves have multiple deficits, if the deficits are caused by different genetic factors, then they will segregate to different groups of relatives. This 7 site collaborative RO1 project will gather a combined total of 420 pedigrees (1680 subjects) and 525 normal subjects over 5 years (each site will contribute 1/7th of these totals). Findings of heritable deficits in specific measures will be used to guide the next generation of studies of the genetics of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE NEURAL CIRCUITRY OF SENSORIMOTOR GATING Principal Investigator & Institution: Hazlett, Erin A. Research Associate Professor; Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2001; Project Start 20-FEB-2001; Project End 31-JAN-2003 Summary: (Adapted from applicant's abstract) Schizophrenia patients frequently describe disturbances suggestive of an impaired ability to gate irrelevant stimuli and

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focus on the relevant stimuli. The prepulse inhibition (PPI) paradigm is a unique psychophysiological tool for studying the initial processing of sensory stimuli by examining the inhibition of the amplitude of the startle eyeblink reflex. Several studies have shown that schizophrenia patients have a dramatic deficit in PPI that occurs when the startle-eliciting stimulus is preceded by a weak stimulus. This finding has been interpreted as a deficit in automatic attentional processing. The applicants have shown that schizophrenia patients exhibit deficits in the attentional modulation of PPI, suggesting an additional controlled processing deficit. In the same study, healthy individuals with greater PPI during an attended prepulse showed greater relative glucose metabolic rates (rGMR) in prefrontal cortex as measured by FDG-PET. Patients showed this relationship only for Brodmann area 10 and had low rGMR in prefrontal cortex. The applicants findings support animal models of deficient sensorimotor gating in schizophrenia. The present pilot study will extend this line of research by further integrating clinical neuroimaging, cognitive, and psychophysiological approaches to understanding attentional abnormalities in schizophrenia. FDG-PET scans will be used to rigorously examine cortical-striatal-thalamic circuitry activation in 12 medicated schizophrenia patients and 12 age-and-sex matched healthy controls. PET scans will be obtained on two separate days one week apart. A standard PPI paradigm including simultaneous psychophysiological measurement of PPI will be employed on both scan days; on one scan day, however, subjects will passively attend to prepulse stimuli and, on the other day, subjects will be instructed to actively attend to particular prepulse stimuli. In addition, structural and event-related functional MRI (fMRl) will be obtained in these same individuals. The fMRI session will involve an attention-to-prepulse task which is similar to that employed in the PET component. This project uses complementary PET and fMRI technology. FDG-PET subtraction will allow an examination of activation in key cortical-striatal-thalamic PPI circuitry based on individually coregistered anatomical MRI region of interest tracings with absolute glucose quantification for specific identification of regional change and 20-slice coverage of whole brain without susceptibility artifacts. fMRl, with intrinsically higher temporal resolution, will allow a parceled examination of brain activation following attended and ignored PPI stimuli separately. Based on animal models, the applicants will test the hypothesis that deficits in automatic and controlled modulation of PPI observed in schizophrenia are associated with specific functional abnormalities in cortical-striatalthalamic circuitry thought to modulate PPI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE PULVINAR IN SCHIZOPHRENIA: A POSTMORTEM STUDY Principal Investigator & Institution: Byne, William M. Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): Recent studies have directed attention to the thalamus in schizophrenia. Many of those studies have focused on the mediodorsal thalamic nucleus because of its connections with the dorsolaeral prefrontal cortex, a brain region consistently implicated in schizophrenia. In addition to the mediodnrsal nucleus, our recent neuroimaging and postmortem histological studies have implicated another thalamic nucleus, the pulvinar, in the diathesis of the disorders. We have found the pulvinar of schizophrenics to be reduced in volume and neuronal number relative to the pulvinar of normal subjects. The pulvinar is a complex nucleus comprising five subnuclei, each with a unique set of connections with other brain regions. Understanding which of its subnuclei are affected in schizophrenia is crucial to

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understanding how schizophrenia impairs communication among various brain regions. We aim to determine which of the subnuclei are characterized by changes in volume and neuronal number. This work must be carried out on postmortem brain material because these subnuclei cannot be seen in brain scans of living subjects. We will use computer-assisted morphometric techniques to measure the volume of each subnucleus in 12 schizophrenic subjects and 12 nonschizophrenic comparison subjects. We will also count the number of neurons in each subnucleus. In addition, will use immunocytochemistry for the calcium binding proteins, parvalbumin and calbindin, to identify neurons that project out of the thalamus to the cortex as opposed to neurons that remain in the thalmaus or project to noncortical regions. We predict that volume and neuron loss will primarily affect the medial subnucleus of the pulvinar because of its connections with other brain regions implicated in schizophrenia, and because it is believed to play a role in a variety of functions that are impaired in schizophrenia including language, selective attention, and saccadic eye movements. Atrophic changes have been described in schizophrenic cortex and hypothesized to be secondary to a lack of excitatory input. Because thalamocortical neurons provide excitatory input to cortex, we hypothesize that the pulvinar of schizophrenics will exhibit a deficit of cortically projecting neurons identified by immunostaining for parvalbumin and calbindin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE STUDY OF EMOTIONAL PROCESSES IN SCHIZOPHRENIA Principal Investigator & Institution: Kohler, Christian G. Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 25-AUG-2000; Project End 31-JUL-2005 Summary: Schizophrenia has traditionally been viewed as an illness with prominent clinical features of psychosis and cognitive dysfunction. However, disturbances in emotional processes, including expression, experience and recognition of emotions, also are common areas of dysfunction in patients with schizophrenia. The purpose of this career development award is to examine emotional processes in relation to the course, symptoms and treatment of schizophrenia, and to develop new instruments to assess emotional processes in schizophrenia. The goals for this application can be broadly separated into two groups: longitudinal assessment of emotional processes in schizophrenia, and development of novel emotional probes that will further delineate emotional dysfunction in schizophrenia. The proposed research would assess emotional processes in schizophrenia and to investigate the interrelationship between emotional processes, psychotic symptoms and cognitive dysfunction. Throughout the early part of the project, expression, experience and recognition of emotion would be evaluated with previously established assessments of affective flattening, mood, and ability to discriminate basic emotions. Novel emotional probes that explore emotional processes in a more fundamental manner would then be developed. In the later stages of the project, schizophrenics would be compared with neuropsychiatric controls, and emotional dysfunction would be treated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSDERMAL SCHIZOPHRENICS

NICOTINE

AND

BUPROPION-SR

IN

Principal Investigator & Institution: Tidey, Jennifer W. Ctr for Alcohol & Addict Studs; Brown University Providence, RI 02912 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-JUL-2005

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Summary: (provided by applicant) There is a high prevalence (60-88 percent) of cigarette smoking among people with schizophrenia, but few smoking cessation interventions have been developed for these patients. Little is known about factors that control smoking in this population or whether interventions that reduce cigarette smoking among the general population are effective in smokers with schizophrenia. Two pharmacotherapies that reduce smoking in the general population are transdermal nicotine and sustained release bupropion. Because of neurochemical dysfunction associated with schizophrenia, these pharmacotherapies may be less effective in smokers with schizophrenia. Clinical and experimental studies on the effects of nicotine replacement in smokers with schizophrenia have yielded equivocal results. Preliminary results from a single treatment study with sustained release bupropion appear promising. The studies in the present proposal are designed to examine under controlled laboratory conditions the effects of transdermal nicotine (0, 21, 42 mg/day) and sustained release bupropion (0, 150, 300 mg/day) on smoking in people with schizophrenia and non-schizophrenic controls. The effects of transdermal nicotine and sustained release bupropion on smoking topography measures, smoking urges, nicotine withdrawal symptoms and affect will be determined. These studies use within-subjects, repeated measures, placebo controlled designs. Together, they will provide muchneeded information on the biological, behavioral and subjective effects of transdermal nicotine and sustained release bupropion on smoking in people with schizophrenia. In turn, this information could contribute to the development of effective smoking cessation treatments for smokers with schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSMISSION SCHIZOPHRENIA

OF

VULNERABILITY

FACTORS

FOR

Principal Investigator & Institution: Nuechterlein, Keith H. Professor; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2002; Project Start 01-SEP-1994; Project End 31-MAR-2007 Summary: This project is designed to test key hypotheses regarding the transmission of measurable nonsymptomatic characteristics of individuals that reflect their predisposition to schizophrenia. Identification of such vulnerability factors and of their interrelationships within and across biological relatives of patients with schizophrenia should allow us to accelerate our progress in detecting the nature of genetic contributions to schizophrenia. The next project phase will primarily focus on the interrelationships among neurocognitive dysfunctions mediated partially by the prefrontal cortex and the medial temporal region, subtle structural anomalies in these two regions, and liability to schizophrenia. Our search for vulnerability factors in neurocognitive functioning and regional brain structure is an attempt to identify intermediate phenotypes or "endophenotypes" that are closer in causal chains to the effects of genes than is schizophrenia itself. Neurocognitive measures will involve the domains of attention, working memory, and consolidation of declarative memory. Morphometric indices from MRI will emphasize subtle volume and gray matter density alterations in the prefrontal cortex and medial temporal structures. Using family data, we will test whether the relationships between these brain structural anomalies, their hypothesized associated neurocognitive deficits, and schizophrenia spectrum disorder across first-degree relatives are consistent with one common underlying familial/genetic factor, or an alternative model in which there is more than one dimension of familial/genetic liability to schizophrenia. These goals will be addressed through data collection with schizophrenic probands and their first-degree relatives as

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well as with demographically matched community controls and their first-degree relatives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TREATMENT OF ALCOHOL USE DISORDERS IN SCHIZOPHRENIA Principal Investigator & Institution: Bennett, Melanie E. Assistant Professor; Psychiatry; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-JUL-2006 Summary: Alcohol use disorders in people with schizophrenia is a serious public health problem that is associated with poor treatment compliance, increased rates of relapse, increased levels of violence, and poor health and life functioning. Schizophrenia is marked by a constellation of symptoms and neurocognitive and psychosocial deficits that make it difficult for patients to engage in the higher level cognitive processes or the sustained, selfdirected behaviors generally required to reduce drinking. What is needed is a comprehensive approach that addresses the many problems that these multiplyhandicapped patients bring to the treatment setting. This application is in response to PA-02-067, Treatment of Alcohol Abuse/Dependent Patients with Psychiatric Comorbidity. The purpose of this project is to develop and pilot test a multifaceted behavioral intervention for treating schizophrenia patients with alcohol use disorders that will incorporate strategies that have been found to be effective in reducing drinking, but tailor them to meet the needs of this population. The intervention will contain several components, including: (1) pre-treatment motivational interviewing to increase engagement and motivation; (2) financial contingency and short-term goal setting at each session; (3) social skills and alcohol refusal skills training; (4) education and coping skills training for managing depression, stress and other forms of negative affect; (5) relapse prevention training; (6) case management aimed at networking with social supports in the participant's environment and linking patients with activities and social networks in the community in order to create a reinforcing, nondrinking environment. We propose to develop preliminary training materials and manuals for each component of the intervention, to implement a pre-pilot trial with 10-12 patients, revise the materials based on findings from the pre-pilot study, and then conduct a carefully monitored pilot trial on 60 patients, comparing patients in the experimental condition to those in a comparison condition. We will then modify materials and program content and procedures based on the results of this initial trial. In addition, we will develop therapist adherence and competence measures and collect preliminary data examining whether therapists can learn to administer the intervention in a reliable and competent manner. Finally, we will examine the relationships among coping skills, neuropsychological variables, and motivation to change alcohol use, and evaluate the use of coping and motivational instruments in a schizophrenia population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TREATMENT OF EARLY ONSET SCHIZOPHRENIA SPECTRUM (TEOSS) Principal Investigator & Institution: Findling, Robert L. Director; Psychiatry; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001; Project Start 19-SEP-2001; Project End 31-AUG-2006 Summary: (Adapted from the Applicant?s Abstract): Objectives: This is one of four identical revised applications of a collaborative R01 proposal being conducted at the University of Washington, Seattle, WA, University of North Carolina (UNC), Chapel

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Hill, NC, Harvard Medical School, Boston, MA and Case Western University, Cleveland, Ohio. The study will examine the long-term effectiveness of three different antipsychotic medications in the treatment of early onset schizophrenia and schizoaffective disorder: risperidone (RIS), olanzapine (OLA), the molindone (MOL) over a one year period. Specific Aims: 1) To determine the efficacy of MOL, RIS, and OLA in reducing psychotic symptoms in youth with schizophrenia and related disorders; 2) To determine the ability to sustain treatment over one year with each of these agents; 3) To examine the effects of treatment on adaptive and neurocognitive functioning; and 4) To examine the safety and tolerability of these agents in the pediatric population, particularly potential effects on neuropyramidal symptoms and weight gain. Research Design: 168 youths (ages 8-19 years) with schizophrenia, schizophreniform disorder or schizoaffective disorder and active psychotic symptoms will be recruited across four sites. Subjects will be randomly assigned to double-blind treatment with one of the three study medications. Standard dosage schedules will be followed, with modifications allowed dependent on the clinical status of subjects. Antipsychotic agents will be cross-tapered over the first week of the study to prevent exacerbation of psychotic symptoms. Symptom ratings and neurocognitive testing will be performed at baseline and repeated at specific intervals. The acute phase of treatment will last 8 weeks. Subjects with clinically significant improvement and without intolerable side effects, will continue maintenance therapy for an additional 44 weeks. Tolerance of the study medications will be systematically monitored with assessments for extrapyramidal side effects and weight gain. Revision of treatment algorithms, reliability testing and data analysis will be coordinated between the four sites. Randomization, preparation of study medications, and overall management of the database will be centralized at UNC. Revisions: To address reviewers concerns, the revised proposal has added a fourth site (Harvard), revised the data management and analysis plan, and adjusted some of the primary outcome measures. Significance: There are very few controlled studies to inform clinical practice for the treatment of youth with psychotic disorders. This study will provide information about the comparative effectiveness of the most commonly used and representative antipsychotic drugs in youth with schizophrenia spectrum disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UNDERSTANDING SCHIZOPHRENIA

PRESCRIPTION

DECISIONS

IN

Principal Investigator & Institution: Kreyenbuhl, Julie A. Psychiatry; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by candidate): This revised application outlines an integrated training and research program for a NIMH K01 Mentored Research Scientist Development Award. My long-term career goal is to develop a program of research focused on medication effectiveness in individuals with serious mental illnesses (SMI) that includes investigating the process and outcomes of medication prescription in typical clinical practice settings, and applying this knowledge to the design of interventions to improve medication prescription decisions. My immediate career goal is to understand the prescription of complex, multi-drug regimens ('polypharmacy') in schizophrenia, focusing specifically on combination antipsychotic regimens in this application. Both clinician-related ('supply-side') and patient and family-related ('demand-side') factors, which are equally important and influential forces affecting medication management decisions will be considered. To achieve these goals, I will

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complete didactic coursework and mentored training activities concurrently with research projects that focus on prescription decision-making, anti-psychotic polypharmacy, and survey methods, as well as the development of interventions to improve prescription decisions in schizophrenia. These activities will be conducted under the guidance of several faculty members from across the country with expertise in mental health services research, psychopharmacology, and both cognitive and clinical psychology. A research plan of four projects is proposed. The first study will use Veterans Administration administrative encounter data to examine the prevalence and correlates of prescription of multiple antipsychotic medications in schizophrenia. This data will permit the evaluation of prescribing patterns across a range of inpatient and outpatient facilities covering a vast geographic area. The second and third studies will be conducted in conjunction with two funded NIMH R01 grants. One project will evaluate the modifiable clinician characteristics/behaviors that influence prescription decisions regarding combined antipsychotic regimens in a nation-wide sample of psychiatrists. The new third research project will examine the willingness of psychiatrists to adopt evidence-based treatments for schizophrenia and their preferences for various formats for educational interventions. The fourth study expands the evaluation of prescription decision-making in schizophrenia by focusing on the roles of both the patient and the family in this process. Understanding the patient, clinician, and treatment setting factors that are correlated with antipsychotic polypharmacy, while also uncovering aspects of the cognitive processes involved in prescription decision-making that may be modifiable, will inform the subsequent development of an R01 application aimed at improving the process of prescription decision-making for persons with schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGRAM

VISUAL

PLASTICITY

IN

SCHIZOPHRENIA:A

TRAINING

Principal Investigator & Institution: Tagamets, Malle-Anne A. Psychiatry; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2002; Project Start 23-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): A wide range of abnormalities in thought processes characterizes schizophrenia. Loose associations a condition in which associations among cognitive elements do not follow the cohesive structure found in normal individuals, is one of the cardinal features of this syndrome. Functionally, abnormalities have been found in a number of different brain regions in schizophrenia. This suggests that associative thought disorder in schizophrenia might be understood in terms of the interactions among widespread brain regions that mediate associations. This study is aimed at characterizing interactions among brain regions during single-word reading, both in schizophrenia and in normal function. Reading is a task that is known to tap into a wide range of associations. More generally, strings of letters or symbols, depending on their content and arrangement, can have a variety of associations ranging from semantic, phonological and lexical familiarity associated with real words to the purely visual properties in strings of unfamiliar symbols. The goal of this study is to perform an in-depth investigation into how interactions among widespread regions of the brain mediate cognitive associations in schizophrenia by using reading tasks with four different types of strings that vary in their similarity to real words. The study includes 3 segments: 1) Identification of the networks that mediate the tasks in normal volunteers and in patients with schizophrenia; 2) Computation of the interactions among the components of this network and assessment of how they differ between the

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two groups; and 3) Examination of how associations are formed when subjects are familiarized with initially unfamiliar strings. This research will lead to a better understanding of language disorganization in schizophrenia. In conjunction with the research, the educational activities proposed will prepare me to begin independent clinical research using both behavioral and pharmacological manipulations. This combined research and educational approach may enhance drug development with respect to specific interacting elements of the brain, and may promote an improvement in schizophrenia treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VISUAL PROCESSING IN SCHIZOPHRENIA AND SPD Principal Investigator & Institution: O'donnell, Brian F. Assistant Professor; Population Inst/Res/Training; Indiana University Bloomington P.O. Box 1847 Bloomington, IN 47402 Timing: Fiscal Year 2001; Project Start 20-JUL-2001; Project End 30-JUN-2004 Summary: (provided by applicant) The overall aim of this research program is to use psychometric, psychophysical, and electrophysiological techniques to characterize visual processing deficits in schizophrenia spectrum disorders. The model motivating this project proposes that patients with schizophrenia (SZ), but not subjects with schizotypal personality disorder (SPD), will demonstrate disturbances of early stage vision and visual event related potentials (ERP) indicative of retino-geniculate or occipital cortex disturbances. Moreover, these disturbances appear to be most profound for stimuli and tasks requiring high temporal resolution or integration, suggestive of disturbed neural synchronization. Because neural synchronization at high firing frequencies may be essential for spatial and temporal binding or integration, this deficit could account for a broad range of disturbances in SZ. The model also suggests that working memory deficits are a core feature of both schizophrenia and SPD, which reflect disrupted frontal lobe function. Discrimination and delayed match-to-sample tests of short-term visual memory will be used to test these behavioral hypotheses. Event-related potential paradigms will be used to assess sensory processes, EEG synchronization to periodic stimulation, sensory gating, and attention and working memory operations. Computational modeling of neural circuits will be used to assess the role of NMDA and nicotinic dysregulation in producing these deficits. These findings may provide evidence regarding how schizophrenia and SPD differentially affect early stage vision and memory operations; implicate specific visual pathways and circuits which may be differentially sensitive to neurodevelopmental insults; and indicate visual processing deficits can identify core features across schizophrenia spectrum disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: WHITE MATTER ABNORMALITIES IN SCHIZOPHRENIA Principal Investigator & Institution: Lim, Kelvin O. Professor; Nathan S. Kline Institute for Psych Res Psychiatric Research Orangeburg, NY 10962 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-AUG-2001 Summary: (Adapted from applicant's abstract): There is increasing evidence that abnormal cortical connectivity may be an important factor in the pathophysiology of schizophrenia. Supporting data has come from studies of schizophrenia, including findings of reduced correlations between volumes of frontal and temporal gray matter regions, of altered activation patterns from PET studies, and indications of aberrant cell

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migration. While white matter provides the physical foundation for corticocortical and subcortico-cortical connectivity, there has been little in vivo study of white matter, perhaps because of a lack of appropriate tools. Diffusion Tensor Imaging (DTI) is a new magnetic resonance imaging (MRI) method which is uniquely suited to the study of white matter since it can be used to quantify the magnitude and directionality of tissue water mobility (i.e., self-diffusion) in three dimensions. Structures in white matter (WM) such as myelin sheaths, membranes, and white matter tracts can act as barriers to water mobility, causing the water molecules to move farther along paths that are parallel to fibers rather than those that are perpendicular to these fibers. When there is a directional dependence of water mobility, the diffusion is described as being anisotropic. This anisotropy can be quantified and used to assess the micro-structural organization of white matter fibers. Highly regular, organized fibers will have high anisotropy; less well organized fibers will have lower anisotropy measures. In a preliminary study of 10 chronic schizophrenic subjects (SZ) and 10 normal controls (NC), we used DTI to assess white matter anisotropy. The WM fractional anisotropy (FA) was found to be significantly reduced in the schizophrenic subjects which was interpreted as evidence of compromised white matter connectivity. Our preliminary study was among the first in vivo reports of WM microstructure abnormality in schizophrenia. This finding is important in that it uncovered an aspect of brain structure and physiology that had not yet been considered important to the pathophysiology of schizophrenia. Further in vivo studies are now needed to confirm this initial finding and to determine its relationship to clinical expression of the disease. The specific aims of this proposal are to: 1) confirm our initial finding of decreased white matter fractional anisotropy (FA) with a new group of schizophrenic patients and normal controls, 2) Examine the functional correlates of abnormal FA in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WHITE MATTER ABNORMALITIES IN SCHIZOPHRENIA Principal Investigator & Institution: Davis, Kenneth L. Professor and Chairman; Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The proposed Mt. Sinai Conte Center for the Neuroscience of Mental Disorders (CCNMD) is designed to be a highly focused effort to elucidate the role of white matter, oligodendrocytes and myelin in schizophrenia. This proposal is informed by increasing evidence of white matter abnormalities in schizophrenia in a variety of areas of scientific exploration. A failure in connectivity has been demonstrated to have a role in schizophrenia. Myelination and those factors that affect myelination, such as the function of oligodendroglia, are critical processes that could profoundly affect neuronal connectivity, especially given the diffuse distribution of oligodendrocytes and the widespread distribution of brain regions that have been implicated in schizophrenia. Multiple lines of evidence now converge to implicate oligodendroglia and myelin in schizophrenia. Imaging and neurocytochemical evidence, similarities with demyelinating diseases, age-related changes in white matter, myelin-related gene abnormalities, and morphological abnormalities in the oligodendroglia demonstrated in schizophrenic brains, all contribute to a hypothesis that oligodendroglial dysfunction and even death, with subsequent abnormalities in myelin maintenance and repair, contribute to the schizophrenic syndrome (see overview and specific projects for detailed references). A broad set of methodologies and expertise will be brought to bear on the questions the CCNMD will pursue,

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including neuroanatomy, neuroimaging, molecular biology, molecular genetics, neuropsychology, phenomenology, statistics, and data management. The CCNMD is comprised of 4 Cores: Core A: Administrative; Core B: Clinical; Core C: Brain Bank; Core D: Data Management and Statistics. The projects of the CCNMD include: Project 1 which will quantify alterations in both numbers of and spatial distribution of oligodendroglia in the brains of schizophrenic patients, focusing on cortical, thalamic, and predominantly white matter areas. Project 2 is based on microarray findings by the laboratory of Dr. Buxbaum of decreased expression of 6 myelin-related genes in the dorsolateral prefrontal cortex of a subgroup of relatively treatment refractory patients. Project 3 examines genes involved in myelination for DNA sequence variation affecting protein sequence and expression in order to assess the possibility that some of these variants are involved in determining susceptibility to schizophrenia. Project 4 brings powerful neuroimaging techniques- diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI)- to the study of white matter in schizophrenia. Project 5 applies proton magnetic resonance spectroscopy (1 MRS) to white matter areas in the brains of schizophrenic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WHITE MATTER MYELIN ABNORMALITIES IN SCHIZOPHRENIA Principal Investigator & Institution: Kubicki, Marek; Psychiatry; Harvard University (Medical School) Medical School Campus Boston, MA 02115 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Evidence suggests that a disruption in white matter connectivity in the brain, especially between the frontal and temporal lobes, may partly explain some of the primary symptoms of schizophrenia. Studies using Diffusion Tensor Imaging (DTI) an MR technique sensitive to the white matter fiber tract disruptions, report white matter abnormalities in schizophrenia. It is, however, not clear what neuropathological processes are responsible for the changes observed (i.e., alterations in axonal size/diameter, orientation, or in myelin sheath). The current research proposal focuses on the myelin sheath, and seeks to determine the extent to which myelin content abnormalities in schizophrenia contribute to the loss of the DTI signal. More specifically, the aim of this project is to use Magnetization Transfer Imaging (MTI- technique sensitive to the myelin content of the brain white matter), in combination with already acquired DTI scans, in order to investigate further white matter abnormalities in patients diagnosed with schizophrenia and in normal control subjects. All subjects will undergo MRI scans that include T1W images with and without magnetization transfer pulse. The first step of the image processing will include creation of so-called magnetization transfer ratio (MTR) images that describe signal attributed to myelin content. In the next step, MTR images will be co-registered with already acquired DTI images. Next, Region of Interest (ROI) analysis as well as voxel wise statistical analysis will be performed to detect myelin abnormalities in schizophrenia. For the ROI analysis, mean MTR and MTR histograms will be calculated within brain fiber tracts that have been already delineated and showed abnormalities in the previous DTI studies (including uncinate fasciculus and cingulate fasciculus). For the voxel wise analysis, MTR images as well as DTI images of all subjects, will be warped to the study specific template and subjected to the between group voxel by voxel statistical analysis. In addition, variables such as age, gender, handedness, chronicity, dose and length of medication as well as clinical and selected neuropsychological symptoms will be included in all statistical analyses. Results from this study will allow us to understand

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better white matter alterations in schizophrenia, and add to what we know about connectivity abnormalities in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WORD ENCODING AND RECOGNITION IN SCHIZOPHRENIA Principal Investigator & Institution: Ragland, John D. Assistant Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2005 Summary: (provided by applicant): The goal of the proposed research is to use functional magnetic resonance imaging (fMRI) to test two primary hypotheses about the nature of memory impairments in schizophrenia. The first is that impaired episodic memory in schizophrenia is related to dysfunctional semantic processing, reflected in failure to activate left inferior frontal gyrus (LIFG) during word encoding and recognition. The second hypothesis is that this LIFG dysfunction is primarily due to patients' impaired controlled processing of semantic information, rather than degradation of their semantic memory knowledge or automatic associative processes. The first hypothesis will be tested in experiments 1 & 2. Experiment one will employ the Penn Word Recognition Test (PWRT) which will allow us to replicate previous Positron Emission Tomography findings that impaired episodic memory is related to LIFG dysfunction during word encoding and retrieval. Experiment 2 will employ a shallow/deep word encoding and recognition paradigm that will permit us to test the role of self-generated organizational strategies in the semantic processing difficulties and related LIFG dysfunction in schizophrenia. The second primary hypothesis will be tested in the final two experiments. Experiment 3 will employ a cued semantic verbal fluency paradigm that will allow us to investigate the effect of reducing controlled processing demands on verbal fluency and LIFG function. The final experiment will use an uncued verbal fluency design that will permit a trial-by-trial examination of the effect of controlled versus automatic processing on LIFG function. This series of studies promises to uncover fundamental mechanisms of impaired semantic processing and related episodic memory and LIFG deficits in schizophrenia. Establishing this mechanism will lay the groundwork for future imaging studies and can help provide a rationale for developing cognitive interventions designed to remediate semantic processing and verbal memory deficits in schizophrenia in order to improve functional outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: WORK SCHIZOPHRENIA

REHABILITATION

FOR

OLDER

ADULTS

WITH

Principal Investigator & Institution: Twamley, Elizabeth W. Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2003; Project Start 16-APR-2003; Project End 31-MAR-2008 Summary: (provided by candidate): The primary goal of this five-year training award is to further develop Dr. Elizabeth Twamley's expertise in the following areas: 1) work rehabilitation for individuals with schizophrenia and related disorders; 2) applied neuropsychological research, focusing on the relationships between neuropsychological test performance and everyday functioning, particularly work abilities; and 3) clinical trials research design, methodology, and statistical analysis that can be used to evaluate these relationships. Her overarching career goal is to bridge neuropsychological and interventions research for persons with severe mental illness. The proposed career

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development plan builds on her doctoral training in clinical psychology, her specialty training in clinical neuropsychology, and her research background in neuropsychology and schizophrenia. The proposed training plan will include structured coursework and regular mentoring from experts in the fields of psychiatric work rehabilitation, neuropsychology, geriatric psychiatry, and schizophrenia research. The training plan is complemented by a research project designed to evaluate the efficacy of a work rehabilitation program for middle-aged and older individuals with schizophrenia. Few of these individuals work, yet about 40% desire paid employment or volunteer work. A type of work rehabilitation called Individualized Placement and Support (IPS), which has achieved the status of evidence-based practice for younger individuals, will be prospectively studied for the first time in a randomized controlled trial for middle-aged and older patients. Retrospective data comparing older schizophrenia patients in IPS programs with those in conventional work rehabilitation programs have shown rates of paid employment to be 69% vs. 29%, respectively. The proposed research will address the IPS program's differential effects on work activity, psychiatric symptoms, functional capacity, and quality of life, as well as cognitive, demographic, and clinical predictors of successful work outcomes. The results of the study will be useful not only in establishing the efficacy of IPS for middle-aged and older consumers, but also in illuminating the relationships between neuropsychological performance, work-related functional capacity, and ultimate work outcomes in this population. Together, the training and research plan will allow Dr. Twamley to transition from a postdoctoral research fellow to an independent investigator in the UCSD Department of Psychiatry, and will provide the foundation for a research career focused on cognition and work rehabilitation for individuals with severe psychiatric disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WORKING SCHIZOPHRENIA

AND

LONG-TERM

MEMORY

DEFICITS

IN

Principal Investigator & Institution: Barch, Deanna M. Associate Professor; Psychology; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 01-DEC-1999; Project End 30-NOV-2002 Summary: (adapted from the applicant's abstract): Diverse evidence suggests that deficits in working memory and long-term memory in patients with schizophrenia reflect deficits in at least two putatively distinct cognitive domains. Furthermore, deficits in working memory have typically been linked to an underlying disturbance in prefrontal cortex function, while deficits in long-term memory (i.e., encoding and/or retrieval) have typically been associated with medial temporal/hippocampal deficits. The investigator proposes to test an alternative hypothesis that deficits in both working memory and long-term memory in patients with schizophrenia reflect a single underlying disturbance in prefrontal cortex function. This hypothesis would be tested by a neuroactivation analysis of cognitive tasks using functional magnetic resonance imaging (fMRI) techniques and an event-related neuroimaging design. The investigator proposes to define the distributed patterns of cortical function and dysfunction associated with the performance of both working memory and long-term memory tasks during the same imaging session and the same patients with schizophrenia and in matched normal comparison subjects. This design is novel in that it represents the first functional neuroimaging study in schizophrenia attempting to simultaneously assess multiple cognitive domains and thus could impact strongly the current understanding of the precise nature and mechanisms underlying cognitive impairments associated with schizophrenia. A related specific aim of the proposal would compare the task-

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related lateralized brain activation for working memory and long-term memory tasks using verbal versus non-verbal (non-nameable faces) stimuli in patients with schizophrenia and healthy comparison subjects. Cognitive impairments are increasingly recognized as core features of schizophrenia. Demonstrating that deficits in both working memory and long-term memory in schizophrenia stem from a single underlying disturbance in prefrontal cortex function would both simplify and clarify the conceptualization of cognitive dysfunction in schizophrenia. These studies could also provide the groundwork for the development of powerful new behavioral, as well as neuroimaging, probes of cognitive and neurobiological function in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WORKING SCHIZOPHRENIA

MEMORY

AND

SOCIAL

FUNCTIONING

IN

Principal Investigator & Institution: Cannon, Tyrone D. Staglin Family Professor; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Neurocognitive deficits, particularly in the domain of working memory/executive processes, are thought to play major roles in the development of schizophrenia and associated deficits in role functioning. We propose a novel translational behavioral science strategy probing the functional architecture of working memory and its disturbance in the developmental course of schizophrenia. We aim to identify major functional subdivisions within working memory using behavioral paradigms drawn from cognitive psychology during trial-based functional magnetic resonance imaging (fMRI) studies with healthy subjects and to translate these paradigms into short-term longitudinal fMRI studies of prodromal and first-episode schizophrenic patients to determine the possible differential relevance of disturbances in specific aspects of these systems to the prediction of schizophrenia onset and socialoccupational outcome after the first year of psychosis. Our basic science goals are to improve our understanding of the cognitive neuroscience of working memory, focusing in particular on the proposed distinction between maintenance- versus manipulationrelated processes and on processes associated with relational binding of elements held in working memory. We expect to detect participation of a number of interacting brain systems in these functions, including areas in dorsolateral prefrontal, inferior prefrontal, posterior parietal, and cingulate cortex, but we also expect to observe differential involvement of dorsolateral prefrontal cortex in executive-related working memory processing and in relational binding operations. Our clinical aims are to improve our understanding of the nature, timing of onset, course, and neurophysiologic correlates of working memory disturbances in the pre-onset and early post-onset phases of schizophrenia and to elucidate the roles of these disturbances in the development of impaired social and work functioning in these patients. We expect to detect differential deficits in behavioral and physiologic indicators of executive-related working memory processing and relational binding in the patient groups. Deterioration in these functions over time should predict a higher risk for conversion to schizophrenia among prodromal patients and poorer social and work outcome after the first year of psychosis in first-episode patients. This information will improve theoretical specification of the nature of working memory disturbances in the pathophysiology of schizophrenia and can be applied in future prodromal research to facilitate prediction of schizophrenia and in designing strategies for primary or secondary prevention. This information will also be pertinent to the development of strategies either to prevent or attenuate social

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and occupational impairments in schizophrenia or compensate for them by optimizing on intact skill acquisition systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “schizophrenia” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for schizophrenia in the PubMed Central database: •

A compelling genetic hypothesis for a complex disease: PRODH2 /DGCR6 variation leads to schizophrenia susceptibility. by Chakravarti A. 2002 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122660

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A decrease of reelin expression as a putative vulnerability factor in schizophrenia. by Impagnatiello F, Guidotti AR, Pesold C, Dwivedi Y, Caruncho H, Pisu MG, Uzunov DP, Smalheiser NR, Davis JM, Pandey GN, Pappas GD, Tueting P, Sharma RP, Costa E. 1998 Dec 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28110

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A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes. by Ilani T, Ben-Shachar D, Strous RD, Mazor M, Sheinkman A, Kotler M, Fuchs S. 2001 Jan 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14638

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A subclass of prefrontal [gamma]-aminobutyric acid axon terminals are selectively altered in schizophrenia. by Woo TU, Whitehead RE, Melchitzky DS, Lewis DA. 1998 Apr 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20262

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Abnormal Expression of Two Microtubule-Associated Proteins (MAP2 and MAP5) in Specific Subfields of the Hippocampal Formation in Schizophrenia. by Arnold SE, Lee VM-, Gur RE, Trojanowski JQ. 1991 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53029

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Altered ratios of alternatively spliced long and short [gamma]2 subunit mRNAs of the [gamma]-amino butyrate type A receptor in prefrontal cortex of schizophrenics. by Huntsman MM, Tran BV, Potkin SG, Bunney WE Jr, Jones EG. 1998 Dec 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24576

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Analysis of Expression of Cholecystokinin in Dopamine Cells in the Ventral Mesencephalon of Several Species and in Humans with Schizophrenia. by Schalling

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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M, Friberg K, Seroogy K, Riederer P, Bird E, Schiffmann SN, Mailleux P, Vanderhaeghen J, Kuga S, Goldstein M, Kitahama K, Luppi PH, Jouvet M, Hokfelt T. 1990 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54969 •

Animal models of schizophrenia: a critical review. by Marcotte ER, Pearson DM, Srivastava LK. 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=167198

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Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. by Koro CE, Fedder DO, L'Italien GJ, Weiss SS, Magder LS, Kreyenbuhl J, Revicki DA, Buchanan RW. 2002 Aug 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117636

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Assessment of premorbid function in first-episode schizophrenia: modifications to the Premorbid Adjustment Scale. by van Mastrigt S, Addington J. 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161638

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Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. by Geddes J, Freemantle N, Harrison P, Bebbington P. 2000 Dec 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27538

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Change of dopamine receptor mRNA expression in lymphocyte of schizophrenic patients. by Kwak YT, Koo MS, Choi CH, Sunwoo IN. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29096

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Cognition, schizophrenia, and the atypical antipsychotic drugs. by Meltzer HY, Park S, Kessler R. 1999 Nov 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33933

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Cognitive functioning in first-episode schizophrenia. by Addington J, Addington D. 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161648

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Computed tomography of the brain morphology of patients with first-episode schizophrenic psychosis. by Malla AK, Mittal C, Lee M, Scholten DJ, Assis L, Norman RM. 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161678

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Content and quality of 2000 controlled trials in schizophrenia over 50 years. by Thornley B, Adams C. 1998 Oct 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28699

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Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia. by Cannon TD, Thompson PM, van Erp TG, Toga AW, Poutanen VP, Huttunen M, Lonnqvist J, StanderskjoldNordenstam CG, Narr KL, Khaledy M, Zoumalan CI, Dail R, Kaprio J. 2002 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122501

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Decreased Expression of the Embryonic Form of the Neural Cell Adhesion Molecule in Schizophrenic Brains. by Barbeau D, Liang JJ, Robitaille Y, Quirion R, Srivastava LK. 1995 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42303

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Detection and Sequence Analysis of Borna Disease Virus p24 RNA from Peripheral Blood Mononuclear Cells of Patients with Mood Disorders or Schizophrenia and of Blood Donors. by Iwata Y, Takahashi K, Peng X, Fukuda K, Ohno K, Ogawa T, Gonda K, Mori N, Niwa SI, Shigeta S. 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110530

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Dietary intake of schizophrenic patients in Nithsdale, Scotland: case-control study. by McCreadie R, Macdonald E, Blacklock C, Tilak-Singh D, Wiles D, Halliday J, Paterson J. 1998 Sep 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28668

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Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. by Honey GD, Bullmore ET, Soni W, Varatheesan M, Williams SC, Sharma T. 1999 Nov 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23965

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Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. by Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldman D, Weinberger DR. 2001 Jun 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34453

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Effect of loxapine on peripheral dopamine-like and serotonin receptors in patients with schizophrenia. by Singh AN, Barlas C, Saeedi H, Mishra RK. 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161724

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Effect of social class at birth on risk and presentation of schizophrenia: case-control study. by Mulvany F, O'Callaghan E, Takei N, Byrne M, Fearon P, Larkin C. 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60984

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Effectiveness of clozapinein neuroleptic-resistant schizophrenia:clinical response and plasma concentrations. by Llorca PM, Lancon C, Disdier B, Farisse J, Sapin C, Auquier P. 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149793

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Endocannabinoid signalling in the blood of patients with schizophrenia. by De Marchi N, De Petrocellis L, Orlando P, Daniele F, Fezza F, Di Marzo V. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=194767

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Estrogenic modulation of brain activity:implications for schizophreniaand Parkinson's disease. by Cyr M, Calon F, Morissette M, Di Paolo T. 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149792

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Gene expression analysis in schizophrenia: Reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22. by Mimmack ML, Ryan M, Baba H, Navarro-Ruiz J, Iritani S, Faull RL, McKenna PJ, Jones PB, Arai H, Starkey M, Emson PC, Bahn S. 2002 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123707

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Genetic and physiological data implicating the new human gene G72 and the gene for d-amino acid oxidase in schizophrenia. by Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H, Bougueleret L, Barry C, Tanaka H, La Rosa P, Puech A, Tahri N, Cohen-Akenine A, Delabrosse S, Lissarrague S, Picard FP, Maurice K, Essioux L, Millasseau P, Grel P, Debailleul V, Simon AM, Caterina D,

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Dufaure I, Malekzadeh K, Belova M, Luan JJ, Bouillot M, Sambucy JL, Primas G, Saumier M, Boubkiri N, Martin-Saumier S, Nasroune M, Peixoto H, Delaye A, Pinchot V, Bastucci M, Guillou S, Chevillon M, Sainz-Fuertes R, Meguenni S, Aurich-Costa J, Cherif D, Gimalac A, Van Duijn C, Gauvreau D, Ouelette G, Fortier I, Realson J, Sherbatich T, Riazanskaia N, Rogaev E, Raeymaekers P, Aerssens J, Konings F, Luyten W, Macciardi F, Sham PC, Straub RE, Weinberger DR, Cohen N, Cohen D. 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129739 •

Genetic variation at the 22q11 PRODH2 /DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. by Liu H, Heath SC, Sobin C, Roos JL, Galke BL, Blundell ML, Lenane M, Robertson B, Wijsman EM, Rapoport JL, Gogos JA, Karayiorgou M. 2002 Mar 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122590

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Genetics of schizophrenia: from animal models to clinical studies. by Joober R, Boksa P, Benkelfat C, Rouleau G. 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161676

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Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. by Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD, Haroutunian V, Fienberg AA. 2001 Apr 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31905

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Geographical and seasonal correlation of multiple sclerosis to sporadic schizophrenia. by Fritzsche M. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149400

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Habitual prospective memory in schizophrenia. by Elvevag B, Maylor EA, Gilbert AL. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=184442

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Hippocampal morphometry in schizophrenia by high dimensional brain mapping. by Csernansky JG, Joshi S, Wang L, Haller JW, Gado M, Miller JP, Grenander U, Miller MI. 1998 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21655

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Incidence of schizophrenia in ethnic minorities in London: ecological study into interactions with environment. by Boydell J, van Os J, McKenzie K, Allardyce J, Goel R, McCreadie RG, Murray RM. 2001 Dec 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60671

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Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. by AbiDargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS, Weiss R, Cooper TB, Mann JJ, Van Heertum RL, Gorman JM, Laruelle M. 2000 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16677

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Increased CNS levels of apolipoprotein D in schizophrenic and bipolar subjects: Implications for the pathophysiology of psychiatric disorders. by Thomas EA, Dean B, Pavey G, Sutcliffe JG. 2001 Mar 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31180

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Left with the voices or hearing right? Lateralization of auditory verbal hallucinations in schizophrenia. by Sommer IE, Aleman A, Kahn RS. 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161746

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Levels of the growth-associated protein GAP-43 are selectively increased in association cortices in schizophrenia. by Perrone-Bizzozero NI, Sower AC, Bird ED, Benowitz LI, Ivins KJ, Neve RL. 1996 Nov 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19514

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Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. by Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A, Davis A, Polymeropoulos M, Holik J, Hopkins J, Hoff M, Rosenthal J, Waldo MC, Reimherr F, Wender P, Yaw J, Young DA, Breese CR, Adams C, Patterson D, Adler LE, Kruglyak L, Leonard S, Byerley W. 1997 Jan 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19557

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Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. by Thompson PM, Vidal C, Giedd JN, Gochman P, Blumenthal J, Nicolson R, Toga AW, Rapoport JL. 2001 Sep 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58784

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Online schizophrenia resources. by OReilly M. 2002 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=100904

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Participation in screening for cardiovascular risk by people with schizophrenia or similar mental illnesses: cross sectional study in general practice. by Osborn DP, King MB, Nazareth I. 2003 May 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156006

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Plasma nitrate levels in deficit versus non-deficit forms of schizophrenia. by Suzuki E, Nakaki T, Nakamura M, Miyaoka H. 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165793

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Prenatal and perinatal risk factors for schizophrenia, affective psychosis, and reactive psychosis of early onset: case-control study. by Hultman CM, Sparen P, Takei N, Murray RM, Cnattingius S. 1999 Feb 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27730

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Psychophysical isolation of a motion-processing deficit in schizophrenics and their relatives and its association with impaired smooth pursuit. by Chen Y, Nakayama K, Levy DL, Matthysse S, Holzman PS. 1999 Apr 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16399

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Quality of life in schizophrenia: A grounded theory approach. by Gee L, Pearce E, Jackson M. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=194222

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Randomised controlled trial of intensive cognitive behaviour therapy for patients with chronic schizophrenia. by Tarrier N, Yusupoff L, Kinney C, McCarthy E, Gledhill A, Haddock G, Morris J. 1998 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28621

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Randomised trial of personalised computer based information for patients with schizophrenia. by Jones RB, Atkinson JM, Coia DA, Paterson L, Morton AR, McKenna K, Craig N, Morrison J, Gilmour WH. 2001 Apr 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30562

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Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia. by Karlsson H, Bachmann S, Schroder J, McArthur J, Torrey EF, Yolken RH. 2001 Apr 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31886

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Retroviruses and the pathogenesis of schizophrenia. by Lewis DA. 2001 Apr 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33324

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Role of Cortical N-methyl-D-aspartate Receptors in Auditory Sensory Memory and Mismatch Negativity Generation: Implications for Schizophrenia. by Javitt DC, Steinschneider M, Schroeder CE, Arezzo JC. 1996 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38166

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Schizophrenia and Cognitive Dysmetria: A Positron-Emission Tomography Study of Dysfunctional Prefrontal--Thalamic--Cerebellar Circuitry. by Andreasen NC, O'Leary DS, Cizadlo T, Arndt S, Rezai K, Ponto LL, Watkins GL, Hichwa RD. 1996 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38542

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Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: Evidence from a novel positron emission tomography method. by Breier A, Su TP, Saunders R, Carson RE, Kolachana BS, de Bartolomeis A, Weinberger DR, Weisenfeld N, Malhotra AK, Eckelman WC, Pickar D. 1997 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20129

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Schizophrenia Susceptibility Associated with Interstitial Deletions of Chromosome 22q11. by Karayiorgou M, Morris MA, Morrow B, Shprintzen RJ, Goldberg R, Borrow J, Gos A, Nestadt G, Wolyniec PS, Lasseter VK, Eisen H, Childs B, Kazazian HH, Kucherlapati R, Antonarakis SE, Pulver AE, Housman DE. 1995 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41195

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Schizophrenia: Genetic Tools for Unraveling the Nature of a Complex Disorder. by Propping P, Nothen MM. 1995 Aug 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=file&artid=41193&blobname=[PNASPDFPath]/1995/92-17/pdf/pq007607.pdf

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Schizophrenia: More dopamine, more D2 receptors. by Seeman P, Kapur S. 2000 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33999

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Schizophrenia: people's perceptions in Quebec. by Stip E, Caron J, Lane CJ. 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81020

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Seasonal correlation of sporadic schizophrenia to Ixodes ticks and Lyme borreliosis. by Fritzsche M. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149397

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Selective Loss of Dopamine D3-Type Receptor mRNA Expression In Parietal and Motor Cortices of Patients with Chronic Schizophrenia. by Schmauss C, Haroutunian V, Davis KL, Davidson M. 1993 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47477

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Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. by Zammit S, Allebeck P, Andreasson S, Lundberg I, Lewis G. 2002 Nov 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135490

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Single Photon Emission Computerized Tomography Imaging of AmphetamineInduced Dopamine Release in Drug-Free Schizophrenic Subjects. by Laruelle M, Abi-

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Dargham A, Dyck CH, Gil R, D'Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB. 1996 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38625 •

St. John's wort and schizophrenia. by Lal S, Iskandar H. 2000 Aug 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=80286

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Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study). by Garcia-Cabeza I, Gomez JC, Sacristan JA, Edgell E, Gonzalez de Chavez M. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65550

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Subnucleus-specific loss of neurons in medial thalamus of schizophrenics. by Popken GJ, Bunney WE Jr, Potkin SG, Jones EG. 2000 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16858

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The (CTG)n polymorphism in the NOTCH4 gene is not associated with schizophrenia in Japanese individuals. by Imai K, Harada S, Kawanishi Y, Tachikawa H, Okubo T, Suzuki T. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=32311

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The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia. by Moises HW, Zoega T, Gottesman II. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117774

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The Neuropathology of Schizophrenia: Progress and Interpretation. by Zipursky RB. 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161649

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Three independent lines of evidence suggest retinoids as causal to schizophrenia. by Goodman AB. 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33865

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Time trends in schizophrenia mortality in Stockholm County, Sweden: cohort study. by Osby U, Correia N, Brandt L, Ekbom A, Sparen P. 2000 Aug 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27463

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Use of the Medication Event Monitoring System to estimate medication compliance in patients with schizophrenia. by Diaz E, Levine HB, Sullivan MC, Sernyak MJ, Hawkins KA, Cramer JA, Woods SW. 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=167186

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Viruses, schizophrenia, and bipolar disorder. by Yolken RH, Torrey EF. 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=172852

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What is a recommended treatment for aggression in a patient with schizophrenia? by Gobbi G. 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165796

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Workshop on Schizophrenia. by Barondes SH, Alberts BM, Andreasen NC, Bargmann C, Benes F, Goldman-Rakic P, Gottesman I, Heinemann SF, Jones EG, Kirschner M, Lewis D, Raff M, Roses A, Rubenstein J, Snyder S, Watson SJ, Weinberger DR, Yolken RH. 1997 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34140

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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with schizophrenia, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “schizophrenia” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for schizophrenia (hyperlinks lead to article summaries): •

A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia. Author(s): Hirsch SR, Kissling W, Bauml J, Power A, O'Connor R. Source: The Journal of Clinical Psychiatry. 2002 June; 63(6): 516-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088164&dopt=Abstract

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A brief neuropsychological testing battery for evaluating patients with schizophrenia. Author(s): Savage RM, Jackson WT, Sourathathone CM. Source: Community Mental Health Journal. 2003 June; 39(3): 253-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836806&dopt=Abstract

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A comparison of gynecological variables and service use among older women with and without schizophrenia. Author(s): Lindamer LA, Buse DC, Auslander L, Unutzer J, Bartels SJ, Jeste DV. Source: Psychiatric Services (Washington, D.C.). 2003 June; 54(6): 902-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773608&dopt=Abstract

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A controlled trial of modified electroconvulsive therapy in schizophrenia in a Nigerian teaching hospital. Author(s): Ukpong DI, Makanjuola RO, Morakinyo O. Source: West Afr J Med. 2002 July-September; 21(3): 237-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744577&dopt=Abstract

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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A critique of the methods and conclusions in the patient outcome research team (PORT) report on psychological treatments for schizophrenia. Author(s): Gottdiener WH, Haslam N. Source: J Am Acad Psychoanal Dyn Psychiatry. 2003 Spring; 31(1): 191-208. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722895&dopt=Abstract

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A diffusion tensor imaging study of middle and superior cerebellar peduncle in male patients with schizophrenia. Author(s): Wang F, Sun Z, Du X, Wang X, Cong Z, Zhang H, Zhang D, Hong N. Source: Neuroscience Letters. 2003 September 18; 348(3): 135-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932812&dopt=Abstract

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A GP guide to schizophrenia. Author(s): MacIntyre DJ. Source: Practitioner. 2003 September; 247(1650): 692-4, 696, 698 Passim. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677707&dopt=Abstract

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A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain. Author(s): Bray NJ, Buckland PR, Williams NM, Williams HJ, Norton N, Owen MJ, O'Donovan MC. Source: American Journal of Human Genetics. 2003 July; 73(1): 152-61. Epub 2003 June 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802784&dopt=Abstract

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A highly significant association between a COMT haplotype and schizophrenia. Author(s): Shifman S, Bronstein M, Sternfeld M, Pisante-Shalom A, Lev-Lehman E, Weizman A, Reznik I, Spivak B, Grisaru N, Karp L, Schiffer R, Kotler M, Strous RD, Swartz-Vanetik M, Knobler HY, Shinar E, Beckmann JS, Yakir B, Risch N, Zak NB, Darvasi A. Source: American Journal of Human Genetics. 2002 December; 71(6): 1296-302. Epub 2002 October 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402217&dopt=Abstract

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A longitudinal analysis of the impact of social and clinical characteristics on the costs of schizophrenia treatment. Author(s): Kilian R, Matschinger H, Becker T, Angermeyer MC. Source: Acta Psychiatrica Scandinavica. 2003 May; 107(5): 351-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752031&dopt=Abstract

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A meaningful day: integrating psychosocial rehabilitation into community treatment of schizophrenia. Author(s): Crosse C. Source: The Medical Journal of Australia. 2003 May 5; 178 Suppl: S76-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720528&dopt=Abstract

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A meta-analysis of family intervention studies in schizophrenia. Author(s): Bentsen H. Source: Psychological Medicine. 2003 May; 33(4): 755-6; Author Reply 756-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785477&dopt=Abstract

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A model of smooth pursuit eye movement deficit associated with the schizophrenia phenotype. Author(s): Thaker GK, Avila MT, Hong EL, Medoff DR, Ross DE, Adami HM. Source: Psychophysiology. 2003 March; 40(2): 277-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820868&dopt=Abstract

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A multivariate prediction model of schizophrenia. Author(s): Carter JW, Schulsinger F, Parnas J, Cannon T, Mednick SA. Source: Schizophrenia Bulletin. 2002; 28(4): 649-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795497&dopt=Abstract

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A pilot study comparing motivational interviewing and an educational intervention in patients with schizophrenia and alcohol use disorders. Author(s): Graeber DA, Moyers TB, Griffith G, Guajardo E, Tonigan S. Source: Community Mental Health Journal. 2003 June; 39(3): 189-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836801&dopt=Abstract

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A post hoc analysis of the impact on hostility and agitation of quetiapine and haloperidol among patients with schizophrenia. Author(s): Chengappa KN, Goldstein JM, Greenwood M, John V, Levine J. Source: Clinical Therapeutics. 2003 February; 25(2): 530-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749512&dopt=Abstract

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A random-assignment, double-blind, clinical trial of once- vs twice-daily administration of quetiapine fumarate in patients with schizophrenia or schizoaffective disorder: a pilot study. Author(s): Chengappa KN, Parepally H, Brar JS, Mullen J, Shilling A, Goldstein JM. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 April; 48(3): 187-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728743&dopt=Abstract

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A randomized single-blind pilot study of compensatory strategies in schizophrenia outpatients. Author(s): Velligan DI, Prihoda TJ, Ritch JL, Maples N, Bow-Thomas CC, Dassori A. Source: Schizophrenia Bulletin. 2002; 28(2): 283-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693434&dopt=Abstract

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A Rasch model analysis to test the cross-cultural validity of the EuroQoL-5D in the Schizophrenia Outpatient Health Outcomes Study. Author(s): Prieto L, Novick D, Sacristan JA, Edgell ET, Alonso J; SOHO Study Group. Source: Acta Psychiatrica Scandinavica. Supplementum. 2003; (416): 24-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755851&dopt=Abstract

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A specific deficit in context processing in the unaffected siblings of patients with schizophrenia. Author(s): MacDonald AW 3rd, Pogue-Geile MF, Johnson MK, Carter CS. Source: Archives of General Psychiatry. 2003 January; 60(1): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511173&dopt=Abstract

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A unitary model of schizophrenia: Bleuler's “fragmented phrene” as schizencephaly. Author(s): Andreasen NC. Source: Archives of General Psychiatry. 1999 September; 56(9): 781-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884883&dopt=Abstract

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Abnormal neural synchrony in schizophrenia. Author(s): Spencer KM, Nestor PG, Niznikiewicz MA, Salisbury DF, Shenton ME, McCarley RW. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 August 13; 23(19): 7407-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917376&dopt=Abstract

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Acute psychiatric admission and menstrual cycle phase in women with schizophrenia. Author(s): Bergemann N, Parzer P, Nagl I, Salbach B, Runnebaum B, Mundt Ch, Resch F. Source: Archives of Women's Mental Health. 2002 November; 5(3): 119-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510215&dopt=Abstract

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Adjuvant topiramate administration: a pharmacologic strategy for addressing NMDA receptor hypofunction in schizophrenia. Author(s): Deutsch SI, Schwartz BL, Rosse RB, Mastropaolo J, Marvel CL, Drapalski AL. Source: Clinical Neuropharmacology. 2003 July-August; 26(4): 199-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897641&dopt=Abstract

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Aging and outcome in schizophrenia. Author(s): Jeste DV, Twamley EW, Eyler Zorrilla LT, Golshan S, Patterson TL, Palmer BW. Source: Acta Psychiatrica Scandinavica. 2003 May; 107(5): 336-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752029&dopt=Abstract

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Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling. Author(s): Schlosser R, Gesierich T, Kaufmann B, Vucurevic G, Hunsche S, Gawehn J, Stoeter P. Source: Neuroimage. 2003 July; 19(3): 751-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880804&dopt=Abstract

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Altered transcript expression of NMDA receptor-associated postsynaptic proteins in the thalamus of subjects with schizophrenia. Author(s): Clinton SM, Haroutunian V, Davis KL, Meador-Woodruff JH. Source: The American Journal of Psychiatry. 2003 June; 160(6): 1100-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777268&dopt=Abstract

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Amisulpride: is there a treatment for negative symptoms in schizophrenia patients? Author(s): Storosum JG, Elferink AJ, van Zwieten BJ, van Strik R, Hoogendijk WJ, Broekmans AW. Source: Schizophrenia Bulletin. 2002; 28(2): 193-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693427&dopt=Abstract

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Amisulpride-induced mania in a patient with schizophrenia. Author(s): Murphy BP. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 August; 183: 172. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893676&dopt=Abstract

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Amyloid beta pathology in Alzheimer's disease and schizophrenia. Author(s): Religa D, Laudon H, Styczynska M, Winblad B, Naslund J, Haroutunian V. Source: The American Journal of Psychiatry. 2003 May; 160(5): 867-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727689&dopt=Abstract

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An expanded role for functional neuroimaging in schizophrenia. Author(s): Callicott JH. Source: Current Opinion in Neurobiology. 2003 April; 13(2): 256-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744982&dopt=Abstract

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An FMRI study of episodic encoding and recognition of words in patients with schizophrenia in remission. Author(s): Hofer A, Weiss EM, Golaszewski SM, Siedentopf CM, Brinkhoff C, Kremser C, Felber S, Fleischhacker WW. Source: The American Journal of Psychiatry. 2003 May; 160(5): 911-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727695&dopt=Abstract

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An integrated analysis of acute treatment-emergent extrapyramidal syndrome in patients with schizophrenia during olanzapine clinical trials: comparisons with placebo, haloperidol, risperidone, or clozapine. Author(s): Carlson CD, Cavazzoni PA, Berg PH, Wei H, Beasley CM, Kane JM. Source: The Journal of Clinical Psychiatry. 2003 August; 64(8): 898-906. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927004&dopt=Abstract

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An integrative physiological approach to polyuria and hyponatraemia: a 'double-take' on the diagnosis and therapy in a patient with schizophrenia. Author(s): Edoute Y, Davids MR, Johnston C, Halperin ML. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 July; 96(7): 531-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881596&dopt=Abstract

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An MRI study of temporal lobe abnormalities and negative symptoms in chronic schizophrenia. Author(s): Anderson JE, Wible CG, McCarley RW, Jakab M, Kasai K, Shenton ME. Source: Schizophrenia Research. 2002 December 1; 58(2-3): 123-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409152&dopt=Abstract

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Analysis of the linkage of the Taq1A and Taq1B loci of the dopamine D2 receptor gene with schizophrenia in patients and their siblings. Author(s): Golimbet VE, Aksenova MG, Nosikov VV, Orlova VA, Kaleda VG. Source: Neuroscience and Behavioral Physiology. 2003 March; 33(3): 223-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762588&dopt=Abstract

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Anticipatory planning for research participants with psychotic disorders like schizophrenia. Author(s): Backlar P. Source: Psychology, Public Policy, and Law : an Official Law Review of the University of Arizona College of Law and the University of Miami School of Law. 1998 September; 4(3): 829-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807102&dopt=Abstract

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Antidepressants for the treatment of depression in people with schizophrenia: a systematic review. Author(s): Whitehead C, Moss S, Cardno A, Lewis G. Source: Psychological Medicine. 2003 May; 33(4): 589-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785461&dopt=Abstract

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Antipsychotic dosing and concurrent psychotropic treatments for Medicaid-insured individuals with schizophrenia. Author(s): dosReis S, Zito JM, Buchanan RW, Lehman AF. Source: Schizophrenia Bulletin. 2002; 28(4): 607-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795494&dopt=Abstract

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Antipsychotic drug treatment for elderly people with late-onset schizophrenia. Author(s): Arunpongpaisal S, Ahmed I, Aqeel N, Suchat P. Source: Cochrane Database Syst Rev. 2003; (2): Cd004162. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804499&dopt=Abstract

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Apolipoprotein E genotype and schizophrenia: further negative evidence. Author(s): Saiz PA, Morales B, G-Portilla MP, Alvarez V, Coto E, Fernandez JM, Bousono M, Bobes J. Source: Acta Psychiatrica Scandinavica. 2002 January; 105(1): 71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086229&dopt=Abstract

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Are communication deviance and expressed emotion related to family history of psychiatric disorders in schizophrenia? Author(s): Subotnik KL, Goldstein MJ, Nuechterlein KH, Woo SM, Mintz J. Source: Schizophrenia Bulletin. 2002; 28(4): 719-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795501&dopt=Abstract

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Aripiprazole, an Antipsychotic With a Novel Mechanism of Action, and Risperidone vs Placebo in Patients With Schizophrenia and Schizoaffective Disorder. Author(s): Potkin SG, Saha AR, Kujawa MJ, Carson WH, Ali M, Stock E, Stringfellow J, Ingenito G, Marder SR. Source: Archives of General Psychiatry. 2003 July; 60(7): 681-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860772&dopt=Abstract

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Assessing and managing compulsive scratching in schizophrenia with chronic renal failure. Author(s): Strickland P, Rostron E, Haddad P, Deakin JF, Dursun SM. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 June; 47(5): 484-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085685&dopt=Abstract

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Assessment of four stakeholder groups' preferences concerning outpatient commitment for persons with schizophrenia. Author(s): Swartz MS, Swanson JW, Wagner HR, Hannon MJ, Burns BJ, Shumway M. Source: The American Journal of Psychiatry. 2003 June; 160(6): 1139-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777273&dopt=Abstract

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Association analysis of serotonin 2A receptor gene T102c polymorphism and schizophrenia. Author(s): Czerski PM, Leszczynska-Rodziewicz A, Dmitrzak-Weglarz M, Kapelski P, Godlewski S, Rybakowski J, Hauser J. Source: World J Biol Psychiatry. 2003 April; 4(2): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692777&dopt=Abstract

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Association analysis of the genetic variants of the N-methyl D-aspartate receptor subunit 2b (NR2b) and treatment-refractory schizophrenia in the Chinese. Author(s): Chiu HJ, Wang YC, Liou YJ, Lai IC, Chen JY. Source: Neuropsychobiology. 2003; 47(4): 178-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824739&dopt=Abstract

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Association and linkage disequilibrium between a functional polymorphism of the dopamine-2 receptor gene and schizophrenia in a genetically homogeneous Portuguese population. Author(s): Schindler KM, Pato MT, Dourado A, Macedo A, Azevedo MH, Kennedy JL, Pato CN. Source: Molecular Psychiatry. 2002; 7(9): 1002-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399954&dopt=Abstract

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Association between a novel polymorphism in the promoter region of the neuropeptide Y gene and schizophrenia in humans. Author(s): Itokawa M, Arai M, Kato S, Ogata Y, Furukawa A, Haga S, Ujike H, Sora I, Ikeda K, Yoshikawa T. Source: Neuroscience Letters. 2003 August 28; 347(3): 202-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875921&dopt=Abstract

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Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia. Author(s): Suzuki T, Iwata N, Kitamura Y, Kitajima T, Yamanouchi Y, Ikeda M, Nishiyama T, Kamatani N, Ozaki N. Source: American Journal of Medical Genetics. 2003 August 15; 121B(1): 7-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898568&dopt=Abstract

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Association of serum antibodies to herpes simplex virus 1 with cognitive deficits in individuals with schizophrenia. Author(s): Dickerson FB, Boronow JJ, Stallings C, Origoni AE, Ruslanova I, Yolken RH. Source: Archives of General Psychiatry. 2003 May; 60(5): 466-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742867&dopt=Abstract

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Association study between glutathione S-transferase P1 polymorphism and schizophrenia in the Korean population. Author(s): Pae CU, Kim JJ, Lee SJ, Lee CU, Lee C, Paik IH, Park HR, Yang S, Serretti A. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 May; 27(3): 519-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691788&dopt=Abstract

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Association study between interleukin-1beta gene (IL-1beta) and schizophrenia. Author(s): Yang J, Si T, Ling Y, Ruan Y, Han Y, Wang X, Zhou M, Zhang D, Zhang H, Kong Q, Liu C, Li X, Yu Y, Liu S, Shu L, Ma D, Wei J, Zhang D. Source: Life Sciences. 2003 May 16; 72(26): 3017-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706488&dopt=Abstract

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Asymmetry of the uncinate fasciculus: a post-mortem study of normal subjects and patients with schizophrenia. Author(s): Highley JR, Walker MA, Esiri MM, Crow TJ, Harrison PJ. Source: Cerebral Cortex (New York, N.Y. : 1991). 2002 November; 12(11): 1218-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379610&dopt=Abstract

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Attitudes of patients with schizophrenia toward placebo-controlled clinical trials. Author(s): Hummer M, Holzmeister R, Kemmler G, Eder U, Hofer A, Kurzthaler I, Oehl M, Weiss E, Fleischhacker WW. Source: The Journal of Clinical Psychiatry. 2003 March; 64(3): 277-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716268&dopt=Abstract

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Atypical and conventional antipsychotic drugs in treatment-naive first-episode schizophrenia: a 52-week randomized trial of clozapine vs chlorpromazine. Author(s): Lieberman JA, Phillips M, Gu H, Stroup S, Zhang P, Kong L, Ji Z, Koch G, Hamer RM. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 May; 28(5): 995-1003. Epub 2003 March 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700715&dopt=Abstract

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Augmenting atypical antipsychotics with a cognitive enhancer (donepezil) improves regional brain activity in schizophrenia patients: a pilot double-blind placebo controlled BOLD fMRI study. Author(s): Nahas Z, George MS, Horner MD, Markowitz JS, Li X, Lorberbaum JP, Owens SD, McGurk S, DeVane L, Risch SC. Source: Neurocase : Case Studies in Neuropsychology, Neuropsychiatry, and Behavioural Neurology. 2003 June; 9(3): 274-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925933&dopt=Abstract

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Basal ganglia volumes in first-episode schizophrenia and healthy comparison subjects. Author(s): Gunduz H, Wu H, Ashtari M, Bogerts B, Crandall D, Robinson DG, Alvir J, Lieberman J, Kane J, Bilder R. Source: Biological Psychiatry. 2002 May 15; 51(10): 801-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12007454&dopt=Abstract

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Baseline personality functioning correlates with 6 month outcome in schizophrenia. Author(s): Fassino S, Piero A, Mongelli E, Caviglia ML, Delsedime N, Busso F, Gramaglia C, Abbate Daga G, Leombruni P, Ferrero A. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2003 May; 18(3): 93-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763293&dopt=Abstract

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Behavioral disorganization in schizophrenia during a daily activity: the kitchen behavioral scoring scale. Author(s): Semkovska M, Stip E, Godbout L, Paquet F, Bedard MA. Source: Brain and Cognition. 2002 March-April; 48(2-3): 546-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030505&dopt=Abstract

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Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia. Author(s): Muller N, Riedel M, Scheppach C, Brandstatter B, Sokullu S, Krampe K, Ulmschneider M, Engel RR, Moller HJ, Schwarz MJ. Source: The American Journal of Psychiatry. 2002 June; 159(6): 1029-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042193&dopt=Abstract

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Beneficial effect of donepezil augmentation for the management of comorbid schizophrenia and dementia. Author(s): Stryjer R, Strous RD, Bar F, Werber E, Shaked G, Buhiri Y, Kotler M, Weizman A, Rabey JM. Source: Clinical Neuropharmacology. 2003 January-February; 26(1): 12-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12567159&dopt=Abstract

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Benzodiazepines in schizophrenia: prefrontal cortex atrophy predicts clinical response to alprazolam augmentation. Author(s): Seeley WW, Turetsky N, Reus VI, Wolkowitz OM. Source: World J Biol Psychiatry. 2002 October; 3(4): 221-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516314&dopt=Abstract

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Betel use and schizophrenia. Author(s): Kuruppuarachchi KA, Williams SS. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 May; 182: 455. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724251&dopt=Abstract

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Beyond a beautiful mind: film choices for teaching schizophrenia. Author(s): Rosenstock J. Source: Academic Psychiatry : the Journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry. 2003 Summer; 27(2): 117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824113&dopt=Abstract

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Beyond principal-component analysis of the positive and negative syndrome scale in patients with schizophrenia. Author(s): White L, Opler LA. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 November; 47(9): 891. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500768&dopt=Abstract

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Biological markers and possibilities for predicting therapeutic results in schizophrenia: a methodological contribution. Author(s): Ceskova E, Drybcak P, Lorenc M. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 May; 26(4): 683-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188100&dopt=Abstract

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Bipolar disorder and schizophrenia: distinct illnesses or a continuum? Author(s): Moller HJ. Source: The Journal of Clinical Psychiatry. 2003; 64 Suppl 6: 23-7; Discussion 28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720477&dopt=Abstract

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Birth insult interacts with stress at adulthood to alter dopaminergic function in animal models: possible implications for schizophrenia and other disorders. Author(s): Boksa P, El-Khodor BF. Source: Neuroscience and Biobehavioral Reviews. 2003 January-March; 27(1-2): 91-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732226&dopt=Abstract

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Bizarre delusions and DSM-IV schizophrenia. Author(s): Nakaya M, Kusumoto K, Okada T, Ohmori K. Source: Psychiatry and Clinical Neurosciences. 2002 August; 56(4): 391-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109956&dopt=Abstract

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Bone mineral density and prolactin associations in patients with chronic schizophrenia. Author(s): Abraham G, Halbreich U, Friedman RH, Josiassen RC. Source: Schizophrenia Research. 2003 January 1; 59(1): 17-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413637&dopt=Abstract

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Both processing speed and semantic memory organization predict verbal fluency in schizophrenia. Author(s): Vinogradov S, Kirkland J, Poole JH, Drexler M, Ober BA, Shenaut GK. Source: Schizophrenia Research. 2003 February 1; 59(2-3): 269-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414084&dopt=Abstract

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Boundaries of schizophrenia. Author(s): Adler CM, Strakowski SM. Source: The Psychiatric Clinics of North America. 2003 March; 26(1): 1-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683257&dopt=Abstract

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Brain activation patterns during a selective attention test-a functional MRI study in healthy volunteers and patients with schizophrenia. Author(s): Weiss EM, Golaszewski S, Mottaghy FM, Hofer A, Hausmann A, Kemmler G, Kremser C, Brinkhoff C, Felber SR, Wolfgang Fleischhacker W. Source: Psychiatry Research. 2003 May 1; 123(1): 1-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738340&dopt=Abstract

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Brain donation for schizophrenia research: gift, consent, and meaning. Author(s): Boyes M, Ward P. Source: Journal of Medical Ethics. 2003 June; 29(3): 165-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796437&dopt=Abstract

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Brain imaging as an approach to phenotype characterization for genetic studies of schizophrenia. Author(s): Callicott JH, Weinberger DR. Source: Methods in Molecular Medicine. 2003; 77: 227-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12298372&dopt=Abstract

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Brain morphology in antipsychotic-naive schizophrenia: a study of multiple brain structures. Author(s): Cahn W, Pol HE, Bongers M, Schnack HG, Mandl RC, Van Haren NE, Durston S, Koning H, Van Der Linden JA, Kahn RS. Source: The British Journal of Psychiatry. Supplement. 2002 September; 43: S66-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271803&dopt=Abstract

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Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Author(s): Cahn W, Pol HE, Lems EB, van Haren NE, Schnack HG, van der Linden JA, Schothorst PF, van Engeland H, Kahn RS. Source: Archives of General Psychiatry. 2002 November; 59(11): 1002-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418933&dopt=Abstract

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Brain volume, asymmetry and intellectual impairment in relation to sex in early-onset schizophrenia. Author(s): Collinson SL, Mackay CE, James AC, Quested DJ, Phillips T, Roberts N, Crow TJ. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 August; 183: 114-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893664&dopt=Abstract

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Branded versus generic clozapine for treatment of schizophrenia. Author(s): Makela EH, Cutlip WD, Stevenson JM, Weimer JM, Abdallah ES, Akhtar RS, Aboraya AS, Gunel E. Source: The Annals of Pharmacotherapy. 2003 March; 37(3): 350-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639161&dopt=Abstract

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CAG-repeat length in exon 1 of KCNN3 does not influence risk for schizophrenia or bipolar disorder: a meta-analysis of association studies. Author(s): Glatt SJ, Faraone SV, Tsuang MT. Source: American Journal of Medical Genetics. 2003 August 15; 121B(1): 14-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898569&dopt=Abstract

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Can breast-feeding protect against schizophrenia? Case-control Study. Author(s): Amore M, Balista C, McCreadie RG, Cimmino C, Pisani F, Bevilacqua G, Ferrari G. Source: Biology of the Neonate. 2003; 83(2): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576752&dopt=Abstract

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Can specific deficits in executive functioning explain the negative symptoms of schizophrenia? A review. Author(s): Donohoe G, Robertson IH. Source: Neurocase : Case Studies in Neuropsychology, Neuropsychiatry, and Behavioural Neurology. 2003 April; 9(2): 97-108. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925934&dopt=Abstract

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Can the social environment cause schizophrenia? Author(s): van Os J, McGuffin P. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 April; 182: 291-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668402&dopt=Abstract

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Cannabis-sensitive dopaminergic markers in postmortem central nervous system: changes in schizophrenia. Author(s): Dean B, Bradbury R, Copolov DL. Source: Biological Psychiatry. 2003 April 1; 53(7): 585-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679236&dopt=Abstract

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Care needs of elderly people with schizophrenia. Assessment of an epidemiologically defined cohort in Scotland. Author(s): McNulty SV, Duncan L, Semple M, Jackson GA, Pelosi AJ. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 March; 182: 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611788&dopt=Abstract

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Catechol O-methyltransferase (COMT) mRNA expression in the dorsolateral prefrontal cortex of patients with schizophrenia. Author(s): Matsumoto M, Weickert CS, Beltaifa S, Kolachana B, Chen J, Hyde TM, Herman MM, Weinberger DR, Kleinman JE. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 August; 28(8): 1521-30. Epub 2003 June 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799619&dopt=Abstract

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Category fluency in first-episode schizophrenia. Author(s): Giovannetti T, Goldstein RZ, Schullery M, Barr WB, Bilder RM. Source: Journal of the International Neuropsychological Society : Jins. 2003 March; 9(3): 384-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12666763&dopt=Abstract

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Cellular and humoral immune system in schizophrenia: a conceptual re-evaluation. Author(s): Muller N, Riedel M, Ackenheil M, Schwarz MJ. Source: World J Biol Psychiatry. 2000 October; 1(4): 173-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607212&dopt=Abstract

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Cerebrospinal fluid tau protein levels in schizophrenia. Author(s): Schonknecht P, Hempel A, Hunt A, Seidl U, Volkmann M, Pantel J, Schroder J. Source: European Archives of Psychiatry and Clinical Neuroscience. 2003 April; 253(2): 100-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799749&dopt=Abstract

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Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Author(s): Lindenmayer JP, Czobor P, Volavka J, Citrome L, Sheitman B, McEvoy JP, Cooper TB, Chakos M, Lieberman JA. Source: The American Journal of Psychiatry. 2003 February; 160(2): 290-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562575&dopt=Abstract

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Characteristics of Korean-Americans with schizophrenia: a cross-ethnic comparison with African-Americans, Latinos, and Euro-Americans. Author(s): Bae SW, Brekke JS. Source: Schizophrenia Bulletin. 2002; 28(4): 703-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795500&dopt=Abstract

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Characteristics of trees drawn by patients with paranoid schizophrenia. Author(s): Inadomi H, Tanaka G, Ohta Y. Source: Psychiatry and Clinical Neurosciences. 2003 August; 57(4): 347-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839513&dopt=Abstract

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Childhood antecedents of schizophrenia: developmental sequencing and specificity of problem behavior. Author(s): Roff JD, Fultz JM. Source: Psychological Reports. 2003 June; 92(3 Pt 1): 793-803. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841445&dopt=Abstract

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Childhood central nervous system viral infections and adult schizophrenia. Author(s): Suvisaari J, Mautemps N, Haukka J, Hovi T, Lonnqvist J. Source: The American Journal of Psychiatry. 2003 June; 160(6): 1183-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777282&dopt=Abstract

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Childhood developmental abnormalities in schizophrenia: evidence from high-risk studies. Author(s): Niemi LT, Suvisaari JM, Tuulio-Henriksson A, Lonnqvist JK. Source: Schizophrenia Research. 2003 April 1; 60(2-3): 239-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591587&dopt=Abstract

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Childhood head injury and expression of schizophrenia in multiply affected families. Author(s): AbdelMalik P, Husted J, Chow EW, Bassett AS. Source: Archives of General Psychiatry. 2003 March; 60(3): 231-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622655&dopt=Abstract

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Children, neurological soft signs and schizophrenia. Author(s): Ambelas A. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 April; 182: 362, Author Reply 362-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668414&dopt=Abstract

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Chlorpromazine versus placebo for schizophrenia. Author(s): Thornley B, Rathbone J, Adams CE, Awad G. Source: Cochrane Database Syst Rev. 2003; (2): Cd000284. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804394&dopt=Abstract

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Clinical aspects of substance abuse in persons with schizophrenia. Author(s): Negrete JC. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 February; 48(1): 14-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635559&dopt=Abstract

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Clinical characteristics and risk factors for Kraepelinian subtype of schizophrenia: replication of previous findings and relation to summer birth. Author(s): Bralet MC, Loas G, Yon V, Marechal V. Source: Psychiatry Research. 2002 August 30; 111(2-3): 147-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374632&dopt=Abstract

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Clinical comparability of schizophrenia patients at two public mental health systems. Author(s): Ascher-Svanum H, Zhu B, Stensland MD, Sterling K. Source: Administration and Policy in Mental Health. 2003 January; 30(3): 231-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854678&dopt=Abstract

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Clinical experience with the management of schizophrenia in the general hospital. Author(s): Freudenreich O, Stern TA. Source: Psychosomatics. 2003 January-February; 44(1): 12-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515833&dopt=Abstract

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Clinical outcome of patients with schizophrenia without maintenance treatment in a nonindustrialized society. Author(s): Kurihara T, Kato M, Reverger R, Yagi G. Source: Schizophrenia Bulletin. 2002; 28(3): 515-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645682&dopt=Abstract

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Clinical practice variations in prescribing antipsychotics for patients with schizophrenia. Author(s): Owen RR, Fischer EP, Kirchner JE, Thrush CR, Williams DK, Cuffel BJ, Elliott CE, Booth BM. Source: American Journal of Medical Quality : the Official Journal of the American College of Medical Quality. 2003 July-August; 18(4): 140-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934949&dopt=Abstract

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Clinical use of quetiapine in disease states other than schizophrenia. Author(s): Adityanjee, Schulz SC. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 13: 32-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562145&dopt=Abstract

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Clinical variables and genetic loading for schizophrenia: analysis of published Danish adoption study data. Author(s): Cardno AG, Thomas K, McGuffin P. Source: Schizophrenia Bulletin. 2002; 28(3): 393-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645672&dopt=Abstract

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Clozapine as a first treatment for schizophrenia. Author(s): Woerner MG, Robinson DG, Alvir JM, Sheitman BB, Lieberman JA, Kane JM. Source: The American Journal of Psychiatry. 2003 August; 160(8): 1514-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900316&dopt=Abstract

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Clozapine in treatment-resistant patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder: a naturalistic 48-month follow-up study. Author(s): Ciapparelli A, Dell'Osso L, Bandettini di Poggio A, Carmassi C, Cecconi D, Fenzi M, Chiavacci MC, Bottai M, Ramacciotti CE, Cassano GB. Source: The Journal of Clinical Psychiatry. 2003 April; 64(4): 451-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716249&dopt=Abstract

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Clozapine pharmacokinetics in children and adolescents with childhood-onset schizophrenia. Author(s): Frazier JA, Cohen LG, Jacobsen L, Grothe D, Flood J, Baldessarini RJ, Piscitelli S, Kim GS, Rapoport JL. Source: Journal of Clinical Psychopharmacology. 2003 February; 23(1): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544379&dopt=Abstract

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Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Author(s): Meltzer HY, Alphs L, Green AI, Altamura AC, Anand R, Bertoldi A, Bourgeois M, Chouinard G, Islam MZ, Kane J, Krishnan R, Lindenmayer JP, Potkin S; International Suicide Prevention Trial Study Group. Source: Archives of General Psychiatry. 2003 January; 60(1): 82-91. Erratum In: Arch Gen Psychiatry.2003 July; 60(7): 735. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511175&dopt=Abstract

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Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination. Author(s): Moncrieff J. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 August; 183: 161-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893670&dopt=Abstract

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Clozapine: in prevention of suicide in patients with schizophrenia or schizoaffective disorder. Author(s): Wagstaff A, Perry C. Source: Cns Drugs. 2003; 17(4): 273-80; Discussion 281-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665398&dopt=Abstract

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Clozapine-induced akathisia in children with schizophrenia. Author(s): Gogtay N, Sporn A, Alfaro CL, Mulqueen A, Rapoport JL. Source: Journal of Child and Adolescent Psychopharmacology. 2002 Winter; 12(4): 347-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625995&dopt=Abstract

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Cognition and the inhibitory control of saccades in schizophrenia and Parkinson's disease. Author(s): Crawford TJ, Bennett D, Lekwuwa G, Shaunak S, Deakin JF. Source: Prog Brain Res. 2002; 140: 449-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508608&dopt=Abstract

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Cognitive experimental approaches to investigating impaired cognition in schizophrenia: a paradigm shift. Author(s): MacDonald AW 3rd, Carter CS. Source: J Clin Exp Neuropsychol. 2002 October; 24(7): 873-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647766&dopt=Abstract

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Cognitive function in schizophrenia. Deficits, functional consequences, and future treatment. Author(s): Sharma T, Antonova L. Source: The Psychiatric Clinics of North America. 2003 March; 26(1): 25-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683258&dopt=Abstract

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Cognitive inhibition and thought disorder in schizophrenia. Author(s): Roesch-Ely D, Spitzer M, Weisbrod M. Source: Psychopathology. 2003 January-February; 36(1): 23-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679589&dopt=Abstract

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Cognitive skills group treatment for schizophrenia. Author(s): Ahmed M, Boisvert CM. Source: Psychiatric Services (Washington, D.C.). 2002 November; 53(11): 1476-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407282&dopt=Abstract

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Cognitive-behavioural therapy for schizophrenia: filling the therapeutic vacuum. Author(s): Turkington D, Kingdon D, Chadwick P. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 August; 183: 98-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893660&dopt=Abstract

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Comorbid substance use reduces the health care contacts of suicide attempters with schizophrenia spectrum or mood disorders. Author(s): Suominen KH, Isometsa ET, Lonnqvist JK. Source: Schizophrenia Bulletin. 2002; 28(4): 637-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795496&dopt=Abstract

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Comorbidity of schizophrenia and galactosemia: effective clozapine treatment with weight gain. Author(s): Haasen C, Lambert M, Yagdiran O, Karow A, Krausz M, Naber D. Source: International Clinical Psychopharmacology. 2003 March; 18(2): 113-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598824&dopt=Abstract

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Comparing patterns and costs of schizophrenia care in five European countries: the EPSILON study. European Psychiatric Services: Inputs Linked to Outcome Domains and Needs. Author(s): Knapp M, Chisholm D, Leese M, Amaddeo F, Tansella M, Schene A, Thornicroft G, Vazquez-Barquero JL, Knudsen HC, Becker T; EPSILON. European Psychiatric Services: Inputs Linked to Outcome Domains and Needs. Source: Acta Psychiatrica Scandinavica. 2002 January; 105(1): 42-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086225&dopt=Abstract

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Comparing the sensitivity of generic effectiveness measures with symptom improvement in persons with schizophrenia. Author(s): Pyne JM, Sullivan G, Kaplan R, Williams DK. Source: Medical Care. 2003 February; 41(2): 208-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555049&dopt=Abstract

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Comparison of cognitive performances during a placebo period and an atypical antipsychotic treatment period in schizophrenia: critical examination of confounds. Author(s): Weickert TW, Goldberg TE, Marenco S, Bigelow LB, Egan MF, Weinberger DR. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 August; 28(8): 1491-500. Epub 2003 June 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799617&dopt=Abstract

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Compounded brain volume deficits in schizophrenia-alcoholism comorbidity. Author(s): Mathalon DH, Pfefferbaum A, Lim KO, Rosenbloom MJ, Sullivan EV. Source: Archives of General Psychiatry. 2003 March; 60(3): 245-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622657&dopt=Abstract

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Comprehensive care for people with schizophrenia living in the community. Author(s): Castle DJ, Pantelis C. Source: The Medical Journal of Australia. 2003 May 5; 178 Suppl: S45-6. Erratum In: Med J Aust. 2003 June 2; 178(11): 591. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720520&dopt=Abstract

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Concealed medicines for people with schizophrenia: a U.S. perspective. Author(s): Stroup S, Swartz M, Appelbaum P. Source: Schizophrenia Bulletin. 2002; 28(3): 537-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645685&dopt=Abstract

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Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. Author(s): Miyakawa T, Leiter LM, Gerber DJ, Gainetdinov RR, Sotnikova TD, Zeng H, Caron MG, Tonegawa S. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 July 22; 100(15): 8987-92. Epub 2003 Jul 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851457&dopt=Abstract

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Connecting the “dots” of brain dysfunction in schizophrenia: what does the picture look like? Author(s): Braff DL. Source: Archives of General Psychiatry. 1999 September; 56(9): 791-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884884&dopt=Abstract

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Consensus on early intervention in schizophrenia. Author(s): McGorry PD, Warner R. Source: Schizophrenia Bulletin. 2002; 28(3): 543-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645686&dopt=Abstract

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Context-processing deficits in schizophrenia: diagnostic specificity, 4-week course, and relationships to clinical symptoms. Author(s): Barch DM, Carter CS, MacDonald AW 3rd, Braver TS, Cohen JD. Source: Journal of Abnormal Psychology. 2003 February; 112(1): 132-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653421&dopt=Abstract

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Correlation between performance on the Continuous Performance Test and economic costs in patients with schizophrenia. Author(s): Ko SY, Chen PS, Yang YK, Liao YC, Lee YD, Yeh TL, Yang MJ. Source: Psychiatry and Clinical Neurosciences. 2003 August; 57(4): 373-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839517&dopt=Abstract

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Correlation of plasma neurosteroid levels to the severity of negative symptoms in male patients with schizophrenia. Author(s): Shirayama Y, Hashimoto K, Suzuki Y, Higuchi T. Source: Schizophrenia Research. 2002 November 1; 58(1): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363392&dopt=Abstract

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Cortical coordination dynamics and the disorganization syndrome in schizophrenia. Author(s): Bressler SL. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 July; 28 Suppl 1: S35-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827142&dopt=Abstract

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Cost-effectiveness of the HIT programme in patients with schizophrenia and persistent auditory hallucinations. Author(s): Stant AD, TenVergert EM, Groen H, Jenner JA, Nienhuis FJ, van de Willige G, Wiersma D. Source: Acta Psychiatrica Scandinavica. 2003 May; 107(5): 361-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752032&dopt=Abstract

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Cross-modal semantic priming in schizophrenia. Author(s): Surguladze S, Rossell S, Rabe-Hesketh S, David AS. Source: Journal of the International Neuropsychological Society : Jins. 2002 November; 8(7): 884-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405539&dopt=Abstract

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Debate over Japanese renaming of term for schizophrenia. Author(s): Desapriya EB, Nobutada I. Source: Lancet. 2003 January 11; 361(9352): 181. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531615&dopt=Abstract

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Decreased calcium-dependent constitutive nitric oxide synthase (cNOS) activity in prefrontal cortex in schizophrenia and depression. Author(s): Xing G, Chavko M, Zhang LX, Yang S, Post RM. Source: Schizophrenia Research. 2002 November 1; 58(1): 21-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363386&dopt=Abstract

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Decreased left amygdala and hippocampal volumes in young offspring at risk for schizophrenia. Author(s): Keshavan MS, Dick E, Mankowski I, Harenski K, Montrose DM, Diwadkar V, DeBellis M. Source: Schizophrenia Research. 2002 December 1; 58(2-3): 173-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409156&dopt=Abstract

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Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia. Author(s): Dean B, McLeod M, Keriakous D, McKenzie J, Scarr E. Source: Molecular Psychiatry. 2002; 7(10): 1083-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476323&dopt=Abstract

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Decreased phorbol ester binding in the parahippocampal gyrus from subjects with schizophrenia is not associated with changes in protein kinase C. Author(s): Scarr E, Pavey G, Robinson PJ, Opeskin K, Copolov DL, Dean B. Source: Molecular Psychiatry. 2002; 7(7): 683-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192611&dopt=Abstract

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Decreased serum albumin levels in Taiwanese patients with schizophrenia. Author(s): Huang TL. Source: Psychiatry and Clinical Neurosciences. 2002 December; 56(6): 627-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485305&dopt=Abstract

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Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia. Author(s): Hashimoto K, Fukushima T, Shimizu E, Komatsu N, Watanabe H, Shinoda N, Nakazato M, Kumakiri C, Okada S, Hasegawa H, Imai K, Iyo M. Source: Archives of General Psychiatry. 2003 June; 60(6): 572-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796220&dopt=Abstract

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Deficits in gain of smooth pursuit eye movements in schizophrenia and affective disorder patients and their unaffected relatives. Author(s): Kathmann N, Hochrein A, Uwer R, Bondy B. Source: The American Journal of Psychiatry. 2003 April; 160(4): 696-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668358&dopt=Abstract

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Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Author(s): Strous RD, Maayan R, Lapidus R, Stryjer R, Lustig M, Kotler M, Weizman A. Source: Archives of General Psychiatry. 2003 February; 60(2): 133-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578430&dopt=Abstract

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Depression in Kraepelinian schizophrenia. Author(s): Kilzieh N, Wood AE, Erdmann J, Raskind M, Tapp A. Source: Comprehensive Psychiatry. 2003 January-February; 44(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524629&dopt=Abstract

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Depression measures and motor side-effects in patients with acute schizophrenia. Author(s): Kontaxakis VP, Havaki-Kontaxaki BJ, Stamouli SS, Margariti MM, Kollias CT, Christodoulou GN. Source: Schizophrenia Research. 2002 July 1; 56(1-2): 197-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084435&dopt=Abstract

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Depressive episodes in stable schizophrenia: critical evaluation of the DSM-IV and ICD-10 diagnostic criteria. Author(s): Bressan RA, Chaves AC, Pilowsky LS, Shirakawa I, Mari JJ. Source: Psychiatry Research. 2003 January 25; 117(1): 47-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581820&dopt=Abstract

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Depressive symptoms at baseline predict fewer negative symptoms at follow-up in patients with first-episode schizophrenia. Author(s): Oosthuizen P, Emsley RA, Roberts MC, Turner J, Keyter L, Keyter N, Torreman M. Source: Schizophrenia Research. 2002 December 1; 58(2-3): 247-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409165&dopt=Abstract

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Depressive symptoms in chronic schizophrenia patients: any differences between patients with and without a major depressive episode? Author(s): Kaneda Y. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2003 May; 18(3): 137-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763301&dopt=Abstract

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Dermatoglyphics and schizophrenia: a Mexican study. Author(s): Elizarras-Rivas J, Fragoso-Herrera R, Cerdan-Sanchez LF, Ramos-Zepeda R, Totsuka-Sutto SE, Gallegos-Arreola P, Saha S, McGrath J. Source: The Australian and New Zealand Journal of Psychiatry. 2002 October; 36(5): 7045. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225464&dopt=Abstract

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Detection and management of comorbidity in patients with schizophrenia. Author(s): Green AI, Canuso CM, Brenner MJ, Wojcik JD. Source: The Psychiatric Clinics of North America. 2003 March; 26(1): 115-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683263&dopt=Abstract

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Determinants of expressed emotion in mothers of schizophrenia patients. Author(s): King S, Ricard N, Rochon V, Steiger H, Nelis S. Source: Psychiatry Research. 2003 March 25; 117(3): 211-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686364&dopt=Abstract

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Determining vulnerability to schizophrenia in methamphetamine psychosis using exploratory eye movements. Author(s): Mikami T, Naruse N, Fukura Y, Ohkubo H, Ohkubo T, Matsuura M, Moriya H, Nishikawa T, Kojima T. Source: Psychiatry and Clinical Neurosciences. 2003 August; 57(4): 433-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839526&dopt=Abstract

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Development of an abbreviated schizophrenia quality of life scale using a new method. Author(s): Bilker WB, Brensinger C, Kurtz MM, Kohler C, Gur RC, Siegel SJ, Gur RE. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 April; 28(4): 773-7. Epub 2002 October 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655324&dopt=Abstract

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Developmental abnormalities of the hippocampus in first-episode schizophrenia. Author(s): Smith GN, Lang DJ, Kopala LC, Lapointe JS, Falkai P, Honer WG. Source: Biological Psychiatry. 2003 April 1; 53(7): 555-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679232&dopt=Abstract

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Developmental precursors of child- and adolescent-onset schizophrenia and affective psychoses: diagnostic specificity and continuity with symptom dimensions. Author(s): Hollis C. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 January; 182: 37-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509316&dopt=Abstract

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Developments in the pharmacological treatment of schizophrenia. Author(s): Kuperberg G, Kerwin R, Murray R. Source: Expert Opinion on Investigational Drugs. 2002 October; 11(10): 1335-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387698&dopt=Abstract

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Diabetes mellitus and impaired glucose tolerance in patients with schizophrenia. Author(s): Subramaniam M, Chong SA, Pek E. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 June; 48(5): 345-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866342&dopt=Abstract

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Diagnostic concepts and the prevention of schizophrenia. Author(s): Tsuang MT, Faraone SV. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 August; 47(6): 515-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211878&dopt=Abstract

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Diazoxide in the treatment of schizophrenia: novel application of potassium channel openers in the treatment of schizophrenia. Author(s): Akhondzadeh S, Mojtahedzadeh V, Mirsepassi GR, Moin M, AminiNooshabadi H, Kamalipour A. Source: Journal of Clinical Pharmacy and Therapeutics. 2002 December; 27(6): 453-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472985&dopt=Abstract

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Did schizophrenia change the course of English history? The mental illness of Henry VI. Author(s): Bark N. Source: Medical Hypotheses. 2002 October; 59(4): 416-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208181&dopt=Abstract

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Differences in age of first hospitalization for schizophrenia among immigrants and nonimmigrants in a national case registry. Author(s): Rabinowitz J, Fennig S. Source: Schizophrenia Bulletin. 2002; 28(3): 491-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645680&dopt=Abstract

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Differences in fMRI and MRS in a monozygotic twin pair discordant for schizophrenia (case report). Author(s): Spaniel F, Hajek T, Tintera J, Harantova P, Dezortova M, Hajek M. Source: Acta Psychiatrica Scandinavica. 2003 February; 107(2): 155-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534442&dopt=Abstract

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Differences in neuroanatomical sites of apoD elevation discriminate between schizophrenia and bipolar disorder. Author(s): Thomas EA, Dean B, Scarr E, Copolov D, Sutcliffe JG. Source: Molecular Psychiatry. 2003 February; 8(2): 167-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610649&dopt=Abstract

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Differential effect of quetiapine on depressive symptoms in patients with partially responsive schizophrenia. Author(s): Emsley RA, Buckley P, Jones AM, Greenwood MR. Source: Journal of Psychopharmacology (Oxford, England). 2003 June; 17(2): 210-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870569&dopt=Abstract

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Differential effects of cigarette smoking on performance of a smooth pursuit and a saccadic eye movement task in schizophrenia. Author(s): Olincy A, Johnson LL, Ross RG. Source: Psychiatry Research. 2003 March 25; 117(3): 223-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686365&dopt=Abstract

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Differential effects of olanzapine and risperidone on cognition in schizophrenia? A saccadic eye movement study. Author(s): Broerse A, Crawford TJ, den Boer JA. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2002 Fall; 14(4): 454-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426415&dopt=Abstract

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Diffusion tensor magnetic resonance imaging of disruption of regional white matter in schizophrenia. Author(s): Minami T, Nobuhara K, Okugawa G, Takase K, Yoshida T, Sawada S, HaKawa S, Ikeda K, Kinoshita T. Source: Neuropsychobiology. 2003; 47(3): 141-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759557&dopt=Abstract

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DISC1 (Disrupted in Schizophrenia-1) is expressed in limbic regions of the primate brain. Author(s): Austin CP, Ma L, Ky B, Morris JA, Shughrue PJ. Source: Neuroreport. 2003 May 23; 14(7): 951-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802181&dopt=Abstract

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Disintegration of the components of language as the path to a revision of Bleuler's and Schneider's concepts of schizophrenia. Linguistic disturbances compared with first-rank symptoms in acute psychosis. Author(s): Ceccherini-Nelli A, Crow TJ. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 March; 182: 233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611787&dopt=Abstract

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Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth. Author(s): Ozeki Y, Tomoda T, Kleiderlein J, Kamiya A, Bord L, Fujii K, Okawa M, Yamada N, Hatten ME, Snyder SH, Ross CA, Sawa A. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 January 7; 100(1): 289-94. Epub 2002 December 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12506198&dopt=Abstract

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Disruption of the neuronal PAS3 gene in a family affected with schizophrenia. Author(s): Kamnasaran D, Muir WJ, Ferguson-Smith MA, Cox DW. Source: Journal of Medical Genetics. 2003 May; 40(5): 325-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746393&dopt=Abstract

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Dissolution profile, tolerability, and acceptability of the orally disintegrating olanzapine tablet in patients with schizophrenia. Author(s): Chue P, Jones B, Taylor CC, Dickson R. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 October; 47(8): 771-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420656&dopt=Abstract

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Distribution of haplotypes derived from three common variants of the NR4A2 gene in Japanese patients with schizophrenia. Author(s): Iwayama-Shigeno Y, Yamada K, Toyota T, Shimizu H, Hattori E, Yoshitsugu K, Fujisawa T, Yoshida Y, Kobayashi T, Toru M, Kurumaji A, Detera-Wadleigh S, Yoshikawa T. Source: American Journal of Medical Genetics. 2003 April 1; 118B(1): 20-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627459&dopt=Abstract

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Distribution of microtubule-associated protein MAP2-immunoreactive interstitial neurons in the parahippocampal white matter in subjects with schizophrenia. Author(s): Rioux L, Nissanov J, Lauber K, Bilker WB, Arnold SE. Source: The American Journal of Psychiatry. 2003 January; 160(1): 149-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505814&dopt=Abstract

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Disturbed communication in schizophrenia: the role of poor pragmatics and poor mind-reading. Author(s): Langdon R, Coltheart M, Ward PB, Catts SV. Source: Psychological Medicine. 2002 October; 32(7): 1273-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420896&dopt=Abstract

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DNA fragmentation decreased in schizophrenia but not bipolar disorder. Author(s): Benes FM, Walsh J, Bhattacharyya S, Sheth A, Berretta S. Source: Archives of General Psychiatry. 2003 April; 60(4): 359-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695312&dopt=Abstract

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Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring? Author(s): Sorensen HJ, Mortensen EL, Reinisch JM, Mednick SA. Source: The American Journal of Psychiatry. 2003 March; 160(3): 464-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611826&dopt=Abstract

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Does community care decrease length of stay and risk of rehospitalization in new patients with schizophrenia disorders? A comparative case register study in Groningen, The Netherlands; Victoria, Australia; and South-Verona, Italy. Author(s): Sytema S, Burgess P, Tansella M. Source: Schizophrenia Bulletin. 2002; 28(2): 273-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693433&dopt=Abstract

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Does considering duration of negative symptoms increase their specificity for schizophrenia? Author(s): Bottlender R, Sato T, Jager M, Kunze I, Groll C, Borski I, Moller HJ. Source: Schizophrenia Research. 2003 April 1; 60(2-3): 321-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591594&dopt=Abstract

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Does 'errorless learning' compensate for neurocognitive impairments in the work rehabilitation of persons with schizophrenia? Author(s): Kern RS, Green MF, Mintz J, Liberman RP. Source: Psychological Medicine. 2003 April; 33(3): 433-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701664&dopt=Abstract

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Does fear of coercion keep people away from mental health treatment? Evidence from a survey of persons with schizophrenia and mental health professionals. Author(s): Swartz MS, Swanson JW, Hannon MJ. Source: Behavioral Sciences & the Law. 2003; 21(4): 459-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898502&dopt=Abstract

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Does guilt proneness predict acute and long-term distress in relatives of patients with schizophrenia? Author(s): Boye B, Bentsen H, Malt UF. Source: Acta Psychiatrica Scandinavica. 2002 November; 106(5): 351-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366469&dopt=Abstract

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Does schizophrenia result from developmental or degenerative processes? Author(s): Church SM, Cotter D, Bramon E, Murray RM. Source: Journal of Neural Transmission. Supplementum. 2002; (63): 129-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597613&dopt=Abstract

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Donepezil for memory dysfunction in schizophrenia. Author(s): Howard AK, Thornton AE, Altman S, Honer WG. Source: Journal of Psychopharmacology (Oxford, England). 2002 September; 16(3): 26770. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236636&dopt=Abstract

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Dopamine D4 receptor gene (DRD4) variants and schizophrenia: meta-analyses. Author(s): Jonsson EG, Sedvall GC, Nothen MM, Cichon S. Source: Schizophrenia Research. 2003 May 1; 61(1): 111-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648742&dopt=Abstract

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Dopaminergic deficit and the role of amisulpride in the treatment of schizophrenia. Author(s): Kasper S. Source: International Clinical Psychopharmacology. 2002 December; 17 Suppl 4: S19-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685918&dopt=Abstract

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Dose-related effects of amisulpride on five dimensions of psychopathology in patients with acute exacerbation of schizophrenia. Author(s): Muller MJ, Wetzel H, Eich FX, Rein W, Puech A, Benkert O; Amisulpride Study Group. Source: Journal of Clinical Psychopharmacology. 2002 December; 22(6): 554-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454554&dopt=Abstract

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Double-blind antiglucocorticoid treatment in schizophrenia and schizoaffective disorder: a pilot study. Author(s): Marco EJ, Wolkowitz OM, Vinogradov S, Poole JH, Lichtmacher J, Reus VI. Source: World J Biol Psychiatry. 2002 July; 3(3): 156-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478881&dopt=Abstract

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DRD4 exon III polymorphism and response to risperidone in Israeli adolescents with schizophrenia: a pilot pharmacogenetic study. Author(s): Zalsman G, Frisch A, Lev-Ran S, Martin A, Michaelovsky E, Bensason D, Gothelf D, Nahshoni E, Tyano S, Weizman A. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2003 May; 13(3): 183-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729944&dopt=Abstract

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Dysregulated brain development in adult men with schizophrenia: a magnetic resonance imaging study. Author(s): Bartzokis G, Nuechterlein KH, Lu PH, Gitlin M, Rogers S, Mintz J. Source: Biological Psychiatry. 2003 March 1; 53(5): 412-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614994&dopt=Abstract

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Early development and unstable genes in schizophrenia: preliminary results. Author(s): Ayton A, Morris AG, Tyson PJ, Hunt D, Mortimer AM, Cottrell D. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2002 October; 17(6): 332-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457743&dopt=Abstract

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Early expression of a pathophysiological feature of schizophrenia: saccadic intrusions into smooth-pursuit eye movements in school-age children vulnerable to schizophrenia. Author(s): Ross RG. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 April; 42(4): 468-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649634&dopt=Abstract

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Early intervention for relapse in schizophrenia: results of a 12-month randomized controlled trial of cognitive behavioural therapy. Author(s): Gumley A, O'Grady M, McNay L, Reilly J, Power K, Norrie J. Source: Psychological Medicine. 2003 April; 33(3): 419-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701663&dopt=Abstract

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Early intervention in schizophrenia: a critique. Author(s): Warner R. Source: Epidemiol Psichiatr Soc. 2002 October-December; 11(4): 248-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585015&dopt=Abstract

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Early intervention in schizophrenia: points of agreement. Author(s): Warner R, McGorry PD. Source: Epidemiol Psichiatr Soc. 2002 October-December; 11(4): 256-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585016&dopt=Abstract

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Early-onset schizophrenia and dopamine-related gene polymorphism. Author(s): Iwata Y, Matsumoto H, Minabe Y, Osada N, Nakamura K, Sekizawa T, Suzuki K, Sekine Y, Takei N, Mori N. Source: American Journal of Medical Genetics. 2003 January 1; 116B(1): 23-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12497608&dopt=Abstract

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Early-onset schizophrenia in children with mental retardation: diagnostic reliability and stability of clinical features. Author(s): Lee P, Moss S, Friedlander R, Donnelly T, Honer W. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 February; 42(2): 162-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544175&dopt=Abstract

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Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia. Author(s): Casey DE, Daniel DG, Wassef AA, Tracy KA, Wozniak P, Sommerville KW. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 January; 28(1): 182-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496955&dopt=Abstract

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Effect of loxapine on peripheral dopamine-like and serotonin receptors in patients with schizophrenia. Author(s): Singh AN, Barlas C, Saeedi H, Mishra RK. Source: Journal of Psychiatry & Neuroscience : Jpn. 2003 January; 28(1): 39-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587849&dopt=Abstract

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Effect of the 5-HT2 antagonist mianserin on cognitive dysfunction in chronic schizophrenia patients: an add-on, double-blind placebo-controlled study. Author(s): Poyurovsky M, Koren D, Gonopolsky I, Schneidman M, Fuchs C, Weizman A, Weizman R. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2003 March; 13(2): 123-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650957&dopt=Abstract

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Effect size of symptom status in withdrawal of typical antipsychotics and subsequent clozapine treatment in patients with treatment-resistant schizophrenia. Author(s): Pickar D, Bartko JJ. Source: The American Journal of Psychiatry. 2003 June; 160(6): 1133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777272&dopt=Abstract

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Effectiveness of psychoeducational intervention for rural Chinese families experiencing schizophrenia--a randomised controlled trial. Author(s): Ran MS, Xiang MZ, Chan CL, Leff J, Simpson P, Huang MS, Shan YH, Li SG. Source: Social Psychiatry and Psychiatric Epidemiology. 2003 February; 38(2): 69-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563548&dopt=Abstract

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Effectiveness of switching to ziprasidone for stable but symptomatic outpatients with schizophrenia. Author(s): Weiden PJ, Simpson GM, Potkin SG, O'Sullivan RL. Source: The Journal of Clinical Psychiatry. 2003 May; 64(5): 580-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755663&dopt=Abstract

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Effectiveness of the anger-control program in reducing anger expression in patients with schizophrenia. Author(s): Chan HY, Lu RB, Tseng CL, Chous KR. Source: Archives of Psychiatric Nursing. 2003 April; 17(2): 88-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701086&dopt=Abstract

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Effects of alcohol dependence comorbidity and antipsychotic medication on volumes of the thalamus and pons in schizophrenia. Author(s): Sullivan EV, Rosenbloom MJ, Serventi KL, Deshmukh A, Pfefferbaum A. Source: The American Journal of Psychiatry. 2003 June; 160(6): 1110-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777269&dopt=Abstract

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Effects of CYP2D6 genotypes on plasma concentrations of risperidone and enantiomers of 9-hydroxyrisperidone in Japanese patients with schizophrenia. Author(s): Yasui-Furukori N, Mihara K, Kondo T, Kubota T, Iga T, Takarada Y, De Vries R, Kaneko S, Tateishi T. Source: Journal of Clinical Pharmacology. 2003 February; 43(2): 122-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616663&dopt=Abstract

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Effects of estrogen on brain development and neuroprotection--implications for negative symptoms in schizophrenia. Author(s): Rao ML, Kolsch H. Source: Psychoneuroendocrinology. 2003 April; 28 Suppl 2: 83-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650683&dopt=Abstract

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Effects of olanzapine on auditory P300 in schizophrenia. Author(s): Gonul AS, Suer C, Coburn K, Ozesmi C, Oguz A, Yilmaz A. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 February; 27(1): 173-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12551741&dopt=Abstract

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Effects of olanzapine plasma concentrations on depressive symptoms in schizophrenia: a pilot study. Author(s): Lane HY, Guo SC, Hwang TJ, Chen YS, Cheng JJ, Lee YC, Hong CJ, Hwu HG, Chang WH. Source: Journal of Clinical Psychopharmacology. 2002 October; 22(5): 530-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352282&dopt=Abstract

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Effects of patient demographics, risperidone dosage, and clinical outcome on body weight in acutely exacerbated schizophrenia. Author(s): Lane HY, Chang YC, Cheng YC, Liu GC, Lin XR, Chang WH. Source: The Journal of Clinical Psychiatry. 2003 March; 64(3): 316-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716274&dopt=Abstract

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Effects of the 5-HT2A agonist psilocybin on mismatch negativity generation and AXcontinuous performance task: implications for the neuropharmacology of cognitive deficits in schizophrenia. Author(s): Umbricht D, Vollenweider FX, Schmid L, Grubel C, Skrabo A, Huber T, Koller R. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 January; 28(1): 170-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496954&dopt=Abstract

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Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. Author(s): Kane JM, Carson WH, Saha AR, McQuade RD, Ingenito GG, Zimbroff DL, Ali MW. Source: The Journal of Clinical Psychiatry. 2002 September; 63(9): 763-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363115&dopt=Abstract

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Efficacy of clozapine in the treatment of atypical antipsychotic refractory schizophrenia: a pilot study. Author(s): Narendran R, Young CM, Pristach CA, Pato MT, Valenti AM, Fass AR. Source: Journal of Clinical Psychopharmacology. 2003 February; 23(1): 103-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544385&dopt=Abstract

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Efficacy of electroconvulsive therapy in treatment-resistant schizophrenia: a prospective open trial. Author(s): Tang WK, Ungvari GS. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 May; 27(3): 373-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691772&dopt=Abstract

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Efficacy of newer generation antipsychotics in the treatment of schizophrenia. Author(s): Tandon R, Jibson MD. Source: Psychoneuroendocrinology. 2003 January; 28 Suppl 1: 9-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504069&dopt=Abstract

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Efficacy, safety, and tolerability of quetiapine in patients with schizophrenia. Author(s): Nasrallah HA, Tandon R. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 13: 12-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562142&dopt=Abstract

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Electrodermal responsivity distinguishes ERP activity and symptom profile in schizophrenia. Author(s): Williams LL, Bahramali H, Hemsley DR, Harris AW, Brown K, Gordon E. Source: Schizophrenia Research. 2003 February 1; 59(2-3): 115-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414068&dopt=Abstract

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Electrodermically nonresponsive schizophrenia patients make more errors in the Stroop Color Word Test, indicating selective attention deficit. Author(s): Lopes-Machado EZ, Crippa JA, Hallak JE, Guimaraes FS, Zuardi AW. Source: Schizophrenia Bulletin. 2002; 28(3): 459-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645677&dopt=Abstract

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Electrolyte-balanced sports drink for polydipsia-hyponatremia in schizophrenia. Author(s): Quitkin FM, Garakani A, Kelly KE. Source: The American Journal of Psychiatry. 2003 February; 160(2): 385-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562594&dopt=Abstract

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Electrophysiological insights into language processing in schizophrenia. Author(s): Sitnikova T, Salisbury DF, Kuperberg G, Holcomb PI. Source: Psychophysiology. 2002 November; 39(6): 851-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462512&dopt=Abstract

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Elevated blood superoxide dismutase in neuroleptic-free schizophrenia: association with positive symptoms. Author(s): Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY. Source: Psychiatry Research. 2003 January 25; 117(1): 85-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581823&dopt=Abstract

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Elevated cerebrospinal fluid SNAP-25 in schizophrenia. Author(s): Thompson PM, Kelley M, Yao J, Tsai G, van Kammen DP. Source: Biological Psychiatry. 2003 June 15; 53(12): 1132-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814864&dopt=Abstract

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Elevated homocysteine levels in young male patients with schizophrenia. Author(s): Levine J, Stahl Z, Sela BA, Gavendo S, Ruderman V, Belmaker RH. Source: The American Journal of Psychiatry. 2002 October; 159(10): 1790-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359692&dopt=Abstract

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Elevated interleukin-6 in the cerebrospinal fluid of a previously delineated schizophrenia subtype. Author(s): Garver DL, Tamas RL, Holcomb JA. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 August; 28(8): 1515-20. Epub 2003 June 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799618&dopt=Abstract

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Elevated prolactin levels in patients with schizophrenia: mechanisms and related adverse effects. Author(s): Halbreich U, Kinon BJ, Gilmore JA, Kahn LS. Source: Psychoneuroendocrinology. 2003 January; 28 Suppl 1: 53-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504072&dopt=Abstract

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Elucidating the pathogenesis of schizophrenia. Author(s): Sawa A, Kamiya A. Source: Bmj (Clinical Research Ed.). 2003 September 20; 327(7416): 632-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500408&dopt=Abstract

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Emotion processing and its relationship to social functioning in schizophrenia patients. Author(s): Hooker C, Park S. Source: Psychiatry Research. 2002 September 15; 112(1): 41-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379449&dopt=Abstract

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Emotional expressiveness and the quality of life of patients with schizophrenia. Author(s): Mubarak AR, Barber JG. Source: Social Psychiatry and Psychiatric Epidemiology. 2003 July; 38(7): 380-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861444&dopt=Abstract

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Emotional responses to psychosocial stress in schizophrenia: the role of individual differences in affective traits and coping. Author(s): Horan WP, Blanchard JJ. Source: Schizophrenia Research. 2003 April 1; 60(2-3): 271-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591589&dopt=Abstract

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Essential polyunsaturated fatty acid and lipid peroxide levels in never-medicated and medicated schizophrenia patients. Author(s): Arvindakshan M, Sitasawad S, Debsikdar V, Ghate M, Evans D, Horrobin DF, Bennett C, Ranjekar PK, Mahadik SP. Source: Biological Psychiatry. 2003 January 1; 53(1): 56-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513945&dopt=Abstract

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Estimating the costs and benefits of new drug therapies: atypical antipsychotic drugs for schizophrenia. Author(s): Mauskopf J, Muroff M, Gibson PJ, Grainger DL. Source: Schizophrenia Bulletin. 2002; 28(4): 619-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795495&dopt=Abstract

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Ethnic differences in use of antipsychotic medication among Texas medicaid clients with schizophrenia. Author(s): Opolka JL, Rascati KL, Brown CM, Barner JC, Johnsrud MT, Gibson PJ. Source: The Journal of Clinical Psychiatry. 2003 June; 64(6): 635-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823076&dopt=Abstract

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Evaluation of a community-based rehabilitation model for chronic schizophrenia in rural India. Author(s): Chatterjee S, Patel V, Chatterjee A, Weiss HA. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 January; 182: 57-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509319&dopt=Abstract

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Everyday memory and laboratory memory tests: general function predictors in schizophrenia and remitted depression. Author(s): Fennig S, Mottes A, Ricter-Levin G, Treves I, Levkovitz Y. Source: The Journal of Nervous and Mental Disease. 2002 October; 190(10): 677-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409861&dopt=Abstract

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Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit. Author(s): Gerber DJ, Hall D, Miyakawa T, Demars S, Gogos JA, Karayiorgou M, Tonegawa S. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 July 22; 100(15): 8993-8. Epub 2003 Jul 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851458&dopt=Abstract

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Evidence-based medicine in the psychological treatment of schizophrenia. Author(s): Margison F. Source: J Am Acad Psychoanal Dyn Psychiatry. 2003 Spring; 31(1): 177-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722894&dopt=Abstract

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Evidence-based psychosocial treatment practices in schizophrenia: lessons from the patient outcomes research team (PORT) project. Author(s): Lehman AF, Steinwachs DM. Source: J Am Acad Psychoanal Dyn Psychiatry. 2003 Spring; 31(1): 141-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722892&dopt=Abstract

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Evolutionary perspectives on schizophrenia. Author(s): Polimeni J, Reiss JP. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 February; 48(1): 34-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635562&dopt=Abstract

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Executive dysfunction in first-episode schizophrenia and relationship to duration of untreated psychosis: the West London Study. Author(s): Joyce E, Hutton S, Mutsatsa S, Gibbins H, Webb E, Paul S, Robbins T, Barnes T. Source: The British Journal of Psychiatry. Supplement. 2002 September; 43: S38-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271799&dopt=Abstract

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Executive function in schizophrenia: is it linked to psychosis and poor life functioning? Author(s): Reed RA, Harrow M, Herbener ES, Martin EM. Source: The Journal of Nervous and Mental Disease. 2002 November; 190(11): 725-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12436011&dopt=Abstract

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Exploratory eye movements during the Benton Visual Retention Test: characteristics of visual behavior in schizophrenia. Author(s): Obayashi S, Matsushima E, Ando H, Ando K, Kojima T. Source: Psychiatry and Clinical Neurosciences. 2003 August; 57(4): 409-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839523&dopt=Abstract

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Exploratory eye movements in schizophrenia: effects of figure size and the instruction on visual search. Author(s): Tonoya Y, Matsui M, Kurachi M, Kurokawa K, Sumiyoshi T. Source: European Archives of Psychiatry and Clinical Neuroscience. 2002 December; 252(6): 255-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563533&dopt=Abstract

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Expressed emotion in relatives of first-episode and chronic patients with schizophrenia and major depressive disorder-a comparison. Author(s): Bachmann S, Bottmer C, Jacob S, Kronmuller KT, Backenstrass M, Mundt C, Renneberg B, Fiedler P, Schroder J. Source: Psychiatry Research. 2002 November 15; 112(3): 239-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450633&dopt=Abstract

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Expression of Fyn, a non-receptor tyrosine kinase in prefrontal cortex from patients with schizophrenia and its correlation with clinical onset. Author(s): Ohnuma T, Kato H, Arai H, McKenna PJ, Emson PC. Source: Brain Research. Molecular Brain Research. 2003 April 10; 112(1-2): 90-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670706&dopt=Abstract

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Extreme weight gain in a youth with schizophrenia: risk/benefit considerations. Author(s): Webster D, Devarajan S, Gallant J, Harris A, Kopala LC. Source: Schizophrenia Research. 2002 July 1; 56(1-2): 187-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084432&dopt=Abstract

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Eye movement disturbances in schizophrenia and a polymorphism of catechol-Omethyltransferase gene. Author(s): Rybakowski JK, Borkowska A, Czerski PM, Hauser J. Source: Psychiatry Research. 2002 December 15; 113(1-2): 49-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467945&dopt=Abstract

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Factor structure of the Wechsler Adult Intelligence Scale-III in schizophrenia. Author(s): Dickinson D, Iannone VN, Gold JM. Source: Assessment. 2002 June; 9(2): 171-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12066832&dopt=Abstract

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Factors affecting the family support system of patients with schizophrenia: a survey in the remote island of Tsushima. Author(s): Hamada Y, Ohta Y, Nakane Y. Source: Psychiatry and Clinical Neurosciences. 2003 April; 57(2): 161-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667162&dopt=Abstract

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Factors of good outcome after discharge from support house (engoryou) for schizophrenia. Author(s): Sakiyama S, Iida J, Minami Y, Kishimoto T. Source: Psychiatry and Clinical Neurosciences. 2002 December; 56(6): 609-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485302&dopt=Abstract

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Fahr's disease and schizophrenia in a patient with secondary hypoparathyroidism. Author(s): Ilievski B, Rodzevski K, Gibbon M, Dwork AJ. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2002 Summer; 14(3): 357-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154165&dopt=Abstract

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Familial aggregation of delusional proneness in schizophrenia and bipolar pedigrees. Author(s): Schurhoff F, Szoke A, Meary A, Bellivier F, Rouillon F, Pauls D, Leboyer M. Source: The American Journal of Psychiatry. 2003 July; 160(7): 1313-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832247&dopt=Abstract

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Familial expressed emotion: outcome and course of Israeli patients with schizophrenia. Author(s): Marom S, Munitz H, Jones PB, Weizman A, Hermesh H. Source: Schizophrenia Bulletin. 2002; 28(4): 731-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795502&dopt=Abstract

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Familiality of clinical characteristics in schizophrenia. Author(s): Wickham H, Walsh C, Asherson P, Gill M, Owen MJ, McGuffin P, Murray R, Sham P. Source: Journal of Psychiatric Research. 2002 September-October; 36(5): 325-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127600&dopt=Abstract

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Family attitude scale: measurement of criticism in the relatives of patients with schizophrenia in Japan. Author(s): Fujita H, Shimodera S, Izumoto Y, Tanaka S, Kii M, Mino Y, Inoue S. Source: Psychiatry Research. 2002 July 31; 110(3): 273-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127477&dopt=Abstract

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Family history of psychiatric disorders and age at first contact in schizophrenia: an epidemiological study. Author(s): Byrne M, Agerbo E, Mortensen PB. Source: The British Journal of Psychiatry. Supplement. 2002 September; 43: S19-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271795&dopt=Abstract

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Family intervention in schizophrenia--impact on family burden and attitude. Author(s): Berglund N, Vahlne JO, Edman A. Source: Social Psychiatry and Psychiatric Epidemiology. 2003 March; 38(3): 116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616308&dopt=Abstract

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Family psychoeducation and schizophrenia: a review of the literature. Author(s): McFarlane WR, Dixon L, Lukens E, Lucksted A. Source: J Marital Fam Ther. 2003 April; 29(2): 223-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728780&dopt=Abstract

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Family-based association studies of COMT gene polymorphisms and schizophrenia in the Chinese population. Author(s): Fan JB, Chen WY, Tang JX, Li S, Gu NF, Feng GY, Breen G, St Clair D, He L. Source: Molecular Psychiatry. 2002; 7(5): 446-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12082558&dopt=Abstract

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Family-based association study of the NOTCH4 gene in schizophrenia using Japanese and Chinese samples. Author(s): Takahashi S, Cui YH, Kojima T, Han YH, Yu SY, Tanabe E, Yara K, Matsuura M, Matsushima E, Nakayama J, Arinami T, Shen YC, Faraone SV, Tsuang MT. Source: Biological Psychiatry. 2003 July 15; 54(2): 129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873802&dopt=Abstract

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Features of obsessive-compulsive disorder in patients primarily diagnosed with schizophrenia. Author(s): Ohta M, Kokai M, Morita Y. Source: Psychiatry and Clinical Neurosciences. 2003 February; 57(1): 67-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519457&dopt=Abstract

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Fertility of patients with schizophrenia, their siblings, and the general population: a cohort study from 1950 to 1959 in Finland. Author(s): Haukka J, Suvisaari J, Lonnqvist J. Source: The American Journal of Psychiatry. 2003 March; 160(3): 460-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611825&dopt=Abstract

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Fetal hypoxia, genetic risk, and schizophrenia. Author(s): Preti A. Source: The American Journal of Psychiatry. 2003 June; 160(6): 1186; Author Reply 1186. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777283&dopt=Abstract

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Financing health care in Europe: context for the Schizophrenia Outpatient Health Outcomes Study. Author(s): Knapp M, Novick D, Genkeer L, Curran CM, McDaid D; SOHO Study Group. Source: Acta Psychiatrica Scandinavica. Supplementum. 2003; (416): 30-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755852&dopt=Abstract

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Fine mapping of the schizophrenia susceptibility locus on chromosome 1q22. Author(s): Brzustowicz LM, Hayter JE, Hodgkinson KA, Chow EW, Bassett AS. Source: Human Heredity. 2002; 54(4): 199-209. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771552&dopt=Abstract

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First person account: a glimpse of schizophrenia. Author(s): Fox V. Source: Schizophrenia Bulletin. 2002; 28(2): 363-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693441&dopt=Abstract

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First-admission rates of schizophrenia in Denmark, 1980-1997: have they been increasing? Author(s): Tsuchiya KJ, Munk-Jorgensen P. Source: Schizophrenia Research. 2002 April 1; 54(3): 187-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950542&dopt=Abstract

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First-episode schizophrenia, bipolar disorder and other psychoses in a rural Irish catchment area: incidence and gender in the Cavan-Monaghan study at 5 years. Author(s): Scully PJ, Quinn JF, Morgan MG, Kinsella A, O'Callaghan E, Owens JM, Waddington JL. Source: The British Journal of Psychiatry. Supplement. 2002 September; 43: S3-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271797&dopt=Abstract

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Fluvoxamine augmentation in risperidone-resistant schizophrenia: an open trial. Author(s): Takashi H, Sugita T, Higuchi H, Shimizu T. Source: Human Psychopharmacology. 2002 March; 17(2): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404698&dopt=Abstract

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Fluvoxamine augmentation of olanzapine in chronic schizophrenia: pharmacokinetic interactions and clinical effects. Author(s): Hiemke C, Peled A, Jabarin M, Hadjez J, Weigmann H, Hartter S, Modai I, Ritsner M, Silver H. Source: Journal of Clinical Psychopharmacology. 2002 October; 22(5): 502-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352274&dopt=Abstract

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Four-year outcome in non-compliant schizophrenia patients treated with or without home-based ambulatory outpatient care. Author(s): Kampman O, Illi A, Poutanen P, Leinonen E. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2003 February; 18(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648888&dopt=Abstract

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Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study. Author(s): Bobes J, Garc A-Portilla MP, Rejas J, Hern Ndez G, Garcia-Garcia M, RicoVillademoros F, Porras A. Source: Journal of Sex & Marital Therapy. 2003 March-April; 29(2): 125-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623765&dopt=Abstract

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Frontal Systems Behavior Scale in schizophrenia: relationships with psychiatric symptomatology, cognition and adaptive function. Author(s): Velligan DI, Ritch JL, Sui D, DiCocco M, Huntzinger CD. Source: Psychiatry Research. 2002 December 30; 113(3): 227-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559479&dopt=Abstract

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Frontal white matter microstructure, aggression, and impulsivity in men with schizophrenia: a preliminary study. Author(s): Hoptman MJ, Volavka J, Johnson G, Weiss E, Bilder RM, Lim KO. Source: Biological Psychiatry. 2002 July 1; 52(1): 9-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079725&dopt=Abstract

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Functional abnormalities of medial temporal cortex during novel picture learning among patients with chronic schizophrenia. Author(s): Eyler Zorrilla LT, Jeste DV, Paulus M, Brown GG. Source: Schizophrenia Research. 2003 February 1; 59(2-3): 187-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414075&dopt=Abstract

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Functional catechol-O-methyltransferase gene polymorphism and susceptibility to schizophrenia. Author(s): Park TW, Yoon KS, Kim JH, Park WY, Hirvonen A, Kang D. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2002 August; 12(4): 299-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126868&dopt=Abstract

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Functional neuroanatomy of sustained attention in schizophrenia: contribution of parietal cortices. Author(s): Ojeda N, Ortuno F, Arbizu J, Lopez P, Marti-Climent JM, Penuelas I, CerveraEnguix S. Source: Human Brain Mapping. 2002 October; 17(2): 116-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353245&dopt=Abstract

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Further postmortem autoradiographic studies of AMPA receptor binding in schizophrenia. Author(s): Noga JT, Wang H. Source: Synapse (New York, N.Y.). 2002 September 15; 45(4): 250-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125046&dopt=Abstract

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Fusiform gyrus volume reduction and facial recognition in chronic schizophrenia. Author(s): Onitsuka T, Shenton ME, Kasai K, Nestor PG, Toner SK, Kikinis R, Jolesz FA, McCarley RW. Source: Archives of General Psychiatry. 2003 April; 60(4): 349-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695311&dopt=Abstract

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Fusiform gyrus volume reduction in first-episode schizophrenia: a magnetic resonance imaging study. Author(s): Lee CU, Shenton ME, Salisbury DF, Kasai K, Onitsuka T, Dickey CC, Yurgelun-Todd D, Kikinis R, Jolesz FA, McCarley RW. Source: Archives of General Psychiatry. 2002 September; 59(9): 775-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215076&dopt=Abstract

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Gabapentin-induced paradoxical exacerbation of psychosis in a patient with schizophrenia. Author(s): Jablonowski K, Margolese HC, Chouinard G. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 December; 47(10): 975-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553139&dopt=Abstract

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Galantamine for treatment-resistant schizophrenia. Author(s): Allen TB, McEvoy JP. Source: The American Journal of Psychiatry. 2002 July; 159(7): 1244-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091212&dopt=Abstract

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Gaze direction determination in schizophrenia. Author(s): Franck N, Montoute T, Labruyere N, Tiberghien G, Marie-Cardine M, Dalery J, d'Amato T, Georgieff N. Source: Schizophrenia Research. 2002 August 1; 56(3): 225-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072171&dopt=Abstract

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Gender differences in living with schizophrenia. A cross-sectional European multisite study. Author(s): Thornicroft G, Leese M, Tansella M, Howard L, Toulmin H, Herran A, Schene A. Source: Schizophrenia Research. 2002 October 1; 57(2-3): 191-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223250&dopt=Abstract

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Gender differences in schizophrenia. Author(s): Hafner H. Source: Psychoneuroendocrinology. 2003 April; 28 Suppl 2: 17-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650680&dopt=Abstract

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Gender related differences in clinical characteristics and hospital based resource utilization among older adults with schizophrenia. Author(s): Sajatovic M, Sultana D, Bingham CR, Buckley P, Donenwirth K. Source: International Journal of Geriatric Psychiatry. 2002 June; 17(6): 542-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112178&dopt=Abstract

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Gender-specific molecular heterosis of dopamine D2 receptor gene (DRD2) for smoking in schizophrenia. Author(s): Lee HS, Kim SH, Lee HJ, Kim L, Lee SK, Jang DW, Lee MS, Son BG, Suh KY, Kim S. Source: American Journal of Medical Genetics. 2002 August 8; 114(6): 593-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210271&dopt=Abstract

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Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. Author(s): Hashimoto T, Volk DW, Eggan SM, Mirnics K, Pierri JN, Sun Z, Sampson AR, Lewis DA. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 July 16; 23(15): 6315-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867516&dopt=Abstract

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Gene expression in bipolar disorder and schizophrenia: new approaches to old problems. Author(s): Bahn S. Source: Bipolar Disorders. 2002; 4 Suppl 1: 70-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479683&dopt=Abstract

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Gene expression profile for schizophrenia: discrete neuron transcription patterns in the entorhinal cortex. Author(s): Hemby SE, Ginsberg SD, Brunk B, Arnold SE, Trojanowski JQ, Eberwine JH. Source: Archives of General Psychiatry. 2002 July; 59(7): 631-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090816&dopt=Abstract

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Genes for schizophrenia. Author(s): Crow T. Source: Lancet. 2003 May 24; 361(9371): 1829; Author Reply 1829-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781574&dopt=Abstract

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Genes for schizophrenia. Author(s): Karayiorgou M, Gogos JA. Source: Lancet. 2003 May 24; 361(9371): 1828-9; Author Reply 1829-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781572&dopt=Abstract

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Genes for schizophrenia? Recent findings and their pathophysiological implications. Author(s): Harrison PJ, Owen MJ. Source: Lancet. 2003 February 1; 361(9355): 417-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573388&dopt=Abstract

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Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. Author(s): Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H, Bougueleret L, Barry C, Tanaka H, La Rosa P, Puech A, Tahri N, CohenAkenine A, Delabrosse S, Lissarrague S, Picard FP, Maurice K, Essioux L, Millasseau P, Grel P, Debailleul V, Simon AM, Caterina D, Dufaure I, Malekzadeh K, Belova M, Luan JJ, Bouillot M, Sambucy JL, Primas G, Saumier M, Boubkiri N, Martin-Saumier S, Nasroune M, Peixoto H, Delaye A, Pinchot V, Bastucci M, Guillou S, Chevillon M, SainzFuertes R, Meguenni S, Aurich-Costa J, Cherif D, Gimalac A, Van Duijn C, Gauvreau D, Ouellette G, Fortier I, Raelson J, Sherbatich T, Riazanskaia N, Rogaev E, Raeymaekers P, Aerssens J, Konings F, Luyten W, Macciardi F, Sham PC, Straub RE, Weinberger DR, Cohen N, Cohen D, Ouelette G, Realson J. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 October 15; 99(21): 13675-80. Epub 2002 Oct 03. Erratum In: Proc Natl Acad Sci U S a 2002 December 24; 99(26): 17221. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364586&dopt=Abstract

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Genetic contributions to altered callosal morphology in schizophrenia. Author(s): Narr KL, Cannon TD, Woods RP, Thompson PM, Kim S, Asunction D, van Erp TG, Poutanen VP, Huttunen M, Lonnqvist J, Standerksjold-Nordenstam CG, Kaprio J, Mazziotta JC, Toga AW. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2002 May 1; 22(9): 3720-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978848&dopt=Abstract

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Genetic epidemiology of schizophrenia: phenotypes, risk factors, and reproductive behavior. Author(s): Jablensky AV, Kalaydjieva LV. Source: The American Journal of Psychiatry. 2003 March; 160(3): 425-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611820&dopt=Abstract

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Genetic heterogeneity in schizophrenia II: conditional analyses of affected schizophrenia sibling pairs provide evidence for an interaction between markers on chromosome 8p and 14q. Author(s): Chiu YF, McGrath JA, Thornquist MH, Wolyniec PS, Nestadt G, Swartz KL, Lasseter VK, Liang KY, Pulver AE. Source: Molecular Psychiatry. 2002; 7(6): 658-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140791&dopt=Abstract

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Genetic linkage and association between chromosome 1q and working memory function in schizophrenia. Author(s): Gasperoni TL, Ekelund J, Huttunen M, Palmer CG, Tuulio-Henriksson A, Lonnqvist J, Kaprio J, Peltonen L, Cannon TD. Source: American Journal of Medical Genetics. 2003 January 1; 116B(1): 8-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12497606&dopt=Abstract

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Genetic linkage in schizophrenia. Author(s): Brown JS Jr. Source: The American Journal of Psychiatry. 2003 March; 160(3): 598; Author Reply 5989. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611866&dopt=Abstract

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Genetic linkage in schizophrenia. Author(s): Pittelli SJ. Source: The American Journal of Psychiatry. 2003 March; 160(3): 597; Author Reply 5989. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611865&dopt=Abstract

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Genetic linkage in schizophrenia. Author(s): Peedicayil J. Source: The American Journal of Psychiatry. 2003 March; 160(3): 597-8; Author Reply 598-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611864&dopt=Abstract

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Genetic variation in the 22q11 locus and susceptibility to schizophrenia. Author(s): Liu H, Abecasis GR, Heath SC, Knowles A, Demars S, Chen YJ, Roos JL, Rapoport JL, Gogos JA, Karayiorgou M. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 December 24; 99(26): 16859-64. Epub 2002 Dec 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477929&dopt=Abstract

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Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. Author(s): Straub RE, Jiang Y, MacLean CJ, Ma Y, Webb BT, Myakishev MV, Harris-Kerr C, Wormley B, Sadek H, Kadambi B, Cesare AJ, Gibberman A, Wang X, O'Neill FA, Walsh D, Kendler KS. Source: American Journal of Human Genetics. 2002 August; 71(2): 337-48. Epub 2002 July 03. Erratum In: Am J Hum Genet 2002 October; 72(4): 1007. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098102&dopt=Abstract

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Genetics and etiopathophysiology of schizophrenia. Author(s): Sobell JL, Mikesell MJ, McMurray CT. Source: Mayo Clinic Proceedings. 2002 October; 77(10): 1068-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374251&dopt=Abstract

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Genetics of schizophrenia: a review of linkage findings. Author(s): Kohn Y, Lerer B. Source: The Israel Journal of Psychiatry and Related Sciences. 2002; 39(4): 340-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756856&dopt=Abstract

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Genome scan for susceptibility loci for schizophrenia and bipolar disorder. Author(s): Bailer U, Leisch F, Meszaros K, Lenzinger E, Willinger U, Strobl R, Heiden A, Gebhardt C, Doge E, Fuchs K, Sieghart W, Kasper S, Hornik K, Aschauer HN. Source: Biological Psychiatry. 2002 July 1; 52(1): 40-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079729&dopt=Abstract

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Genome scan meta-analysis of schizophrenia and bipolar disorder, part I: Methods and power analysis. Author(s): Levinson DF, Levinson MD, Segurado R, Lewis CM. Source: American Journal of Human Genetics. 2003 July; 73(1): 17-33. Epub 2003 June 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802787&dopt=Abstract

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Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Author(s): Lewis CM, Levinson DF, Wise LH, DeLisi LE, Straub RE, Hovatta I, Williams NM, Schwab SG, Pulver AE, Faraone SV, Brzustowicz LM, Kaufmann CA, Garver DL, Gurling HM, Lindholm E, Coon H, Moises HW, Byerley W, Shaw SH, Mesen A, Sherrington R, O'Neill FA, Walsh D, Kendler KS, Ekelund J, Paunio T, Lonnqvist J, Peltonen L, O'Donovan MC, Owen MJ, Wildenauer DB, Maier W, Nestadt G, Blouin JL, Antonarakis SE, Mowry BJ, Silverman JM, Crowe RR, Cloninger CR, Tsuang MT, Malaspina D, Harkavy-Friedman JM, Svrakic DM, Bassett AS, Holcomb J, Kalsi G, McQuillin A, Brynjolfson J, Sigmundsson T, Petursson H, Jazin E, Zoega T, Helgason T. Source: American Journal of Human Genetics. 2003 July; 73(1): 34-48. Epub 2003 June 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802786&dopt=Abstract

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Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: Bipolar disorder. Author(s): Segurado R, Detera-Wadleigh SD, Levinson DF, Lewis CM, Gill M, Nurnberger JI Jr, Craddock N, DePaulo JR, Baron M, Gershon ES, Ekholm J, Cichon S, Turecki G, Claes S, Kelsoe JR, Schofield PR, Badenhop RF, Morissette J, Coon H, Blackwood D, McInnes LA, Foroud T, Edenberg HJ, Reich T, Rice JP, Goate A, McInnis MG, McMahon FJ, Badner JA, Goldin LR, Bennett P, Willour VL, Zandi PP, Liu J, Gilliam C, Juo SH, Berrettini WH, Yoshikawa T, Peltonen L, Lonnqvist J, Nothen MM, Schumacher J, Windemuth C, Rietschel M, Propping P, Maier W, Alda M, Grof P, Rouleau GA, Del-Favero J, Van Broeckhoven C, Mendlewicz J, Adolfsson R, Spence MA, Luebbert H, Adams LJ, Donald JA, Mitchell PB, Barden N, Shink E, Byerley W, Muir W, Visscher PM, Macgregor S, Gurling H, Kalsi G, McQuillin A, Escamilla MA, Reus VI, Leon P, Freimer NB, Ewald H, Kruse TA, Mors O, Radhakrishna U, Blouin JL, Antonarakis SE, Akarsu N. Source: American Journal of Human Genetics. 2003 July; 73(1): 49-62. Epub 2003 June 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802785&dopt=Abstract

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Genome scan of three quantitative traits in schizophrenia pedigrees. Author(s): Wilcox MA, Faraone SV, Su J, Van Eerdewegh P, Tsuang MT. Source: Biological Psychiatry. 2002 November 1; 52(9): 847-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399137&dopt=Abstract

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Genome scans and microarrays: converging on genes for schizophrenia? Author(s): Williams NM, O'Donovan MC, Owen MJ. Source: Genome Biology. 2002; 3(4): Reviews1011. Epub 2002 March 27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983064&dopt=Abstract

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Genome-based drug discovery: prioritizing disease-susceptibility/disease-associated genes as novel drug targets for schizophrenia. Author(s): Williams M. Source: Curr Opin Investig Drugs. 2003 January; 4(1): 31-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625025&dopt=Abstract

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Genomewide linkage scan for schizophrenia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 10q22. Author(s): Fallin MD, Lasseter VK, Wolyniec PS, McGrath JA, Nestadt G, Valle D, Liang KY, Pulver AE. Source: American Journal of Human Genetics. 2003 September; 73(3): 601-11. Epub 2003 August 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929083&dopt=Abstract

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Genome-wide multipoint linkage analyses of multiplex schizophrenia pedigrees from the oceanic nation of Palau. Author(s): Devlin B, Bacanu SA, Roeder K, Reimherr F, Wender P, Galke B, Novasad D, Chu A, TCuenco K, Tiobek S, Otto C, Byerley W. Source: Molecular Psychiatry. 2002; 7(7): 689-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192612&dopt=Abstract

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Genome-wide scan for linkage to schizophrenia in a Spanish-origin cohort from Costa Rica. Author(s): DeLisi LE, Mesen A, Rodriguez C, Bertheau A, LaPrade B, Llach M, Riondet S, Razi K, Relja M, Byerley W, Sherrington R. Source: American Journal of Medical Genetics. 2002 July 8; 114(5): 497-508. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116183&dopt=Abstract

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Genome-wide scans of three independent sets of 90 Irish multiplex schizophrenia families and follow-up of selected regions in all families provides evidence for multiple susceptibility genes. Author(s): Straub RE, MacLean CJ, Ma Y, Webb BT, Myakishev MV, Harris-Kerr C, Wormley B, Sadek H, Kadambi B, O'Neill FA, Walsh D, Kendler KS. Source: Molecular Psychiatry. 2002; 7(6): 542-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140777&dopt=Abstract

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Glasgow's community care programme: 10 year follow up of discharged patients with schizophrenia. Author(s): Ward RJ, McLaughlin ME, Livingston MG. Source: Scott Med J. 2003 May; 48(2): 38-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12774592&dopt=Abstract

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Glucocorticoid hormones and early brain development in schizophrenia. Author(s): Koenig JI, Kirkpatrick B, Lee P. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 August; 27(2): 309-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093605&dopt=Abstract

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Glucose metabolism, schizophrenia, and antipsychotic drugs: comments to the paper of Dwyer et al. Author(s): Baptista T, Beaulieu S. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 2001 December; 13(4): 241-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11958367&dopt=Abstract

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Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Author(s): Theberge J, Bartha R, Drost DJ, Menon RS, Malla A, Takhar J, Neufeld RW, Rogers J, Pavlosky W, Schaefer B, Densmore M, Al-Semaan Y, Williamson PC. Source: The American Journal of Psychiatry. 2002 November; 159(11): 1944-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411236&dopt=Abstract

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Glutamine synthetase and glutamate dehydrogenase in the prefrontal cortex of patients with schizophrenia. Author(s): Burbaeva GSh, Boksha IS, Turishcheva MS, Vorobyeva EA, Savushkina OK, Tereshkina EB. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 June; 27(4): 675-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787856&dopt=Abstract

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Glycine modulators in schizophrenia. Author(s): Javitt DC. Source: Curr Opin Investig Drugs. 2002 July; 3(7): 1067-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186269&dopt=Abstract

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GPs' role in the prevention of suicide in schizophrenia. Author(s): Pompili M, Mancinelli I, Tatarelli R. Source: Family Practice. 2002 June; 19(3): 221. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978708&dopt=Abstract

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Gray and white matter brain abnormalities in first-episode schizophrenia inferred from magnetization transfer imaging. Author(s): Bagary MS, Symms MR, Barker GJ, Mutsatsa SH, Joyce EM, Ron MA. Source: Archives of General Psychiatry. 2003 August; 60(8): 779-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912761&dopt=Abstract

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Guideline recommendations for treatment of schizophrenia: the impact of managed care. Author(s): Dickey B, Normand SL, Hermann RC, Eisen SV, Cortes DE, Cleary PD, Ware N. Source: Archives of General Psychiatry. 2003 April; 60(4): 340-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695310&dopt=Abstract

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Habit and skill learning in schizophrenia: evidence of normal striatal processing with abnormal cortical input. Author(s): Weickert TW, Terrazas A, Bigelow LB, Malley JD, Hyde T, Egan MF, Weinberger DR, Goldberg TE. Source: Learning & Memory (Cold Spring Harbor, N.Y.). 2002 November-December; 9(6): 430-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464703&dopt=Abstract

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Haloperidol dose for the acute phase of schizophrenia. Author(s): Waraich PS, Adams CE, Roque M, Hamill KM, Marti J. Source: Cochrane Database Syst Rev. 2002; (3): Cd001951. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137638&dopt=Abstract

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Head size and schizophrenia. Author(s): Buckley PF, Friedman L, Jesberger JA, Schulz SC, Jaskiw G. Source: Schizophrenia Research. 2002 May 1; 55(1-2): 99-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955969&dopt=Abstract

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Health behaviors and health status of older women with schizophrenia. Author(s): Dickerson FB, Pater A, Origoni AE. Source: Psychiatric Services (Washington, D.C.). 2002 July; 53(7): 882-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096174&dopt=Abstract

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Heart transplantation and schizophrenia. Author(s): Taborda JG, Bordignon S, Bertolote JM, Taborda ML. Source: Psychosomatics. 2003 May-June; 44(3): 264-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724514&dopt=Abstract

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Heritability and number of quantitative trait loci of neurocognitive functions in families with schizophrenia. Author(s): Tuulio-Henriksson A, Haukka J, Partonen T, Varilo T, Paunio T, Ekelund J, Cannon TD, Meyer JM, Lonnqvist J. Source: American Journal of Medical Genetics. 2002 July 8; 114(5): 483-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116181&dopt=Abstract

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Heterogeneity in functional status among older outpatients with schizophrenia: employment history, living situation, and driving. Author(s): Palmer BW, Heaton RK, Gladsjo JA, Evans JD, Patterson TL, Golshan S, Jeste DV. Source: Schizophrenia Research. 2002 June 1; 55(3): 205-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048144&dopt=Abstract

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High-dose olanzapine for treatment-refractory schizophrenia. Author(s): Lerner V. Source: Clinical Neuropharmacology. 2003 March-April; 26(2): 58-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671523&dopt=Abstract

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Hippocampal deformities in schizophrenia characterized by high dimensional brain mapping. Author(s): Csernansky JG, Wang L, Jones D, Rastogi-Cruz D, Posener JA, Heydebrand G, Miller JP, Miller MI. Source: The American Journal of Psychiatry. 2002 December; 159(12): 2000-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450948&dopt=Abstract

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Hippocampal neurons in schizophrenia. Author(s): Heckers S, Konradi C. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2002 May; 109(5-6): 891905. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111476&dopt=Abstract

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Hippocampal volume in schizophrenia and its relationship with risperidone treatment: a stereological study. Author(s): Savas HA, Unal B, Erbagci H, Inaloz S, Herken H, Canan S, Gumusburun E, Zoroglu SS. Source: Neuropsychobiology. 2002; 46(2): 61-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378121&dopt=Abstract

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Historical aspects of the dichotomy between manic-depressive disorders and schizophrenia. Author(s): Angst J. Source: Schizophrenia Research. 2002 September 1; 57(1): 5-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165371&dopt=Abstract

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Historical development of the dopamine hypothesis of schizophrenia. Author(s): Baumeister AA, Francis JL. Source: Journal of the History of the Neurosciences. 2002 September; 11(3): 265-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481477&dopt=Abstract

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Historical, psychopathological, neurological, and neuropsychological aspects of deficit schizophrenia: a multicenter study. Author(s): Galderisi S, Maj M, Mucci A, Cassano GB, Invernizzi G, Rossi A, Vita A, Dell'Osso L, Daneluzzo E, Pini S. Source: The American Journal of Psychiatry. 2002 June; 159(6): 983-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042187&dopt=Abstract

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Homicidality in schizophrenia: a replication study. Author(s): Schwartz RC, Reynolds CA, Austin JF, Petersen S. Source: The American Journal of Orthopsychiatry. 2003 January; 73(1): 74-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674521&dopt=Abstract

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Hopelessness, neurocognitive function, and insight in schizophrenia: relationship to suicidal behavior. Author(s): Kim CH, Jayathilake K, Meltzer HY. Source: Schizophrenia Research. 2003 March 1; 60(1): 71-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505140&dopt=Abstract

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Hospital and community-based care for patients with chronic schizophrenia in Hong Kong--quality of life and its correlates. Author(s): Chan GW, Ungvari GS, Shek DT, Leung Dagger JJ. Source: Social Psychiatry and Psychiatric Epidemiology. 2003 April; 38(4): 196-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664230&dopt=Abstract

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How specific are deficits in mismatch negativity generation to schizophrenia? Author(s): Umbricht D, Koller R, Schmid L, Skrabo A, Grubel C, Huber T, Stassen H. Source: Biological Psychiatry. 2003 June 15; 53(12): 1120-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814863&dopt=Abstract

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Human leukocyte antigen-A specificities and its relation with season of birth in Japanese patients with schizophrenia. Author(s): Tochigi M, Ohashi J, Umekage T, Kohda K, Hibino H, Otowa T, Marui T, Masui K, Sugahara Y, Kanamori R, Juji T, Kato N, Tokunaga K, Sasaki T. Source: Neuroscience Letters. 2002 August 30; 329(2): 201-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165412&dopt=Abstract

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Hydrocortisone induced regional cerebral activity changes in schizophrenia: a PET scan study. Author(s): Ganguli R, Singh A, Brar J, Carter C, Mintun M. Source: Schizophrenia Research. 2002 August 1; 56(3): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072173&dopt=Abstract

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Immunity and schizophrenia: autoimmunity, cytokines, and immune responses. Author(s): Gaughran F. Source: Int Rev Neurobiol. 2002; 52: 275-302. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12498108&dopt=Abstract

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Impact of risperidone versus haloperidol on activities of daily living in the treatment of refractory schizophrenia. Author(s): Liberman RP, Gutkind D, Mintz J, Green M, Marshall BD Jr, Robertson MJ, Hayden J. Source: Comprehensive Psychiatry. 2002 November-December; 43(6): 469-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439835&dopt=Abstract

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Impaired detection of visual motion in schizophrenia patients. Author(s): Li CS. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 June; 26(5): 929-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369268&dopt=Abstract

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Impaired distractor inhibition in patients with schizophrenia on a negative priming task. Author(s): MacQueen GM, Galway T, Goldberg JO, Tipper SP. Source: Psychological Medicine. 2003 January; 33(1): 121-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537043&dopt=Abstract

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Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Author(s): Ryan MC, Collins P, Thakore JH. Source: The American Journal of Psychiatry. 2003 February; 160(2): 284-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562574&dopt=Abstract

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Impaired hippocampal recruitment during normal modulation of memory performance in schizophrenia. Author(s): Weiss AP, Schacter DL, Goff DC, Rauch SL, Alpert NM, Fischman AJ, Heckers S. Source: Biological Psychiatry. 2003 January 1; 53(1): 48-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513944&dopt=Abstract

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Impaired prefrontal inhibition in schizophrenia: relevance for cognitive dysfunction. Author(s): Volk DW, Lewis DA. Source: Physiology & Behavior. 2002 December; 77(4-5): 501-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526990&dopt=Abstract

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Impaired strategic regulation of contents of conscious awareness in schizophrenia. Author(s): Sonntag P, Gokalsing E, Olivier C, Robert P, Burglen F, Kauffmann-Muller F, Huron C, Salame P, Danion JM. Source: Consciousness and Cognition. 2003 June; 12(2): 190-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763004&dopt=Abstract

Studies 197

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Impaired temporal lobe processing of preattentive auditory discrimination in schizophrenia. Author(s): Pekkonen E, Katila H, Ahveninen J, Karhu J, Huotilainen M, Tiihonen J. Source: Schizophrenia Bulletin. 2002; 28(3): 467-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645678&dopt=Abstract

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Impaired Trail-Making Test-B performance in patients with acute schizophrenia is related to inefficient sequencing of planning and acting. Author(s): Wolwer W, Gaebel W. Source: Journal of Psychiatric Research. 2002 November-December; 36(6): 407-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393310&dopt=Abstract

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Impairment in basal limbic function in schizophrenia during affect recognition. Author(s): Hempel A, Hempel E, Schonknecht P, Stippich C, Schroder J. Source: Psychiatry Research. 2003 February 15; 122(2): 115-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714175&dopt=Abstract

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Impairments in perceptual competency and maintenance on a visual delayed matchto-sample test in first-episode schizophrenia. Author(s): Lencz T, Bilder RM, Turkel E, Goldman RS, Robinson D, Kane JM, Lieberman JA. Source: Archives of General Psychiatry. 2003 March; 60(3): 238-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622656&dopt=Abstract

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Implications for the neural basis of social cognition for the study of schizophrenia. Author(s): Pinkham AE, Penn DL, Perkins DO, Lieberman J. Source: The American Journal of Psychiatry. 2003 May; 160(5): 815-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727681&dopt=Abstract

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Improvement in negative symptoms of schizophrenia with antibodies to tumor necrosis factor-alpha and to interferon-gamma: a case report. Author(s): Skurkovich SV, Aleksandrovsky YA, Chekhonin VP, Ryabukhin IA, Chakhava KO, Skurkovich B. Source: The Journal of Clinical Psychiatry. 2003 June; 64(6): 734-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823095&dopt=Abstract

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In vivo determination of muscarinic acetylcholine receptor availability in schizophrenia. Author(s): Raedler TJ, Knable MB, Jones DW, Urbina RA, Gorey JG, Lee KS, Egan MF, Coppola R, Weinberger DR. Source: The American Journal of Psychiatry. 2003 January; 160(1): 118-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505810&dopt=Abstract

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Incidence of schizophrenia in south-east London between 1965 and 1997. Author(s): Boydell J, Van Os J, Lambri M, Castle D, Allardyce J, McCreadie RG, Murray RM. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 January; 182: 45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509317&dopt=Abstract

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Incidental radiological findings on brain magnetic resonance imaging in first-episode psychosis and chronic schizophrenia. Author(s): Lubman DI, Velakoulis D, McGorry PD, Smith DJ, Brewer W, Stuart G, Desmond P, Tress B, Pantelis C. Source: Acta Psychiatrica Scandinavica. 2002 November; 106(5): 331-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366466&dopt=Abstract

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Increased corneal temperature in drug-free male schizophrenia patients. Author(s): Shiloh R, Portuguese S, Bodinger L, Katz N, Sigler M, Hermesh H, Munitz H, Weizman A. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2003 January; 13(1): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480122&dopt=Abstract

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Increased early life stress and depressive symptoms in patients with comorbid substance abuse and schizophrenia. Author(s): Scheller-Gilkey G, Thomas SM, Woolwine BJ, Miller AH. Source: Schizophrenia Bulletin. 2002; 28(2): 223-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693429&dopt=Abstract

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Increased expression of c-Jun transcription factor in cerebellar vermis of patients with schizophrenia. Author(s): Todorova VK, Elbein AD, Kyosseva SV. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 August; 28(8): 1506-14. Epub 2003 June 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799614&dopt=Abstract

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Increased phospholipase A2 activity in schizophrenia with absent response to niacin. Author(s): Tavares H, Yacubian J, Talib LL, Barbosa NR, Gattaz WF. Source: Schizophrenia Research. 2003 May 1; 61(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648730&dopt=Abstract

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Increasing age does not decrease risk of schizophrenia up to age 40. Author(s): Haukka J, Suvisaari J, Lonnqvist J. Source: Schizophrenia Research. 2003 May 1; 61(1): 105-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648741&dopt=Abstract

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Independence and overlap among neurocognitive correlates of community functioning in schizophrenia. Author(s): Dickinson D, Coursey RD. Source: Schizophrenia Research. 2002 July 1; 56(1-2): 161-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084430&dopt=Abstract

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Infection, treatment and immune response in patients with bipolar disorder versus patients with major depression, schizophrenia or healthy controls. Author(s): Hinze-Selch D. Source: Bipolar Disorders. 2002; 4 Suppl 1: 81-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479687&dopt=Abstract

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Inferior frontal white matter anisotropy and negative symptoms of schizophrenia: a diffusion tensor imaging study. Author(s): Wolkin A, Choi SJ, Szilagyi S, Sanfilipo M, Rotrosen JP, Lim KO. Source: The American Journal of Psychiatry. 2003 March; 160(3): 572-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611842&dopt=Abstract

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Influence of gender on social outcome in schizophrenia. Author(s): Usall J, Haro JM, Ochoa S, Marquez M, Araya S; Needs of Patients with Schizophrenia group. Source: Acta Psychiatrica Scandinavica. 2002 November; 106(5): 337-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366467&dopt=Abstract

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Influence of genetic loading, obstetric complications and premorbid adjustment on brain morphology in schizophrenia: a MRI study. Author(s): Falkai P, Schneider-Axmann T, Honer WG, Vogeley K, Schonell H, Pfeiffer U, Scherk H, Block W, Traber F, Schild HH, Maier W, Tepest R; MRI study. Source: European Archives of Psychiatry and Clinical Neuroscience. 2003 April; 253(2): 92-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799748&dopt=Abstract

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Information processing and attentional dysfunctions as vulnerability indicators in schizophrenia spectrum disorders. Author(s): Bredgaard R, Glenthoj BY. Source: World J Biol Psychiatry. 2000 January; 1(1): 5-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607228&dopt=Abstract

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Informed consent for research in schizophrenia.: an alternative for special studies. Author(s): Posever TA, Chelmow T. Source: Irb. 2001 January-February; 23(1): 10-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530451&dopt=Abstract

200 Schizophrenia

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Inhibitory deficit in schizophrenia is not necessarily a GABAergic deficit. Author(s): Lara DR. Source: Cellular and Molecular Neurobiology. 2002 June; 22(3): 239-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469867&dopt=Abstract

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Initial and final work performance in schizophrenia: cognitive and symptom predictors. Author(s): Bryson G, Bell MD. Source: The Journal of Nervous and Mental Disease. 2003 February; 191(2): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586961&dopt=Abstract

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Injection of depot antipsychotic medications in patients with schizophrenia. Author(s): Fleishman M. Source: The Journal of Clinical Psychiatry. 2002 September; 63(9): 840-1; Author Reply 841-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363128&dopt=Abstract

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Insight and neuropsychological function in patients with schizophrenia and bipolar disorder with psychotic features. Author(s): Arduini L, Kalyvoka A, Stratta P, Rinaldi O, Daneluzzo E, Rossi A. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 June; 48(5): 338-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866340&dopt=Abstract

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Insight and personal narratives of illness in schizophrenia. Author(s): Lysaker PH, Clements CA, Plascak-Hallberg CD, Knipscheer SJ, Wright DE. Source: Psychiatry. 2002 Fall; 65(3): 197-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405078&dopt=Abstract

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Insight in persons with schizophrenia: effects of switching from conventional neuroleptics to atypical antipsychotics. Author(s): Aguglia E, De Vanna M, Onor ML, Ferrara D. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 December; 26(7-8): 1229-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502008&dopt=Abstract

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Insight in schizophrenia: a meta-analysis. Author(s): Mintz AR, Dobson KS, Romney DM. Source: Schizophrenia Research. 2003 May 1; 61(1): 75-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648738&dopt=Abstract

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Insight into illness and attitudes toward medications among inpatients with schizophrenia. Author(s): Sajatovic M, Rosch DS, Sivec HJ, Sultana D, Smith DA, Alamir S, Buckley P, Bingham CR. Source: Psychiatric Services (Washington, D.C.). 2002 October; 53(10): 1319-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364685&dopt=Abstract

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Insight, psychopathology, and interpersonal relationships in schizophrenia. Author(s): Vaz FJ, Bejar A, Casado M. Source: Schizophrenia Bulletin. 2002; 28(2): 311-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693436&dopt=Abstract

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Insight, social knowledge and working memory in schizophrenia. Author(s): Upthegrove R, Oyebode F, George M, Haque MS. Source: Psychopathology. 2002 November-December; 35(6): 341-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590192&dopt=Abstract

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Insight: its relationship with cognitive function, brain volume and symptoms in schizophrenia. Author(s): Rossell SL, Coakes J, Shapleske J, Woodruff PW, David AS. Source: Psychological Medicine. 2003 January; 33(1): 111-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537042&dopt=Abstract

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Institutionalisation and schizophrenia in Japan: social environments and negative symptoms: Nationwide survey of in-patients. Author(s): Oshima I, Mino Y, Inomata Y. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 July; 183: 50-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835244&dopt=Abstract

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Integrated care in schizophrenia: a 2-year randomized controlled study of two community-based treatment programs. Author(s): Malm U, Ivarsson B, Allebeck P, Falloon IR. Source: Acta Psychiatrica Scandinavica. 2003 June; 107(6): 415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752017&dopt=Abstract

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Interleukin-10 gene promoter polymorphism is not associated with schizophrenia in the Korean population. Author(s): Jun TY, Pae CU, Kim KS, Han H, Serretti A. Source: Psychiatry and Clinical Neurosciences. 2003 April; 57(2): 153-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667161&dopt=Abstract

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Interpersonal aspects of the syndromes of schizophrenia. Author(s): Shean G, Abel E, DeSalvo C. Source: Psychopathology. 2003 January-February; 36(1): 13-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679587&dopt=Abstract

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Interpreting narratives of motivation and schizophrenia: a biopsychosocial understanding. Author(s): Boydell KM, Gladstone BM, Volpe T. Source: Psychiatric Rehabilitation Journal. 2003 Spring; 26(4): 422-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739914&dopt=Abstract

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Invited commentary: Gaining traction on the epidemiologic landscape of schizophrenia. Author(s): McGrath JJ. Source: American Journal of Epidemiology. 2003 August 15; 158(4): 301-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915494&dopt=Abstract

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In-vitro immunomodulatory effects of haloperidol and perazine in schizophrenia. Author(s): Kowalski J, Blada P, Kucia K, Lawniczek T, Madej A, Belowski D, Herman ZS. Source: World J Biol Psychiatry. 2000 October; 1(4): 190-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607215&dopt=Abstract

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Ionotropic glutamate receptors as therapeutic targets in schizophrenia. Author(s): Coyle JT, Tsai G, Goff DC. Source: Current Drug Targets. Cns and Neurological Disorders. 2002 April; 1(2): 183-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769626&dopt=Abstract

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Is earlier better? At the beginning of schizophrenia: timing and opportunities for early intervention. Author(s): Clarke M, O'Callaghan E. Source: The Psychiatric Clinics of North America. 2003 March; 26(1): 65-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683260&dopt=Abstract

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Is schizophrenia linked to chromosome 1q? Author(s): Bassett AS, Chow EW, Vieland VJ, Brzustowicz L. Source: Science. 2002 December 20; 298(5602): 2277; Author Reply 2277. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494945&dopt=Abstract

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Is schizophrenia linked to chromosome 1q? Author(s): Macgregor S, Visscher PM, Knott S, Porteous D, Muir W, Millar K, Blackwood D. Source: Science. 2002 December 20; 298(5602): 2277; Author Reply 2277. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493873&dopt=Abstract

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Is the arginine-nitric oxide pathway involved in the pathogenesis of schizophrenia? Author(s): Yanik M, Vural H, Kocyigit A, Tutkun H, Zoroglu SS, Herken H, Savas HA, Koylu A, Akyol O. Source: Neuropsychobiology. 2003; 47(2): 61-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707486&dopt=Abstract

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Is the time course of clozapine response correlated to the time course of clozapine plasma levels? A one-year prospective study in drug-resistant patients with schizophrenia. Author(s): Fabrazzo M, La Pia S, Monteleone P, Esposito G, Pinto A, De Simone L, Bencivenga R, Maj M. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 December; 27(6): 1050-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464462&dopt=Abstract

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Is theory of mind in schizophrenia more strongly associated with clinical and social functioning than with neurocognitive deficits? Author(s): Roncone R, Falloon IR, Mazza M, De Risio A, Pollice R, Necozione S, Morosini P, Casacchia M. Source: Psychopathology. 2002 September-October; 35(5): 280-8. Erratum In: Psychopathology. 2002 November-December; 35(6): 368. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457019&dopt=Abstract

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Is there a familial overlap between schizophrenia and bipolar disorder? Author(s): Somnath CP, Janardhan Reddy YC, Jain S. Source: Journal of Affective Disorders. 2002 December; 72(3): 243-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450641&dopt=Abstract

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Is there disproportionate impairment in semantic or phonemic fluency in schizophrenia? Author(s): Kremen WS, Seidman LJ, Faraone SV, Tsuang MT. Source: Journal of the International Neuropsychological Society : Jins. 2003 January; 9(1): 79-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570361&dopt=Abstract

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Itemized clinician ratings versus global ratings of symptom severity in patients with schizophrenia. Author(s): Shores-Wilson K, Biggs MM, Miller AL, Carmody TJ, Chiles JA, Rush AJ, Crismon ML, Toprac MG, Witte BP, Webster JC. Source: Int J Methods Psychiatr Res. 2002; 11(1): 45-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459804&dopt=Abstract

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I've recently read that urban environments are associated with schizophrenia. Does city living really cause schizophrenia? Author(s): Miller MC. Source: The Harvard Mental Health Letter / from Harvard Medical School. 2003 July; 20(1): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889492&dopt=Abstract

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Lack of awareness and nonadherence in schizophrenia. Author(s): Kozuki Y, Froelicher ES. Source: Western Journal of Nursing Research. 2003 February; 25(1): 57-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584964&dopt=Abstract

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Lack of normal structural asymmetry of the anterior cingulate gyrus in female patients with schizophrenia: a volumetric magnetic resonance imaging study. Author(s): Takahashi T, Kawasaki Y, Kurokawa K, Hagino H, Nohara S, Yamashita I, Nakamura K, Murata M, Matsui M, Suzuki M, Seto H, Kurachi M. Source: Schizophrenia Research. 2002 May 1; 55(1-2): 69-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955965&dopt=Abstract

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Language comprehension and working memory language comprehension and working memory deficits in patients with schizophrenia. Author(s): Bagner DM, Melinder MR, Barch DM. Source: Schizophrenia Research. 2003 April 1; 60(2-3): 299-309. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591591&dopt=Abstract

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Language lateralization in female patients with schizophrenia: an fMRI study. Author(s): Sommer IE, Ramsey NF, Mandl RC, Kahn RS. Source: Schizophrenia Research. 2003 April 1; 60(2-3): 183-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591582&dopt=Abstract

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Latent inhibition and schizophrenia: Pavlovian conditioning of autonomic responses. Author(s): Vaitl D, Lipp O, Bauer U, Schuler G, Stark R, Zimmermann M, Kirsch P. Source: Schizophrenia Research. 2002 May 1; 55(1-2): 147-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955974&dopt=Abstract

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Launch of the Cardiac Safety in Schizophrenia Group (CSISG). Author(s): Kohen D. Source: World J Biol Psychiatry. 2001 October; 2(4): 199. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587150&dopt=Abstract

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Layer-specific reductions in GFAP-reactive astroglia in the dorsolateral prefrontal cortex in schizophrenia. Author(s): Rajkowska G, Miguel-Hidalgo JJ, Makkos Z, Meltzer H, Overholser J, Stockmeier C. Source: Schizophrenia Research. 2002 October 1; 57(2-3): 127-38. Erratum In: Schizophr Res. 2003 March 1; 60(1): 103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223243&dopt=Abstract

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Learning (potential) and social functioning in schizophrenia. Author(s): Woonings FM, Appelo MT, Kluiter H, Slooff CJ, van den Bosch RJ. Source: Schizophrenia Research. 2003 February 1; 59(2-3): 287-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414086&dopt=Abstract

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Left hippocampal volume as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric study of nonpsychotic first-degree relatives. Author(s): Seidman LJ, Faraone SV, Goldstein JM, Kremen WS, Horton NJ, Makris N, Toomey R, Kennedy D, Caviness VS, Tsuang MT. Source: Archives of General Psychiatry. 2002 September; 59(9): 839-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215084&dopt=Abstract

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Left with the voices or hearing right? Lateralization of auditory verbal hallucinations in schizophrenia. Author(s): Sommer IE, Aleman A, Kahn RS. Source: Journal of Psychiatry & Neuroscience : Jpn. 2003 May; 28(3): 217-8; Author Reply 218-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790162&dopt=Abstract

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Lessons from psychotherapy research for psychological interventions for people with schizophrenia. Author(s): Paley G, Shapiro DA. Source: Psychology and Psychotherapy. 2002 March; 75(Pt 1): 5-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006196&dopt=Abstract

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Levels of analysis in etiological research on schizophrenia. Author(s): Cannon TD, Rosso IM. Source: Development and Psychopathology. 2002 Summer; 14(3): 653-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12349878&dopt=Abstract

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Limbic cortical injury sustained during adulthood leads to schizophrenia-like syndrome. Author(s): Jaskiw GE, Kenny JF. Source: Schizophrenia Research. 2002 December 1; 58(2-3): 205-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409160&dopt=Abstract

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Linkage of chromosome 13q32 to schizophrenia in a large veterans affairs cooperative study sample. Author(s): Faraone SV, Skol AD, Tsuang DW, Bingham S, Young KA, Prabhudesai S, Haverstock SL, Mena F, Menon AS, Bisset D, Pepple J, Sautter F, Baldwin C, Weiss D, Collins J, Keith T, Boehnke M, Tsuang MT, Schellenberg GD. Source: American Journal of Medical Genetics. 2002 August 8; 114(6): 598-604. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210272&dopt=Abstract

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Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder. Author(s): Kuloglu M, Ustundag B, Atmaca M, Canatan H, Tezcan AE, Cinkilinc N. Source: Cell Biochemistry and Function. 2002 June; 20(2): 171-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979513&dopt=Abstract

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Lithium for schizophrenia. Author(s): Leucht S, McGrath J, Kissling W. Source: Cochrane Database Syst Rev. 2003; (3): Cd003834. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917990&dopt=Abstract

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Living situation, subjective quality of life and social network among individuals with schizophrenia living in community settings. Author(s): Hansson L, Middelboe T, Sorgaard KW, Bengtsson-Tops A, Bjarnason O, Merinder L, Nilsson L, Sandlund M, Korkeila J, Vinding HR. Source: Acta Psychiatrica Scandinavica. 2002 November; 106(5): 343-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366468&dopt=Abstract

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Local-global processing in early-onset schizophrenia: evidence for an impairment in shifting the spatial scale of attention. Author(s): Bellgrove MA, Vance A, Bradshaw JL. Source: Brain and Cognition. 2003 February; 51(1): 48-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633589&dopt=Abstract

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Longitudinal assessment of premorbid cognitive functioning in patients with schizophrenia through examination of standardized scholastic test performance. Author(s): Fuller R, Nopoulos P, Arndt S, O'Leary D, Ho BC, Andreasen NC. Source: The American Journal of Psychiatry. 2002 July; 159(7): 1183-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091197&dopt=Abstract

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Longitudinal follow-up of neurochemical changes during the first year of antipsychotic treatment in schizophrenia patients with minimal previous medication exposure. Author(s): Schizophr Res. 2003 Apr 1;60(2-3):313-7 Source: Schizophrenia Research. 2002 December 1; 58(2-3): 313-21. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12591592

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Longitudinal study of symptoms and cognitive function in chronic schizophrenia. Author(s): Hughes C, Kumari V, Soni W, Das M, Binneman B, Drozd S, O'Neil S, Mathew V, Sharma T. Source: Schizophrenia Research. 2003 February 1; 59(2-3): 137-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414070&dopt=Abstract

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Longitudinal Wisconsin card sorting performance in schizophrenia patients in rehabilitation. Author(s): Bryson G, Greig T, Lysaker P, Bell M. Source: Applied Neuropsychology. 2002; 9(4): 203-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584074&dopt=Abstract

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Long-term trends in sunshine duration and its association with schizophrenia birth rates and age at first registration--data from Australia and the Netherlands. Author(s): McGrath J, Selten JP, Chant D. Source: Schizophrenia Research. 2002 April 1; 54(3): 199-212. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950544&dopt=Abstract

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Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia. Author(s): Hof PR, Haroutunian V, Friedrich VL Jr, Byne W, Buitron C, Perl DP, Davis KL. Source: Biological Psychiatry. 2003 June 15; 53(12): 1075-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814859&dopt=Abstract

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Low medial and lateral right pulvinar volumes in schizophrenia: a postmortem study. Author(s): Highley JR, Walker MA, Crow TJ, Esiri MM, Harrison PJ. Source: The American Journal of Psychiatry. 2003 June; 160(6): 1177-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777280&dopt=Abstract

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Low olfactory bulb volume in first-degree relatives of patients with schizophrenia. Author(s): Turetsky BI, Moberg PJ, Arnold SE, Doty RL, Gur RE. Source: The American Journal of Psychiatry. 2003 April; 160(4): 703-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668359&dopt=Abstract

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Lower corneal temperature in neuroleptic-treated vs. drug-free schizophrenia patients. Author(s): Shiloh R, Bodinger L, Katz N, Sigler M, Stryjer R, Hermesh H, Munitz H, Weizman A. Source: Neuropsychobiology. 2003; 48(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886032&dopt=Abstract

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Machiavellianism and Theory of Mind in people affected by schizophrenia. Author(s): Mazza M, De Risio A, Tozzini C, Roncone R, Casacchia M. Source: Brain and Cognition. 2003 April; 51(3): 262-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727180&dopt=Abstract

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Magnetic resonance imaging of the thalamus in male patients with schizophrenia. Author(s): Deicken RF, Eliaz Y, Chosiad L, Feiwell R, Rogers L. Source: Schizophrenia Research. 2002 December 1; 58(2-3): 135-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409153&dopt=Abstract

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Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes. Author(s): Marder SR, Glynn SM, Wirshing WC, Wirshing DA, Ross D, Widmark C, Mintz J, Liberman RP, Blair KE. Source: The American Journal of Psychiatry. 2003 August; 160(8): 1405-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900301&dopt=Abstract

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Making sense of psychosis. Part 3. Schizophrenia: care for the 21st century. Author(s): Gillam T. Source: Nurs Times. 2002 October 1-8; 98(40): 36-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382441&dopt=Abstract

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Managing care of the patient with schizophrenia--before and after surgery. Author(s): Lynch M, Wagstaff C. Source: J Pract Nurs. 1999 December; 49(4): 12-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11951253&dopt=Abstract

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Managing patients with “treatment-resistant” schizophrenia. Author(s): Pantelis C, Lambert TJ. Source: The Medical Journal of Australia. 2003 May 5; 178 Suppl: S62-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720525&dopt=Abstract

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Map of candidate genes and STSs on 18p11.2, a bipolar disorder and schizophrenia susceptibility region. Author(s): Reyes GD, Esterling LE, Corona W, Ferraren D, Rollins DY, Padigaru M, Yoshikawa T, Monje VD, Detera-Wadleigh SD. Source: Molecular Psychiatry. 2002; 7(4): 337-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986976&dopt=Abstract

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Marine fat and brain function in manic-depressive psychosis and schizophrenia: circumstantial evidence for a 2nd aquatic period. Author(s): Saugstad LF. Source: Nutr Health. 2002; 16(1): 11-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083403&dopt=Abstract

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Maternal bonding behaviour in schizophrenia and schizoaffective disorder, considering premorbid personality traits. Author(s): Willinger U, Heiden AM, Meszaros K, Formann AK, Aschauer HN. Source: The Australian and New Zealand Journal of Psychiatry. 2002 October; 36(5): 6638. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225451&dopt=Abstract

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Maternal recall bias, obstetric history and schizophrenia. Author(s): McIntosh AM, Holmes S, Gleeson S, Burns JK, Hodges AK, Byrne MM, Dobbie R, Miller P, Lawrie SM, Johnstone EC. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2002 December; 181: 520-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456523&dopt=Abstract

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Maternal separation at birth and schizophrenia--a long-term follow-up of the Finnish Christmas Seal Home Children. Author(s): Maki P, Veijola J, Joukamaa M, Laara E, Hakko H, Jones PB, Isohanni M. Source: Schizophrenia Research. 2003 March 1; 60(1): 13-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505134&dopt=Abstract

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Maximizing the synergy between pharmacotherapy and psychosocial therapies for schizophrenia. Author(s): Lauriello J, Lenroot R, Bustillo JR. Source: The Psychiatric Clinics of North America. 2003 March; 26(1): 191-211. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683266&dopt=Abstract

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Measurement of simple reaction time in antipsychotic treatment of patients with schizophrenia. Author(s): Kores Plesnicar B, Zalar B, Tomori M, Krajnc I. Source: Wiener Klinische Wochenschrift. 2003 January 31; 115(1-2): 58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658913&dopt=Abstract

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Medical comorbidity and receipt of medical care by older homeless people with schizophrenia or depression. Author(s): Folsom DP, McCahill M, Bartels SJ, Lindamer LA, Ganiats TG, Jeste DV. Source: Psychiatric Services (Washington, D.C.). 2002 November; 53(11): 1456-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407275&dopt=Abstract

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Medical comorbidity in schizophrenia. Author(s): Lambert TJ, Velakoulis D, Pantelis C. Source: The Medical Journal of Australia. 2003 May 5; 178 Suppl: S67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720526&dopt=Abstract

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Medication compliance and comorbid substance abuse in schizophrenia: impact on community survival 4 years after a relapse. Author(s): Hunt GE, Bergen J, Bashir M. Source: Schizophrenia Research. 2002 April 1; 54(3): 253-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950550&dopt=Abstract

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Medication for schizophrenia. Author(s): Gray R. Source: Nurs Times. 2001 August 2-8; 97(31): 38-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11957534&dopt=Abstract

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Medication management for people with a diagnosis of schizophrenia. Author(s): Gray R, Robson D, Bressington D. Source: Nurs Times. 2002 November 19-25; 98(47): 38-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494838&dopt=Abstract

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Membrane Na(+)-K+ ATPase mediated cascade in bipolar mood disorder, major depressive disorder, and schizophrenia--relationship to hemispheric dominance. Author(s): Kurup AR, Kurup PA. Source: The International Journal of Neuroscience. 2002 August; 112(8): 965-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12448837&dopt=Abstract

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Memory and dating of past events in schizophrenia. Author(s): Venneri A, Bartolo A, McCrimmon S, St Clair D. Source: Journal of the International Neuropsychological Society : Jins. 2002 September; 8(6): 861-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12240751&dopt=Abstract

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Memory confidence and false memories in schizophrenia. Author(s): Moritz S, Woodward TS. Source: The Journal of Nervous and Mental Disease. 2002 September; 190(9): 641-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357100&dopt=Abstract

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Memory-delineated subtypes of schizophrenia: relationship to clinical, neuroanatomical, and neurophysiological measures. Author(s): Turetsky BI, Moberg PJ, Mozley LH, Moelter ST, Agrin RN, Gur RC, Gur RE. Source: Neuropsychology. 2002 October; 16(4): 481-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382987&dopt=Abstract

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Mental correlates of neuromotoric deviation in 6-year-olds at heightened risk for schizophrenia. Author(s): McNeil TF, Cantor-Graae E, Blennow G. Source: Schizophrenia Research. 2003 April 1; 60(2-3): 219-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591585&dopt=Abstract

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Mental Health QUERI Initiative: expert ratings of criteria to assess performance for major depressive disorder and schizophrenia. Author(s): Owen RR, Cannon D, Thrush CR; Quality Enhancement Research Initiative. Source: American Journal of Medical Quality : the Official Journal of the American College of Medical Quality. 2003 January-February; 18(1): 15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583641&dopt=Abstract

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Mental health. Penny-pinching at a cost to patients with schizophrenia. Author(s): Legge A. Source: Nurs Times. 2001 July 19-25; 97(29): 14. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11957494&dopt=Abstract

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Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Author(s): Badner JA, Gershon ES. Source: Molecular Psychiatry. 2002; 7(4): 405-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986984&dopt=Abstract

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Metabolic syndrome in patients with schizophrenia. Author(s): Heiskanen T, Niskanen L, Lyytikainen R, Saarinen PI, Hintikka J. Source: The Journal of Clinical Psychiatry. 2003 May; 64(5): 575-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755662&dopt=Abstract

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Metabotropic glutamate receptors: potential drug targets for the treatment of schizophrenia. Author(s): Chavez-Noriega LE, Schaffhauser H, Campbell UC. Source: Current Drug Targets. Cns and Neurological Disorders. 2002 June; 1(3): 261-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769619&dopt=Abstract

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Microarray analysis of gene expression in the prefrontal cortex in schizophrenia: a preliminary study. Author(s): Vawter MP, Crook JM, Hyde TM, Kleinman JE, Weinberger DR, Becker KG, Freed WJ. Source: Schizophrenia Research. 2002 November 1; 58(1): 11-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363385&dopt=Abstract

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Micrometer-sized particles in cerebrospinal fluid (CSF) in patients with schizophrenia. Author(s): Wetterberg L, Nybom R, Bratlid T, Fladby T, Olsson B, Wigzell H. Source: Neuroscience Letters. 2002 August 23; 329(1): 91-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161270&dopt=Abstract

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Migration as a risk factor for schizophrenia: a Danish population-based cohort study. Author(s): Cantor-Graae E, Pedersen CB, McNeil TF, Mortensen PB. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 February; 182: 117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562738&dopt=Abstract

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Mild procedural learning disturbances in neuroleptic-naive patients with schizophrenia. Author(s): Scherer H, Stip E, Paquet F, Bedard MA. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Winter; 15(1): 58-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556572&dopt=Abstract

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Minor physical anomalies in childhood and adolescent onset schizophrenia. Author(s): Hata K, Iida J, Iwasaka H, Negoro HI, Ueda F, Kishimoto T. Source: Psychiatry and Clinical Neurosciences. 2003 February; 57(1): 17-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519450&dopt=Abstract

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Minor physical anomalies in schizophrenia: is age a confounding factor? Author(s): Lloyd T, Doody G, Brewin J, Park B, Jones P. Source: Schizophrenia Research. 2003 May 1; 61(1): 67-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648737&dopt=Abstract

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Misdiagnosis of schizophrenia in a patient with psychotic symptoms. Author(s): Duwe BV, Turetsky BI. Source: Neuropsychiatry, Neuropsychology, and Behavioral Neurology. 2002 December; 15(4): 252-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464752&dopt=Abstract

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Mismatch negativity in detection of interval duration deviation in schizophrenia. Author(s): Davalos DB, Kisley MA, Polk SD, Ross RG. Source: Neuroreport. 2003 July 1; 14(9): 1283-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824776&dopt=Abstract

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Mitochondrial dysfunction in schizophrenia: a possible linkage to dopamine. Author(s): Ben-Shachar D. Source: Journal of Neurochemistry. 2002 December; 83(6): 1241-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472879&dopt=Abstract

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Modelling the impact of clozapine on suicide in patients with treatment-resistant schizophrenia in the UK. Author(s): Duggan A, Warner J, Knapp M, Kerwin R. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 June; 182: 505-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777341&dopt=Abstract

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Moderators of placebo response to antipsychotic treatment in patients with schizophrenia: a meta-regression. Author(s): Welge JA, Keck PE Jr. Source: Psychopharmacology. 2003 February; 166(1): 1-10. Epub 2002 December 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494247&dopt=Abstract

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Modest evidence for linkage and possible confirmation of association between NOTCH4 and schizophrenia in a large Veterans Affairs Cooperative Study sample. Author(s): Skol AD, Young KA, Tsuang DW, Faraone SV, Haverstock SL, Bingham S, Prabhudesai S, Mena F, Menon AS, Yu CE, Rundell P, Pepple J, Sauter F, Baldwin C, Weiss D, Collins J, Keith T, Boehnke M, Schellenberg GD, Tsuang MT. Source: American Journal of Medical Genetics. 2003 April 1; 118B(1): 8-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627457&dopt=Abstract

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Molecular and cellular evidence for an oligodendrocyte abnormality in schizophrenia. Author(s): Hof PR, Haroutunian V, Copland C, Davis KL, Buxbaum JD. Source: Neurochemical Research. 2002 October; 27(10): 1193-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462417&dopt=Abstract

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Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment. Author(s): Konradi C, Heckers S. Source: Pharmacology & Therapeutics. 2003 February; 97(2): 153-79. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559388&dopt=Abstract

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Molecular characterization of a 2.7-kb, 12q13-specific, retroviral-related sequence isolated by RDA from monozygotic twin pairs discordant for schizophrenia. Author(s): Deb-Rinker P, O'Reilly RL, Torrey EF, Singh SM. Source: Genome / National Research Council Canada = Genome / Conseil National De Recherches Canada. 2002 April; 45(2): 381-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11962635&dopt=Abstract

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Molecular genetic studies of schizophrenia: challenges and insights. Author(s): Kato C, Petronis A, Okazaki Y, Tochigi M, Umekage T, Sasaki T. Source: Neuroscience Research. 2002 August; 43(4): 295-304. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135773&dopt=Abstract

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Morbidity risk of psychiatric disorders among the first degree relatives of schizophrenia patients in Taiwan. Author(s): Chang CJ, Chen WJ, Liu SK, Cheng JJ, Yang WC, Chang HJ, Lane HY, Lin SK, Yang TW, Hwu HG. Source: Schizophrenia Bulletin. 2002; 28(3): 379-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645671&dopt=Abstract

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Morphology of the lateral superior temporal gyrus in neuroleptic nai;ve patients with schizophrenia: relationship to symptoms. Author(s): Kim JJ, Crespo-Facorro B, Andreasen NC, O'Leary DS, Magnotta V, Nopoulos P. Source: Schizophrenia Research. 2003 April 1; 60(2-3): 173-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591581&dopt=Abstract

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Morphology of the ventral frontal cortex in schizophrenia: relationship with social dysfunction. Author(s): Chemerinski E, Nopoulos PC, Crespo-Facorro B, Andreasen NC, Magnotta V. Source: Biological Psychiatry. 2002 July 1; 52(1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079724&dopt=Abstract

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Morphometric abnormality of the insula in schizophrenia: a comparison with obsessive-compulsive disorder and normal control using MRI. Author(s): Kim JJ, Youn T, Lee JM, Kim IY, Kim SI, Kwon JS. Source: Schizophrenia Research. 2003 April 1; 60(2-3): 191-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591583&dopt=Abstract

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Mortality in chronic schizophrenia during decreasing number of psychiatric beds in Finland. Author(s): Salokangas RK, Honkonen T, Stengard E, Koivisto AM. Source: Schizophrenia Research. 2002 April 1; 54(3): 265-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950551&dopt=Abstract

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Motivational interviewing to improve insight and treatment adherence in schizophrenia. Author(s): Rusch N, Corrigan PW. Source: Psychiatric Rehabilitation Journal. 2002 Summer; 26(1): 23-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171279&dopt=Abstract

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Motor cortical excitability in schizophrenia. Author(s): Pascual-Leone A, Manoach DS, Birnbaum R, Goff DC. Source: Biological Psychiatry. 2002 July 1; 52(1): 24-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079727&dopt=Abstract

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Moyamoya disease in a patient with schizophrenia. Author(s): Lubman DI, Pantelis C, Desmond P, Proffitt TM, Velakoulis D. Source: Journal of the International Neuropsychological Society : Jins. 2003 July; 9(5): 806-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901786&dopt=Abstract

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MRNA expression patterns and distribution of white matter neurons in dorsolateral prefrontal cortex of depressed patients differ from those in schizophrenia patients. Author(s): Molnar M, Potkin SG, Bunney WE, Jones EG. Source: Biological Psychiatry. 2003 January 1; 53(1): 39-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513943&dopt=Abstract

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Multidimensional scaling of integrated neurocognitive function and schizophrenia as a disconnexion disorder. Author(s): Welchew DE, Honey GD, Sharma T, Robbins TW, Bullmore ET. Source: Neuroimage. 2002 November; 17(3): 1227-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414263&dopt=Abstract

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Multiregional 1H-MRSI of the hippocampus, thalamus, and basal ganglia in schizophrenia. Author(s): Ende G, Braus DF, Walter S, Weber-Fahr W, Henn FA. Source: European Archives of Psychiatry and Clinical Neuroscience. 2003 February; 253(1): 9-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664307&dopt=Abstract

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Muscarinic receptors as a target for drugs treating schizophrenia. Author(s): Bymaster FP, Felder C, Ahmed S, McKinzie D. Source: Current Drug Targets. Cns and Neurological Disorders. 2002 April; 1(2): 163-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769625&dopt=Abstract

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Musical hallucinations in schizophrenia. 2. Relations with verbal hallucinations. Author(s): Baba A, Hamada H, Kocha H. Source: Psychopathology. 2003 March-April; 36(2): 104-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766321&dopt=Abstract

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Mutation screening and LD mapping in the VCFS deleted region of chromosome 22q11 in schizophrenia using a novel DNA pooling approach. Author(s): Williams NM, Spurlock G, Norton N, Williams HJ, Hamshere ML, Krawczak M, Kirov G, Nikolov I, Georgieva L, Jones S, Cardno AG, O'Donovan MC, Owen MJ. Source: Molecular Psychiatry. 2002; 7(10): 1092-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476324&dopt=Abstract

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Mutational analysis of the connexin 36 gene (CX36) and exclusion of the coding sequence as a candidate region for catatonic schizophrenia in a large pedigree. Author(s): Meyer J, Mai M, Ortega G, Mossner R, Lesch KP. Source: Schizophrenia Research. 2002 November 1; 58(1): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363395&dopt=Abstract

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N400 abnormalities in unmedicated patients with schizophrenia during a lexical decision task. Author(s): Hokama H, Hiramatsu K, Wang J, O'Donnell BF, Ogura C. Source: International Journal of Psychophysiology : Official Journal of the International Organization of Psychophysiology. 2003 April; 48(1): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694896&dopt=Abstract

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N400 and automatic semantic processing abnormalities in patients with schizophrenia. Author(s): Mathalon DH, Faustman WO, Ford JM. Source: Archives of General Psychiatry. 2002 July; 59(7): 641-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090817&dopt=Abstract

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N-acetylaspartate and N-Acetylaspartylglutamate deficits in superior temporal cortex in schizophrenia and bipolar disorder: a postmortem study. Author(s): Nudmamud S, Reynolds LM, Reynolds GP. Source: Biological Psychiatry. 2003 June 15; 53(12): 1138-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814865&dopt=Abstract

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Narcolepsy presenting as schizophrenia. Author(s): Bhat SK, Galang R. Source: The American Journal of Psychiatry. 2002 July; 159(7): 1245. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091214&dopt=Abstract

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Narcolepsy: differential diagnosis or etiology in some cases of bipolar disorder and schizophrenia? Author(s): Douglass AB. Source: Cns Spectr. 2003 February; 8(2): 120-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612497&dopt=Abstract

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Narrative incoherence in schizophrenia: the absent agent-protagonist and the collapse of internal dialogue. Author(s): Lysaker PH, Wickett AM, Wilke N, Lysaker J. Source: American Journal of Psychotherapy. 2003; 57(2): 153-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817547&dopt=Abstract

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National prescribing patterns in the management of extrapyramidal symptoms among patients with schizophrenia. Author(s): Luo RD, Belleti DA, Tran D, Arcona S, Salen PN. Source: International Journal of Psychiatry in Medicine. 2002; 32(3): 261-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12489701&dopt=Abstract

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Need assessment and quality of life in outpatients with schizophrenia: a 5-year follow-up study. Author(s): Foldemo A, Bogren L. Source: Scandinavian Journal of Caring Sciences. 2002 December; 16(4): 393-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445109&dopt=Abstract

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Negative symptoms and neuroleptics in catatonic schizophrenia. Author(s): Salokangas RK, Honkonen T, Stengard E, Koivisto AM, Hietala J. Source: Schizophrenia Research. 2003 January 1; 59(1): 73-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413645&dopt=Abstract

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Neural damage in the lenticular nucleus linked with tardive dyskinesia in schizophrenia: a preliminary study using proton magnetic resonance spectroscopy. Author(s): Ando K, Takei N, Matsumoto H, Iyo M, Isoda H, Mori N. Source: Schizophrenia Research. 2002 October 1; 57(2-3): 273-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223259&dopt=Abstract

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Neuregulin 1 and susceptibility to schizophrenia. Author(s): Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S, Brynjolfsson J, Gunnarsdottir S, Ivarsson O, Chou TT, Hjaltason O, Birgisdottir B, Jonsson H, Gudnadottir VG, Gudmundsdottir E, Bjornsson A, Ingvarsson B, Ingason A, Sigfusson S, Hardardottir H, Harvey RP, Lai D, Zhou M, Brunner D, Mutel V, Gonzalo A, Lemke G, Sainz J, Johannesson G, Andresson T, Gudbjartsson D, Manolescu A, Frigge ML, Gurney ME, Kong A, Gulcher JR, Petursson H, Stefansson K. Source: American Journal of Human Genetics. 2002 October; 71(4): 877-92. Epub 2002 July 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145742&dopt=Abstract

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Neuroanatomy and neurophysiology in schizophrenia. Author(s): Kasai K, Iwanami A, Yamasue H, Kuroki N, Nakagome K, Fukuda M. Source: Neuroscience Research. 2002 June; 43(2): 93-110. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067745&dopt=Abstract

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Neurocognition and community outcome in schizophrenia: long-term predictive validity. Author(s): Fujii DE, Wylie AM. Source: Schizophrenia Research. 2003 February 1; 59(2-3): 219-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414078&dopt=Abstract

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Neurocognitive and psychosocial correlates of hostility among persons in a post-acute phase of schizophrenia spectrum disorders. Author(s): Lysaker PH, Wright DE, Clements CA, Plascak-Hallberg CD. Source: Comprehensive Psychiatry. 2002 July-August; 43(4): 319-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107869&dopt=Abstract

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Neurocognitive correlates of response to treatment in formal thought disorder in patients with first-episode schizophrenia. Author(s): Goldstein RZ, Giovannetti T, Schullery M, Zuffante PA, Lieberman JA, Robinson DG, Barr WB, Bilder RM. Source: Neuropsychiatry, Neuropsychology, and Behavioral Neurology. 2002 June; 15(2): 88-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050471&dopt=Abstract

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Neurocognitive correlates of schizotypy in first degree relatives of schizophrenia patients. Author(s): Vollema MG, Postma B. Source: Schizophrenia Bulletin. 2002; 28(3): 367-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645670&dopt=Abstract

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Neurocognitive correlates of the COMT Val(158)Met polymorphism in chronic schizophrenia. Author(s): Bilder RM, Volavka J, Czobor P, Malhotra AK, Kennedy JL, Ni X, Goldman RS, Hoptman MJ, Sheitman B, Lindenmayer JP, Citrome L, McEvoy JP, Kunz M, Chakos M, Cooper TB, Lieberman JA. Source: Biological Psychiatry. 2002 October 1; 52(7): 701-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372660&dopt=Abstract

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Neurocognitive deficits and quality of life in outpatients with schizophrenia. Author(s): Aksaray G, Oflu S, Kaptanoglu C, Bal C. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 October; 26(6): 1217-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452550&dopt=Abstract

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Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. Author(s): Bilder RM, Goldman RS, Volavka J, Czobor P, Hoptman M, Sheitman B, Lindenmayer JP, Citrome L, McEvoy J, Kunz M, Chakos M, Cooper TB, Horowitz TL, Lieberman JA. Source: The American Journal of Psychiatry. 2002 June; 159(6): 1018-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042192&dopt=Abstract

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Neurocognitive impairments in nonpsychotic parents of children with schizophrenia and attention-deficit/hyperactivity disorder: the University of California, Los Angeles Family Study. Author(s): Asarnow RF, Nuechterlein KH, Subotnik KL, Fogelson DL, Torquato RD, Payne DL, Asamen J, Mintz J, Guthrie D. Source: Archives of General Psychiatry. 2002 November; 59(11): 1053-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418939&dopt=Abstract

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Neurodevelopmental models of schizophrenia: pathophysiologic synthesis and directions for intervention research. Author(s): Lencz T, Cornblatt B, Bilder RM. Source: Psychopharmacology Bulletin. 2001 Winter; 35(1): 95-125. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397874&dopt=Abstract

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Neuroendocrine effects of a short-term osmotic stimulus in patients with chronic schizophrenia. Author(s): Hundt W, Kellner M, Wiedemann K. Source: World J Biol Psychiatry. 2001 January; 2(1): 27-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587182&dopt=Abstract

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Neurofibrillary tangles in elderly patients with late onset schizophrenia. Author(s): Bozikas VP, Kovari E, Bouras C, Karavatos A. Source: Neuroscience Letters. 2002 May 17; 324(2): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11988339&dopt=Abstract

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Neuroimaging in schizophrenia: from theory to practice. Author(s): Sheringham J, Kumari V, Sumich A, Sharma T. Source: Hosp Med. 2002 June; 63(6): 328-31. Review. Erratum In: Hosp Med 2002 August; 63(8): 497. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096660&dopt=Abstract

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Neuroleptic dose reduction in stable chronic schizophrenia. Author(s): Tsuruta S, Nomura S, Yoshino A. Source: Schizophrenia Research. 2003 January 1; 59(1): 95-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413649&dopt=Abstract

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Neuroleptic malignant syndrome associated with risperidone and olanzapine in firstepisode schizophrenia. Author(s): Aboraya A, Schumacher J, Abdalla E, LePage J, McGhee M, Butcher D, Griffin H, Shahda M. Source: W V Med J. 2002 March-April; 98(2): 63-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048741&dopt=Abstract

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Neuroleptics and mortality in schizophrenia: prospective analysis of deaths in a French cohort of schizophrenic patients. Author(s): Montout C, Casadebaig F, Lagnaoui R, Verdoux H, Philippe A, Begaud B, Moore N. Source: Schizophrenia Research. 2002 October 1; 57(2-3): 147-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223245&dopt=Abstract

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Neurological soft signs (NSS) in 200 treatment-naive cases with schizophrenia: a community-based study in a rural setting. Author(s): Shibre T, Kebede D, Alem A, Kebreab S, Melaku Z, Deyassa N, Negash A, Fekadu A, Fekadu D, Medhin G, Negeri C, Jacobsson L, Kullgren G. Source: Nordic Journal of Psychiatry. 2002; 56(6): 425-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495537&dopt=Abstract

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Neuromagnetic correlates of impaired automatic categorical perception of speech sounds in schizophrenia. Author(s): Kasai K, Yamada H, Kamio S, Nakagome K, Iwanami A, Fukuda M, Yumoto M, Itoh K, Koshida I, Abe O, Kato N. Source: Schizophrenia Research. 2003 February 1; 59(2-3): 159-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414072&dopt=Abstract

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Neuronal calcium-binding proteins and schizophrenia. Author(s): Eyles DW, McGrath JJ, Reynolds GP. Source: Schizophrenia Research. 2002 September 1; 57(1): 27-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165373&dopt=Abstract

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Neuropathological features of a case with schizophrenia and prion protein gene P102L mutation before onset of Gerstmann-Straussler-Scheinker disease. Author(s): Sasaki K, Doh-ura K, Furuta A, Nakashima S, Morisada Y, Tateishi J, Iwaki T. Source: Acta Neuropathologica. 2003 July; 106(1): 92-6. Epub 2003 April 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682740&dopt=Abstract

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Neurophysiological evidence of error-monitoring deficits in patients with schizophrenia. Author(s): Alain C, McNeely HE, He Y, Christensen BK, West R. Source: Cerebral Cortex (New York, N.Y. : 1991). 2002 August; 12(8): 840-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122032&dopt=Abstract

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Neurophysiological markers of vulnerability to schizophrenia: sensitivity and specificity of specific quantitative eye movement measures. Author(s): Avila MT, McMahon RP, Elliott AR, Thaker GK. Source: Journal of Abnormal Psychology. 2002 May; 111(2): 259-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003448&dopt=Abstract

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Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study. Author(s): Cosway R, Byrne M, Clafferty R, Hodges A, Grant E, Abukmeil SS, Lawrie SM, Miller P, Johnstone EC. Source: Psychological Medicine. 2000 September; 30(5): 1111-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027047&dopt=Abstract

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Neuropsychological differentiation of late-onset schizophrenia and dementia of the Alzheimer's type. Author(s): Zakzanis KK, Andrikopoulos J, Young DA, Campbell Z, Sethian T. Source: Applied Neuropsychology. 2003; 10(2): 105-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788685&dopt=Abstract

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Neuropsychological functioning in elderly patients with schizophrenia and Alzheimer's disease. Author(s): McBride T, Moberg PJ, Arnold SE, Mozley LH, Mahr RN, Gibney M, Kumar A, Gur RE. Source: Schizophrenia Research. 2002 June 1; 55(3): 217-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048145&dopt=Abstract

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Neuropsychological profiles delineate distinct profiles of schizophrenia, an interaction between memory and executive function, and uneven distribution of clinical subtypes. Author(s): Hill SK, Ragland JD, Gur RC, Gur RE. Source: J Clin Exp Neuropsychol. 2002 September; 24(6): 765-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424651&dopt=Abstract

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Neuropsychology, genetic liability, and psychotic symptoms in those at high risk of schizophrenia. Author(s): Byrne M, Clafferty BA, Cosway R, Grant E, Hodges A, Whalley HC, Lawrie SM, Owens DG, Johnstone EC. Source: Journal of Abnormal Psychology. 2003 February; 112(1): 38-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653412&dopt=Abstract

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Neuroscience. Deconstructing schizophrenia. Author(s): Holden C. Source: Science. 2003 January 17; 299(5605): 333-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531993&dopt=Abstract

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Neurotensin receptor binding abnormalities in the entorhinal cortex in schizophrenia and affective disorders. Author(s): Hamid EH, Hyde TM, Egan MF, Wolf SS, Herman MM, Nemeroff CB, Kleinman JE. Source: Biological Psychiatry. 2002 May 15; 51(10): 795-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12007453&dopt=Abstract

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New antipsychotic agents for schizophrenia: pharmacokinetics and metabolism update. Author(s): Caccia S. Source: Curr Opin Investig Drugs. 2002 July; 3(7): 1073-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186270&dopt=Abstract

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New developments in the pharmacotherapy of schizophrenia. Author(s): Fleischhacker WW. Source: Journal of Neural Transmission. Supplementum. 2003; (64): 105-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830932&dopt=Abstract

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NICE guidance “a real victory” for people with schizophrenia. National Institute for Clinical Excellence. Author(s): Vass A. Source: Bmj (Clinical Research Ed.). 2002 June 15; 324(7351): 1413. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065259&dopt=Abstract

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NICE guidelines address social aspect of schizophrenia. Author(s): Hargreaves S; NICE. Source: Bmj (Clinical Research Ed.). 2003 March 29; 326(7391): 679. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663393&dopt=Abstract

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Nicotine and behavioral markers of risk for schizophrenia: a double-blind, placebocontrolled, cross-over study. Author(s): Depatie L, O'Driscoll GA, Holahan AL, Atkinson V, Thavundayil JX, Kin NN, Lal S. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 December; 27(6): 1056-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464463&dopt=Abstract

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Nicotine and familial vulnerability to schizophrenia: a discordant twin study. Author(s): Lyons MJ, Bar JL, Kremen WS, Toomey R, Eisen SA, Goldberg J, Faraone SV, Tsuang M. Source: Journal of Abnormal Psychology. 2002 November; 111(4): 687-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428784&dopt=Abstract

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Nicotine decreases bradykinesia-rigidity in haloperidol-treated patients with schizophrenia. Author(s): Yang YK, Nelson L, Kamaraju L, Wilson W, McEvoy JP. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 October; 27(4): 684-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377405&dopt=Abstract

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Nithsdale Schizophrenia Surveys 23: movement disorders. 20-year review. Author(s): Halliday J, Farrington S, Macdonald S, MacEwan T, Sharkey V, McCreadie R. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2002 November; 181: 422-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411269&dopt=Abstract

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Nithsdale Schizophrenia Surveys 24: sexual dysfunction. Case-control study. Author(s): Macdonald S, Halliday J, MacEWAN T, Sharkey V, Farrington S, Wall S, McCreadie RG. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 January; 182: 50-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509318&dopt=Abstract

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N-methyl-D-aspartate receptor-coupled glycineB receptors in the pathogenesis and treatment of schizophrenia: a critical review. Author(s): Millan MJ. Source: Current Drug Targets. Cns and Neurological Disorders. 2002 April; 1(2): 191213. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769627&dopt=Abstract

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No association between a transcription factor Activating Protein 2beta (AP-2beta) gene variant and schizophrenia. Author(s): Jonsson EG, Damberg M, Forslund K, Mattila-Evenden M, Rylander G, Asberg M, Oreland L, Sedvall GC. Source: Neuroscience Letters. 2002 September 27; 330(3): 290-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270648&dopt=Abstract

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No association between the G308A polymorphism of the tumor necrosis factor-alpha gene and schizophrenia. Author(s): Riedel M, Kronig H, Schwarz MJ, Engel RR, Kuhn KU, Sikorski C, Sokullu S, Ackenheil M, Moller HJ, Muller N. Source: European Archives of Psychiatry and Clinical Neuroscience. 2002 October; 252(5): 232-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12451465&dopt=Abstract

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No evidence for an association between the 5-hydroxytryptamine 5-HT2a receptor gene and schizophrenia in Kuwaiti Arabs. Author(s): Haider MZ, Zahid MA. Source: Psychiatry and Clinical Neurosciences. 2002 August; 56(4): 465-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109966&dopt=Abstract

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No evidence for phenotypic variation between probands in case-control versus family-based association studies of schizophrenia. Author(s): Malhotra AK, Bates JA, Jaeger J, Petrides G, Robinson DG, Bilder RM, Nassauer KW. Source: American Journal of Medical Genetics. 2002 July 8; 114(5): 509-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116184&dopt=Abstract

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No major schizophrenia locus detected on chromosome 1q in a large multicenter sample. Author(s): Levinson DF, Holmans PA, Laurent C, Riley B, Pulver AE, Gejman PV, Schwab SG, Williams NM, Owen MJ, Wildenauer DB, Sanders AR, Nestadt G, Mowry BJ, Wormley B, Bauche S, Soubigou S, Ribble R, Nertney DA, Liang KY, Martinolich L, Maier W, Norton N, Williams H, Albus M, Carpenter EB, DeMarchi N, Ewen-White KR, Walsh D, Jay M, Deleuze JF, O'Neill FA, Papadimitriou G, Weilbaecher A, Lerer B, O'Donovan MC, Dikeos D, Silverman JM, Kendler KS, Mallet J, Crowe RR, Walters M. Source: Science. 2002 April 26; 296(5568): 739-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11976456&dopt=Abstract

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No missense mutation of WKL1 in a subgroup of probands with schizophrenia. Author(s): Devaney JM, Donarum EA, Brown KM, Meyer J, Stober G, Lesch KP, Nestadt G, Stephan DA, Pulver AE. Source: Molecular Psychiatry. 2002; 7(4): 419-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986987&dopt=Abstract

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Non-Picks frontotemporal dementia imitating schizophrenia in a 22-year-old man. Author(s): Stone J, Griffiths TD, Rastogi S, Perry RH, Cleland PG. Source: Journal of Neurology. 2003 March; 250(3): 369-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749325&dopt=Abstract

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Non-right-handedness and schizophrenia. Author(s): Annett M. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2002 October; 181: 349-50. Erratum In: Br J Psychiatry. 2003 July; 183: 80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356665&dopt=Abstract

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Normative emotion-modulated startle response in individuals at risk for schizophrenia-spectrum disorders. Author(s): Gooding DC, Davidson RJ, Putnam KM, Tallent KA. Source: Schizophrenia Research. 2002 September 1; 57(1): 109-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165381&dopt=Abstract

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NOTCH4 and the frontal lobe in schizophrenia. Author(s): Wassink TH, Nopoulos P, Pietila J, Crowe RR, Andreasen NC. Source: American Journal of Medical Genetics. 2003 April 1; 118B(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627456&dopt=Abstract

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Obsessive-compulsive disorder in adolescent schizophrenia patients. Author(s): Nechmad A, Ratzoni G, Poyurovsky M, Meged S, Avidan G, Fuchs C, Bloch Y, Weizman R. Source: The American Journal of Psychiatry. 2003 May; 160(5): 1002-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727709&dopt=Abstract

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Obstetric complications and breast feeding in schizophrenia. Author(s): Amore M, Balista C, Di Fazio C, Merli V, Ferrari G, McCreadie RG. Source: The Journal of Nervous and Mental Disease. 2002 October; 190(10): 705-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409865&dopt=Abstract

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Obstetric complications and schizophrenia. Author(s): Crow TJ. Source: The American Journal of Psychiatry. 2003 May; 160(5): 1011-2; Author Reply 1012. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727712&dopt=Abstract

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Obstetric complications and schizophrenia: historical and meta-analytic review. Author(s): Cannon M, Jones PB, Murray RM. Source: The American Journal of Psychiatry. 2002 July; 159(7): 1080-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091183&dopt=Abstract

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Odor identification, eye tracking and deficit syndrome schizophrenia. Author(s): Malaspina D, Coleman E, Goetz RR, Harkavy-Friedman J, Corcoran C, Amador X, Yale S, Gorman JM. Source: Biological Psychiatry. 2002 May 15; 51(10): 809-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12007455&dopt=Abstract

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Oestrogen effects in schizophrenia and their potential therapeutic implications-review. Author(s): Riecher-Rossler A. Source: Archives of Women's Mental Health. 2002 November; 5(3): 111-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510214&dopt=Abstract

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Oestrogens and schizophrenia--introduction. Author(s): Riecher-Rossler A, Seeman MV. Source: Archives of Women's Mental Health. 2002 November; 5(3): 91-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510210&dopt=Abstract

Studies 227

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Olanzapine for schizophrenia. Author(s): Duggan L, Fenton M, Dardennes RM, El-Dosoky A, Indran S. Source: Cochrane Database Syst Rev. 2003; (1): Cd001359. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535408&dopt=Abstract

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Olanzapine for the treatment of chronic refractory schizophrenia: a 12-month followup naturalistic study. Author(s): Rodriguez-Perez V, Lopez A, Blanco C, Pena C, Lopez A, Abel A, Gomez Y, Ferreiro MJ, Rego C, Lopez A, Cudeiro F, Alvarez V, Prieto R, Ciudad A. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 October; 26(6): 1055-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452526&dopt=Abstract

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Olanzapine in refractory schizophrenia after failure of typical or atypical antipsychotic treatment: an open-label switch study. Author(s): Lindenmayer JP, Czobor P, Volavka J, Lieberman JA, Citrome L, Sheitman B, Chakos M, McEvoy JP. Source: The Journal of Clinical Psychiatry. 2002 October; 63(10): 931-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416603&dopt=Abstract

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Olanzapine treatment for patients with schizophrenia and cocaine abuse. Author(s): Tsuang J, Marder SR, Han A, Hsieh W. Source: The Journal of Clinical Psychiatry. 2002 December; 63(12): 1180 -1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530415&dopt=Abstract

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Olanzapine versus risperidone in the treatment of schizophrenia : a comparison of costs among Texas Medicaid recipients. Author(s): Rascati KL, Johnsrud MT, Crismon ML, Lage MJ, Barber BL. Source: Pharmacoeconomics. 2003; 21(10): 683-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828491&dopt=Abstract

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Olanzapine vs. haloperidol in the treatment of elderly chronic schizophrenia patients. Author(s): Barak Y, Shamir E, Zemishlani H, Mirecki I, Toren P, Weizman R. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 October; 26(6): 1199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452546&dopt=Abstract

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Olanzapine, risperidone and haloperidol in the treatment of adolescent patients with schizophrenia. Author(s): Gothelf D, Apter A, Reidman J, Brand-Gothelf A, Bloch Y, Gal G, Kikinzon L, Tyano S, Weizman R, Ratzoni G. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2003 May; 110(5): 54560. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721815&dopt=Abstract

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Olanzapine-induced weight gain in patients with first-episode schizophrenia: a double-blind, placebo-controlled study of fluoxetine addition. Author(s): Poyurovsky M, Pashinian A, Gil-Ad I, Maayan R, Schneidman M, Fuchs C, Weizman A. Source: The American Journal of Psychiatry. 2002 June; 159(6): 1058-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042201&dopt=Abstract

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Olanzapine-sertraline combination in schizophrenia with obsessive-compulsive disorder. Author(s): Poyurovsky M, Kurs R, Weizman A. Source: The Journal of Clinical Psychiatry. 2003 May; 64(5): 611. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755669&dopt=Abstract

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Older patients with schizophrenia: nature of dwelling status and symptom severity. Author(s): Gupta S, Steinmeyer C, Frank B, Lockwood K, Lentz B, Schultz K. Source: The American Journal of Psychiatry. 2003 February; 160(2): 383-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562592&dopt=Abstract

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Olfaction and social drive in schizophrenia. Author(s): Malaspina D, Coleman E. Source: Archives of General Psychiatry. 2003 June; 60(6): 578-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796221&dopt=Abstract

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On the broad applicability of the affective circumplex: representations of affective knowledge among schizophrenia patients. Author(s): Kring AM, Barrett LF, Gard DE. Source: Psychological Science : a Journal of the American Psychological Society / Aps. 2003 May; 14(3): 207-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741742&dopt=Abstract

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Optimal dose of risperidone and olanzapine for patients with schizophrenia in Taiwan. Author(s): Liu CY, Chiu NY, Wu CK, Yuan LM, Hsiao MC, Liao O. Source: International Clinical Psychopharmacology. 2003 January; 18(1): 49-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490775&dopt=Abstract

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Ordinary logic in unordinary lay theories: a key to understanding proneness to medication nonadherence in schizophrenia. Author(s): Navon L, Ozer N. Source: Archives of Psychiatric Nursing. 2003 June; 17(3): 108-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840803&dopt=Abstract

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Outcome measures and needs assessment tools for schizophrenia and related disorders. Author(s): Gilbody SM, House AO, Sheldon TA. Source: Cochrane Database Syst Rev. 2003; (1): Cd003081. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535453&dopt=Abstract

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Overcoming barriers to reintegration of patients with schizophrenia: developing a best-practice model for discharge from specialist care. Author(s): Meadows GN. Source: The Medical Journal of Australia. 2003 May 5; 178 Suppl: S53-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720523&dopt=Abstract

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Overlap between emotional blunting, depression, and extrapyramidal symptoms in schizophrenia. Author(s): Muller M. Source: Schizophrenia Research. 2002 October 1; 57(2-3): 307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223263&dopt=Abstract

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Paracingulate sulcus morphology in men with early-onset schizophrenia. Author(s): Le Provost JB, Bartres-Faz D, Paillere-Martinot ML, Artiges E, Pappata S, Recasens C, Perez-Gomez M, Bernardo M, Baeza I, Bayle F, Martinot JL. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 March; 182: 228-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611786&dopt=Abstract

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Paraphrase procedures for assessing comprehension of health outcome measures: an illustration from schizophrenia research. Author(s): Shumway M, Chouljian TL, Rozewicz F. Source: Evaluation & the Health Professions. 2003 March; 26(1): 73-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629923&dopt=Abstract

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Parental age and risk of schizophrenia: a case-control study. Author(s): Byrne M, Agerbo E, Ewald H, Eaton WW, Mortensen PB. Source: Archives of General Psychiatry. 2003 July; 60(7): 673-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860771&dopt=Abstract

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Parental schizophrenia spectrum disorders in childhood-onset and adult-onset schizophrenia. Author(s): Nicolson R, Brookner FB, Lenane M, Gochman P, Ingraham LJ, Egan MF, Kendler KS, Pickar D, Weinberger DR, Rapoport JL. Source: The American Journal of Psychiatry. 2003 March; 160(3): 490-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611830&dopt=Abstract

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Participation in screening for cardiovascular risk by people with schizophrenia or similar mental illnesses: cross sectional study in general practice. Author(s): Osborn DP, King MB, Nazareth I. Source: Bmj (Clinical Research Ed.). 2003 May 24; 326(7399): 1122-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763984&dopt=Abstract

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Pathogenesis of schizophrenia: Part I. Symptomatology, cognitive characteristics and brain morphology. Author(s): Kurachi M. Source: Psychiatry and Clinical Neurosciences. 2003 February; 57(1): 3-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519448&dopt=Abstract

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Patient characteristics and prescription patterns of atypical antipsychotics among patients with schizophrenia. Author(s): Ren XS, Kazis LE, Lee AF, Hamed A, Huang YH, Cunningham F, Miller DR. Source: Journal of Clinical Pharmacy and Therapeutics. 2002 December; 27(6): 441-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472984&dopt=Abstract

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Patients' and their relatives' causal explanations of schizophrenia. Author(s): Holzinger A, Kilian R, Lindenbach I, Petscheleit A, Angermeyer MC. Source: Social Psychiatry and Psychiatric Epidemiology. 2003 March; 38(3): 155-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616314&dopt=Abstract

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Patterns of neurocognitive deficits and unawareness of illness in schizophrenia. Author(s): Lysaker PH, Lancaster RS, Davis LW, Clements CA. Source: The Journal of Nervous and Mental Disease. 2003 January; 191(1): 38-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544598&dopt=Abstract

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Patterns of service use among persons with schizophrenia and other psychotic disorders. Author(s): Carr VJ, Johnston PJ, Lewin TJ, Rajkumar S, Carter GL, Issakidis C. Source: Psychiatric Services (Washington, D.C.). 2003 February; 54(2): 226-35. Erratum In: Psychiatr Serv. 2003 March; 54(3): 339. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556605&dopt=Abstract

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Perigenual cingulate gyrus volume in patients with schizophrenia: a magnetic resonance imaging study. Author(s): Takahashi T, Suzuki M, Kawasaki Y, Hagino H, Yamashita I, Nohara S, Nakamura K, Seto H, Kurachi M. Source: Biological Psychiatry. 2003 April 1; 53(7): 593-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679237&dopt=Abstract

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Perseveration in schizophrenia: failure to generate a plan and relationship with the psychomotor poverty subsyndrome. Author(s): Lanser MG, Berger HJ, Ellenbroek BA, Cools AR, Zitman FG. Source: Psychiatry Research. 2002 September 15; 112(1): 13-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379447&dopt=Abstract

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Personality dimensions in schizophrenia: associations with symptoms and coping. Author(s): Lysaker PH, Wilt MA, Plascak-Hallberg CD, Brenner CA, Clements CA. Source: The Journal of Nervous and Mental Disease. 2003 February; 191(2): 80-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586960&dopt=Abstract

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Pharmacological approaches to the management of schizophrenia. Author(s): Lambert TJ, Castle DJ. Source: The Medical Journal of Australia. 2003 May 5; 178 Suppl: S57-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720524&dopt=Abstract

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Phenomenology of anomalous self-experience in early schizophrenia. Author(s): Parnas J, Handest P. Source: Comprehensive Psychiatry. 2003 March-April; 44(2): 121-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658621&dopt=Abstract

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Physical anomalies and schizophrenia spectrum disorders. Author(s): Kelly BD. Source: The American Journal of Psychiatry. 2003 February; 160(2): 393; Author Reply 394. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562609&dopt=Abstract

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Physiologic impairment of olfactory stimulus processing in schizophrenia. Author(s): Turetsky BI, Moberg PJ, Owzar K, Johnson SC, Doty RL, Gur RE. Source: Biological Psychiatry. 2003 March 1; 53(5): 403-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614993&dopt=Abstract

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Plasma levels of homovanillic acid and the response to risperidone in first episode untreated acute schizophrenia. Author(s): Yoshimura R, Ueda N, Shinkai K, Nakamura J. Source: International Clinical Psychopharmacology. 2003 March; 18(2): 107-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598823&dopt=Abstract

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Plasma nitrate levels in deficit versus non-deficit forms of schizophrenia. Author(s): Suzuki E, Nakaki T, Nakamura M, Miyaoka H. Source: Journal of Psychiatry & Neuroscience : Jpn. 2003 July; 28(4): 288-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921223&dopt=Abstract

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Platelet-associated antibodies mediate protective autoimmune response in schizophrenia. Author(s): Sinyakov MS, Kessler B, Karp L, Weizman A, Kessler AR. Source: Neuropsychobiology. 2003; 48(1): 41-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886040&dopt=Abstract

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Polymorphism analysis of the upstream region of the human N-methyl-D-aspartate receptor subunit NR1 gene (GRIN1): implications for schizophrenia. Author(s): Tani A, Kikuta R, Itoh K, Joo A, Shibata H, Ninomiya H, Tashiro N, Fukumaki Y. Source: Schizophrenia Research. 2002 November 1; 58(1): 83-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363394&dopt=Abstract

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Polymorphism of the serotonin transporter gene and symptomatic dimensions of schizophrenia in the Korean population. Author(s): Pae CU, Kim JJ, Lee SJ, Lee CU, Lee C, Paik IH, Park HR, Yang S, Serretti A. Source: Neuropsychobiology. 2003; 47(4): 182-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824740&dopt=Abstract

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Polymorphisms of dopamine receptors and tardive dyskinesia among Chinese patients with schizophrenia. Author(s): Chong SA, Tan EC, Tan CH, Mythily, Chan YH. Source: American Journal of Medical Genetics. 2003 January 1; 116B(1): 51-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12497614&dopt=Abstract

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Polymorphisms of interleukin-4 promoter and receptor gene for schizophrenia in the Korean population. Author(s): Jun TY, Lee KU, Pae CU, Chae JH, Bahk WM, Kim KS, Han H. Source: Psychiatry and Clinical Neurosciences. 2003 June; 57(3): 283-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753568&dopt=Abstract

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Positive association of the AMPA receptor subunit GluR4 gene (GRIA4) haplotype with schizophrenia: linkage disequilibrium mapping using SNPs evenly distributed across the gene region. Author(s): Makino C, Fujii Y, Kikuta R, Hirata N, Tani A, Shibata A, Ninomiya H, Tashiro N, Shibata H, Fukumaki Y. Source: American Journal of Medical Genetics. 2003 January 1; 116B(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12497607&dopt=Abstract

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Postcode prescribing for schizophrenia. Author(s): Hayhurst KP, Brown P, Lewis SW. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 April; 182: 281-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668398&dopt=Abstract

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Precautionary measures reduce risk of definite neuroleptic malignant syndrome in newly typical neuroleptic-treated schizophrenia inpatients. Author(s): Shiloh R, Valevski A, Bodinger L, Misgav S, Aizenberg D, Dorfman-Etrog P, Weizman A, Munitz H. Source: International Clinical Psychopharmacology. 2003 May; 18(3): 147-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702893&dopt=Abstract

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Preclinical pharmacology of mGlu2/3 receptor agonists: novel agents for schizophrenia? Author(s): DD DD, Marek GJ. Source: Current Drug Targets. Cns and Neurological Disorders. 2002 April; 1(2): 215-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769628&dopt=Abstract

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Predicting changes in domain-specific quality of life of schizophrenia patients. Author(s): Ritsner M. Source: The Journal of Nervous and Mental Disease. 2003 May; 191(5): 287-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819547&dopt=Abstract

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Predicting vocational functioning and outcome in schizophrenia outpatients attending a vocational rehabilitation program. Author(s): Hoffmann H, Kupper Z, Zbinden M, Hirsbrunner HP. Source: Social Psychiatry and Psychiatric Epidemiology. 2003 February; 38(2): 76-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563549&dopt=Abstract

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Predictors of noncompliance in patients with schizophrenia. Author(s): Perkins DO. Source: The Journal of Clinical Psychiatry. 2002 December; 63(12): 1121-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523871&dopt=Abstract

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Predictors of risk of nonadherence in outpatients with schizophrenia and other psychotic disorders. Author(s): Weiss KA, Smith TE, Hull JW, Piper AC, Huppert JD. Source: Schizophrenia Bulletin. 2002; 28(2): 341-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693439&dopt=Abstract

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Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Author(s): Manoach DS. Source: Schizophrenia Research. 2003 April 1; 60(2-3): 285-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591590&dopt=Abstract

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Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia. Author(s): Perlstein WM, Dixit NK, Carter CS, Noll DC, Cohen JD. Source: Biological Psychiatry. 2003 January 1; 53(1): 25-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513942&dopt=Abstract

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Prefrontal-posterior parietal networks in schizophrenia: primary dysfunctions and secondary compensations. Author(s): Quintana J, Wong T, Ortiz-Portillo E, Kovalik E, Davidson T, Marder SR, Mazziotta JC. Source: Biological Psychiatry. 2003 January 1; 53(1): 12-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513941&dopt=Abstract

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Pregnancy and birth complications in patients with schizophrenia in Trinidad and London. Author(s): Bhugra D, Hutchinson G, Hilwig M, Takei N, Fahy TA, Neehall J, Murray RM. Source: The West Indian Medical Journal. 2003 June; 52(2): 124-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974062&dopt=Abstract

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Premorbid IQ and schizophrenia. Increasing cognitive reduction by episodes. Author(s): Eberhard J, Riley F, Levander S. Source: European Archives of Psychiatry and Clinical Neuroscience. 2003 April; 253(2): 84-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799746&dopt=Abstract

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Prenatal exposure to influenza as a risk factor for adult schizophrenia. Author(s): Limosin F, Rouillon F, Payan C, Cohen JM, Strub N. Source: Acta Psychiatrica Scandinavica. 2003 May; 107(5): 331-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752028&dopt=Abstract

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Prenatal underdevelopment and schizophrenia: a case report of monozygotic twins. Author(s): Kunugi H, Urushibara T, Murray RM, Nanko S, Hirose T. Source: Psychiatry and Clinical Neurosciences. 2003 June; 57(3): 271-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753566&dopt=Abstract

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Prescribers' nonadherence to treatment guidelines for schizophrenia when prescribing neuroleptics. Author(s): Sernyak MJ, Dausey D, Desai R, Rosenheck R. Source: Psychiatric Services (Washington, D.C.). 2003 February; 54(2): 246-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556608&dopt=Abstract

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Pre-therapy: a newer development in the psychotherapy of schizophrenia. Author(s): Prouty G. Source: J Am Acad Psychoanal Dyn Psychiatry. 2003 Spring; 31(1): 59-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722888&dopt=Abstract

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Prevalence and relationship to delusions and hallucinations of anxiety disorders in schizophrenia. Author(s): Tibbo P, Swainson J, Chue P, LeMelledo JM. Source: Depression and Anxiety. 2003; 17(2): 65-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621594&dopt=Abstract

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Prevalence of hepatitis B virus among chronic schizophrenia patients. Author(s): Said WM, Saleh R, Jumaian N. Source: East Mediterr Health J. 2001 May; 7(3): 526-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690775&dopt=Abstract

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Prevalence of obsessive compulsive disorder in first- and multi-episode male patients with schizophrenia-spectrum disorders. Author(s): Koen L, Oosthuizen PP, Niehaus DJ, Emsley RA, Muller JE, Stein DJ, Keyter N, Lochner C, Seedat S. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2003 July; 93(7): 517-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939924&dopt=Abstract

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Prevention and early intervention in schizophrenia: facts and visions. Author(s): Hafner H. Source: Seishin Shinkeigaku Zasshi. 2002; 104(11): 1033-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642908&dopt=Abstract

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Problem substance use and schizophrenia. Author(s): Bates P, Rutherford J. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 May; 182: 455; Author Reply 455. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724253&dopt=Abstract

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Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Author(s): Kasai K, Shenton ME, Salisbury DF, Hirayasu Y, Onitsuka T, Spencer MH, Yurgelun-Todd DA, Kikinis R, Jolesz FA, McCarley RW. Source: Archives of General Psychiatry. 2003 August; 60(8): 766-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912760&dopt=Abstract

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Progressive decrease of left superior temporal gyrus gray matter volume in patients with first-episode schizophrenia. Author(s): Kasai K, Shenton ME, Salisbury DF, Hirayasu Y, Lee CU, Ciszewski AA, Yurgelun-Todd D, Kikinis R, Jolesz FA, McCarley RW. Source: The American Journal of Psychiatry. 2003 January; 160(1): 156-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505815&dopt=Abstract

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Progressive loss of cerebellar volume in childhood-onset schizophrenia. Author(s): Keller A, Castellanos FX, Vaituzis AC, Jeffries NO, Giedd JN, Rapoport JL. Source: The American Journal of Psychiatry. 2003 January; 160(1): 128-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505811&dopt=Abstract

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Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. Author(s): Ho BC, Andreasen NC, Nopoulos P, Arndt S, Magnotta V, Flaum M. Source: Archives of General Psychiatry. 2003 June; 60(6): 585-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796222&dopt=Abstract

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Prolactin and schizophrenia: clinical consequences of hyperprolactinaemia. Author(s): Meaney AM, O'Keane V. Source: Life Sciences. 2002 July 19; 71(9): 979-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088758&dopt=Abstract

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Prospective analysis of premature mortality in schizophrenia in relation to health service engagement: a 7.5-year study within an epidemiologically complete, homogeneous population in rural Ireland. Author(s): Morgan MG, Scully PJ, Youssef HA, Kinsella A, Owens JM, Waddington JL. Source: Psychiatry Research. 2003 February 15; 117(2): 127-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606015&dopt=Abstract

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Proton magnetic resonance spectroscopy (1H MRS) in schizophrenia: investigation of the right and left hippocampus, thalamus, and prefrontal cortex. Author(s): Delamillieure P, Constans JM, Fernandez J, Brazo P, Benali K, Courtheoux P, Thibaut F, Petit M, Dollfus S. Source: Schizophrenia Bulletin. 2002; 28(2): 329-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693438&dopt=Abstract

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Psychiatrists' attitudes to maintenance medication for patients with schizophrenia. Author(s): Patel MX, Nikolaou V, David AS. Source: Psychological Medicine. 2003 January; 33(1): 83-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537039&dopt=Abstract

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Psychometrically matched visual-processing tasks in schizophrenia spectrum disorders. Author(s): Brenner CA, Wilt MA, Lysaker PH, Koyfman A, O'Donnell BF. Source: Journal of Abnormal Psychology. 2003 February; 112(1): 28-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653411&dopt=Abstract

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Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Author(s): Kapur S. Source: The American Journal of Psychiatry. 2003 January; 160(1): 13-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505794&dopt=Abstract

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Public attitudes towards people with mental illness in six German cities: results of a public survey under special consideration of schizophrenia. Author(s): Gaebel W, Baumann A, Witte AM, Zaeske H. Source: European Archives of Psychiatry and Clinical Neuroscience. 2002 December; 252(6): 278-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563536&dopt=Abstract

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Quality of life and coping with schizophrenia symptoms. Author(s): Ritsner M, Ben-Avi I, Ponizovsky A, Timinsky I, Bistrov E, Modai I. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2003 February; 12(1): 1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625513&dopt=Abstract

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Quality of life benefits of paid work activity in schizophrenia. Author(s): Bryson G, Lysaker P, Bell M. Source: Schizophrenia Bulletin. 2002; 28(2): 249-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693431&dopt=Abstract

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Quality of life in patients with schizophrenia in five European countries: the EPSILON study. Author(s): Gaite L, Vazquez-Barquero JL, Borra C, Ballesteros J, Schene A, Welcher B, Thornicroft G, Becker T, Ruggeri M, Herran A; EPSILON Study Group. Source: Acta Psychiatrica Scandinavica. 2002 April; 105(4): 283-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11942933&dopt=Abstract

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Quality of life in schizophrenia measured by the MOS SF-36 and the Lancashire Quality of Life Profile: a comparison. Author(s): Meijer CJ, Schene AH, Koeter MW. Source: Acta Psychiatrica Scandinavica. 2002 April; 105(4): 293-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11942934&dopt=Abstract

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Quality of life in schizophrenia: a review of the literature from 1995 to 2000. Author(s): Pinikahana J, Happell B, Hope J, Keks NA. Source: International Journal of Mental Health Nursing. 2002 June; 11(2): 103-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430191&dopt=Abstract

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Quality of life: an assessment of the state of psychosocial rehabilitation of patients with schizophrenia in the community. Author(s): Hasanah CI, Razali MS. Source: J R Soc Health. 2002 December; 122(4): 251-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12557735&dopt=Abstract

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Quantification of frontal and temporal lobe brain-imaging findings in schizophrenia: a meta-analysis. Author(s): Davidson LL, Heinrichs RW. Source: Psychiatry Research. 2003 February 15; 122(2): 69-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714172&dopt=Abstract

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Quantification of lateral ventricular subdivisions in schizophrenia by high-resolution three-dimensional magnetic resonance imaging. Author(s): Yotsutsuji T, Saitoh O, Suzuki M, Hagino H, Mori K, Takahashi T, Kurokawa K, Matsui M, Seto H, Kurachi M. Source: Psychiatry Research. 2003 January 20; 122(1): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589878&dopt=Abstract

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Quetiapine impact on quality of life in patients with schizophrenia. Author(s): Kaneda Y, Ohmori T. Source: The Annals of Pharmacotherapy. 2003 June; 37(6): 917-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773086&dopt=Abstract

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Quetiapine-associated and dose-related hypomania in a woman with schizophrenia. Author(s): Atmaca M, Kuloglu M, Buyukbayram A, Tezcan E. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2002 September; 17(5): 292-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381500&dopt=Abstract

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Quetiapine-induced improvement of tardive dyskinesia in three patients with schizophrenia. Author(s): Alptekin K, Kivircik BB. Source: International Clinical Psychopharmacology. 2002 September; 17(5): 263-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12177588&dopt=Abstract

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Randomised controlled trial of cognitive-behavioural therapy in early schizophrenia: acute-phase outcomes. Author(s): Lewis S, Tarrier N, Haddock G, Bentall R, Kinderman P, Kingdon D, Siddle R, Drake R, Everitt J, Leadley K, Benn A, Grazebrook K, Haley C, Akhtar S, Davies L, Palmer S, Faragher B, Dunn G. Source: The British Journal of Psychiatry. Supplement. 2002 September; 43: S91-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271807&dopt=Abstract

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Ratings of different olfactory judgements in schizophrenia. Author(s): Hudry J, Saoud M, D'Amato T, Dalery J, Royet JP. Source: Chemical Senses. 2002 June; 27(5): 407-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052777&dopt=Abstract

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Re: Schizophrenia, suicide, and blood count during treatment with clozapine. Author(s): Pompili M, Mancinelli I, Tatarelli R. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 December; 47(10): 977. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553141&dopt=Abstract

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Readability of consent forms in schizophrenia research. Author(s): Mathew J. Source: The Australian and New Zealand Journal of Psychiatry. 2002 August; 36(4): 5645. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169166&dopt=Abstract

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Readmission risk in schizophrenia: selection explains previous findings of a progressive course of disorder. Author(s): Olesen AV, Mortensen PB. Source: Psychological Medicine. 2002 October; 32(7): 1301-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420899&dopt=Abstract

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Reasons for the diagnostic discordance between clinicians and researchers in schizophrenia in the Northern Finland 1966 Birth Cohort. Author(s): Moilanen K, Veijola J, Laksy K, Makikyro T, Miettunen J, Kantojarvi L, Kokkonen P, Karvonen JT, Herva A, Joukamaa M, Jarvelin MR, Moring J, Jones PB, Isohanni M. Source: Social Psychiatry and Psychiatric Epidemiology. 2003 June; 38(6): 305-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799780&dopt=Abstract

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Recent trends in antipsychotic combination therapy of schizophrenia and schizoaffective disorder: implications for state mental health policy. Author(s): Clark RE, Bartels SJ, Mellman TA, Peacock WJ. Source: Schizophrenia Bulletin. 2002; 28(1): 75-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047024&dopt=Abstract

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Reciprocal alterations in pre- and postsynaptic inhibitory markers at chandelier cell inputs to pyramidal neurons in schizophrenia. Author(s): Volk DW, Pierri JN, Fritschy JM, Auh S, Sampson AR, Lewis DA. Source: Cerebral Cortex (New York, N.Y. : 1991). 2002 October; 12(10): 1063-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12217970&dopt=Abstract

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Recognition memory for faces in schizophrenia patients and their first-degree relatives. Author(s): Conklin HM, Calkins ME, Anderson CW, Dinzeo TJ, Iacono WG. Source: Neuropsychologia. 2002; 40(13): 2314-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417461&dopt=Abstract

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Reconsidering the classification of schizophrenia and manic depressive illness--a critical analysis and new conceptual model. Author(s): Boteva K, Lieberman J. Source: World J Biol Psychiatry. 2003 April; 4(2): 81-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692779&dopt=Abstract

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Recovery from psychosis in schizophrenia and schizoaffective disorder: symptoms and neurocognitive rate-limiters for the development of social behavior skills. Author(s): Smith TE, Hull JW, Huppert JD, Silverstein SM. Source: Schizophrenia Research. 2002 June 1; 55(3): 229-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048146&dopt=Abstract

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Redefining parental identity: caregiving and schizophrenia. Author(s): Milliken PJ, Northcott HC. Source: Qualitative Health Research. 2003 January; 13(1): 100-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12564265&dopt=Abstract

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Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations. Author(s): Lawrie SM, Buechel C, Whalley HC, Frith CD, Friston KJ, Johnstone EC. Source: Biological Psychiatry. 2002 June 15; 51(12): 1008-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062886&dopt=Abstract

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Reduced grey and white matter volumes in the temporal lobe of male patients with chronic schizophrenia. Author(s): Okugawa G, Sedvall GC, Agartz I. Source: European Archives of Psychiatry and Clinical Neuroscience. 2002 June; 252(3): 120-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192469&dopt=Abstract

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Reduced hippocampal activation during encoding and recognition of words in schizophrenia patients. Author(s): Jessen F, Scheef L, Germeshausen L, Tawo Y, Kockler M, Kuhn KU, Maier W, Schild HH, Heun R. Source: The American Journal of Psychiatry. 2003 July; 160(7): 1305-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832246&dopt=Abstract

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Reduced hippocampal anisotropy related to anteriorization of alpha EEG in schizophrenia. Author(s): Begre S, Federspiel A, Kiefer C, Schroth G, Dierks T, Strik WK. Source: Neuroreport. 2003 April 15; 14(5): 739-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692474&dopt=Abstract

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Reduced Kamin blocking in non paranoid schizophrenia: associations with schizotypy. Author(s): Moran PM, Al-Uzri MM, Watson J, Reveley MA. Source: Journal of Psychiatric Research. 2003 March-April; 37(2): 155-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842169&dopt=Abstract

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Reduced levels of specific autobiographical memories in schizophrenia. Author(s): Riutort M, Cuervo C, Danion JM, Peretti CS, Salame P. Source: Psychiatry Research. 2003 January 25; 117(1): 35-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581819&dopt=Abstract

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Reduced or increased influence of non-pertinent information in patients with schizophrenia? Author(s): Giersch A, Danion JM, Boucart M, Roeser C, Abenhaim K. Source: Acta Psychologica. 2002 September; 111(2): 171-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227434&dopt=Abstract

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Reduced P300 amplitude in a visual recognition task in patients with schizophrenia. Author(s): Vianin P, Posada A, Hugues E, Franck N, Bovet P, Parnas J, Jeannerod M. Source: Neuroimage. 2002 October; 17(2): 911-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377165&dopt=Abstract

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Reduced pineal volume in male patients with schizophrenia: no relationship to clinical features of the illness. Author(s): Bersani G, Garavini A, Iannitelli A, Quartini A, Nordio M, Di Biasi C, Pancheri P. Source: Neuroscience Letters. 2002 August 30; 329(2): 246-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165423&dopt=Abstract

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Reduced pyramidal cell somal volume in auditory association cortex of subjects with schizophrenia. Author(s): Sweet RA, Pierri JN, Auh S, Sampson AR, Lewis DA. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 March; 28(3): 599-609. Epub 2002 December 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629543&dopt=Abstract

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Reduction of chromogranin B-like immunoreactivity in distinct subregions of the hippocampus from individuals with schizophrenia. Author(s): Nowakowski C, Kaufmann WA, Adlassnig C, Maier H, Salimi K, Jellinger KA, Marksteiner J. Source: Schizophrenia Research. 2002 November 1; 58(1): 43-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363389&dopt=Abstract

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Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia. Author(s): Vawter MP, Thatcher L, Usen N, Hyde TM, Kleinman JE, Freed WJ. Source: Molecular Psychiatry. 2002; 7(6): 571-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140780&dopt=Abstract

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Regional specificity in the neuropathologic substrates of schizophrenia: a morphometric analysis of Broca's area 44 and area 9. Author(s): Selemon LD, Mrzljak J, Kleinman JE, Herman MM, Goldman-Rakic PS. Source: Archives of General Psychiatry. 2003 January; 60(1): 69-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511174&dopt=Abstract

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Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders. Author(s): Webster MJ, Knable MB, O'Grady J, Orthmann J, Weickert CS. Source: Molecular Psychiatry. 2002; 7(9): 985-94, 924. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399952&dopt=Abstract

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Rehab rounds: use of the Americans with Disabilities Act by young adults with schizophrenia. Author(s): Gioia D, Brekke JS. Source: Psychiatric Services (Washington, D.C.). 2003 March; 54(3): 302-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610236&dopt=Abstract

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Relapse and rehospitalisation rates in patients with schizophrenia: effects of second generation antipsychotics. Author(s): Csernansky JG, Schuchart EK. Source: Cns Drugs. 2002; 16(7): 473-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12056922&dopt=Abstract

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Relapse prevention in patients with schizophrenia. Author(s): van Meijel B, van der Gaag M, Kahn RS, Grypdonck MH. Source: Archives of Psychiatric Nursing. 2003 June; 17(3): 117-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840804&dopt=Abstract

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Relapse prevention in schizophrenia with new-generation antipsychotics: a systematic review and exploratory meta-analysis of randomized, controlled trials. Author(s): Leucht S, Barnes TR, Kissling W, Engel RR, Correll C, Kane JM. Source: The American Journal of Psychiatry. 2003 July; 160(7): 1209-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832232&dopt=Abstract

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Relationship between adverse effects of antipsychotic treatment and dopamine D(2) receptor polymorphisms in patients with schizophrenia. Author(s): Kaiser R, Tremblay PB, Klufmoller F, Roots I, Brockmoller J. Source: Molecular Psychiatry. 2002; 7(7): 695-705. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192613&dopt=Abstract

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Relationship between tobacco smoking and positive and negative symptoms in schizophrenia. Author(s): Patkar AA, Gopalakrishnan R, Lundy A, Leone FT, Certa KM, Weinstein SP. Source: The Journal of Nervous and Mental Disease. 2002 September; 190(9): 604-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357094&dopt=Abstract

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Relationships between anhedonia, depression, and schizophrenia. Author(s): Loas G. Source: The Journal of Nervous and Mental Disease. 2002 October; 190(10): 717-8; Author Reply 718-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409870&dopt=Abstract

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Reliabilities and intercorrelations of reported and objective measures of smoking in patients with schizophrenia. Author(s): Yang YK, McEvoy JP, Wilson WH, Levin ED, Rose JE. Source: Schizophrenia Research. 2003 March 1; 60(1): 9-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505133&dopt=Abstract

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Reliable change indexes for memory performance in schizophrenia as a means to determine drug-induced cognitive decline. Author(s): Moritz S, Iverson GL, Woodward TS. Source: Applied Neuropsychology. 2003; 10(2): 115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788686&dopt=Abstract

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REM sleep latency and wakefulness in the first sleep cycle as markers of major depression: a controlled study vs. schizophrenia and normal controls. Author(s): Rotenberg VS, Shami E, Barak Y, Indursky P, Kayumov L, Mark M. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 October; 26(6): 1211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452549&dopt=Abstract

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Remediation of facial affect recognition impairments in patients with schizophrenia: a new training program. Author(s): Frommann N, Streit M, Wolwer W. Source: Psychiatry Research. 2003 March 25; 117(3): 281-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686371&dopt=Abstract

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Remediation of problem-solving skills in schizophrenia: evidence of a persistent effect. Author(s): Medalia A, Revheim N, Casey M. Source: Schizophrenia Research. 2002 October 1; 57(2-3): 165-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223247&dopt=Abstract

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Remembering or knowing: electrophysiological evidence for an episodic memory deficit in schizophrenia. Author(s): Tendolkar I, Ruhrmann S, Brockhaus A, Pukrop R, Klosterkotter J. Source: Psychological Medicine. 2002 October; 32(7): 1261-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420895&dopt=Abstract

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Renaming the term schizophrenia in Japan. Author(s): Kim Y; Committee of Renaming the Term Schizophrenia of the Japanese Society of Pyschiatry and Neurology. Source: Lancet. 2002 September 14; 360(9336): 879. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12243954&dopt=Abstract

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Repetitive behaviors in chronic schizophrenia: using the Japanese version of the Elgin Behavior Rating Scale (JEBRS). Author(s): Kaneda Y, Kawamura I, Fujii A, Ohmori T. Source: The International Journal of Neuroscience. 2003 June; 113(6): 879-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775350&dopt=Abstract

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Response to Amar J. Klar: The chromosome 1;11 translocation provides the best evidence supporting genetic etiology for schizophrenia and bipolar affective disorders. Author(s): Millar JK, Thomson PA, Wray NR, Muir WJ, Blackwood DH, Porteous DJ. Source: Genetics. 2003 February; 163(2): 833-5; Author Reply 837-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645576&dopt=Abstract

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Reversed cerebellar asymmetry in men with first-episode schizophrenia. Author(s): Szeszko PR, Gunning-Dixon F, Ashtari M, Snyder PJ, Lieberman JA, Bilder RM. Source: Biological Psychiatry. 2003 March 1; 53(5): 450-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614998&dopt=Abstract

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Reversed hemispheric asymmetry during simple visual perception in schizophrenia. Author(s): Heckers S, Goff D, Weiss AP. Source: Psychiatry Research. 2002 November 30; 116(1-2): 25-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426031&dopt=Abstract

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RHD maternal-fetal genotype incompatibility increases schizophrenia susceptibility. Author(s): Palmer CG, Turunen JA, Sinsheimer JS, Minassian S, Paunio T, Lonnqvist J, Peltonen L, Woodward JA. Source: American Journal of Human Genetics. 2002 December; 71(6): 1312-9. Epub 2002 November 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439825&dopt=Abstract

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Right lateral fusiform gyrus dysfunction during facial information processing in schizophrenia. Author(s): Quintana J, Wong T, Ortiz-Portillo E, Marder SR, Mazziotta JC. Source: Biological Psychiatry. 2003 June 15; 53(12): 1099-112. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814861&dopt=Abstract

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Rightward cerebral asymmetry in subtypes of schizophrenia according to Leonhard's classification and to DSM-IV: a structural MRI study. Author(s): Sallet PC, Elkis H, Alves TM, Oliveira JR, Sassi E, de Castro CC, Busatto GF, Gattaz WF. Source: Psychiatry Research. 2003 May 1; 123(1): 65-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738344&dopt=Abstract

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Risk of cardiovascular disease and sudden death in schizophrenia. Author(s): Davidson M. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 9: 5-11. Review. Erratum In: J Clin Psychiatry 2002 August; 63(8): 744. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088174&dopt=Abstract

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Risperidone decreases craving and relapses in individuals with schizophrenia and cocaine dependence. Author(s): Smelson DA, Losonczy MF, Davis CW, Kaune M, Williams J, Ziedonis D. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 September; 47(7): 671-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355680&dopt=Abstract

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Risperidone in chronic schizophrenia: a detailed audit, open switch study and twoyear follow-up of patients on depot medication. Author(s): Conlon L, Fahy TJ, OToole R, Gilligan J, Prescott P. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2002 December; 17(8): 459-65. Erratum In: Eur Psychiatry. 2003 February; 18(1): 45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504262&dopt=Abstract

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Risperidone in the treatment of Hispanic inpatients with schizophrenia: a pilot study. Author(s): Frackiewicz EJ, Herrera JM, Sramek JJ, Collazo Y, Lawson WB. Source: Psychiatry. 2002 Winter; 65(4): 371-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530340&dopt=Abstract

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Risperidone treatment of schizophrenia: improvement in psychopathology and neuropsychological tests. Author(s): Borkowska A, Araszkiewicz A, Rajewski A, Rybakowski JK. Source: Neuropsychobiology. 2002; 46(2): 85-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378125&dopt=Abstract

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Risperidone versus typical antipsychotic medication for schizophrenia. Author(s): Hunter RH, Joy CB, Kennedy E, Gilbody SM, Song F. Source: Cochrane Database Syst Rev. 2003; (2): Cd000440. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804396&dopt=Abstract

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Risperidone, but not olanzapine, decreases bone mineral density in female premenopausal schizophrenia patients. Author(s): Becker D, Liver O, Mester R, Rapoport M, Weizman A, Weiss M. Source: The Journal of Clinical Psychiatry. 2003 July; 64(7): 761-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934975&dopt=Abstract

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Ritanserin antagonism of m-chlorophenylpiperazine effects in neuroleptic-free schizophrenics patients: support for serotonin-2 receptor modulation of schizophrenia symptoms. Author(s): Abi-Saab W, Seibyl JP, D'Souza DC, Karper LP, Gueorgueva R, Abi-Dargham A, Wong ML, Rajhans S, Erdos JP, Heninger GR, Charney DS, Krystal JH. Source: Psychopharmacology. 2002 June; 162(1): 55-62. Epub 2002 April 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107618&dopt=Abstract

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Rostral anterior cingulate cortex dysfunction during error processing in schizophrenia. Author(s): Laurens KR, Ngan ET, Bates AT, Kiehl KA, Liddle PF. Source: Brain; a Journal of Neurology. 2003 March; 126(Pt 3): 610-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566282&dopt=Abstract

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Safety, effectiveness, and quality of life of olanzapine in first-episode schizophrenia: a naturalistic study. Author(s): Montes JM, Ciudad A, Gascon J, Gomez JC; EFESO Study Group. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 June; 27(4): 667-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787855&dopt=Abstract

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Schizophrenia and episodic ataxia type 2. Author(s): Mechtcheriakov S, Oehl MA, Hausmann A, Fleischhacker WW, Boesch S, Schocke M, Donnemiller E. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 May; 74(5): 688-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700326&dopt=Abstract

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Schizophrenia in late life. Author(s): Tune LE, Salzman C. Source: The Psychiatric Clinics of North America. 2003 March; 26(1): 103-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683262&dopt=Abstract

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Schizophrenia stigma among medical and nursing undergraduates. Author(s): Llerena A, Caceres MC, Penas-LLedo EM. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2002 September; 17(5): 298-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381503&dopt=Abstract

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Schizophrenia subjects show intact success-related neural activation but impaired uncertainty processing during decision-making. Author(s): Paulus MP, Frank L, Brown GG, Braff DL. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 April; 28(4): 795-806. Epub 2002 November 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655327&dopt=Abstract

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Schizophrenia, I. Author(s): Tamminga CA. Source: The American Journal of Psychiatry. 2003 May; 160(5): 846. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727684&dopt=Abstract

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Schizophrenia, II: amygdalar fiber alteration as etiology? Author(s): Benes FM. Source: The American Journal of Psychiatry. 2003 June; 160(6): 1053. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777259&dopt=Abstract

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Schizophrenia, III: brain-derived neurotropic factor and genetic risk. Author(s): Egan MF, Weinberger DR, Lu B. Source: The American Journal of Psychiatry. 2003 July; 160(7): 1242. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832235&dopt=Abstract

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Schizophrenia, IV: neuregulin-1 in the human brain. Author(s): Law A. Source: The American Journal of Psychiatry. 2003 August; 160(8): 1392. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900297&dopt=Abstract

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Schizophrenia. Author(s): Magorrian K. Source: Prof Nurse. 2002 June; 17(10): 577-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12087703&dopt=Abstract

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Schizophrenia: breakdown in the well-regulated lifelong process of brain development and maturation. Author(s): Bartzokis G. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 October; 27(4): 672-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377404&dopt=Abstract

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Schizophrenia: from phenomenology to neurobiology. Author(s): Wong AH, Van Tol HH. Source: Neuroscience and Biobehavioral Reviews. 2003 May; 27(3): 269-306. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788337&dopt=Abstract

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Schizophrenia: neural mechanisms for novel therapies. Author(s): Sawa A, Snyder SH. Source: Molecular Medicine (Cambridge, Mass.). 2003 January-February; 9(1-2): 3-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765334&dopt=Abstract

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Schizophrenia: solving the puzzle. Author(s): Kelly BD, O'Callaghan E, Lane A, Larkin C. Source: Ir J Med Sci. 2003 January-March; 172(1): 37-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760463&dopt=Abstract

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Schizophrenia: the 'not-so-nice' guidelines. Author(s): Barker P, Buchanan-Barker P. Source: Journal of Psychiatric and Mental Health Nursing. 2003 June; 10(3): 374-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755926&dopt=Abstract

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Schizophrenia-like presentation of neuroacanthocytosis. Author(s): Bruneau MA, Lesperance P, Chouinard S. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Summer; 15(3): 378-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928518&dopt=Abstract

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Schizophrenia--the spirit possessed 23 year old male from rural Kpando Dzoanti, Volta Region in Ghana: case report. Author(s): Turkson SN. Source: East Afr Med J. 2000 November; 77(11): 629-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862112&dopt=Abstract

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School performance as a premorbid marker for schizophrenia: a twin study. Author(s): van Oel CJ, Sitskoorn MM, Cremer MP, Kahn RS. Source: Schizophrenia Bulletin. 2002; 28(3): 401-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645673&dopt=Abstract

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Screening the human protocadherin 8 (PCDH8) gene in schizophrenia. Author(s): Bray NJ, Kirov G, Owen RJ, Jacobsen NJ, Georgieva L, Williams HJ, Norton N, Spurlock G, Jones S, Zammit S, O'Donovan MC, Owen MJ. Source: Genes, Brain, and Behavior. 2002 August; 1(3): 187-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884975&dopt=Abstract

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Searching for schizophrenia in ancient Greek and Roman literature: a systematic review. Author(s): Evans K, McGrath J, Milns R. Source: Acta Psychiatrica Scandinavica. 2003 May; 107(5): 323-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752027&dopt=Abstract

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Selective deficits in prefrontal cortical GABAergic neurons in schizophrenia defined by the presence of calcium-binding proteins. Author(s): Beasley CL, Zhang ZJ, Patten I, Reynolds GP. Source: Biological Psychiatry. 2002 October 1; 52(7): 708-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372661&dopt=Abstract

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Self-esteem in schizophrenia: relationships between self-evaluation, family attitudes, and symptomatology. Author(s): Barrowclough C, Tarrier N, Humphreys L, Ward J, Gregg L, Andrews B. Source: Journal of Abnormal Psychology. 2003 February; 112(1): 92-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653417&dopt=Abstract

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Sensory-perceptual dysfunction in patients with schizophrenia and comorbid alcoholism. Author(s): Goldstein G, Allen DN, Sanders RD. Source: J Clin Exp Neuropsychol. 2002 December; 24(8): 1010-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650227&dopt=Abstract

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Sex differences in the risk of schizophrenia: evidence from meta-analysis. Author(s): Aleman A, Kahn RS, Selten JP. Source: Archives of General Psychiatry. 2003 June; 60(6): 565-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796219&dopt=Abstract

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Short-term effect of ECT in middle-aged and elderly patients with intractable catatonic schizophrenia. Author(s): Suzuki K, Awata S, Matsuoka H. Source: The Journal of Ect. 2003 June; 19(2): 73-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792454&dopt=Abstract

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Similarity and disparity of obsessive-compulsive disorder and schizophrenia in MR volumetric abnormalities of the hippocampus-amygdala complex. Author(s): Kwon JS, Shin YW, Kim CW, Kim YI, Youn T, Han MH, Chang KH, Kim JJ. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 July; 74(7): 962-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810792&dopt=Abstract

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Sinistrality in subtypes of schizophrenia. Author(s): Dollfus S, Buijsrogge JA, Benali K, Delamillieure P, Brazo P. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2002 September; 17(5): 272-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381497&dopt=Abstract

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Sleep and daily activity preferences in schizophrenia: associations with neurocognition and symptoms. Author(s): Hofstetter JR, Mayeda AR, Happel CG, Lysaker PH. Source: The Journal of Nervous and Mental Disease. 2003 June; 191(6): 408-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826923&dopt=Abstract

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Smoking and substance abuse in outpatients with schizophrenia: a 2-year follow-up study in Turkey. Author(s): Uzun O, Cansever A, Basoglu C, Ozsahin A. Source: Drug and Alcohol Dependence. 2003 May 21; 70(2): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732412&dopt=Abstract

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SNAP-25 reduction in the hippocampus of patients with schizophrenia. Author(s): Thompson PM, Egbufoama S, Vawter MP. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 May; 27(3): 411-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691775&dopt=Abstract

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Social cognition and neurocognitive deficits in schizophrenia. Author(s): Lancaster RS, Evans JD, Bond GR, Lysaker PH. Source: The Journal of Nervous and Mental Disease. 2003 May; 191(5): 295-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819548&dopt=Abstract

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Somal size of prefrontal cortical pyramidal neurons in schizophrenia: differential effects across neuronal subpopulations. Author(s): Pierri JN, Volk CL, Auh S, Sampson A, Lewis DA. Source: Biological Psychiatry. 2003 July 15; 54(2): 111-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873800&dopt=Abstract

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Some possible genetic parallels across alcoholism, bipolar disorder and schizophrenia. Author(s): Schuckit MA, Kelsoe JR, Braff DL, Wilhelmsen KC. Source: J Stud Alcohol. 2003 March; 64(2): 157-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12713187&dopt=Abstract

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Source monitoring impairments in schizophrenia: characterisation and associations with positive and negative symptomatology. Author(s): Brebion G, Gorman JM, Amador X, Malaspina D, Sharif Z. Source: Psychiatry Research. 2002 September 15; 112(1): 27-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379448&dopt=Abstract

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Spatial EEG structure in schizophrenia. Author(s): Irisawa S, Isotani T, Kinoshita T. Source: Methods Find Exp Clin Pharmacol. 2002; 24 Suppl D: 111. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809086&dopt=Abstract

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Spatial working memory as an endophenotype for schizophrenia. Author(s): Glahn DC, Therman S, Manninen M, Huttunen M, Kaprio J, Lonnqvist J, Cannon TD. Source: Biological Psychiatry. 2003 April 1; 53(7): 624-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679242&dopt=Abstract

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Spontaneous dyskinesia in first-degree relatives of chronically ill, never-treated people with schizophrenia. Author(s): McCreadie RG, Thara R, Srinivasan TN, Padmavathi R. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 July; 183: 45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835243&dopt=Abstract

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Stability of formal thought disorder and referential communication disturbances in schizophrenia. Author(s): Docherty NM, Cohen AS, Nienow TM, Dinzeo TJ, Dangelmaier RE. Source: Journal of Abnormal Psychology. 2003 August; 112(3): 469-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943025&dopt=Abstract

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State-dependent alterations in mitochondrial complex I activity in platelets: a potential peripheral marker for schizophrenia. Author(s): Dror N, Klein E, Karry R, Sheinkman A, Kirsh Z, Mazor M, Tzukerman M, Ben-Shachar D. Source: Molecular Psychiatry. 2002; 7(9): 995-1001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399953&dopt=Abstract

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Statistical parametric mapping of LORETA using high density EEG and individual MRI: application to mismatch negativities in schizophrenia. Author(s): Park HJ, Kwon JS, Youn T, Pae JS, Kim JJ, Kim MS, Ha KS. Source: Human Brain Mapping. 2002 November; 17(3): 168-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391570&dopt=Abstract

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Stereological quantitation in cerebella from people with schizophrenia. Author(s): Andersen BB, Pakkenberg B. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 April; 182: 354-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668413&dopt=Abstract

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Structural and functional abnormalities of the amygdala in schizophrenia. Author(s): Lawrie SM, Whalley HC, Job DE, Johnstone EC. Source: Annals of the New York Academy of Sciences. 2003 April; 985: 445-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724176&dopt=Abstract

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Structural disconnectivity in schizophrenia: a diffusion tensor magnetic resonance imaging study. Author(s): Burns J, Job D, Bastin ME, Whalley H, Macgillivray T, Johnstone EC, Lawrie SM. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 May; 182: 439-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724248&dopt=Abstract

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Studies of individuals with schizophrenia never treated with antipsychotic medications: a review. Author(s): Torrey EF. Source: Schizophrenia Research. 2002 December 1; 58(2-3): 101-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409150&dopt=Abstract

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Subjective burden over 12 months in parents of patients with schizophrenia. Author(s): Jungbauer J, Wittmund B, Dietrich S, Angermeyer MC. Source: Archives of Psychiatric Nursing. 2003 June; 17(3): 126-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840805&dopt=Abstract

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Subjective experience of language impairment and psychopathology in schizophrenia. Author(s): Maggini C, Raballo A, Pelizza L, Paini M, Croci R. Source: Psychopathology. 2003 January-February; 36(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679588&dopt=Abstract

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Subjective qualities of memories associated with the picture superiority effect in schizophrenia. Author(s): Huron C, Danion JM, Rizzo L, Killofer V, Damiens A. Source: Journal of Abnormal Psychology. 2003 February; 112(1): 152-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653423&dopt=Abstract

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Substance misuse in patients with schizophrenia: a primary care guide. Author(s): Lubman DI, Sundram S. Source: The Medical Journal of Australia. 2003 May 5; 178 Suppl: S71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720527&dopt=Abstract

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Substance use and schizophrenia: effects on symptoms, social functioning and service use. Author(s): Cantwell R; Scottish Comorbidity Study Group. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 April; 182: 324-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668408&dopt=Abstract

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Substrate kinetics of erythrocyte membrane Na,K-ATPase and lipid peroxides in schizophrenia. Author(s): Petronijevic ND, Micic DV, Duricic B, Marinkovic D, Paunovic VR. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 May; 27(3): 431-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691778&dopt=Abstract

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Suicide and schizophrenia: a review of literature for the decade (1990-1999) and implications for mental health nursing. Author(s): Pinikahana J, Happell B, Keks NA. Source: Issues in Mental Health Nursing. 2003 January-February; 24(1): 27-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735073&dopt=Abstract

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Suicide attempts in schizophrenia: the role of command auditory hallucinations for suicide. Author(s): Harkavy-Friedman JM, Kimhy D, Nelson EA, Venarde DF, Malaspina D, Mann JJ. Source: The Journal of Clinical Psychiatry. 2003 August; 64(8): 871-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927000&dopt=Abstract

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Suicide risk in placebo vs active treatment in placebo-controlled trials for schizophrenia. Author(s): Storosum JG, van Zwieten BJ, Wohlfarth T, de Haan L, Khan A, van den Brink W. Source: Archives of General Psychiatry. 2003 April; 60(4): 365-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695313&dopt=Abstract

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Suspiciousness and alcohol use disorders in schizophrenia. Author(s): Messias E, Bienvenu OJ. Source: The Journal of Nervous and Mental Disease. 2003 June; 191(6): 387-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826920&dopt=Abstract

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Switching from depot antipsychotic drugs to olanzapine in patients with chronic schizophrenia. Author(s): Godleski LS, Goldsmith LJ, Vieweg WV, Zettwoch NC, Stikovac DM, Lewis SJ. Source: The Journal of Clinical Psychiatry. 2003 February; 64(2): 119-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633119&dopt=Abstract

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Symptomatology of the initial prodromal phase in schizophrenia. Author(s): Gourzis P, Katrivanou A, Beratis S. Source: Schizophrenia Bulletin. 2002; 28(3): 415-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645674&dopt=Abstract

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The antecedents of aggressive behavior among men with schizophrenia: a prospective investigation of patients in community treatment. Author(s): Hodgins S, Hiscoke UL, Freese R. Source: Behavioral Sciences & the Law. 2003; 21(4): 523-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898506&dopt=Abstract

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The characteristics of expressed emotion among relatives of patients with schizophrenia in Chengdu, China. Author(s): Ran MS, Leff J, Hou ZJ, Xiang MZ, Chan CL. Source: Culture, Medicine and Psychiatry. 2003 March; 27(1): 95-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825786&dopt=Abstract

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The Clinical Global Impression-Schizophrenia scale: a simple instrument to measure the diversity of symptoms present in schizophrenia. Author(s): Haro JM, Kamath SA, Ochoa S, Novick D, Rele K, Fargas A, Rodriguez MJ, Rele R, Orta J, Kharbeng A, Araya S, Gervin M, Alonso J, Mavreas V, Lavrentzou E, Liontos N, Gregor K, Jones PB; SOHO Study Group. Source: Acta Psychiatrica Scandinavica. Supplementum. 2003; (416): 16-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755850&dopt=Abstract

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The concept of schizophrenia and phase-specific treatment: cognitive-behavioral treatment in pre-psychosis and in nonresponders. Author(s): Larsen TK, Bechdolf A, Birchwood M. Source: J Am Acad Psychoanal Dyn Psychiatry. 2003 Spring; 31(1): 209-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722896&dopt=Abstract

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The configuration of mental health services to facilitate care for people with schizophrenia. Author(s): Harvey CA, Fielding JM. Source: The Medical Journal of Australia. 2003 May 5; 178 Suppl: S49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720522&dopt=Abstract

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The cortical serotonin2A receptor and the pathology of schizophrenia: a likely accomplice. Author(s): Dean B. Source: Journal of Neurochemistry. 2003 April; 85(1): 1-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641722&dopt=Abstract

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The dimensional symptom structure of schizophrenia and its association with temperament and character. Author(s): Guillem F, Bicu M, Semkovska M, Debruille JB. Source: Schizophrenia Research. 2002 July 1; 56(1-2): 137-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084428&dopt=Abstract

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The effect of age on the pharmacological management of ambulatory patients treated with depot neuroleptic medications for schizophrenia and related psychotic disorders. Author(s): Mamo DC, Sweet RA, Chengappa KN, Reddy RR, Jeste DV. Source: International Journal of Geriatric Psychiatry. 2002 November; 17(11): 1012-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404650&dopt=Abstract

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The effect of peripheral visual motion on focal contrast sensitivity in positive- and negative-symptom schizophrenia. Author(s): Slaghuis WL, Thompson AK. Source: Neuropsychologia. 2003; 41(8): 968-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667532&dopt=Abstract

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The effect of risperidone treatment on superoxide dismutase in schizophrenia. Author(s): Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC. Source: Journal of Clinical Psychopharmacology. 2003 April; 23(2): 128-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640213&dopt=Abstract

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The effects of clozapine versus haloperidol on measures of impulsive aggression and suicidality in chronic schizophrenia patients: an open, nonrandomized, 6-month study. Author(s): Spivak B, Shabash E, Sheitman B, Weizman A, Mester R. Source: The Journal of Clinical Psychiatry. 2003 July; 64(7): 755-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934974&dopt=Abstract

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The effects of nicotine on specific eye tracking measures in schizophrenia. Author(s): Sherr JD, Myers C, Avila MT, Elliott A, Blaxton TA, Thaker GK. Source: Biological Psychiatry. 2002 October 1; 52(7): 721-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372663&dopt=Abstract

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The etiology of schizophrenia and the origin of language: overview of a theory. Author(s): Berlim MT, Mattevi BS, Belmonte-de-Abreu P, Crow TJ. Source: Comprehensive Psychiatry. 2003 January-February; 44(1): 7-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524630&dopt=Abstract

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The European Schizophrenia Outpatient Health Outcomes Study: baseline findings across country and treatment. Author(s): Haro JM, Edgell ET, Frewer P, Alonso J, Jones PB; SOHO Study Group. Source: Acta Psychiatrica Scandinavica. Supplementum. 2003; (416): 7-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755849&dopt=Abstract

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The experience of schizophrenia: what's gender got to do with it? A critical review of the current status of research on schizophrenia. Author(s): Nasser EH, Walders N, Jenkins JH. Source: Schizophrenia Bulletin. 2002; 28(2): 351-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693440&dopt=Abstract

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The Friedrich-Lively Instrument to Assess the Impact of Schizophrenia on Siblings (FLIISS): Part I--instrument construction. Author(s): Friedrich RM, Lively S, Rubenstein L, Buckwalter K. Source: J Nurs Meas. 2002 Winter; 10(3): 219-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885147&dopt=Abstract

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The Friedrich-Lively Instrument to Assess the Impact of Schizophrenia on Siblings (FLIISS): Part II--reliability and validity assessment. Author(s): Rubenstein L, Friedrich RM, Lively S, Buckwalter K. Source: J Nurs Meas. 2002 Winter; 10(3): 231-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885148&dopt=Abstract

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The frontal lobe neuropsychological tests in patients with schizophrenia and/or obsessive-compulsive disorder. Author(s): Borkowska A, Pilaczynska E, Rybakowski JK. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Summer; 15(3): 359-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928513&dopt=Abstract

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The human dihydropyrimidinase-related protein 2 gene on chromosome 8p21 is associated with paranoid-type schizophrenia. Author(s): Nakata K, Ujike H, Sakai A, Takaki M, Imamura T, Tanaka Y, Kuroda S. Source: Biological Psychiatry. 2003 April 1; 53(7): 571-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679234&dopt=Abstract

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The impact of novel antipsychotic drugs on quality of life among people suffering from schizophrenia. Author(s): Jukic V, Baric V, Culav-Sumic J, Herceg M, Majdancic Z, Werft-Cop M. Source: Coll Antropol. 2003; 27 Suppl 1: 119-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955901&dopt=Abstract

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The impact of prolactin elevation with antipsychotic medications on subjective quality of life in patients with schizophrenia. Author(s): Kaneda Y. Source: Clinical Neuropharmacology. 2003 July-August; 26(4): 182-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897637&dopt=Abstract

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The impact of weight gain on quality of life among persons with schizophrenia. Author(s): Allison DB, Mackell JA, McDonnell DD. Source: Psychiatric Services (Washington, D.C.). 2003 April; 54(4): 565-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663847&dopt=Abstract

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The impact upon extra-pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia. Author(s): Ritchie CW, Chiu E, Harrigan S, Hall K, Hassett A, Macfarlane S, Mastwyk M, O'Connor DW, Opie J, Ames D. Source: International Journal of Geriatric Psychiatry. 2003 May; 18(5): 432-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766921&dopt=Abstract

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The importance of nicotinic acetylcholine receptors in schizophrenia, bipolar disorder and Tourette's syndrome. Author(s): McEvoy JP, Allen TB. Source: Current Drug Targets. Cns and Neurological Disorders. 2002 August; 1(4): 43342. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769615&dopt=Abstract

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The improvement of obsessive- compulsive symptoms in a patient with schizophrenia treated with clozapine. Author(s): Kumar S, Ng B, Howie W. Source: Psychiatry and Clinical Neurosciences. 2003 April; 57(2): 235-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667173&dopt=Abstract

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The influence of olanzapine on immune cells in patients with schizophrenia. Author(s): Bilici M, Tekelioglu Y, Efendioglu S, Ovali E, Ulgen M. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 May; 27(3): 483-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691784&dopt=Abstract

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The influence of risperidone on cognitive functions in schizophrenia. Author(s): Barkic J, Filakovic P, Radanovic-Grguric L, Koic O, Laufer D, Pozgain I, Koic E, Hotujac L. Source: Coll Antropol. 2003; 27 Suppl 1: 111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955900&dopt=Abstract

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The language system in schizophrenia: effects of capacity and linguistic structure. Author(s): Condray R, Steinhauer SR, van Kammen DP, Kasparek A. Source: Schizophrenia Bulletin. 2002; 28(3): 475-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645679&dopt=Abstract

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The management of schizophrenia: cognitive behavioural therapy. Author(s): Siddle R, Kingdon D. Source: British Journal of Community Nursing. 2000 January; 5(1): 20-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784789&dopt=Abstract

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The neurodevelopmental hypothesis of schizophrenia: a review of recent developments. Author(s): McGrath JJ, Feron FP, Burne TH, Mackay-Sim A, Eyles DW. Source: Annals of Medicine. 2003; 35(2): 86-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795338&dopt=Abstract

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The new and evolving pharmacotherapy of schizophrenia. Author(s): Emsley R, Oosthuizen P. Source: The Psychiatric Clinics of North America. 2003 March; 26(1): 141-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683264&dopt=Abstract

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The new genetics of schizophrenia. Author(s): McDonald C, Murphy KC. Source: The Psychiatric Clinics of North America. 2003 March; 26(1): 41-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683259&dopt=Abstract

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The pharmacological treatment of schizophrenia in Chinese patients: a comparison of prescription patterns between 1996 and 1999. Author(s): Ungvari GS, Chung YG, Chee YK, Fung-Shing N, Kwong TW, Chiu HF. Source: British Journal of Clinical Pharmacology. 2002 October; 54(4): 437-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392594&dopt=Abstract

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The phonological similarity effect in short-term memory serial recall in schizophrenia. Author(s): Elvevag B, Weinberger DR, Goldberg TE. Source: Psychiatry Research. 2002 September 15; 112(1): 77-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379453&dopt=Abstract

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The relationship between psychoanalysis and schizophrenia. Author(s): Lucas R. Source: The International Journal of Psycho-Analysis. 2003 February; 84(Pt 1): 3-9; Discussion 9-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639260&dopt=Abstract

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The relationship of clinical factors and environmental opportunities to social functioning in young adults with schizophrenia. Author(s): Angell B, Test MA. Source: Schizophrenia Bulletin. 2002; 28(2): 259-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693432&dopt=Abstract

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The relationship of needs and quality of life in persons with schizophrenia living in the community. A Nordic multi-center study. Author(s): Hansson L, Sandlund M, Bengtsson-Tops A, Bjarnason O, Karlsson H, Mackeprang T, Merinder L, Nilsson L, Sorgaard K, Vinding H, Middelboe T. Source: Nordic Journal of Psychiatry. 2003; 57(1): 5-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745786&dopt=Abstract

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The role of estrogen in schizophrenia: implications for schizophrenia practice guidelines for women. Author(s): Grigoriadis S, Seeman MV. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 June; 47(5): 437-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085678&dopt=Abstract

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The role of psychoanalytic theory and practice in understanding and treating schizophrenia: a rejoinder to the PORT report's condemnation of psychoanalysis. Author(s): Ver Eecke W. Source: J Am Acad Psychoanal Dyn Psychiatry. 2003 Spring; 31(1): 11-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722885&dopt=Abstract

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The study of cytosolic phospholipase A2 gene polymorphism in schizophrenia using eye movement disturbances as an endophenotypic marker. Author(s): Rybakowski JK, Borkowska A, Czerski PM, Dmitrzak-Weglarz M, Hauser J. Source: Neuropsychobiology. 2003; 47(3): 115-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759552&dopt=Abstract

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The synaptic hypothesis of schizophrenia. Author(s): Frankle WG, Lerma J, Laruelle M. Source: Neuron. 2003 July 17; 39(2): 205-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873379&dopt=Abstract

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The temporal relationship between schizophrenia and crime. Author(s): Munkner R, Haastrup S, Joergensen T, Kramp P. Source: Social Psychiatry and Psychiatric Epidemiology. 2003 July; 38(7): 347-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861439&dopt=Abstract

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The tragedy of schizophrenia without psychotherapy. Author(s): Karon BP. Source: J Am Acad Psychoanal Dyn Psychiatry. 2003 Spring; 31(1): 89-118. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722890&dopt=Abstract

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The validity and reliability of the measurement of the concept 'expressed emotion' in the family members and nurses of Hong Kong patients with schizophrenia. Author(s): Arthur D; Nursing Research Group. Source: International Journal of Mental Health Nursing. 2002 September; 11(3): 192-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510597&dopt=Abstract

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Theory-based research in schizophrenia. Author(s): Beebe LH. Source: Perspectives in Psychiatric Care. 2003 April-June; 39(2): 67-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894600&dopt=Abstract

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Thyroid dysfunction in chronic schizophrenia within a state psychiatric hospital. Author(s): Sim K, Chong SA, Chan YH, Lum WM. Source: Ann Acad Med Singapore. 2002 September; 31(5): 641-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395653&dopt=Abstract

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TNFB polymorphism may be associated with schizophrenia in the Korean population. Author(s): Jun TY, Pae CU, Chae JH, Bahk WM, Kim KS, Han H, Serretti A. Source: Schizophrenia Research. 2003 May 1; 61(1): 39-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648734&dopt=Abstract

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Translating advances in schizophrenia treatment: a glass ceiling. Author(s): McGorry PD. Source: The Medical Journal of Australia. 2003 May 5; 178(9): 425-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720506&dopt=Abstract

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Trauma and posttraumatic stress disorder in people with schizophrenia. Author(s): Resnick SG, Bond GR, Mueser KT. Source: Journal of Abnormal Psychology. 2003 August; 112(3): 415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943020&dopt=Abstract

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Traumatic life events and PTSD among women with substance use disorders and schizophrenia. Author(s): Gearon JS, Kaltman SI, Brown C, Bellack AS. Source: Psychiatric Services (Washington, D.C.). 2003 April; 54(4): 523-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663840&dopt=Abstract

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Treatment of schizophrenia and comorbid substance use disorder. Author(s): Green AI, Salomon MS, Brenner MJ, Rawlins K. Source: Current Drug Targets. Cns and Neurological Disorders. 2002 April; 1(2): 129-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769622&dopt=Abstract

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Treatment of schizophrenia: preventing the progression of disease. Author(s): Csernansky JG. Source: The Psychiatric Clinics of North America. 2003 June; 26(2): 367-79. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778839&dopt=Abstract

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Tumor necrosis factor haplotype analysis amongst schizophrenia probands from four distinct populations in the Asia-Pacific region. Author(s): Handoko HY, Nancarrow DJ, Hayward NK, Ohaeri JU, Aghanwa H, McGrath JJ, Levinson DF, Johns C, Walters MK, Nertney DA, Srinivasan TN, Thara R, Mowry BJ. Source: American Journal of Medical Genetics. 2003 August 15; 121B(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898567&dopt=Abstract

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Tumor necrosis factor-alpha gene polymorphism at position -308 and schizophrenia in the Korean population. Author(s): Pae CU, Chae JH, Bahk WM, Han H, Jun TY, Kim KS, Kwon YS, Serretti A. Source: Psychiatry and Clinical Neurosciences. 2003 August; 57(4): 399-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839521&dopt=Abstract

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Two clusters of serum midkine levels in drug-naive patients with schizophrenia. Author(s): Shimizu E, Hashimoto K, Salama RH, Watanabe H, Komatsu N, Okamura N, Koike K, Shinoda N, Nakazato M, Kumakiri C, Okada S, Muramatsu H, Muramatsu T, Iyo M. Source: Neuroscience Letters. 2003 June 26; 344(2): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782336&dopt=Abstract

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Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia: evidence for decreased neuronal somal size and increased neuronal density. Author(s): Chana G, Landau S, Beasley C, Everall IP, Cotter D. Source: Biological Psychiatry. 2003 June 15; 53(12): 1086-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814860&dopt=Abstract

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Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study. Author(s): Kubicki M, Westin CF, Maier SE, Frumin M, Nestor PG, Salisbury DF, Kikinis R, Jolesz FA, McCarley RW, Shenton ME. Source: The American Journal of Psychiatry. 2002 May; 159(5): 813-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986136&dopt=Abstract

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Understanding predisposition to schizophrenia: toward intervention and prevention. Author(s): Tsuang MT, Stone WS, Faraone SV. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 August; 47(6): 518-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211879&dopt=Abstract

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Understanding the neurotransmitter pathology of schizophrenia: selective deficits of subtypes of cortical GABAergic neurons. Author(s): Reynolds GP, Beasley CL, Zhang ZJ. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2002 May; 109(5-6): 8819. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111475&dopt=Abstract

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Understanding the new and evolving profile of adverse drug effects in schizophrenia. Author(s): Wirshing DA, Pierre JM, Erhart SM, Boyd JA. Source: The Psychiatric Clinics of North America. 2003 March; 26(1): 165-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683265&dopt=Abstract

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Undiagnosed hyperglycemia in clozapine-treated patients with schizophrenia. Author(s): Sernyak MJ, Gulanski B, Leslie DL, Rosenheck R. Source: The Journal of Clinical Psychiatry. 2003 May; 64(5): 605-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755666&dopt=Abstract

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Unilateral auditory hallucinations in schizophrenia after damage to the right hippocampus. Author(s): Takebayashi H, Takei N, Mori N, Suzuki S. Source: Schizophrenia Research. 2002 December 1; 58(2-3): 329-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409174&dopt=Abstract

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Unirhinal olfactory identification deficits in young male patients with schizophrenia and related disorders: association with impaired memory function. Author(s): Good KP, Martzke JS, Milliken HI, Honer WG, Kopala LC. Source: Schizophrenia Research. 2002 August 1; 56(3): 211-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072170&dopt=Abstract

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Unit costs in international economic evaluations: resource costing of the Schizophrenia Outpatient Health Outcomes Study. Author(s): Urdahl H, Knapp M, Edgell ET, Ghandi G, Haro JM; SOHO Study Group. Source: Acta Psychiatrica Scandinavica. Supplementum. 2003; (416): 41-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755853&dopt=Abstract

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Untreated initial psychosis: relation to cognitive deficits and brain morphology in first-episode schizophrenia. Author(s): Ho BC, Alicata D, Ward J, Moser DJ, O'Leary DS, Arndt S, Andreasen NC. Source: The American Journal of Psychiatry. 2003 January; 160(1): 142-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505813&dopt=Abstract

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Upper-extremity self-amputation in a case with schizophrenia. Author(s): Kobayashi T, Osawa T, Kato S. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2002 May; 17(3): 172-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052580&dopt=Abstract

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Up-regulation of striatal adenosine A(2A) receptors in schizophrenia. Author(s): Deckert J, Brenner M, Durany N, Zochling R, Paulus W, Ransmayr G, Tatschner T, Danielczyk W, Jellinger K, Riederer P. Source: Neuroreport. 2003 March 3; 14(3): 313-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634474&dopt=Abstract

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Up-regulation of the D1 dopamine receptor-interacting protein, calcyon, in patients with schizophrenia. Author(s): Koh PO, Bergson C, Undie AS, Goldman-Rakic PS, Lidow MS. Source: Archives of General Psychiatry. 2003 March; 60(3): 311-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622665&dopt=Abstract

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Use and automation of a rule in schizophrenia. Author(s): Posada A, Franck N. Source: Psychiatry Research. 2002 April 15; 109(3): 289-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959365&dopt=Abstract

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Use of conventional antipsychotics and the cost of treating schizophrenia. Author(s): Lyu RR, McCombs JS, Johnstone BM, Muse DN. Source: Health Care Financing Review. 2001 Winter; 23(2): 83-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500340&dopt=Abstract

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Use of drugs, alcohol and tobacco by people with schizophrenia: case-control study. Author(s): McCreadie RG; Scottish Comorbidity Study Group. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2002 October; 181: 321-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356659&dopt=Abstract

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Use of mood stabilizers among patients with schizophrenia, 1994-2001. Author(s): Citrome L, Jaffe A, Levine J, Allingham B. Source: Psychiatric Services (Washington, D.C.). 2002 October; 53(10): 1212. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364663&dopt=Abstract

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Use of the Beck Scale for suicide ideation with psychiatric inpatients diagnosed with schizophrenia, schizoaffective, or bipolar disorders. Author(s): Pinninti N, Steer RA, Rissmiller DJ, Nelson S, Beck AT. Source: Behaviour Research and Therapy. 2002 September; 40(9): 1071-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296492&dopt=Abstract

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Using an explicit guideline-based criterion and implicit review to assess antipsychotic dosing performance for schizophrenia. Author(s): Owen RR, Thrush CR, Hudson TJ, Mallory SR, Fischer EP, Clardy JA, Williams DK. Source: International Journal for Quality in Health Care : Journal of the International Society for Quality in Health Care / Isqua. 2002 June; 14(3): 199-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12108530&dopt=Abstract

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Using figure ground perception to examine the unitary and heterogeneity models for psychopathology in schizophrenia. Author(s): Malaspina D, Simon N, Corcoran C, Mujica-Parodi L, Goetz RR, Gorman J. Source: Schizophrenia Research. 2003 February 1; 59(2-3): 297-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414087&dopt=Abstract

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Using state administrative and pharmacy data bases to develop a clinical decision support tool for schizophrenia guidelines. Author(s): Finnerty M, Altmansberger R, Bopp J, Carpinello S, Docherty JP, Fisher W, Jensen P, Krishnan P, Mittleman M, Olfson M, Tricarico J, White T, Felton C. Source: Schizophrenia Bulletin. 2002; 28(1): 85-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047025&dopt=Abstract

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Using the rating scale for psychotic symptoms to characterize delusions expressed in a schizophrenia patient with “Internet psychosis”. Author(s): Margolese HC, Chouinard G, Beauclair L, Miller R. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 June; 47(5): 485. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085686&dopt=Abstract

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Validity of the depressive dimension extracted from principal component analysis of the PANSS in drug-free patients with schizophrenia. Author(s): El Yazaji M, Battas O, Agoub M, Moussaoui D, Gutknecht C, Dalery J, d'Amato T, Saoud M. Source: Schizophrenia Research. 2002 July 1; 56(1-2): 121-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084426&dopt=Abstract

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Very late-onset schizophrenia-like psychosis: clinical and imaging characteristics in comparison with elderly patients with schizophrenia. Author(s): Barak Y, Aizenberg D, Mirecki I, Mazeh D, Achiron A. Source: The Journal of Nervous and Mental Disease. 2002 November; 190(11): 733-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12436012&dopt=Abstract

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Victim relations and victim gender in violent crimes committed by offenders with schizophrenia. Author(s): Nordstrom A, Kullgren G. Source: Social Psychiatry and Psychiatric Epidemiology. 2003 June; 38(6): 326-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799783&dopt=Abstract

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Violence and schizophrenia: examining the evidence. Author(s): Walsh E, Buchanan A, Fahy T. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2002 June; 180: 490-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042226&dopt=Abstract

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Violent behavior in chronic schizophrenia and inpatient psychiatry. Author(s): O'Connor S. Source: J Am Acad Psychoanal Dyn Psychiatry. 2003 Spring; 31(1): 31-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722886&dopt=Abstract

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Viruses and schizophrenia, connection or coincidence? Author(s): Karlsson H. Source: Neuroreport. 2003 March 24; 14(4): 535-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657880&dopt=Abstract

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Visual backward-masking deficits in schizophrenia: relationship to visual pathway function and symptomatology. Author(s): Butler PD, DeSanti LA, Maddox J, Harkavy-Friedman JM, Amador XF, Goetz RR, Javitt DC, Gorman JM. Source: Schizophrenia Research. 2003 February 1; 59(2-3): 199-209. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414076&dopt=Abstract

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Visual feature conjunction in patients with schizophrenia: an event-related brain potential study. Author(s): Alain C, Bernstein LJ, He Y, Cortese F, Zipursky RB. Source: Schizophrenia Research. 2002 September 1; 57(1): 69-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165377&dopt=Abstract

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Visual masking as a probe for abnormal gamma range activity in schizophrenia. Author(s): Green MF, Mintz J, Salveson D, Nuechterlein KH, Breitmeyer B, Light GA, Braff DL. Source: Biological Psychiatry. 2003 June 15; 53(12): 1113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814862&dopt=Abstract

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Visual object processing in schizophrenia: evidence for an associative agnosic deficit. Author(s): Gabrovska VS, Laws KR, Sinclair J, McKenna PJ. Source: Schizophrenia Research. 2003 February 1; 59(2-3): 277-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414085&dopt=Abstract

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Visual object working memory function and clinical symptoms in schizophrenia. Author(s): Park S, Puschel J, Sauter BH, Rentsch M, Hell D. Source: Schizophrenia Research. 2003 February 1; 59(2-3): 261-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414083&dopt=Abstract

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Visual processing and neuropsychological function in schizophrenia and schizoaffective disorder. Author(s): Brenner CA, Lysaker PH, Wilt MA, O'Donnell BF. Source: Psychiatry Research. 2002 August 30; 111(2-3): 125-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374630&dopt=Abstract

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Visual scanpaths to positive and negative facial emotions in an outpatient schizophrenia sample. Author(s): Loughland CM, Williams LM, Gordon E. Source: Schizophrenia Research. 2002 May 1; 55(1-2): 159-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955975&dopt=Abstract

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Visuospatial memory and learning in first-episode schizophreniform psychosis and established schizophrenia: a functional correlate of hippocampal pathology? Author(s): Wood SJ, Proffitt T, Mahony K, Smith DJ, Buchanan JA, Brewer W, Stuart GW, Velakoulis D, McGorry PD, Pantelis C. Source: Psychological Medicine. 2002 April; 32(3): 429-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11989988&dopt=Abstract

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VNTR polymorphism of tyrosine hydroxylase gene and schizophrenia in the Korean population. Author(s): Pae CU, Kim JJ, Serretti A, Lee CU, Lee SJ, Lee C, Paik IH. Source: Neuropsychobiology. 2003; 47(3): 131-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759555&dopt=Abstract

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Volumes of association thalamic nuclei in schizophrenia: a postmortem study. Author(s): Danos P, Baumann B, Kramer A, Bernstein HG, Stauch R, Krell D, Falkai P, Bogerts B. Source: Schizophrenia Research. 2003 April 1; 60(2-3): 141-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591578&dopt=Abstract

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Voxel-based morphometric analysis of gray matter in first episode schizophrenia. Author(s): Kubicki M, Shenton ME, Salisbury DF, Hirayasu Y, Kasai K, Kikinis R, Jolesz FA, McCarley RW. Source: Neuroimage. 2002 December; 17(4): 1711-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12498745&dopt=Abstract

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Vulnerability to schizophrenia: relevance of patients' subjective experience for empirical and clinical work. Author(s): Bovet P, Gamma F. Source: American Journal of Medical Genetics. 2002 December 8; 114(8): 923-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457387&dopt=Abstract

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Weight gain, serum leptin and triglyceride levels in patients with schizophrenia on antipsychotic treatment with quetiapine, olanzapine and haloperidol. Author(s): Atmaca M, Kuloglu M, Tezcan E, Gecici O, Ustundag B. Source: Schizophrenia Research. 2003 March 1; 60(1): 99-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505146&dopt=Abstract

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What does the Edinburgh high-risk study tell us about schizophrenia? Author(s): Johnstone EC, Lawrie SM, Cosway R. Source: American Journal of Medical Genetics. 2002 December 8; 114(8): 906-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457384&dopt=Abstract

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What is a recommended treatment for aggression in a patient with schizophrenia? Author(s): Gobbi G, Debonnel G. Source: Journal of Psychiatry & Neuroscience : Jpn. 2003 July; 28(4): 320. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921225&dopt=Abstract

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White matter changes in schizophrenia: evidence for myelin-related dysfunction. Author(s): Davis KL, Stewart DG, Friedman JI, Buchsbaum M, Harvey PD, Hof PR, Buxbaum J, Haroutunian V. Source: Archives of General Psychiatry. 2003 May; 60(5): 443-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742865&dopt=Abstract

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Women with schizophrenia: pregnancy outcome and infant death among their offspring. Author(s): Nilsson E, Lichtenstein P, Cnattingius S, Murray RM, Hultman CM. Source: Schizophrenia Research. 2002 December 1; 58(2-3): 221-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409162&dopt=Abstract

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Working and long-term memory deficits in schizophrenia: is there a common prefrontal mechanism? Author(s): Barch DM, Csernansky JG, Conturo T, Snyder AZ. Source: Journal of Abnormal Psychology. 2002 August; 111(3): 478-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150424&dopt=Abstract

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Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression. Author(s): Barch DM, Sheline YI, Csernansky JG, Snyder AZ. Source: Biological Psychiatry. 2003 March 1; 53(5): 376-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614990&dopt=Abstract

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Working memory and schizophrenia: evidence for slowed encoding. Author(s): Hartman M, Steketee MC, Silva S, Lanning K, McCann H. Source: Schizophrenia Research. 2003 February 1; 59(2-3): 99-113. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414067&dopt=Abstract

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Working memory correlates of three symptom clusters in schizophrenia. Author(s): Cameron AM, Oram J, Geffen GM, Kavanagh DJ, McGrath JJ, Geffen LB. Source: Psychiatry Research. 2002 May 15; 110(1): 49-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12007593&dopt=Abstract

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Working memory for visual features and conjunctions in schizophrenia. Author(s): Gold JM, Wilk CM, McMahon RP, Buchanan RW, Luck SJ. Source: Journal of Abnormal Psychology. 2003 February; 112(1): 61-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653414&dopt=Abstract

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Would smokers with schizophrenia benefit from a more flexible approach to smoking treatment? Author(s): McChargue DE, Gulliver SB, Hitsman B. Source: Addiction (Abingdon, England). 2002 July; 97(7): 785-93; Discussion 795-800. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133113&dopt=Abstract

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Young cases of schizophrenia identified in a national inpatient register--are the diagnoses valid? Author(s): Dalman Ch, Broms J, Cullberg J, Allebeck P. Source: Social Psychiatry and Psychiatric Epidemiology. 2002 November; 37(11): 527-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395142&dopt=Abstract

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Ziprasidone in the management of schizophrenia : the QT interval issue in context. Author(s): Taylor D. Source: Cns Drugs. 2003; 17(6): 423-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697001&dopt=Abstract

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Ziprasidone: a review of its use in schizophrenia and schizoaffective disorder. Author(s): Gunasekara NS, Spencer CM, Keating GM. Source: Drugs. 2002; 62(8): 1217-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12010089&dopt=Abstract

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CHAPTER 2. NUTRITION AND SCHIZOPHRENIA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and schizophrenia.

Finding Nutrition Studies on Schizophrenia The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “schizophrenia” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following is a typical result when searching for recently indexed consumer information on schizophrenia: •

Human nature is unique in the mismatch between the usual diet and the need for “food for the brain” (marine fat, DHA). Adding marine fat is beneficial in schizophrenia and manic-depressive psychosis. This underlines brain dysfunction in these neurological disorders is associated with deficient intake of marine fat(DHA). Source: Saugstad, L F Nutr-Health. 2002; 16(1): 41-4 0260-1060

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Marine fat and brain function in manic-depressive psychosis and schizophrenia: circumstantial evidence for a 2nd aquatic period. Source: Saugstad, L F Nutr-Health. 2002; 16(1): 11-2 0260-1060

The following information is typical of that found when using the “Full IBIDS Database” to search for “schizophrenia” (or a synonym): •

A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. Author(s): Swallownest Court, Aughton Road, S26 4TH, Sheffield, UK. Source: Peet, Malcolm Horrobin, David F J-Psychiatr-Res. 2002 Jan-February; 36(1): 7-18 0022-3956

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A glutamatergic deficiency model of schizophrenia. Author(s): Department of Pharmacology, University of Goteborg, Sweden. Source: Carlsson, A Hansson, L O Waters, N Carlsson, M L Br-J-Psychiatry-Suppl. 1999; (37): 2-6 0960-5371

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A study of light/dark rhythm of melatonin in relation to cortisol and prolactin secretion in schizophrenia. Author(s): Division of Psychiatry, S.Gerardo dei Tintori Hospital, 20052 Monza (Milan), Italy. Source: Vigano, D Lissoni, P Rovelli, F Roselli, M G Malugani, F Gavazzeni, C Conti, A Maestroni, G Neuroendocrinol-Lett. 2001 April; 22(2): 137-41 0172-780X

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Abnormal phospholipid metabolism in schizophrenia: evidence from epidemiological findings, clinical observations, and preliminary clinical trials. Author(s): Joseph L. Mailman School of Public Health, Columbia University, New York, New York 10032, USA. [email protected] Source: Opler, M G Opler, L A Front-Biosci. 2001 September 1; 6: E61-5 1093-4715

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Adjunctive high-dose glycine in the treatment of schizophrenia. Author(s): Program in Cognitive Neuroscience and Schizophrenia, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA. [email protected] Source: Javitt, D C Silipo, G Cienfuegos, A Shelley, A M Bark, N Park, M Lindenmayer, J P Suckow, R Zukin, S R Int-J-Neuropsychopharmacol. 2001 December; 4(4): 385-91 14611457

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Advances and pathophysiological models of hallucinogenic drug actions in humans: a preamble to schizophrenia research. Author(s): Research Department, Psychiatric University Hospital Zurich, Switzerland. Source: Vollenweider, F X Pharmacopsychiatry. 1998 July; 31 Suppl 292-103 0176-3679

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Attitudes towards and beliefs about schizophrenia in Xhosa families with affected probands. Author(s): Department of Psychiatry, University of Stellenbosch. Source: Mbanga, N I Niehaus, D J H Mzamo, N C Wessels, C J Allen, A Emsley, R A Stein, D J Curationis. 2002 February; 25(1): 69-73 0379-8577

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Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study. Author(s): Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. [email protected] Source: Dursun, S M Deakin, J F J-Psychopharmacol. 2001 December; 15(4): 297-301 0269-8811

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Biophysical shunt theory for neuropsychopathology: pentaphasic lipid-induced model for schizophrenia. Author(s): Geha Psychiatric Hospital, Beilinson Medical Center, Petah Tiqva, Israel. Source: Naisberg, Y Weizman, A Med-Hypotheses. 1999 March; 52(3): 183-6 0306-9877

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Candidate gene polymorphisms among North Indians and their association with schizophrenia in a case-control study. Author(s): Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi 110 021, India. Source: Semwal, P Prasad, S Varma, P G Bhagwat, A M Deshpande, S N Thelma, B K JGenet. 2002 August; 81(2): 65-71 0022-1333

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Cannabinoid/anandamide system and schizophrenia: is there evidence for association? Author(s): Department of Clinical Psychiatry and Psychotherapy, Medical School, Hannover, Germany. Source: Schneider, U Leweke, F M Mueller Vahl, K R Emrich, H M Pharmacopsychiatry. 1998 July; 31 Suppl 2110-3 0176-3679

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Carbamazepine as an adjunct in the treatment of schizophrenia-like psychosis related to cannabis abuse. Author(s): Department of Psychiatry, Heinrich Heine University Duesseldorf, Germany. [email protected] Source: Leweke, F M Emrich, H M Int-Clin-Psychopharmacol. 1999 January; 14(1): 37-9 0268-1315

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Catechol-O-methyltransferase gene polymorphism in schizophrenia: evidence for association between symptomatology and prognosis. Author(s): Department of Psychiatry, Medical Faculty of Gaziantep University, Kolejtepe, Turkey. [email protected] Source: Herken, H Erdal, M E Psychiatr-Genet. 2001 June; 11(2): 105-9 0955-8829

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Cereals and schizophrenia. Source: Lorenz, K. Adv-Cereal-Sci-Technol. St. Paul, Minn. : American Association of Cereal Chemists. 1990. volume 10 page 435-469.

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Chromosomal fragile site expression in lymphocytes from patients with schizophrenia. Author(s): Division of Psychiatry, Tzu-Chi General Hospital, Hualien City, Taiwan, ROC. Source: Chen, C H Shih, H H Wang Wuu, S Tai, J J Wuu, K D Hum-Genet. 1998 December; 103(6): 702-6 0340-6717

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Combined treatment of schizophrenic psychoses with haloperidol and valproate. Author(s): Psychiatric District Hospital, Taufkirchen, Germany. Source: Dose, M Hellweg, R Yassouridis, A Theison, M Emrich, H Pharmacopsychiatry. 1998 July; 31(4): 122-5 0176-3679

M

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D4 dopamine receptor-mediated phospholipid methylation and its implications for mental illnesses such as schizophrenia. Author(s): Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, USA. Source: Sharma, A Kramer, M L Wick, P F Liu, D Chari, S Shim, S Tan, W Ouellette, D Nagata, M DuRand, C J Kotb, M Deth, R C Mol-Psychiatry. 1999 May; 4(3): 235-46 13594184

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Development, disease and degeneration in schizophrenia: a unitary pathophysiological model. Author(s): University of Pittsburgh Medical Center, PA 15213, USA. [email protected] Source: Keshavan, M S J-Psychiatr-Res. 1999 Nov-December; 33(6): 513-21 0022-3956

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Disturbed neural circuits in a subtype of chronic catatonic schizophrenia demonstrated by F-18-FDG-PET and F-18-DOPA-PET. Author(s): Department of Psychiatry and Psychotherapy, University of Wurzburg, Federal Republic of Germany. [email protected] Source: Lauer, M Schirrmeister, H Gerhard, A Ellitok, E Beckmann, H Reske, S N Stober, G J-Neural-Transm. 2001; 108(6): 661-70 0300-9564

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Divalproex as a calmative adjunct for aggressive schizophrenic patients. Author(s): University of Louisville School of Medicine, Department of Psychiatry and Behavioral Sciences, USA. Source: Afaq, Irfan Riaz, Jawad Sedky, Karim Chung, Dong Joon Vanina, Yelena el Mallakh, Rif Lippmann, Steven J-Ky-Med-Assoc. 2002 January; 100(1): 17-22 0023-0294

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Effect of epidural analgesia on postoperative paralytic ileus in chronic schizophrenia. Author(s): Department of Anesthesiology, Hirosaki National Hospital, Hirosaki, Aomori, Japan. Source: Kudoh, A Katagai, H Takazawa, T Reg-Anesth-Pain-Med. 2001 Sep-October; 26(5): 456-60 1098-7339

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Elevated response of growth hormone to graded doses of apomorphine in schizophrenic patients. Author(s): University of Basel, Department of Psychiatry, Switzerland. Source: Muller Spahn, F Modell, S Ackenheil, M Brachner, A Kurtz, G J-Psychiatr-Res. 1998 Sep-October; 32(5): 265-71 0022-3956

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Estrogen supplementation for female schizophrenics treated with atypical antipsychotics. Author(s): Department of Psychiatry, Executive Yuan Department of Health, Pali Psychiatric Hospital, Taipei, Taiwan, Republic of China. Source: Liao, D L Chen, H Lee, S M Tsai, S J Gen-Hosp-Psychiatry. 2002 Sep-October; 24(5): 357-9 0163-8343

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Functional catechol-O-methyltransferase gene polymorphism and susceptibility to schizophrenia. Author(s): Department of Psychiatry, Chonbuk National University Hospital, Chonju, South Korea. Source: Park, T W Yoon, K S Kim, J H Park, W Y Hirvonen, A Kang, D EurNeuropsychopharmacol. 2002 August; 12(4): 299-303 0924-977X

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Functioning and neuronal viability of the anterior cingulate neurons following antipsychotic treatment: MR-spectroscopic imaging in chronic schizophrenia. Author(s): NMR-Research and Clinic for Psychiatry and Psychotherapy, Central Institute of Mental Health, J5, D-68159 Mannheim, Germany. [email protected] Source: Braus, Dieter F Ende, Gabriele Weber Fahr, Wolfgang Demirakca, Traute Tost, Heike Henn, Fritz A Eur-Neuropsychopharmacol. 2002 April; 12(2): 145-52 0924-977X

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GABAergic neuronal subtypes in the human frontal cortex--development and deficits in schizophrenia. Author(s): Department of Biomedical Science, The University of Sheffield, Western Bank, S10 2TN, Sheffield, UK. [email protected] Source: Reynolds, G P Beasley, C L J-Chem-Neuroanat. 2001 July; 22(1-2): 95-100 08910618

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Glucose-induced increase in memory performance in patients with schizophrenia. Author(s): Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA. Source: Newcomer, J W Craft, S Fucetola, R Moldin, S O Selke, G Paras, L Miller, R Schizophr-Bull. 1999; 25(2): 321-35 0586-7614

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Glycine modulators in schizophrenia. Author(s): Nathan Kline Institute for Psychiatric Research, New York University School of Medicine, Orangeburg 10962, USA. [email protected] Source: Javitt, D C Curr-Opin-Investig-Drugs. 2002 July; 3(7): 1067-72 1472-4472

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Histamine and prostaglandins in schizophrenia: revisited. Author(s): Institute For Behavioral Awareness, Springfield, NJ, USA. Source: Heleniak, E O'Desky, I Med-Hypotheses. 1999 January; 52(1): 37-42 0306-9877

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How shamanism and group selection may reveal the origins of schizophrenia. Author(s): Department of Psychiatry, Faculty of Medicine, University of Manitoba, 771 Bannatyne Ave., Winnipeg, Manitoba R3E 3N4, Canada. Source: Polimeni, J Reiss, J P Med-Hypotheses. 2002 March; 58(3): 244-8 0306-9877

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Human nature is unique in the mismatch between the usual diet and the need for “food for the brain” (marine fat, DHA). Adding marine fat is beneficial in schizophrenia and manic-depressive psychosis. This underlines brain dysfunction in these neurological disorders is associated with deficient intake of marine fat(DHA). Source: Saugstad, L F Nutr-Health. 2002; 16(1): 41-4 0260-1060

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Implications of lipid biology for the pathogenesis of schizophrenia. Author(s): Early Psychosis Prevention and Intervention Centre, MH-SKY (EPPIC), Victoria. [email protected] Source: Berger, G E Wood, S J Pantelis, C Velakoulis, D Wellard, R M McGorry, P D Aust-N-Z-J-Psychiatry. 2002 June; 36(3): 355-66 0004-8674

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Inhibitory deficit in schizophrenia is not necessarily a GABAergic deficit. Author(s): Departamento de Ciencias Fisiologicas, Faculdade de Ciencias Biologicas, PUCRS, Porto Alegre, Brazil. [email protected] Source: Lara, D R Cell-Mol-Neurobiol. 2002 June; 22(3): 239-47 0272-4340

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Interactions between catecholamines and serotonin: relevance to the pharmacology of schizophrenia. Author(s): Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. Source: Svensson, T H Mathe, J M Nomikos, G G Schilstrom, B Marcus, M Fagerquist, M Adv-Pharmacol. 1998; 42814-8 1054-3589

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Kainic acid lesions in adult rats as a model of schizophrenia: changes in auditory information processing. Author(s): Department of Psychiatry, University of Colorado Health Sciences Center, Denver, USA. Source: Stevens, K E Nagamoto, H Johnson, R G Adams, C E Rose, G M Neuroscience. 1998 February; 82(3): 701-8 0306-4522

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Laterality changes accompanying symptom remission in schizophrenia following treatment with eicosapentaenoic acid. Author(s): Division of Neurosciences and Psychological Medicine, Imperial College School of Medicine, Charing Cross Campus, London, UK. [email protected] Source: Richardson, A J Easton, T Gruzelier, J H Puri, B K Int-J-Psychophysiol. 1999 December; 34(3): 333-9 0167-8760

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Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder. Author(s): Department of Psychiatry, College of Medicine and Firat Medical Center, Firat (Euphrates) University, Elazig, Turkey. [email protected] Source: Kuloglu, Murat Ustundag, Bilal Atmaca, Murad Canatan, Halit Tezcan, A Ertan Cinkilinc, Nadire Cell-Biochem-Funct. 2002 June; 20(2): 171-5 0263-6484

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Manic depressive psychosis and schizophrenia are neurological disorders at the extremes of CNS maturation and nutritional disorders associated with a deficit in marine fat. Author(s): Department of Anatomy, Institute for Basic Medical Sciences, University of Oslo, Norway. Source: Saugstad, L F Med-Hypotheses. 2001 December; 57(6): 679-92 0306-9877

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Marine fat and brain function in manic-depressive psychosis and schizophrenia: circumstantial evidence for a 2nd aquatic period. Source: Saugstad, L F Nutr-Health. 2002; 16(1): 11-2 0260-1060

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Megavitamin and dietary treatment in schizophrenia: a randomised, controlled trial. Author(s): Palmerston Centre, Hornsby Hospital, New South Wales, Australia. Source: Vaughan, K McConaghy, N Aust-N-Z-J-Psychiatry. 1999 February; 33(1): 84-8 0004-8674

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Microscopic polyangiitis presenting as schizophrenia. Author(s): Medical School, Jordan University of Science and Technology, Irbid, Jordan. Source: Askari, A Saadeh, A Buheis, N I Rheumatol-Int. 1999; 18(5-6): 215-7 0172-8172

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Molecular genetics of schizophrenia: past, present and future. Author(s): Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi 110 021, India. Source: Prasad, S Semwal, P Deshpande, S Bhatia, T Nimgaonkar, V L Thelma, B K JBiosci. 2002 February; 27(1 Suppl 1): 35-52 0250-5991

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Neural development, cell-cell signaling, and the “two-hit” hypothesis of schizophrenia. Author(s): Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill 27599, USA. Source: Maynard, T M Sikich, L Lieberman, J A LaMantia, A S Schizophr-Bull. 2001; 27(3): 457-76 0586-7614

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Neuroleptic effects on autonomic activity in schizophrenia: between-group and within-subject paradigms and comparisons with controls. Author(s): Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1366, USA. [email protected] Source: Zahn, T P Pickar, D van Kammen, D P Schizophr-Bull. 2001; 27(3): 503-15 05867614

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Nicotine binding in human striatum: elevation in schizophrenia and reductions in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease and in relation to neuroleptic medication. Author(s): MRC Neurochemical Pathology Unit, Newcastle General Hospital, Westgate Road, NE4 6BE, Newcastle upon Tyne, UK. [email protected] Source: Court, J A Piggott, M A Lloyd, S Cookson, N Ballard, C G McKeith, I G Perry, R H Perry, E K Neuroscience. 2000; 98(1): 79-87 0306-4522

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Omega-3 fatty acids as a psychotherapeutic agent for a pregnant schizophrenic patient. Author(s): Department of Psychiatry, Taipei Medical University Wan Fang Hospital and School of Medicine, Taipei, Taiwan. Source: Su, K P Shen, W W Huang, S Y Eur-Neuropsychopharmacol. 2001 August; 11(4): 295-9 0924-977X

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Polyunsaturated fatty acid (fish or evening primrose oil) for schizophrenia. Author(s): Cochrane Schizophrenia Group, Summertown Pavillion, Middle Way, Oxford, UK, OX2 7LG. [email protected] Source: Joy, C B Mumby Croft, R Joy, L A Cochrane-Database-Syst-Revolume 2000; (2): CD001257 1469-493X

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Psychopharmacological treatment of aggression in schizophrenic patients. Author(s): Department of Psychiatry and Psychotherapy, Hamburg-Eppendorf University Hospital, Germany. Source: Brieden, T Ujeyl, M Naber, D Pharmacopsychiatry. 2002 May; 35(3): 83-9 01763679

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Red cell and plasma fatty acid changes accompanying symptom remission in a patient with schizophrenia treated with eicosapentaenoic acid. Author(s): Division of Neurosciences and Psychological Medicine, Imperial College School of Medicine, Charing Cross Campus, St Dunstan's Road, London, UK. [email protected] Source: Richardson, A J Easton, T Puri, B K Eur-Neuropsychopharmacol. 2000 May; 10(3): 189-93 0924-977X

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Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Author(s): Unit on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, 10-4C101, 9000 Rockville Pike, Bethesda, Maryland 208921365, USA. [email protected] Source: Meyer Lindenberg, Andreas Miletich, Robert S Kohn, Philip D Esposito, Giuseppe Carson, Richard E Quarantelli, Mario Weinberger, Daniel R Berman, Karen Faith Nat-Neurosci. 2002 Mar; 5(3): 267-71 1097-6256

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Risperidone-associated, benign transient visual disturbances in schizophrenic patients with a past history of LSD abuse. Author(s): Lev Hasharon Mental Health Medical Center, Pardessya, 90000, Netanya 42100, Israel. [email protected]

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Source: Lerner, Arturo G Shufman, Emi Kodesh, Arad Rudinski, Dmitri Kretzmer, Gavin Sigal, Mircea Isr-J-Psychiatry-Relat-Sci. 2002; 39(1): 57-60 0333-7308 •

Schizophrenia: is the potato the environmental culprit? Author(s): Emeritus Consultant Pathologist, The Wollongong Hospital, New South Wales, Australia. Source: Christie, A C Med-Hypotheses. 1999 July; 53(1): 80-6 0306-9877

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Schizophrenic patients who smoke have a faster finger tapping rate than nonsmokers. Author(s): Flugelman (Mazra) Psychiatric Hospital, Doar Na Ashrat, Israel. [email protected] Source: Silver, Henry Shlomo, Nili Hiemke, Christoph Rao, Marie Luise Ritsner, Michael Modai, Ilan Eur-Neuropsychopharmacol. 2002 April; 12(2): 141-4 0924-977X

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Serotonin model of schizophrenia: emerging role of glutamate mechanisms. Author(s): Departments of Psychiatry, Yale University School of Medicine and the Connecticut Mental Health Center, 34 Park St., New Haven, CT, USA. [email protected] Source: Aghajanian, G K Marek, G J Brain-Res-Brain-Res-Revolume 2000 Mar; 31(2-3): 302-12 0165-0173

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Small effects of valproic acid on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenic or affective disorders. Author(s): Institute of Pharmacology, University of Messina, Italy. Source: Facciola, G Avenoso, A Scordo, M G Madia, A G Ventimiglia, A Perucca, E Spina, E Ther-Drug-Monit. 1999 June; 21(3): 341-5 0163-4356

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Smoking cessation in schizophrenia. General practice guidelines. Author(s): SANE Australia, Melbourne, Victoria. [email protected] Source: Strasser, Kathryn Moeller Saxone, Kristen Meadows, Graham Hocking, Barbara Stanton, John Kee, Pat Aust-Fam-Physician. 2002 January; 31(1): 21-4 0300-8495

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The Dutch famine and schizophrenia spectrum disorders. Author(s): The Hague Psychiatric Institute, The Netherlands. [email protected] Source: Hoek, H W Brown, A S Susser, E Soc-Psychiatry-Psychiatr-Epidemiol. 1998 August; 33(8): 373-9 0933-7954

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The effect of vitamin E addition to acute neuroleptic treatment on the emergence of extrapyramidal side effects in schizophrenic patients: an open label study. Author(s): Geha Psychiatric Hospital and Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel. Source: Dorfman Etrog, P Hermesh, H Prilipko, L Weizman, A Munitz, H EurNeuropsychopharmacol. 1999 December; 9(6): 475-7 0924-977X

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The unhealthy lifestyle of people with schizophrenia. Author(s): Department of Psychiatry, University of Southampton. Source: Brown, S Birtwistle, J Roe, L Thompson, C Psychol-Med. 1999 May; 29(3): 697701 0033-2917

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Traditional Chinese medical treatment to invigorate blood and relieve stasis treatment of schizophrenia: comparison with antipsychotics treatment. Author(s): Xianyue Hospital, Xiamen, China. Source: Wang, B Psychiatry-Clin-Neurosci. 1998 December; 52 SupplS329-30 1323-1316

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Understanding the neurotransmitter pathology of schizophrenia: selective deficits of subtypes of cortical GABAergic neurons. Author(s): Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom. [email protected] Source: Reynolds, G P Beasley, C L Zhang, Z J J-Neural-Transm. 2002 May; 109(5-6): 8819 0300-9564

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Would smokers with schizophrenia benefit from a more flexible approach to smoking treatment? Author(s): Edward Hines Jr VA Hospital, Hines, IL 60607-7137, USA. Source: McChargue, D E Gulliver, S B Hitsman, B Addiction. 2002 July; 97(7): 785-93; discussion 795-800 0965-2140

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to schizophrenia; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Folic Acid Source: Healthnotes, Inc. www.healthnotes.com Vitamin B12 Source: Healthnotes, Inc. www.healthnotes.com Vitamin B3 Source: Healthnotes, Inc. www.healthnotes.com Vitamin B6 Source: Healthnotes, Inc. www.healthnotes.com Vitamin C Source: Healthnotes, Inc. www.healthnotes.com

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Minerals Manganese Source: Integrative Medicine Communications; www.drkoop.com

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Food and Diet Gluten-Free Diet Source: Healthnotes, Inc. www.healthnotes.com Omega-3 fatty acids Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,992,00.html

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CHAPTER 3. SCHIZOPHRENIA

ALTERNATIVE

MEDICINE

AND

Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to schizophrenia. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to schizophrenia and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “schizophrenia” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to schizophrenia: •

5-HT2A receptor blockade in patients with schizophrenia treated with risperidone or clozapine. A SPET study using the novel 5-HT2A ligand 123I-5-I-R-91150. Author(s): Travis MJ, Busatto GF, Pilowsky LS, Mulligan R, Acton PD, Gacinovic S, Mertens J, Terriere D, Costa DC, Ell PJ, Kerwin RW. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1998 September; 173: 236-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9926100&dopt=Abstract

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A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia. Author(s): Zhang XY, Zhou DF, Zhang PY, Wu GY, Su JM, Cao LY. Source: The Journal of Clinical Psychiatry. 2001 November; 62(11): 878-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11775047&dopt=Abstract

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A functional anatomic study of emotion in schizophrenia. Author(s): Taylor SF, Liberzon I, Decker LR, Koeppe RA. Source: Schizophrenia Research. 2002 December 1; 58(2-3): 159-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409155&dopt=Abstract

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A functional magnetic resonance imaging study of auditory mismatch in schizophrenia. Author(s): Wible CG, Kubicki M, Yoo SS, Kacher DF, Salisbury DF, Anderson MC, Shenton ME, Hirayasu Y, Kikinis R, Jolesz FA, McCarley RW. Source: The American Journal of Psychiatry. 2001 June; 158(6): 938-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11384903&dopt=Abstract

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A Janusian perspective on the nature, development and structure of schizophrenia and schizotypy. Author(s): Gruzelier J. Source: Schizophrenia Research. 2002 March 1; 54(1-2): 95-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11853983&dopt=Abstract

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A new look at reaction time in schizophrenia. Author(s): Gale HJ, Holzman PS. Source: Schizophrenia Research. 2000 December 15; 46(2-3): 149-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11120427&dopt=Abstract

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A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Author(s): Fenton WS, Dickerson F, Boronow J, Hibbeln JR, Knable M. Source: The American Journal of Psychiatry. 2001 December; 158(12): 2071-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729030&dopt=Abstract

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A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy. Author(s): Kapur S, Zipursky R, Jones C, Shammi CS, Remington G, Seeman P. Source: Archives of General Psychiatry. 2000 June; 57(6): 553-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10839333&dopt=Abstract

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A topographic event-related potential follow-up study on 'prepulse inhibition' in first and second episode patients with schizophrenia. Author(s): Bender S, Schall U, Wolstein J, Grzella I, Zerbin D, Oades RD. Source: Psychiatry Research. 1999 February 22; 90(1): 41-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10320210&dopt=Abstract

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Abnormal patterns of regional cerebral blood flow in schizophrenia with primary negative symptoms during an effortful auditory recognition task. Author(s): Lahti AC, Holcomb HH, Medoff DR, Weiler MA, Tamminga CA, Carpenter WT Jr. Source: The American Journal of Psychiatry. 2001 November; 158(11): 1797-808. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11691685&dopt=Abstract

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Abnormal peripheral auditory asymmetry in schizophrenia. Author(s): Veuillet E, Georgieff N, Philibert B, Dalery J, Marie-Cardine M, Collet L. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2001 January; 70(1): 88-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11118254&dopt=Abstract

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Abnormalities of auditory P300 cortical current density in patients with schizophrenia using high density recording. Author(s): Wang J, Hiramatsu K, Hokama H, Miyazato H, Ogura C. Source: International Journal of Psychophysiology : Official Journal of the International Organization of Psychophysiology. 2003 March; 47(3): 243-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663068&dopt=Abstract

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Abnormalities of brain function during a nonverbal theory of mind task in schizophrenia. Author(s): Brunet E, Sarfati Y, Hardy-Bayle MC, Decety J. Source: Neuropsychologia. 2003; 41(12): 1574-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12887982&dopt=Abstract

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Abnormalities of motor imagery associated with somatic passivity phenomena in schizophrenia. Author(s): Maruff P, Wilson P, Currie J. Source: Schizophrenia Research. 2003 April 1; 60(2-3): 229-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591586&dopt=Abstract

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Addressing the needs of women living with Schizophrenia. Author(s): Clarke DE, Chernomas WM, Chisholm FA. Source: Can Nurse. 2001 October; 97(9): 14-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868400&dopt=Abstract

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Alcohol and cannabis use in schizophrenia: effects of clozapine vs. risperidone. Author(s): Green AI, Burgess ES, Dawson R, Zimmet SV, Strous RD. Source: Schizophrenia Research. 2003 March 1; 60(1): 81-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505141&dopt=Abstract

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Alcohol dependence and hospitalization in schizophrenia. Author(s): Gerding LB, Labbate LA, Measom MO, Santos AB, Arana GW.

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Source: Schizophrenia Research. 1999 July 27; 38(1): 71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10427612&dopt=Abstract •

Altered hemispheric asymmetry of auditory magnetic fields to tones and syllables in schizophrenia. Author(s): Rockstroh B, Kissler J, Mohr B, Eulitz C, Lommen U, Wienbruch C, Cohen R, Elbert T. Source: Biological Psychiatry. 2001 April 15; 49(8): 694-703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11313037&dopt=Abstract

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An algorithm for the treatment of schizophrenia in the correctional setting: the Forensic Algorithm Project. Author(s): Buscema CA, Abbasi QA, Barry DJ, Lauve TH. Source: The Journal of Clinical Psychiatry. 2000 October; 61(10): 767-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11078038&dopt=Abstract

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Applying social skills training in the context of vocational rehabilitation for people with schizophrenia. Author(s): Tsang HW. Source: The Journal of Nervous and Mental Disease. 2001 February; 189(2): 90-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11225692&dopt=Abstract

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Art therapy for schizophrenia or schizophrenia-like illnesses. Author(s): Ruddy R, Milnes D. Source: Cochrane Database Syst Rev. 2003; (2): Cd003728. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804485&dopt=Abstract

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Associated deficits in mismatch negativity generation and tone matching in schizophrenia. Author(s): Javitt DC, Shelley A, Ritter W. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2000 October; 111(10): 1733-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11018486&dopt=Abstract

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Attitudes towards and beliefs about schizophrenia in Xhosa families with affected probands. Author(s): Mbanga NI, Niehaus DJ, Mzamo NC, Wessels CJ, Allen A, Emsley RA, Stein DJ. Source: Curationis. 2002 February; 25(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096574&dopt=Abstract

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Auditory sensory dysfunction in schizophrenia: imprecision or distractibility? Author(s): Rabinowicz EF, Silipo G, Goldman R, Javitt DC.

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Source: Archives of General Psychiatry. 2000 December; 57(12): 1149-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115328&dopt=Abstract •

Auditory sensory memory in schizophrenia: inadequate trace formation? Author(s): Todd J, Michie PT, Budd TW, Rock D, Jablensky AV. Source: Psychiatry Research. 2000 October 30; 96(2): 99-115. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063783&dopt=Abstract

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Awareness of action in schizophrenia. Author(s): Haggard P, Martin F, Taylor-Clarke M, Jeannerod M, Franck N. Source: Neuroreport. 2003 May 23; 14(7): 1081-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802207&dopt=Abstract

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Ayahoasca: an experimental psychosis that mirrors the transmethylation hypothesis of schizophrenia. Author(s): Pomilio AB, Vitale AA, Ciprian-Ollivier J, Cetkovich-Bakmas M, Gomez R, Vazquez G. Source: Journal of Ethnopharmacology. 1999 April; 65(1): 29-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10350367&dopt=Abstract

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Cannabis psychosis and acute schizophrenia. a case-control study from India. Author(s): Basu D, Malhotra A, Bhagat A, Varma VK. Source: European Addiction Research. 1999 June; 5(2): 71-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10394036&dopt=Abstract

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Cannabis-induced psychosis: a cross-sectional comparison with acute schizophrenia. Author(s): Nunez LA, Gurpegui M. Source: Acta Psychiatrica Scandinavica. 2002 March; 105(3): 173-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11939970&dopt=Abstract

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Carbamazepine as an adjunct in the treatment of schizophrenia-like psychosis related to cannabis abuse. Author(s): Leweke FM, Emrich HM. Source: International Clinical Psychopharmacology. 1999 January; 14(1): 37-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10221641&dopt=Abstract

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Cerebral metabolic patterns in chronic and recent-onset schizophrenia. Author(s): Desco M, Gispert JD, Reig S, Sanz J, Pascau J, Sarramea F, Benito C, Santos A, Palomo T, Molina V. Source: Psychiatry Research. 2003 February 15; 122(2): 125-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714176&dopt=Abstract

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Cerebral metabolism and risperidone treatment in schizophrenia. Author(s): Molina V, Gispert JD, Reig S, Sanz J, Pascau J, Santos A, Palomo T, Desco M. Source: Schizophrenia Research. 2003 March 1; 60(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505132&dopt=Abstract

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Characterisation of cognitive impairment in schizophrenia. Author(s): Sharma T. Source: Lancet. Neurology. 2003 January; 2(1): 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849291&dopt=Abstract

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Childhood-onset schizophrenia: premorbid and prodromal diagnostic and treatment histories. Author(s): Schaeffer JL, Ross RG. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 May; 41(5): 538-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014786&dopt=Abstract

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Choosing the right dose of antipsychotics in schizophrenia: lessons from neuroimaging studies. Author(s): Tauscher J, Kapur S. Source: Cns Drugs. 2001; 15(9): 671-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11580306&dopt=Abstract

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Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. Author(s): Kapur S, Zipursky RB, Remington G. Source: The American Journal of Psychiatry. 1999 February; 156(2): 286-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9989565&dopt=Abstract

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Cognitive impairment in schizophrenia: its impact on social functioning. Author(s): Liddle PF. Source: Acta Psychiatrica Scandinavica. Supplementum. 2000; 400: 11-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10823306&dopt=Abstract

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Comparison of the effects of risperidone and haloperidol on regional cerebral blood flow in schizophrenia. Author(s): Miller DD, Andreasen NC, O'Leary DS, Watkins GL, Boles Ponto LL, Hichwa RD. Source: Biological Psychiatry. 2001 April 15; 49(8): 704-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11313038&dopt=Abstract

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Conduct disorder, antisocial personality disorder and substance use disorders in schizophrenia and major affective disorders.

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Author(s): Mueser KT, Rosenberg SD, Drake RE, Miles KM, Wolford G, Vidaver R, Carrieri K. Source: J Stud Alcohol. 1999 March; 60(2): 278-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10091967&dopt=Abstract •

Cortical activation associated with the experience of auditory hallucinations and perception of human speech in schizophrenia: a PET correlation study. Author(s): Copolov DL, Seal ML, Maruff P, Ulusoy R, Wong MT, Tochon-Danguy HJ, Egan GF. Source: Psychiatry Research. 2003 April 1; 122(3): 139-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694889&dopt=Abstract

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Cortical oscillations and schizophrenia: timing is of the essence. Author(s): Green MF, Nuechterlein KH. Source: Archives of General Psychiatry. 1999 November; 56(11): 1007-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10565500&dopt=Abstract

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Cortical responsiveness during inner speech in schizophrenia: an event-related potential study. Author(s): Ford JM, Mathalon DH, Kalba S, Whitfield S, Faustman WO, Roth WT. Source: The American Journal of Psychiatry. 2001 November; 158(11): 1914-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11691701&dopt=Abstract

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Could the hypofrontality pattern in schizophrenia be modified through neuropsychological rehabilitation? Author(s): Penades R, Boget T, Lomena F, Mateos JJ, Catalan R, Gasto C, Salamero M. Source: Acta Psychiatrica Scandinavica. 2002 March; 105(3): 202-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11939974&dopt=Abstract

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Current perspectives on the pathophysiology of schizophrenia, depression, and anxiety disorders. Author(s): Krystal JH, D'Souza DC, Sanacora G, Goddard AW, Charney DS. Source: The Medical Clinics of North America. 2001 May; 85(3): 559-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349473&dopt=Abstract

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Current progress in schizophrenia research: sensory gating deficit in schizophrenia: is the nicotinic alpha-7 receptor implicated? Author(s): Thaker GK. Source: The Journal of Nervous and Mental Disease. 2002 August; 190(8): 550-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12193840&dopt=Abstract

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D(2) and 5HT(2A) receptor occupancy of different doses of quetiapine in schizophrenia: a PET study.

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Author(s): Gefvert O, Lundberg T, Wieselgren IM, Bergstrom M, Langstrom B, Wiesel F, Lindstrom L. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2001 April; 11(2): 105-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11313155&dopt=Abstract •

Decreased serotonin 2A receptor densities in neuroleptic-naive patients with schizophrenia: A PET study using [(18)F]setoperone. Author(s): Ngan ET, Yatham LN, Ruth TJ, Liddle PF. Source: The American Journal of Psychiatry. 2000 June; 157(6): 1016-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10831488&dopt=Abstract

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Deficit psychopathology and a paradigm shift in schizophrenia research. Author(s): Carpenter WT Jr, Arango C, Buchanan RW, Kirkpatrick B. Source: Biological Psychiatry. 1999 August 1; 46(3): 352-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10435200&dopt=Abstract

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Deficits in automatically detecting changes in conjunction of auditory features in patients with schizophrenia. Author(s): Alain C, Bernstein LJ, Cortese F, Yu H, Zipursky RB. Source: Psychophysiology. 2002 September; 39(5): 599-606. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236326&dopt=Abstract

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Deficits in prepulse inhibition and habituation in never-medicated, first-episode schizophrenia. Author(s): Ludewig K, Geyer MA, Vollenweider FX. Source: Biological Psychiatry. 2003 July 15; 54(2): 121-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873801&dopt=Abstract

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Detection of illicit substance use among persons with schizophrenia by radioimmunoassay of hair. Author(s): Swartz MS, Swanson JW, Hannon MJ. Source: Psychiatric Services (Washington, D.C.). 2003 June; 54(6): 891-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773606&dopt=Abstract

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Do loudness cues contribute to duration mismatch negativity reduction in schizophrenia? Author(s): Todd J, Michie PT, Jablensky AV. Source: Neuroreport. 2001 December 21; 12(18): 4069-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742240&dopt=Abstract

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Dopamine- and serotonin-receptors in schizophrenia: results of imaging-studies and implications for pharmacotherapy in schizophrenia. Author(s): Kasper S, Tauscher J, Kufferle B, Barnas C, Pezawas L, Quiner S. Source: European Archives of Psychiatry and Clinical Neuroscience. 1999; 249 Suppl 4: 83-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10654113&dopt=Abstract

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Dopamine D(2) receptor blockade in schizophrenia. Author(s): Bressan RA, Jones HM, Ell PJ, Pilowsky LS. Source: The American Journal of Psychiatry. 2001 June; 158(6): 971-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11384924&dopt=Abstract

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Dopamine D2 receptor occupancy by olanzapine or risperidone in young patients with schizophrenia. Author(s): Lavalaye J, Linszen DH, Booij J, Reneman L, Gersons BP, van Royen EA. Source: Psychiatry Research. 1999 November 8; 92(1): 33-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10688158&dopt=Abstract

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Dopamine D2 receptor occupancy measured by single photon emission computed tomography with 123I-Iodobenzamide in chronic schizophrenia. Author(s): Volk S, Maul FD, Hor G, Schreiner M, Weppner M, Holzmann T, Pflug B. Source: Psychiatry Research. 1994 June; 55(2): 111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711799&dopt=Abstract

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Dopamine receptors, antipsychotic action and schizophrenia. Author(s): Reynolds GP. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(2): 202-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10475731&dopt=Abstract

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Dopamine transporter density in young patients with schizophrenia assessed with [123]FP-CIT SPECT. Author(s): Lavalaye J, Linszen DH, Booij J, Dingemans PM, Reneman L, Habraken JB, Gersons BP, van Royen EA. Source: Schizophrenia Research. 2001 January 15; 47(1): 59-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11163545&dopt=Abstract

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Dual diagnosis of substance abuse in schizophrenia: prevalence and impact on outcomes. Author(s): Dixon L. Source: Schizophrenia Research. 1999 March 1; 35 Suppl: S93-100. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10190230&dopt=Abstract

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Duration and frequency mismatch negativity in schizophrenia. Author(s): Michie PT, Budd TW, Todd J, Rock D, Wichmann H, Box J, Jablensky AV. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2000 June; 111(6): 1054-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10825713&dopt=Abstract

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Duration mismatch negativity in biological relatives of patients with schizophrenia spectrum disorders. Author(s): Michie PT, Innes-Brown H, Todd J, Jablensky AV. Source: Biological Psychiatry. 2002 October 1; 52(7): 749-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372666&dopt=Abstract

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Effect of treatment status on prepulse inhibition of acoustic startle in schizophrenia. Author(s): Duncan EJ, Szilagyi S, Efferen TR, Schwartz MP, Parwani A, Chakravorty S, Madonick SH, Kunzova A, Harmon JW, Angrist B, Gonzenbach S, Rotrosen JP. Source: Psychopharmacology. 2003 April; 167(1): 63-71. Epub 2003 March 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632245&dopt=Abstract

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Effects of acute procyclidine administration on prepulse inhibition of the startle response in schizophrenia: a double-blind, placebo-controlled study. Author(s): Kumari V, Zachariah E, Galea A, Jones HC, Das M, Mehrotra R, Taylor D, Sharma T. Source: Journal of Psychopharmacology (Oxford, England). 2003 March; 17(1): 89-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680744&dopt=Abstract

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Effects of chewing betel nut (Areca catechu) on the symptoms of people with schizophrenia in Palau, Micronesia. Author(s): Sullivan RJ, Allen JS, Otto C, Tiobech J, Nero K. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2000 August; 177: 174-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11026959&dopt=Abstract

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Effects of clozapine on substance use in patients with schizophrenia and schizoaffective disorder: a retrospective survey. Author(s): Zimmet SV, Strous RD, Burgess ES, Kohnstamm S, Green AI. Source: Journal of Clinical Psychopharmacology. 2000 February; 20(1): 94-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10653215&dopt=Abstract

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Effects of contextual processing on visual conditional associative learning in schizophrenia. Author(s): Gold JM, Bish JA, Iannone VN, Hobart MP, Queern CA, Buchanan RW.

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Source: Biological Psychiatry. 2000 September 1; 48(5): 406-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10978724&dopt=Abstract •

Effects of temporal variability on p50 and the gating ratio in schizophrenia: a frequency domain adaptive filter single-trial analysis. Author(s): Patterson JV, Jin Y, Gierczak M, Hetrick WP, Potkin S, Bunney WE Jr, Sandman CA. Source: Archives of General Psychiatry. 2000 January; 57(1): 57-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10632233&dopt=Abstract

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Effects of typical and atypical antipsychotics on prepulse inhibition and latent inhibition in chronic schizophrenia. Author(s): Leumann L, Feldon J, Vollenweider FX, Ludewig K. Source: Biological Psychiatry. 2002 October 1; 52(7): 729-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372664&dopt=Abstract

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Effects of typical and atypical antipsychotics on the prepulse inhibition of the startle reflex in patients with schizophrenia. Author(s): Oranje B, Van Oel CJ, Gispen-De Wied CC, Verbaten MN, Kahn RS. Source: Journal of Clinical Psychopharmacology. 2002 August; 22(4): 359-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172334&dopt=Abstract

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Eicosapentaenoic acid treatment in schizophrenia associated with symptom remission, normalisation of blood fatty acids, reduced neuronal membrane phospholipid turnover and structural brain changes. Author(s): Puri BK, Richardson AJ, Horrobin DF, Easton T, Saeed N, Oatridge A, Hajnal JV, Bydder GM. Source: Int J Clin Pract. 2000 January-February; 54(1): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10750263&dopt=Abstract

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Electrodermal activity in schizophrenia: a quantitative study using a short interstimulus paradigm. Author(s): Lim CL, Gordon E, Harris A, Bahramali H, Li WM, Manor B, Rennie C. Source: Biological Psychiatry. 1999 January 1; 45(1): 127-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9894584&dopt=Abstract

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Elevated plasma level of apolipoprotein D in schizophrenia and its treatment and outcome. Author(s): Mahadik SP, Khan MM, Evans DR, Parikh VV. Source: Schizophrenia Research. 2002 November 1; 58(1): 55-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363390&dopt=Abstract

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Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia. Author(s): Fenton WS, Hibbeln J, Knable M. Source: Biological Psychiatry. 2000 January 1; 47(1): 8-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10650444&dopt=Abstract

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Ethnicity and treatment response in schizophrenia: a comparison of 3 ethnic groups. Author(s): Emsley RA, Roberts MC, Rataemane S, Pretorius J, Oosthuizen PP, Turner J, Niehaus DJ, Keyter N, Stein DJ. Source: The Journal of Clinical Psychiatry. 2002 January; 63(1): 9-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11841075&dopt=Abstract

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Extract of Ginkgo biloba added to haloperidol was effective for positive symptoms in refractory schizophrenia. Author(s): Knable MB. Source: Evidence-Based Mental Health. 2002 August; 5(3): 90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180457&dopt=Abstract

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Extrastriatal and striatal D(2) dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. Author(s): Xiberas X, Martinot JL, Mallet L, Artiges E, Loc'H C, Maziere B, PaillereMartinot ML. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2001 December; 179: 503-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731352&dopt=Abstract

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Failure of dominant left-hemispheric activation to right-ear stimulation in schizophrenia. Author(s): Rockstroh B, Clementz BA, Pantev C, Blumenfeld LD, Sterr A, Elbert T. Source: Neuroreport. 1998 December 1; 9(17): 3819-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9875711&dopt=Abstract

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Failures of automatic and strategic processing in schizophrenia: comparisons of event-related brain potential and startle blink modification. Author(s): Ford JM, Roth WT, Menon V, Pfefferbaum A. Source: Schizophrenia Research. 1999 May 25; 37(2): 149-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10374650&dopt=Abstract

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Family treatment and medication dosage reduction in schizophrenia: effects on patient social functioning, family attitudes, and burden. Author(s): Mueser KT, Sengupta A, Schooler NR, Bellack AS, Xie H, Glick ID, Keith SJ.

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Source: Journal of Consulting and Clinical Psychology. 2001 February; 69(1): 3-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11302274&dopt=Abstract •

Frontal and temporal dysfunction of auditory stimulus processing in schizophrenia. Author(s): Gallinat J, Mulert C, Bajbouj M, Herrmann WM, Schunter J, Senkowski D, Moukhtieva R, Kronfeldt D, Winterer G. Source: Neuroimage. 2002 September; 17(1): 110-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482071&dopt=Abstract

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Gamma frequency-range abnormalities to auditory stimulation in schizophrenia. Author(s): Kwon JS, O'Donnell BF, Wallenstein GV, Greene RW, Hirayasu Y, Nestor PG, Hasselmo ME, Potts GF, Shenton ME, McCarley RW. Source: Archives of General Psychiatry. 1999 November; 56(11): 1001-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10565499&dopt=Abstract

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Gender differences in the effect of repetitive transcranial magnetic stimulation in schizophrenia. Author(s): Huber TJ, Schneider U, Rollnik J. Source: Psychiatry Research. 2003 August 30; 120(1): 103-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500119&dopt=Abstract

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Glutamatergic aspects of schizophrenia. Author(s): Tamminga C. Source: The British Journal of Psychiatry. Supplement. 1999; (37): 12-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211134&dopt=Abstract

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Hallucinations in schizophrenia: imbalance between imagery and perception? Author(s): Aleman A, de Haan EH, Bocker KB, Hijman R, Kahn RS. Source: Schizophrenia Research. 2002 October 1; 57(2-3): 315-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223265&dopt=Abstract

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Hemispheric differences on auditory evoked response suppression in schizophrenia. Author(s): Blumenfeld LD, Clementz BA. Source: Neuroreport. 1999 August 20; 10(12): 2587-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10574374&dopt=Abstract

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Higher occupancy of muscarinic receptors by olanzapine than risperidone in patients with schizophrenia. A[123I]-IDEX SPECT study. Author(s): Lavalaye J, Booij J, Linszen DH, Reneman L, van Royen EA. Source: Psychopharmacology. 2001 June; 156(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465633&dopt=Abstract

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How people with schizophrenia build their hope. Author(s): Kirkpatrick H, Landeen J, Woodside H, Byrne C. Source: Journal of Psychosocial Nursing and Mental Health Services. 2001 January; 39(1): 46-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197995&dopt=Abstract

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How shamanism and group selection may reveal the origins of schizophrenia. Author(s): Polimeni J, Reiss JP. Source: Medical Hypotheses. 2002 March; 58(3): 244-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018978&dopt=Abstract

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Human nature is unique in the mismatch between the usual diet and the need for “food for the brain” (marine fat, DHA). Adding marine fat is beneficial in schizophrenia and manic-depressive psychosis. This underlines brain dysfunction in these neurological disorders is associated with deficient intake of marine fat(DHA). Author(s): Saugstad LF. Source: Nutr Health. 2002; 16(1): 41-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083411&dopt=Abstract

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Identification of a novel variant of the human NR2B gene promoter region and its possible association with schizophrenia. Author(s): Miyatake R, Furukawa A, Suwaki H. Source: Molecular Psychiatry. 2002; 7(10): 1101-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476325&dopt=Abstract

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Identifying psychophysiological risk for psychopathology: examples from substance abuse and schizophrenia research. Author(s): Iacono WG. Source: Psychophysiology. 1998 November; 35(6): 621-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9844425&dopt=Abstract

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Impaired P600 in neuroleptic naive patients with first-episode schizophrenia. Author(s): Papageorgiou C, Kontaxakis VP, Havaki-Kontaxaki BJ, Stamouli S, Vasios C, Asvestas P, Matsopoulos GK, Kontopantelis E, Rabavilas A, Uzunoglu N, Christodoulou GN. Source: Neuroreport. 2001 September 17; 12(13): 2801-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588580&dopt=Abstract

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Impaired prepulse inhibition of acoustic startle in schizophrenia. Author(s): Parwani A, Duncan EJ, Bartlett E, Madonick SH, Efferen TR, Rajan R, Sanfilipo M, Chappell PB, Chakravorty S, Gonzenbach S, Ko GN, Rotrosen JP.

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Source: Biological Psychiatry. 2000 April 1; 47(7): 662-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10745060&dopt=Abstract •

Impaired sensory gating and attention in rats with developmental abnormalities of the mesocortex. Implications for schizophrenia. Author(s): Talamini LM, Ellenbroek B, Koch T, Korf J. Source: Annals of the New York Academy of Sciences. 2000 June; 911: 486-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10911899&dopt=Abstract

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Impairment in frontal but not temporal components of mismatch negativity in schizophrenia. Author(s): Baldeweg T, Klugman A, Gruzelier JH, Hirsch SR. Source: International Journal of Psychophysiology : Official Journal of the International Organization of Psychophysiology. 2002 February; 43(2): 111-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809515&dopt=Abstract

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In vivo extrastriatal and striatal D2 dopamine receptor blockade by amisulpride in schizophrenia. Author(s): Xiberas X, Martinot JL, Mallet L, Artiges E, Canal M, Loc'h C, Maziere B, Paillere-Martinot ML. Source: Journal of Clinical Psychopharmacology. 2001 April; 21(2): 207-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11270918&dopt=Abstract

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In vivo neuropharmacology of schizophrenia. Author(s): Bigliani V, Pilowsky LS. Source: The British Journal of Psychiatry. Supplement. 1999; (38): 23-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10884897&dopt=Abstract

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Information processing deficits in acutely psychotic schizophrenia patients medicated and unmedicated at the time of admission. Author(s): Perry W, Feifel D, Minassian A, Bhattacharjie I, Braff DL. Source: The American Journal of Psychiatry. 2002 August; 159(8): 1375-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153831&dopt=Abstract

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Is schizophrenia a metabolic brain disorder? Membrane phospholipid dysregulation and its therapeutic implications. Author(s): Mahadik SP, Evans DR. Source: The Psychiatric Clinics of North America. 2003 March; 26(1): 85-102. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683261&dopt=Abstract

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Is schizophrenia a neurodegenerative disorder? A clinical and neurobiological perspective. Author(s): Lieberman JA.

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Source: Biological Psychiatry. 1999 September 15; 46(6): 729-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10494440&dopt=Abstract •

Kraepelinian and non-Kraepelinian schizophrenia subgroup differences in cerebral metabolic rate. Author(s): Buchsbaum MS, Shihabuddin L, Hazlett EA, Schroder J, Haznedar MM, Powchik P, Spiegel-Cohen J, Wei T, Singer MB, Davis KL. Source: Schizophrenia Research. 2002 May 1; 55(1-2): 25-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955961&dopt=Abstract

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Lateral gene transfer of foreign DNA: the missing link between cannabis psychosis and schizophrenia. Author(s): Fritzsche M. Source: American Journal of Medical Genetics. 2002 July 8; 114(5): 512-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116185&dopt=Abstract

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Laterality changes accompanying symptom remission in schizophrenia following treatment with eicosapentaenoic acid. Author(s): Richardson AJ, Easton T, Gruzelier JH, Puri BK. Source: International Journal of Psychophysiology : Official Journal of the International Organization of Psychophysiology. 1999 December; 34(3): 333-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10610057&dopt=Abstract

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Left temporal lobe dysfunction in schizophrenia: event-related potential and behavioral evidence from phonetic and tonal dichotic listening tasks. Author(s): Bruder G, Kayser J, Tenke C, Amador X, Friedman M, Sharif Z, Gorman J. Source: Archives of General Psychiatry. 1999 March; 56(3): 267-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10078505&dopt=Abstract

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Left temporoparietal transcranial magnetic stimulation in treatment-resistant schizophrenia with verbal hallucinations. Author(s): Franck N, Poulet E, Terra JL, Dalery J, d'Amato T. Source: Psychiatry Research. 2003 August 30; 120(1): 107-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500120&dopt=Abstract

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Lessons about “The schizophrenia of the body”: a comment on Anna Cassirer Appelbaum's “Observations on the disintegration of the self”. Author(s): Miller DW. Source: Advances in Mind-Body Medicine. 2000 Fall; 16(4): 304-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11015772&dopt=Abstract

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Lipid supplementation in schizophrenia. Author(s): Maurer I, Volz HP.

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Source: The British Journal of Psychiatry; the Journal of Mental Science. 1999 September; 175: 287-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10645336&dopt=Abstract •

Magico-religious beliefs in schizophrenia: a study from north India. Author(s): Kulhara P, Avasthi A, Sharma A. Source: Psychopathology. 2000 March-April; 33(2): 62-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10705248&dopt=Abstract

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Medication management ability assessment: results from a performance-based measure in older outpatients with schizophrenia. Author(s): Patterson TL, Lacro J, McKibbin CL, Moscona S, Hughs T, Jeste DV. Source: Journal of Clinical Psychopharmacology. 2002 February; 22(1): 11-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11799337&dopt=Abstract

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Megavitamin and dietary treatment in schizophrenia: a randomised, controlled trial. Author(s): Vaughan K, McConaghy N. Source: The Australian and New Zealand Journal of Psychiatry. 1999 February; 33(1): 848. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10197889&dopt=Abstract

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Mental health nurses' beliefs about interventions for schizophrenia and depression: a comparison with psychiatrists and the public. Author(s): Caldwell TM, Jorm AF. Source: The Australian and New Zealand Journal of Psychiatry. 2000 August; 34(4): 60211. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10954391&dopt=Abstract

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Methods of changing patterns of substance use among individuals with co-occurring schizophrenia and substance use disorder. Author(s): Maisto SA, Carey KB, Carey MP, Purnine DM, Barnes KL. Source: Journal of Substance Abuse Treatment. 1999 October; 17(3): 221-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10531628&dopt=Abstract

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Mismatch negativity and N2b attenuation as an indicator for dysfunction of the preattentive and controlled processing for deviance detection in schizophrenia: a topographic event-related potential study. Author(s): Kasai K, Okazawa K, Nakagome K, Hiramatsu K, Hata A, Fukuda M, Honda M, Miyauchi M, Matsushita M. Source: Schizophrenia Research. 1999 January 11; 35(2): 141-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9988851&dopt=Abstract

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Mismatch negativity in chronic schizophrenia and first-episode schizophrenia. Author(s): Salisbury DF, Shenton ME, Griggs CB, Bonner-Jackson A, McCarley RW. Source: Archives of General Psychiatry. 2002 August; 59(8): 686-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150644&dopt=Abstract

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Modulation of language processing in schizophrenia: effects of context and haloperidol on the event-related potential. Author(s): Condray R, Steinhauer SR, Cohen JD, van Kammen DP, Kasparek A. Source: Biological Psychiatry. 1999 May 15; 45(10): 1336-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10349041&dopt=Abstract

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Multichannel electroencephalographic assessment of auditory evoked response suppression in schizophrenia. Author(s): Clementz BA, Blumenfeld LD. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 2001 August; 139(4): 377-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11534861&dopt=Abstract

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Neonatal cytomegalovirus exposure decreases prepulse inhibition in adult rats: implications for schizophrenia. Author(s): Rothschild DM, O'Grady M, Wecker L. Source: Journal of Neuroscience Research. 1999 August 15; 57(4): 429-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10440892&dopt=Abstract

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Neonatal lesions in the amygdala or ventral hippocampus disrupt prepulse inhibition of the acoustic startle response; implications for an animal model of neurodevelopmental disorders like schizophrenia. Author(s): Daenen EW, Wolterink G, Van Der Heyden JA, Kruse CG, Van Ree JM. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2003 May; 13(3): 187-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729945&dopt=Abstract

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Normal P50 suppression in schizophrenia patients treated with atypical antipsychotic medications. Author(s): Light GA, Geyer MA, Clementz BA, Cadenhead KS, Braff DL. Source: The American Journal of Psychiatry. 2000 May; 157(5): 767-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10784470&dopt=Abstract

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Normal time course of auditory recognition in schizophrenia, despite impaired precision of the auditory sensory (“echoic”) memory code. Author(s): March L, Cienfuegos A, Goldbloom L, Ritter W, Cowan N, Javitt DC.

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Normalization of information processing deficits in schizophrenia with clozapine. Author(s): Kumari V, Soni W, Sharma T. Source: The American Journal of Psychiatry. 1999 July; 156(7): 1046-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10401450&dopt=Abstract

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omega-3 Fatty acid for schizophrenia. Author(s): Horrobin DF. Source: The American Journal of Psychiatry. 2003 January; 160(1): 188-9; Author Reply 189. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505833&dopt=Abstract

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On the clinical and cognitive meaning of impaired sensorimotor gating in schizophrenia. Author(s): Dawson ME, Schell AM, Hazlett EA, Nuechterlein KH, Filion DL. Source: Psychiatry Research. 2000 November 20; 96(3): 187-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11084215&dopt=Abstract

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Oxidative stress and role of antioxidant and omega-3 essential fatty acid supplementation in schizophrenia. Author(s): Mahadik SP, Evans D, Lal H. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2001 April; 25(3): 463-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11370992&dopt=Abstract

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Perception of stigma among family members of individuals with schizophrenia and major affective disorders in rural Ethiopia. Author(s): Shibre T, Negash A, Kullgren G, Kebede D, Alem A, Fekadu A, Fekadu D, Madhin G, Jacobsson L. Source: Social Psychiatry and Psychiatric Epidemiology. 2001 June; 36(6): 299-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11583460&dopt=Abstract

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Pharmacogenomics in schizophrenia: the quest for individualized therapy. Author(s): Basile VS, Masellis M, Potkin SG, Kennedy JL. Source: Human Molecular Genetics. 2002 October 1; 11(20): 2517-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351588&dopt=Abstract

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Placebo response in a double-blind therapeutic supplementation trial in stabilized outpatients with schizophrenia. Author(s): Dickerson FB, Boronow JJ, Stallings CR, Lee BA, Agarwal R, Fenton WS, Yolken RH.

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Source: Schizophrenia Research. 2003 January 1; 59(1): 97-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413650&dopt=Abstract •

Polyunsaturated fatty acid (fish or evening primrose oil) for schizophrenia. Author(s): Joy CB, Mumby-Croft R, Joy LA. Source: Cochrane Database Syst Rev. 2000; (2): Cd001257. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796622&dopt=Abstract

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Polyunsaturated fatty acid supplementation for schizophrenia. Author(s): Joy CB, Mumby-Croft R, Joy LA. Source: Cochrane Database Syst Rev. 2003; (2): Cd001257. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804400&dopt=Abstract

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Poor P50 suppression among schizophrenia patients and their first-degree biological relatives. Author(s): Clementz BA, Geyer MA, Braff DL. Source: The American Journal of Psychiatry. 1998 December; 155(12): 1691-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9842777&dopt=Abstract

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Predicting EEG responses using MEG sources in superior temporal gyrus reveals source asynchrony in patients with schizophrenia. Author(s): Huang MX, Edgar JC, Thoma RJ, Hanlon FM, Moses SN, Lee RR, Paulson KM, Weisend MP, Irwin JG, Bustillo JR, Adler LE, Miller GA, Canive JM. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 May; 114(5): 835-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738429&dopt=Abstract

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Prepulse inhibition of the startle response in men with schizophrenia: effects of age of onset of illness, symptoms, and medication. Author(s): Kumari V, Soni W, Mathew VM, Sharma T. Source: Archives of General Psychiatry. 2000 June; 57(6): 609-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10839340&dopt=Abstract

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Probing the human hippocampus using rCBF: contrasts in schizophrenia. Author(s): Medoff DR, Holcomb HH, Lahti AC, Tamminga CA. Source: Hippocampus. 2001; 11(5): 543-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732707&dopt=Abstract

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Providing quality care to patients with schizophrenia. Author(s): Joubert AF.

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Source: The Psychiatric Clinics of North America. 2003 March; 26(1): 213-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683267&dopt=Abstract •

Psychiatry in traditional song: catatonic schizophrenia. Author(s): Campbell GD, Daynes WG. Source: Adler Mus Bull. 1997 July; 23(2): 18-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11619484&dopt=Abstract

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Psychophysiological correlates of social skills deficits in persons with schizophrenia. Author(s): Ohno T, Ikebuchi E, Henomatsu K, Kasai K, Nakagome K, Iwanami A, Hiramatsu K, Hata A, Fukuda M, Honda M, Miyauchi M. Source: Psychiatry Research. 2000 December 22; 100(3): 155-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11120442&dopt=Abstract

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Psychophysiological measures of (dis)inhibition as liability indicators for schizophrenia. Author(s): Clementz BA. Source: Psychophysiology. 1998 November; 35(6): 648-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9844427&dopt=Abstract

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Quetiapine: an effective antipsychotic in first-episode schizophrenia despite only transiently high dopamine-2 receptor blockade. Author(s): Tauscher-Wisniewski S, Kapur S, Tauscher J, Jones C, Daskalakis ZJ, Papatheodorou G, Epstein I, Christensen BK, Zipursky RB. Source: The Journal of Clinical Psychiatry. 2002 November; 63(11): 992-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444812&dopt=Abstract

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Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Author(s): Emsley R, Myburgh C, Oosthuizen P, van Rensburg SJ. Source: The American Journal of Psychiatry. 2002 September; 159(9): 1596-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202284&dopt=Abstract

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Receptor and transporter imaging studies in schizophrenia, depression, bulimia and Tourette's disorder--implications for psychopharmacology. Author(s): Kasper S, Tauscher J, Willeit M, Stamenkovic M, Neumeister A, Kufferle B, Barnas C, Stastny J, Praschak-Rieder N, Pezawas L, de Zwaan M, Quiner S, Pirker W, Asenbaum S, Podreka I, Brucke T. Source: World J Biol Psychiatry. 2002 July; 3(3): 133-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478878&dopt=Abstract

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Red cell and plasma fatty acid changes accompanying symptom remission in a patient with schizophrenia treated with eicosapentaenoic acid. Author(s): Richardson AJ, Easton T, Puri BK. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2000 May; 10(3): 189-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10793321&dopt=Abstract

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Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics. Author(s): Khan MM, Evans DR, Gunna V, Scheffer RE, Parikh VV, Mahadik SP. Source: Schizophrenia Research. 2002 November 1; 58(1): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363384&dopt=Abstract

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Regional cerebral blood flow in schizophrenia before and after neuroleptic medication. Author(s): Yildiz A, Eryilmaz M, Gungor F, Erkilic M, Karayalcin B. Source: Nuclear Medicine Communications. 2000 December; 21(12): 1113-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11200015&dopt=Abstract

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Relations of clinical features, subgroups and medication to serum monoamines in schizophrenia. Author(s): Oades RD, Klimke A, Henning U, Rao ML. Source: Human Psychopharmacology. 2002 January; 17(1): 15-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404703&dopt=Abstract

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Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Author(s): Kapur S, Zipursky R, Jones C, Remington G, Houle S. Source: The American Journal of Psychiatry. 2000 April; 157(4): 514-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10739409&dopt=Abstract

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Reliability and validity of a simple measure for assessing the social skills of people with schizophrenia necessary for seeking and securing a job. Author(s): Tsang H, Pearson V. Source: Can J Occup Ther. 2000 October; 67(4): 250-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11147375&dopt=Abstract

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Religious coping and psychological wellbeing in carers of relatives with schizophrenia. Author(s): Rammohan A, Rao K, Subbakrishna DK.

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Source: Acta Psychiatrica Scandinavica. 2002 May; 105(5): 356-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11942942&dopt=Abstract •

Renaissance exempla of schizophrenia: the cure by charity in Luther and Cervantes. Author(s): Schleiner W. Source: Renaiss Reform. 1985; 21: 157-76. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11618021&dopt=Abstract

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Repetitive transcranial magnetic stimulation in the treatment of chronic negative schizophrenia: a pilot study. Author(s): Cohen E, Bernardo M, Masana J, Arrufat FJ, Navarro V, Valls-Sole, Boget T, Barrantes N, Catarineu S, Font M, Lomena FJ. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1999 July; 67(1): 129-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10454880&dopt=Abstract

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Response to the first stimulus determines reduced auditory evoked response suppression in schizophrenia: single trials analysis using MEG. Author(s): Blumenfeld LD, Clementz BA. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2001 September; 112(9): 1650-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11514248&dopt=Abstract

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Retinal function as a marker for cell membrane omega-3 fatty acid depletion in schizophrenia: a pilot study. Author(s): Warner R, Laugharne J, Peet M, Brown L, Rogers N. Source: Biological Psychiatry. 1999 May 1; 45(9): 1138-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10331105&dopt=Abstract

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Right prefrontal slow repetitive transcranial magnetic stimulation in schizophrenia: a double-blind sham-controlled pilot study. Author(s): Klein E, Kolsky Y, Puyerovsky M, Koren D, Chistyakov A, Feinsod M. Source: Biological Psychiatry. 1999 November 15; 46(10): 1451-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10578460&dopt=Abstract

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Savoxepine versus haloperidol. Reasons for a failed controlled clinical trial in patients with an acute episode of schizophrenia. Author(s): Volz HP, Moller HJ, Gerebtzoff A, Bischoff S. Source: European Archives of Psychiatry and Clinical Neuroscience. 2002 April; 252(2): 76-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111340&dopt=Abstract

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Schizophrenia and schizotypal personality: a tribute to Peter H. Venables. Author(s): Raine A, Green MF.

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Source: Schizophrenia Research. 2002 March 1; 54(1-2): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11853972&dopt=Abstract •

Schizophrenia. 1939. Author(s): Hildreth AG, Still FM. Source: J Am Osteopath Assoc. 2000 August; 100(8): 506-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979260&dopt=Abstract

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Schizophrenia: an illness of distorted reality. Author(s): Dean B. Source: Biologist (London, England). 2000 September; 47(4): 202-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11153121&dopt=Abstract

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Schizophrenia: genesis, receptorology and current therapeutics. Author(s): Capuano B, Crosby IT, Lloyd EJ. Source: Current Medicinal Chemistry. 2002 March; 9(5): 521-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11945123&dopt=Abstract

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Schizophrenia: illness impact on family members in a traditional society--rural Ethiopia. Author(s): Shibre T, Kebede D, Alem A, Negash A, Deyassa N, Fekadu A, Fekadu D, Jacobsson L, Kullgren G. Source: Social Psychiatry and Psychiatric Epidemiology. 2003 January; 38(1): 27-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563556&dopt=Abstract

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Schizophrenia: reduced signal-to-noise ratio and impaired phase-locking during information processing. Author(s): Winterer G, Ziller M, Dorn H, Frick K, Mulert C, Wuebben Y, Herrmann WM, Coppola R. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2000 May; 111(5): 837-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10802455&dopt=Abstract

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Schizophrenia-like deficits in auditory P1 and N1 refractoriness induced by the psychomimetic agent phencyclidine (PCP). Author(s): Javitt DC, Jayachandra M, Lindsley RW, Specht CM, Schroeder CE. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2000 May; 111(5): 833-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10802454&dopt=Abstract

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Self regulation of electrocortical activity in schizophrenia and schizotypy: a review. Author(s): Gruzelier J.

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Source: Clin Electroencephalogr. 2000 January; 31(1): 23-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10638349&dopt=Abstract •

Sensory gating impairment associated with schizophrenia persists into REM sleep. Author(s): Kisley MA, Olincy A, Robbins E, Polk SD, Adler LE, Waldo MC, Freedman R. Source: Psychophysiology. 2003 January; 40(1): 29-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751801&dopt=Abstract

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Serotonergic basis of antipsychotic drug effects in schizophrenia. Author(s): Lieberman JA, Mailman RB, Duncan G, Sikich L, Chakos M, Nichols DE, Kraus JE. Source: Biological Psychiatry. 1998 December 1; 44(11): 1099-117. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9836014&dopt=Abstract

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Serotonin 5-HT2 receptors in schizophrenia: a PET study using [18F]setoperone in neuroleptic-naive patients and normal subjects. Author(s): Lewis R, Kapur S, Jones C, DaSilva J, Brown GM, Wilson AA, Houle S, Zipursky RB. Source: The American Journal of Psychiatry. 1999 January; 156(1): 72-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9892300&dopt=Abstract

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Sex differences, gamma activity and schizophrenia. Author(s): Slewa-Younan S, Gordon E, Williams L, Haig AR, Goldberg E. Source: The International Journal of Neuroscience. 2001 March; 107(1-2): 131-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328687&dopt=Abstract

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Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder. Author(s): Hibbeln JR, Makino KK, Martin CE, Dickerson F, Boronow J, Fenton WS. Source: Biological Psychiatry. 2003 March 1; 53(5): 431-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614996&dopt=Abstract

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Social cognition and social skills in schizophrenia: the role of self-monitoring. Author(s): Penn DL, Corrigan PW, Martin J, Ihnen G, Racenstein JM, Nelson D, Cassisi J, Hope DA. Source: The Journal of Nervous and Mental Disease. 1999 March; 187(3): 188-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10086476&dopt=Abstract

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St. John's wort and schizophrenia. Author(s): Lal S, Iskandar H.

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Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2000 August 8; 163(3): 262-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10951721&dopt=Abstract •

Stability of the acoustic startle reflex, prepulse inhibition, and habituation in schizophrenia. Author(s): Ludewig K, Geyer MA, Etzensberger M, Vollenweider FX. Source: Schizophrenia Research. 2002 May 1; 55(1-2): 129-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955972&dopt=Abstract

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Stigma and public health policy for schizophrenia. Author(s): Thompson K. Source: The Psychiatric Clinics of North America. 2003 March; 26(1): 273-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683269&dopt=Abstract

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Subjective effects of AMPT-induced dopamine depletion in schizophrenia: correlation between dysphoric responses and striatal D(2) binding ratios on SPECT imaging. Author(s): Voruganti L, Slomka P, Zabel P, Costa G, So A, Mattar A, Awad AG. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 November; 25(5): 642-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11682247&dopt=Abstract

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Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study. Author(s): de Haan L, van Bruggen M, Lavalaye J, Booij J, Dingemans PM, Linszen D. Source: The American Journal of Psychiatry. 2003 February; 160(2): 303-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562577&dopt=Abstract

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Subjective experience and striatal dopamine D(2) receptor occupancy in patients with schizophrenia stabilized by olanzapine or risperidone. Author(s): de Haan L, Lavalaye J, Linszen D, Dingemans PM, Booij J. Source: The American Journal of Psychiatry. 2000 June; 157(6): 1019-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10831489&dopt=Abstract

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Supplementation with a combination of omega-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophrenia. Author(s): Arvindakshan M, Ghate M, Ranjekar PK, Evans DR, Mahadik SP. Source: Schizophrenia Research. 2003 August 1; 62(3): 195-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837515&dopt=Abstract

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Symmetry reversal in schizophrenia. Author(s): Kalb R, Raydt G, Reulbach U, Kornhuber J. Source: Psychiatry and Clinical Neurosciences. 2003 August; 57(4): 353-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839514&dopt=Abstract

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Teaching in a new key: effects of a co-taught seminar on medical students' attitudes toward schizophrenia. Author(s): Coodin S, Chisholm F. Source: Psychiatric Rehabilitation Journal. 2001 Winter; 24(3): 299-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11315216&dopt=Abstract

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Thalamic alterations in schizophrenia. Author(s): Makela J, Kotila M, Henriksson M. Source: The American Journal of Psychiatry. 2001 February; 158(2): 323-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11156824&dopt=Abstract

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The brain metabolic patterns of clozapine- and fluphenazine-treated female patients with schizophrenia: evidence of a sex effect. Author(s): Cohen RM, Nordahl TE, Semple WE, Pickar D. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1999 November; 21(5): 632-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10516959&dopt=Abstract

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The difference in Mismatch negativity between the acute and post-acute phase of schizophrenia. Author(s): Shinozaki N, Yabe H, Sato Y, Hiruma T, Sutoh T, Nashida T, Matsuoka T, Kaneko S. Source: Biological Psychology. 2002 March; 59(2): 105-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911934&dopt=Abstract

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The effect of clozapine on the speed and accuracy of information processing in schizophrenia. Author(s): Galletly CA, Clark CR, McFarlane AC, Weber DL. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2000 November; 24(8): 1329-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11125857&dopt=Abstract

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The effect of extract of ginkgo biloba added to haloperidol on superoxide dismutase in inpatients with chronic schizophrenia. Author(s): Zhang XY, Zhou DF, Su JM, Zhang PY. Source: Journal of Clinical Psychopharmacology. 2001 February; 21(1): 85-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11199954&dopt=Abstract

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The effects of classic antipsychotic haloperidol plus the extract of ginkgo biloba on superoxide dismutase in patients with chronic refractory schizophrenia. Author(s): Zhou D, Zhang X, Su J, Nan Z, Cui Y, Liu J, Guan Z, Zhang P, Shen Y. Source: Chin Med J (Engl). 1999 December; 112(12): 1093-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721446&dopt=Abstract

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The effects of support groups on caregivers of patients with schizophrenia. Author(s): Chou KR, Liu SY, Chu H. Source: International Journal of Nursing Studies. 2002 September; 39(7): 713-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231028&dopt=Abstract

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The long and the short of it: influence of interstimulus interval on auditory P300 abnormalities in schizophrenia. Author(s): Mathalon DH, Ford JM. Source: Clin Electroencephalogr. 2002 July; 33(3): 125-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192662&dopt=Abstract

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The opinion of caregivers on aspects of schizophrenia and major affective disorders in a Nigerian setting. Author(s): Ohaeri JU, Fido AA. Source: Social Psychiatry and Psychiatric Epidemiology. 2001 October; 36(10): 493-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768847&dopt=Abstract

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The orienting response in schizophrenia and mania. Author(s): Schnur DB, Smith S, Smith A, Marte V, Horwitz E, Sackeim HA, Mukherjee S, Bernstein AS. Source: Psychiatry Research. 1999 October 18; 88(1): 41-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10641585&dopt=Abstract

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The relation between asymmetry and amplitude of the P300 field in schizophrenia. Author(s): Hill H, Weisbrod M. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 1999 September; 110(9): 1611-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10479028&dopt=Abstract

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The role of immune function in schizophrenia: an overview. Author(s): Muller N, Riedel M, Ackenheil M, Schwarz MJ. Source: European Archives of Psychiatry and Clinical Neuroscience. 1999; 249 Suppl 4: 62-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10654111&dopt=Abstract

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Traditional Chinese medical treatment to invigorate blood and relieve stasis treatment of schizophrenia: comparison with antipsychotics treatment. Author(s): Wang B. Source: Psychiatry and Clinical Neurosciences. 1998 December; 52 Suppl: S329-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9895184&dopt=Abstract

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Transcranial magnetic stimulation in schizophrenia. Author(s): Yu HC, Liao KK, Chang TJ, Tsai SJ. Source: The American Journal of Psychiatry. 2002 March; 159(3): 494-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870025&dopt=Abstract

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Treating substance abuse in schizophrenia. An initial report. Author(s): Bennett ME, Bellack AS, Gearon JS. Source: Journal of Substance Abuse Treatment. 2001 March; 20(2): 163-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306219&dopt=Abstract

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Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Author(s): Peet M, Brind J, Ramchand CN, Shah S, Vankar GK. Source: Schizophrenia Research. 2001 April 30; 49(3): 243-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11356585&dopt=Abstract

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Typical antipsychotic drugs -- D(2) receptor occupancy and depressive symptoms in schizophrenia. Author(s): Bressan RA, Costa DC, Jones HM, Ell PJ, Pilowsky LS. Source: Schizophrenia Research. 2002 July 1; 56(1-2): 31-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084417&dopt=Abstract

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Use of traditional treatment methods in a Xhosa schizophrenia population. Author(s): Koen L, Niehaus D, Muller J, Laurent C. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2003 June; 93(6): 443. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916383&dopt=Abstract

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Visualizing fronto-striatal circuitry and neuroleptic effects in schizophrenia. Author(s): Buchsbaum MS, Hazlett EA, Haznedar MM, Spiegel-Cohen J, Wei TC. Source: Acta Psychiatrica Scandinavica. Supplementum. 1999; 395: 129-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10225342&dopt=Abstract

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What has MMN revealed about the auditory system in schizophrenia? Author(s): Michie PT.

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Source: International Journal of Psychophysiology : Official Journal of the International Organization of Psychophysiology. 2001 October; 42(2): 177-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587775&dopt=Abstract •

Working memory control in patients with schizophrenia: a PET study during a random number generation task. Author(s): Artiges E, Salame P, Recasens C, Poline JB, Attar-Levy D, De La Raillere A, Paillere-Martinot ML, Danion JM, Martinot JL. Source: The American Journal of Psychiatry. 2000 September; 157(9): 1517-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10964875&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to schizophrenia; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com

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Diabetes Source: Prima Communications, Inc.www.personalhealthzone.com Epilepsy Source: Healthnotes, Inc. www.healthnotes.com Hypochondriasis Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Healthnotes, Inc. www.healthnotes.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Prima Communications, Inc.www.personalhealthzone.com Schizophrenia Source: Healthnotes, Inc. www.healthnotes.com Schizophrenia Source: Integrative Medicine Communications; www.drkoop.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com Tardive Dyskinesia Source: Healthnotes, Inc. www.healthnotes.com •

Alternative Therapy Fasting Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,694,00.html Magnet therapy Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,715,00.html Music therapy Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,719,00.html

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Herbs and Supplements Ava Alternative names: Kava Kava Source: Integrative Medicine Communications; www.drkoop.com Beta-Carotene Source: Prima Communications, Inc.www.personalhealthzone.com Clozapine Source: Healthnotes, Inc. www.healthnotes.com Evening Primrose Alternative names: Oenothera biennis, Sun Drop Source: Integrative Medicine Communications; www.drkoop.com GABA (Gamma-Amino Butyric Acid) Source: Healthnotes, Inc. www.healthnotes.com Gamma Oryzanol Source: Prima Communications, Inc.www.personalhealthzone.com Gamma-Linolenic Acid (GLA) Source: Integrative Medicine Communications; www.drkoop.com Ginkgo Source: Prima Communications, Inc.www.personalhealthzone.com GLA Source: Integrative Medicine Communications; www.drkoop.com GLA (Gamma-Linolenic Acid) Source: Prima Communications, Inc.www.personalhealthzone.com Glutamine Source: Integrative Medicine Communications; www.drkoop.com Glutamine Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10030,00.html Glycine Source: Healthnotes, Inc. www.healthnotes.com Haloperidol Source: Healthnotes, Inc. www.healthnotes.com Kava Kava Alternative names: Piper methysticum, Ava Source: Integrative Medicine Communications; www.drkoop.com

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Lithium Source: Healthnotes, Inc. www.healthnotes.com Melatonin Source: Healthnotes, Inc. www.healthnotes.com Melatonin Source: Prima Communications, Inc.www.personalhealthzone.com Milk Thistle Alternative names: Silybum marianum, Carduus marianus Source: Healthnotes, Inc. www.healthnotes.com Mixed Amphetamines Source: Healthnotes, Inc. www.healthnotes.com Oenothera biennis Alternative names: Evening Primrose Source: Integrative Medicine Communications; www.drkoop.com Olanzapine Source: Healthnotes, Inc. www.healthnotes.com Perphenazine Source: Healthnotes, Inc. www.healthnotes.com Phenothiazines Source: Prima Communications, Inc.www.personalhealthzone.com Phenylalanine Source: Prima Communications, Inc.www.personalhealthzone.com Piper methysticum Alternative names: Kava Kava Source: Integrative Medicine Communications; www.drkoop.com Risperidone Source: Healthnotes, Inc. www.healthnotes.com Sassafras Alternative names: Sassafras albidum (Nuttall) Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Sun Drop Alternative names: Evening Primrose Source: Integrative Medicine Communications; www.drkoop.com Thioridazine Source: Healthnotes, Inc. www.healthnotes.com

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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON SCHIZOPHRENIA Overview In this chapter, we will give you a bibliography on recent dissertations relating to schizophrenia. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “schizophrenia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on schizophrenia, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Schizophrenia ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to schizophrenia. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

A Biocultural Perspective on Schizophrenic Communication in New Zealand and Papua New Guinea by Schmidt, Karen Lynne, Phd from University of California, Berkeley, 1997, 237 pages http://wwwlib.umi.com/dissertations/fullcit/9803345

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A Comparative Analysis of Varying Treatment Approaches on the Level of Community Adjustment among Schizophrenic Outpatients by Coyle, Patricia F., Dsw from Adelphi University, School of Social Work, 1988, 136 pages http://wwwlib.umi.com/dissertations/fullcit/8917186

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A Comparison of Two Therapeutic Approaches with Schizophrenia by White, Tommie Lee, Phd from University of Southern California, 1982 http://wwwlib.umi.com/dissertations/fullcit/f3175269

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A Grounded Theory Study of the Experience of Spirituality among Persons Living with Schizophrenia by Tarko, Michel Andre; Phd from The University of British Columbia (canada), 2002, 225 pages http://wwwlib.umi.com/dissertations/fullcit/NQ73252

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A Latent Structural Analysis of the Prognosis of Current Functioning in Schizophrenia with the Intra-psychic Deficit Syndrome As a Mediating Variable by Levin, Shelley Jean, Phd from University of Southern California, 1994 http://wwwlib.umi.com/dissertations/fullcit/f2109235

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A Study of the Subjective Experiences of Ten Schizophrenic Persons Incarcerated for Violent Crimes (psychopathology) by Clark, James Joseph, Phd from The University of Chicago, 1995, 268 pages http://wwwlib.umi.com/dissertations/fullcit/9610004

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Adaptive Behavior of Children with Infantile Autism Compared to Children with Down's Syndrome and Children with Schizophrenia (developmental Disability, Childhood Disorders) by Wood, Jesse David, Phd from Texas A&m University, 1984, 200 pages http://wwwlib.umi.com/dissertations/fullcit/8417790

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Aerobic Conditioning in the Therapeutic Treatment of Chronic Schizophrenia by Jorgensen, Cathy, Edd from Northern Arizona University, 1986, 201 pages http://wwwlib.umi.com/dissertations/fullcit/8625579

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Aging and Sleep in Schizophrenia Patients and Normal Comparison Subjects: Subjective Reports and Objective Findings by Martin, Jennifer Lynn; Phd from University of California, San Diego and San Diego State University, 2002, 135 pages http://wwwlib.umi.com/dissertations/fullcit/3049676

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Altered Inhibitory Circuitry in the Prefrontal Cortex in Schizophrenia by Volk, David William; Phd from University of Pittsburgh, 2002, 125 pages http://wwwlib.umi.com/dissertations/fullcit/3066997

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An Assessment of Thought Disorder in Schizophrenia by Goodman, Jeffrey I; Phd from York University (canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK61535

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An Evaluation of Coping Ability As a Guide to the Treatment of Persons Diagnosed with Schizophrenia and Substance Abuse by Dumaine, Marian Lee, Phd from Florida International University, 1997, 186 pages http://wwwlib.umi.com/dissertations/fullcit/9811003

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An Exploration of Suicide Prevention and Intervention among Homosexual Schizophrenic Males by Sharples, Jennifer Lee; Psyd from Alliant International University, San Francisco Bay, 2002, 179 pages http://wwwlib.umi.com/dissertations/fullcit/3053011

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Aspects of Emotional Expression in Flat Affect Schizophrenia and Depression by Novack, Danielle Lee; Phd from New York University, 2002, 213 pages http://wwwlib.umi.com/dissertations/fullcit/3048851

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Attentional Bias and Craving in Cocaine-dependent Individuals with and without Comorbid Schizophrenia by Copersino, Marc Louis; Phd from Hofstra University, 2002, 126 pages http://wwwlib.umi.com/dissertations/fullcit/3041338

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Autonomic Correlates of Chronic Schizophrenia : a Reaction Time Paradigm by Gray, Arne L; Phd from University of Waterloo (canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK19316

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Awareness of Schizophrenia and Caregiver Burden by Thompson, Monica Yvette; Phd from Drexel University, 2002, 52 pages http://wwwlib.umi.com/dissertations/fullcit/3035502

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Bali As It Might Have Been Known: Margaret Mead, Gregory Bateson, Wolfgang Weck, Schizophrenia and Human Agency by Sullivan, Gerald Winfield, Phd from University of Virginia, 1998, 568 pages http://wwwlib.umi.com/dissertations/fullcit/9840445

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Basal Ganglia Structure and the Effects of Neuroleptic Treatment in Schizophrenia by Lang, Donna Jane-mai; Phd from The University of British Columbia (canada), 2002, 157 pages http://wwwlib.umi.com/dissertations/fullcit/NQ75036

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Boundaries of the Self: Poetry by Frost, Roethke and Berryman, Considered in the Light of the Language of Schizophrenia. by Thompson, Susan, Phd from The University of Texas at Austin, 1974, 173 pages http://wwwlib.umi.com/dissertations/fullcit/7504465

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Can Average People Detect Differences in Transcribed Speech Samples Spoken by People Either Diagnosed with Schizophrenia or Not Diagnosed with Schizophrenia? by Hopson, Tina Marie; Ma from University of the Pacific, 2002, 150 pages http://wwwlib.umi.com/dissertations/fullcit/1407673

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Caregivers' Characteristics and Schizophrenic Residents' Community Tenure by Tracy, Regina Ann, Dsw from Adelphi University, School of Social Work, 1996, 138 pages http://wwwlib.umi.com/dissertations/fullcit/9722323

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Caregiving and Schizophrenia: Understanding the Worldview of Asian Indian Families by Menon, Goutham M., Phd from University of Illinois at Urbana-champaign, 1997, 216 pages http://wwwlib.umi.com/dissertations/fullcit/9812704

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Causal Attributions about Schizophrenia in Families in China: Expressed Emotion, Perceived Stigma and Patient Relapse by Yang, Lawrence Hsin; Phd from Boston University, 2002, 156 pages http://wwwlib.umi.com/dissertations/fullcit/3031596

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Children and Adolescents at Risk for Schizophrenia: Influence of Familial Expressed Emotion by Montrose, Debra Marie; Phd from University of Pittsburgh, 2000, 171 pages http://wwwlib.umi.com/dissertations/fullcit/9974458

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Client Characteristics, Service Characteristics, and Psychosocial Outcomes in the Community Treatment of Schizophrenia by Ansel, Mark Gerard, Phd from University of Southern California, 1996, 121 pages http://wwwlib.umi.com/dissertations/fullcit/9636319

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Cognitive Factors Contributing to Adaptive Coping and Quality of Life in Individuals with Schizophrenia by Guyer, Margaret Elizabeth; Phd from Boston University, 2002, 166 pages http://wwwlib.umi.com/dissertations/fullcit/3031575

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Cognitive Inhibition in Schizophrenia: an Investigation of Negative Priming in Chronic Schizophrenic Patients and the First-degree Relatives of Schizophrenic

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Patients by Nolet, Michael Wayne; Phd from University of Maryland Baltimore County, 2002, 78 pages http://wwwlib.umi.com/dissertations/fullcit/3038709 •

Cognitive Structures for Self and Others in Adolescents at Risk for Schizophrenia by O'rourke, Christine; Phd from Concordia University (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL21849

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Collaboration and Congruence between Family Member and Case Manager Perceptions in the Treatment of Individuals with Schizophrenia by Bichsel, Susan Lynn; Phd from Cleveland State University, 2001, 159 pages http://wwwlib.umi.com/dissertations/fullcit/3004654

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Commonality of Factors in the Personal Histories of Severely Disabled Schizophrenia and Bipolar Disorder/major Depression Clients by Monschke, Alice Allen, Phd from Kansas State University, 1997, 239 pages http://wwwlib.umi.com/dissertations/fullcit/9817170

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Comparative Analysis of Two Microcounseling Learning Environments with People Who Are Schizophrenic by Hunter, William Livingstone, Edd from University of Massachusetts, 1984, 228 pages http://wwwlib.umi.com/dissertations/fullcit/8500081

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Cortical Inhibition in Schizophrenia by Daskalakis, Zafiris Jeffrey; Phd from University of Toronto (canada), 2002, 188 pages http://wwwlib.umi.com/dissertations/fullcit/NQ74728

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Coyote Walks the Line: a Study of Boundaries in People Being Treated for Schizophrenia and Their Art by Buck, Judysharon; Phd from Pacifica Graduate Institute, 2002, 375 pages http://wwwlib.umi.com/dissertations/fullcit/3077730

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Dermatoglyphic Fluctuating Asymmetry, Negative Symptoms, and Role Functioning in a Schizophrenic Sample by Shannon-mcgowan, Erin Colleen; Psyd from Pepperdine University, 2002, 136 pages http://wwwlib.umi.com/dissertations/fullcit/3066082

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Diagnostic Efficiency Calculations for Two Measures of Personality with Schizophrenic, Schizoaffective, and Depressed Populations by Boller, Janet Lynn; Psyd from Seton Hall University, College of Education and Human Services, 2002, 126 pages http://wwwlib.umi.com/dissertations/fullcit/3081006

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Differences between Schizophrenics and Normals in Maintaining a Mental Set When Presented with Stimuli Pertaining to People and to Things by Isenberg, Beth Rachel, Phd from State University of New York at Buffalo, 1985, 62 pages http://wwwlib.umi.com/dissertations/fullcit/8518756

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Differential Decision Strategy between Schizophrenia and Mania Within the Context of a Recognition Memory Task by Halpern, Anita; Phd from York University (canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL30903

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Differential Utilization of Mental Health Services in Chronic Schizophrenia by Mcgill, Christine Wood, Phd from University of Southern California, 1990 http://wwwlib.umi.com/dissertations/fullcit/f2790404

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Discovering and Empowering the Voices of Schizophrenics by Alexander-molloy, Jennifer Anne, Phd from Wayne State University, 1999, 341 pages http://wwwlib.umi.com/dissertations/fullcit/9932950

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Dopamine D1 and D2 Receptors in Schizophrenia, Alzheimer's, Huntington's, and Parkinson's Diseases by Bzowej, Natalie Helen; Phd from University of Toronto (canada), 1990 http://wwwlib.umi.com/dissertations/fullcit/NL56988

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Dopamine Transporter Signal in Patients with Schizophrenia: Relevance to Clinical Symptoms and Pathophysiology by Yoder, Karmen Kay; Phd from Indiana University, 2002, 143 pages http://wwwlib.umi.com/dissertations/fullcit/3054371

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Dreams of Different Things: the Experience of Schizophrenia As Represented in Journals, Clinical Accounts and Fiction in the Early Modern Period by Toomey, David, Phd from University of Virginia, 1998, 332 pages http://wwwlib.umi.com/dissertations/fullcit/9916327

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Effects of Education in Reducing Negative Attitudes in Primary Caretakers of Schizophrenic Patients by Dewey, Elaine Krohn, Phd from Florida Institute of Technology, 1988, 57 pages http://wwwlib.umi.com/dissertations/fullcit/8809202

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Ego Function, Ambiguity and Schizophrenia by Westerman, Barrie, Phd from Boston University Graduate School, 1973, 123 pages http://wwwlib.umi.com/dissertations/fullcit/7323529

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Engaging Smokers with Schizophrenia in Treatment for Tobacco Dependence: a Brief Motivational Interviewing Intervention by Steinberg, Marc L. Phd from University of South Florida, 2003, 105 pages http://wwwlib.umi.com/dissertations/fullcit/3082981

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Ethnicity and Treatment Outcomes of Schizophrenia from Community-based Psychosocial Rehabilitation Interventions: a Longitudinal and Multidimensional Approach by Bae, Sung-woo; Phd from University of Southern California, 2001, 127 pages http://wwwlib.umi.com/dissertations/fullcit/3065760

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Experiences Following Hospital Discharge of Males Diagnosed with Schizophrenia: a Qualitative Study of Modified Labeling Theory (stigmatization) by Schleuse, Doris Laird, Phd from The University of Texas at Austin, 1991, 214 pages http://wwwlib.umi.com/dissertations/fullcit/9128357

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Experiencing the Demands of Motherhood and Schizophrenia by Shea, Loretta (lori) Ann; Msc from Queen's University at Kingston (canada), 2003, 123 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74923

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Explaining Crises in Rental Housing Construction: Myth and Schizophrenia in Policy Analysis by Baar, Kenneth Kalvin, Phd from University of California, Los Angeles, 1989, 305 pages http://wwwlib.umi.com/dissertations/fullcit/9012981

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Factors Associated with Expressed Emotion in Schizophrenia by Hall, Michael John; Phd from Kent State University, 2002, 81 pages http://wwwlib.umi.com/dissertations/fullcit/3081316

322 Schizophrenia

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Familial Attributions in the Parental Tats of Adolescents at Risk for Schizophrenia Spectrum Disorders. by Aguayo, Joseph Richard, Phd from University of California, Los Angeles, 1977, 169 pages http://wwwlib.umi.com/dissertations/fullcit/7801714

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Family-based Intervention with Schizophrenia: a Clinical Outcome Study by Bentley, Kia J., Phd from The Florida State University, 1987, 252 pages http://wwwlib.umi.com/dissertations/fullcit/8721833

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Fire in the Library: Paranoia and Schizophrenia As Models of Linguistic Crisis in Elias Canetti's 'die Blendung' by Lovett, Marilyn Smith, Phd from Indiana University, 1982, 201 pages http://wwwlib.umi.com/dissertations/fullcit/8211159

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Frontal Lobe Functioning, Psychiatric Symptoms and Quality of Life in Outpatients with Schizophrenia by Kennedy, Annette; Psyd from The Wright Institute, 2002, 136 pages http://wwwlib.umi.com/dissertations/fullcit/3069390

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Functional Anatomy of the Human Forebrain Assessed by Fluorodeoxyglucose-18 Positron Emission Tomography and Coregistered Standardized Magnetic Resonance Imaging in Normal Subjects and Patients with Schizophrenia by Opole, Isaac Ogwel; Phd from University of California, Irvine, 2002, 390 pages http://wwwlib.umi.com/dissertations/fullcit/3039219

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Functional Variability of the Brain in Psychoses: a Neuropsychological Investigation of Schizophrenia and the Affective Disorders by Berg, Glenda Theresa, Phd from University of Washington, 1983, 180 pages http://wwwlib.umi.com/dissertations/fullcit/8312123

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Functioning in Schizophrenia and Schizoaffective Disorder: Quality of Life, Symptom Presentation, Language Production, and Neurocognitive Abilities by Hegeman, Bridget Mary; Phd from University of Montana, 2002, 211 pages http://wwwlib.umi.com/dissertations/fullcit/3053335

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Group Cohesion and Self-disclosure in Group Therapy for Patients with Schizophrenia and Substance Use Disorders by Sena, Philomena; Phd from New School for Social Research, 2002, 98 pages http://wwwlib.umi.com/dissertations/fullcit/3062387

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Health Beliefs and Medication Compliance among Outpatients with Schizophrenia by Kelly, Gerard Ralph, Phd from University of Maryland at Baltimore, 1984, 383 pages http://wwwlib.umi.com/dissertations/fullcit/8503391

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High Field in Vivo Phosphorus Magnetic Resonance Spectroscopy: Optimization and Application to the Study of Schizophrenia by Jensen, Joan Eric Nestler; Phd from The University of Western Ontario (canada), 2002, 175 pages http://wwwlib.umi.com/dissertations/fullcit/NQ77094

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Highly Potent Nt[8-13] Analogues That Cross the Blood-brain Barrier: in Vitro and in Vivo Evaluation of Novel Peptides with the Potential for Treating Schizophrenia by Kokko, Kyle Pentti; Phd from Medical University of South Carolina, 2002, 183 pages http://wwwlib.umi.com/dissertations/fullcit/3050233

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Hopelessness, Negative Symptoms, and Global Functioning in Chronic Schizophrenia by Arlow, Phyllis Bessam; Dsw from Adelphi University, School of Social Work, 2001, 124 pages http://wwwlib.umi.com/dissertations/fullcit/3035134

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Humorousness and Job Success among Adults with Schizophrenia by Mougenot, Timothy, Phd from The University of Connecticut, 1998, 73 pages http://wwwlib.umi.com/dissertations/fullcit/9909118

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Identical Twins Concordant and Discordant for Schizophrenia: the Roles of Developmental Instability and Neurodevelopment in Etiology by Reilly, James Lockwood; Phd from University of Virginia, 2003, 151 pages http://wwwlib.umi.com/dissertations/fullcit/3067484

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Images of the Center in Schizophrenia: Myth, Text, Theory (carl G. Jung, J. Weir Perry) by Trueman, Leslie Doris; Phd from Rutgers the State University of New Jersey New Brunswick, 2002, 290 pages http://wwwlib.umi.com/dissertations/fullcit/3066789

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Immediate and Delayed Neurochemical Effects of Transient Neonatal N-methyl-daspartate Receptor Blockade: Implications for Schizophrenia by Dagnone, Robert Vico; Msc from Queen's University at Kingston (canada), 2002, 109 pages http://wwwlib.umi.com/dissertations/fullcit/MQ73004

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Immediate Memory in Schizophrenia by Bauman, Edward,; Advdeg from Queen's University at Kingston (canada), 1968 http://wwwlib.umi.com/dissertations/fullcit/NK02793

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Increasing Motivation to Stop Smoking among Persons with Schizophrenia and Other Chronic Mental Illnesses by Wells, Mary Elizabeth; Phd from Ohio University, 2002, 234 pages http://wwwlib.umi.com/dissertations/fullcit/3062179

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Individual and Job Site Factors in the Development of Reasonable Accommodations for Workers with Schizophrenia by Symanski-tondora, Janis L. Psyd from University of Hartford, 2002, 153 pages http://wwwlib.umi.com/dissertations/fullcit/3061474

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Insight in Schizophrenia: a Meta-analysis by Mintz, Alisa Robin; Msc from University of Calgary (canada), 2002, 60 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76243

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Insight in Schizophrenia: Associations with Premorbid Adjustment, Positive and Negative Symptoms, Depression, and Suicidality by Kohl, Lisa Jil; Phd from Columbia University, 2003, 124 pages http://wwwlib.umi.com/dissertations/fullcit/3088358

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Latent Inhibition in Schizophrenic Participants and Their First-degree Relatives by Hirshkowitz, Debra; Phd from New School University, 2002, 74 pages http://wwwlib.umi.com/dissertations/fullcit/3075256

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Lawful Fictions: Schizophrenia and the Law of Fiction in the Work of John Barth by Britt, Theron Christopher, Phd from University of California, Irvine, 1990, 284 pages http://wwwlib.umi.com/dissertations/fullcit/9103377

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Linguistic Indices of Schizophrenia. by Shamis, Sandra Lee, Phd from University of California, Berkeley, 1975, 137 pages http://wwwlib.umi.com/dissertations/fullcit/7615366

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Madness in Zanzibar: 'schizophrenia' in Three Families in the 'developing' World (tanzania) by Mcgruder, Juli Helen, Phd from University of Washington, 1999, 385 pages http://wwwlib.umi.com/dissertations/fullcit/9924117

324 Schizophrenia

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Mapping Brain Abnormalities in Schizophrenia: Hemispheric, Gender and Genetic Effects by Narr, Katherine Louise; Phd from University of California, Los Angeles, 2002, 496 pages http://wwwlib.umi.com/dissertations/fullcit/3066419

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Maurice Merleau-ponty and the Psychology of Time Experience: with Special Reference to Depressive and Schizophrenic Distortions by Goodrich, Barbara Gwenn, Phd from University of Colorado at Boulder, 1994, 276 pages http://wwwlib.umi.com/dissertations/fullcit/9524306

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Memory Attributes in Schizophrenia by Robertson, Roberta Gail; Phd from The University of Manitoba (canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK37816

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Moral and Social Schizophrenia: a View of the Bourgeoisie in Naturalistic Drama by Stevenson, Mark Philip, Phd from University of Pittsburgh, 1983, 284 pages http://wwwlib.umi.com/dissertations/fullcit/8327643

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Mother-child Interaction: a Reciprocity Model (schizophrenia) by Donovan, Georgeanne Holland, Phd from University of Pittsburgh, 1983, 235 pages http://wwwlib.umi.com/dissertations/fullcit/8417690

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Mothering Adult Children with Schizophrenia: the Hidden Realities of Caring by Vatri Boydell, Katherine Mary, Phd from York University (canada), 1996, 262 pages http://wwwlib.umi.com/dissertations/fullcit/NN10331

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Multidisciplinary School-based Program for Hispanic Adolescents at Risk of Developing Schizophrenia by Pena Montalvo, Grace; Psyd from Carlos Albizu University, 2002, 138 pages http://wwwlib.umi.com/dissertations/fullcit/3073499

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Multiple Family Group (mfg) Treatment and Negative Symptoms in Schizophrenia: Two-year Outcomes by Voss, William David; Phd from Washington State University, 2002, 115 pages http://wwwlib.umi.com/dissertations/fullcit/3069657

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Neuroanatomical Aspects of Schizophrenia by Bankier, Robert Gordon; Phd from The University of Manitoba (canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK54643

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Neurocognition, Symptomatology, and Social-adaptive Functioning in Alcoholabusing Schizophrenia Patients by Bowie, Christopher Robert; Phd from Hofstra University, 2002, 77 pages http://wwwlib.umi.com/dissertations/fullcit/3072167

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Neurological Correlates of Thought Disorder in Schizophrenic Patients by Chiu, Chen-huan; Phd from Boston University, 2003, 122 pages http://wwwlib.umi.com/dissertations/fullcit/3083828

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Neuropsychological Assessment and the Differentiation of Chronic Schizophrenia from Brain Damage by Young, Donald Allen; Edd from University of Toronto (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL23522

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Neuropsychological Characteristics of Positive and Negative Symptoms of Schizophrenia Implications for Cognitive Remediation by Bird, Daniel Ralph; Phd from Mcmaster University (canada), 1990 http://wwwlib.umi.com/dissertations/fullcit/NL57935

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Neuropsychological Differences between Patients Diagnosed with Schizophrenia and Comorbid Schizophrenia and Alcohol Dependence by Nazzaro, Dolores Marie; Phd from University of Pittsburgh, 2002, 168 pages http://wwwlib.umi.com/dissertations/fullcit/3054318

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Neuropsychological Patterns of Functioning of Positive, Negative and Mixed Symptom Schizophrenics by Mitchell, Stephanie Ann, Phd from University of Alberta (canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/f3844980

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Object Relations Theory and Family Dynamics in Schizophrenic Patients, Nonpsychotic Patients, and Controls: an Empirical Study by Chamberlain, Charles Calvin; Phd from University of Detroit Mercy, 2002, 115 pages http://wwwlib.umi.com/dissertations/fullcit/3062891

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Outpatient Treatment Compliance among First-episode Patients with Schizophrenia by Mark, Joshua H. Phd from Yeshiva University, 2002, 229 pages http://wwwlib.umi.com/dissertations/fullcit/3055231

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Paranoid and Undifferentiated Types of Schizophrenia and Their Relationship to Types of Substance Abuse by Grillo-didomenico, Beatrice, Phd from Fordham University, 1998, 147 pages http://wwwlib.umi.com/dissertations/fullcit/9825880

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Parental Status Dissonance and the Occurrence of Schizophrenia in Offspring by Wooden, Wayne Stanley, Phd from University of Pennsylvania, 1972, 101 pages http://wwwlib.umi.com/dissertations/fullcit/7313490

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Patient Education on the Nature, Course, and Treatment of Schizophrenia and Its Effect on Patient Knowledge, Awareness of Illness, and Therapeutic Compliance by Jewart, Rita D., Phd from Virginia Commonwealth University, 1987, 198 pages http://wwwlib.umi.com/dissertations/fullcit/8720750

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Personality, Insight, and Compliance: a Longitudinal Study of Treatment Adherence in Outpatients with Schizophrenia and Schizoaffective Disorder by Wilson, Scott Thomas; Phd from Columbia University, 2003, 250 pages http://wwwlib.umi.com/dissertations/fullcit/3088453

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Physiological Concomitants to the Reduncancy Associated Deficit in Process Schizophrenia by Bradley, Ian Francis; Phd from University of Waterloo (canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK33479

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Planning Needs of Aging Parental Caregivers of People with Schizophrenia by Simmons, Mark William; Psyd from Massachusetts School of Professional Psychology, 2003, 186 pages http://wwwlib.umi.com/dissertations/fullcit/3088246

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Political Phenomena of Schizophrenia from Emil Kraepelin to R. D. Laing. by Weaver, Daniel Joseph, Phd from University of Hawaii, 1977, 395 pages http://wwwlib.umi.com/dissertations/fullcit/7810262

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'practical Extravagance': a Study of Hawthorne's Study of Schizophrenia As a Creative Process. by Karlow, Martin Peter, Phd from Yale University, 1975, 374 pages http://wwwlib.umi.com/dissertations/fullcit/7524557

326 Schizophrenia

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Precision Teaching As an Instructional Procedure for Training Social Skills in Individuals Diagnosed with Schizophrenia by Mullin, Jill Evelyn; Ma from University of the Pacific, 2002, 76 pages http://wwwlib.umi.com/dissertations/fullcit/1412113

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Predictive Validity of Mmpi-2 and Rorschach in the Diagnosis of Depression and Schizophrenia by Morgan-gillard, Shannon; Psyd from Seton Hall University, College of Education and Human Services, 2002, 163 pages http://wwwlib.umi.com/dissertations/fullcit/3066141

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Premorbid Asocial Adjustment and Prognosis in Schizophrenia: the Relationship of Process Schizophrenia to Outcome. by Gittelman, Rachel Kravetz, Phd from Columbia University, 1966, 217 pages http://wwwlib.umi.com/dissertations/fullcit/6705821

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Prenatal Lead Exposure and Schizophrenia Spectrum Disorders by Opler, Mark Gregory; Phd from Columbia University, 2002, 216 pages http://wwwlib.umi.com/dissertations/fullcit/3066885

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Professionals' Knowledge of the Early Signs of Relapse in Schizophrenia by O'toole, Lawrence; Phd from New York University, 2000, 274 pages http://wwwlib.umi.com/dissertations/fullcit/9963438

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Prognosis and Outcome of First-episode Psychoses in Hawai'i: Results of the 15-year Follow-up of the Honolulu Cohort of the Who International Study of Schizophrenia by Suarez, Edward; Phd from University of Hawaii, 2002, 247 pages http://wwwlib.umi.com/dissertations/fullcit/3045444

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Psychosocial Stressors and Major Depression, Schizophrenia, and Schizophreniform Disorder by Williams, Janet B. W., Dsw from Columbia University, 1981, 229 pages http://wwwlib.umi.com/dissertations/fullcit/8204553

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Reaction Time Performance in Schizophrenia : Three Studies of Trial Contextual Influences on the Crossover Phenomenon by Bellissimo, Anthony; Phd from University of Waterloo (canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK19304

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Redefining Parental Identity: a Grounded Theory of Caregiving and Schizophrenia by Milliken, Patricia Jane, Phd from University of Alberta (canada), 1998, 357 pages http://wwwlib.umi.com/dissertations/fullcit/NQ29081

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Referential Speaker Processes in Process-reactive Schizophrenia by Putterman, Allan H; Phd from York University (canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK13101

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Relationships among Work Personality, Social Adjustment, Demographic Variables, Psychiatric Symptoms, and Work Status in Outpatients with Schizophrenia by Silvestri, Marie Christine, Phd from New York University, 1993, 179 pages http://wwwlib.umi.com/dissertations/fullcit/9423010

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Representing the Double Bind: Doubleness and Schizophrenia in the Works of Annie Ernaux, Agota Kristof, and Farida Belghoul (french Text, Algeria) by Bacholle, Michele Sandrine, Phd from The University of Connecticut, 1998, 208 pages http://wwwlib.umi.com/dissertations/fullcit/9906540

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Schizophrenia and Body Experience: Theoretical Elucidation and Case Study in a Group of Young Psychotic Adults Starting from a Psychodynamical Perspective by Soenen, Stefaan; Phd from Katholieke Universiteit Leuven (belgium), 2002, 701 pages http://wwwlib.umi.com/dissertations/fullcit/f875777

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Schizophrenia and Creative Archetypes As Shown in Works by Thomas Bernhard by Moseley, Karen Appaline, Phd from The Louisiana State University and Agricultural and Mechanical Col., 1982, 168 pages http://wwwlib.umi.com/dissertations/fullcit/8216860

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Schizophrenia and Orthomolecular Techniques: How Food Can Affect Symptoms by Gaw, Heather Marie; Psyd from University of Hartford, 2002, 75 pages http://wwwlib.umi.com/dissertations/fullcit/3061469

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Schizophrenia and Story: Intimate Threads Weaving Psyche's Fabric by Montana, Clare; Phd from Pacifica Graduate Institute, 2002, 213 pages http://wwwlib.umi.com/dissertations/fullcit/3054549

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Schizophrenia and Subjective Experience of Symptoms: the Role of Environmental Variables by Marley, James A., Phd from University of Illinois at Chicago, 1995, 135 pages http://wwwlib.umi.com/dissertations/fullcit/9532408

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Schizophrenia and Substance Use Disorders: Comparisons of Non-abusing, Currently Using and Currently Abstinent Individuals by Bunkley, Darrell Timothy; Phd from Northwestern University, 2002, 109 pages http://wwwlib.umi.com/dissertations/fullcit/3050496

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Schizophrenia and the Family Life Cycle by Jones, Samuel Carl, Dsw from City University of New York, 1992, 255 pages http://wwwlib.umi.com/dissertations/fullcit/9304678

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Schizophrenia and the Family: Expressed Emotion among Mexican Americans and Anglo Americans by Jenkins, Janis D., Phd from University of California, Los Angeles, 1984, 272 pages http://wwwlib.umi.com/dissertations/fullcit/8420192

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Schizophrenia: a Phenomenological Analysis of the People and Experiences Behind the Diagnosis by Vela, Juvencio Reynaldo, Ii; Psyd from The Wright Institute, 2002, 128 pages http://wwwlib.umi.com/dissertations/fullcit/3044819

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Schizophrenia: a Resource for the Genetic Counselor by Jackson, Sarah Ann; Ms from Sarah Lawrence College, 2003, 46 pages http://wwwlib.umi.com/dissertations/fullcit/1413585

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Schizophrenia: an Analysis of the Relationship between Stressful Life Events and Social Support Systems by Land, Helen Marianne, Phd from University of Pittsburgh, 1983, 312 pages http://wwwlib.umi.com/dissertations/fullcit/8327646

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Selected Effects of Underlying Neuropsychiatric Impairment on Adaptation of Persons with Schizophrenia to a Chronic Mental Illness by Farmer, Rosemary L., Phd from Virginia Commonwealth University, 1993, 237 pages http://wwwlib.umi.com/dissertations/fullcit/9321238

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Single Systems Evaluation of a Psychoeducation Program for Families with a Schizophrenic Family Member: Implications for Practice by Simon, Cassandra E., Phd from The University of Texas at Arlington, 1992, 193 pages http://wwwlib.umi.com/dissertations/fullcit/9315994

328 Schizophrenia

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Smooth Pursuit Functional Asymmetry Interacts with Age in Patients with Schizophrenia: Evidence for a Neurodynamic Model by Chan, Tak Chun; Phd from New School for Social Research, 2002, 94 pages http://wwwlib.umi.com/dissertations/fullcit/3062363

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Social Anhedonia and Schizophrenia-spectrum Personality Traits in Genetic Highrisk Adolescents and Young Adults by Auther, Andrea M. Phd from St. John's University (new York), 2002, 94 pages http://wwwlib.umi.com/dissertations/fullcit/3059407

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Social Class and Schizophrenia in Maryland: a Study of First Admissions and Chronicity. by Eaton, William Wright, Jr., Phd from The University of Wisconsin Madison, 1973, 175 pages http://wwwlib.umi.com/dissertations/fullcit/7330315

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Social Interaction and Intimacy in Pre-schizophrenia by Kreisman, Dolores Esther, Phd from Columbia University, 1969, 142 pages http://wwwlib.umi.com/dissertations/fullcit/7007011

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Social Relations and Community Tenure in Schizophrenia by Wagenfeld, Morton Oliver, Phd from Syracuse University, 1966, 160 pages http://wwwlib.umi.com/dissertations/fullcit/6707140

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Social Relationships in Adults with Schizophrenia: a Multi-method Study by Angell, Kathryn Elizabeth; Phd from The University of Wisconsin - Madison, 1999, 219 pages http://wwwlib.umi.com/dissertations/fullcit/9938743

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Social Support Networks and Emotional Environment of Families Coping with Schizophrenia (maine) by Stiefel, Susanne, Phd from Arizona State University, 1986, 262 pages http://wwwlib.umi.com/dissertations/fullcit/8704526

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Sources of Variability in Neuroimaging Findings of Frontal Lobe Dysfunction in Schizophrenia: Single Subject Contributions to Group Effects by Holt, John Leonard; Phd from Rutgers the State University of New Jersey - New Brunswick, 2002, 126 pages http://wwwlib.umi.com/dissertations/fullcit/3055059

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Speech Disturbance Reactivity to Stress in Schizophrenia Inpatients Measured by Fast Fourier Transform Analysis by Dombrowski, Margaret Eileen; Phd from Kent State University, 2002, 79 pages http://wwwlib.umi.com/dissertations/fullcit/3081318

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Stages of Smoking Cessation in Schizophrenic Patients: a Psychometric Study by Shats, Mark; Psyd from The Wright Institute, 2002, 60 pages http://wwwlib.umi.com/dissertations/fullcit/3058321

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Stimulus Structure and Schizophrenia by Jackson-whaley, Iris Patricia; Phd from University of Waterloo (canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK45986

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Stress and Coping in Middle-aged Mothers with Adult Schizophrenic Offspring by Smelson-kanwal, Bari, Phd from New York University, 1997, 209 pages http://wwwlib.umi.com/dissertations/fullcit/9717729

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Stroop Performance in Schizophrenic and Bipolar Patients: an Fmri Study by Gruber, Staci Ann; Phd from Tufts University, 2002, 134 pages http://wwwlib.umi.com/dissertations/fullcit/3042932

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Structural and Functional Magnetic Resonance Imaging of the Cerebellum in Schizophrenia and Bipolar Disorder by Loeber, Russell Todd; Phd from Boston University, 2002, 201 pages http://wwwlib.umi.com/dissertations/fullcit/3028902

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Structures and Strategies of Attentional Deployment in Schizophrenia by George, Leonard Robert; Phd from The University of Western Ontario (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK66054

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Support: a Psycho-educational Program for Families of Schizophrenic Patients (development) by Scheidt, Susan Diane, Psyd from Rutgers the State University of New Jersey, G.s.a.p.p., 1984, 308 pages http://wwwlib.umi.com/dissertations/fullcit/8516698

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Televisual Representation, Schizophrenic Experience, and Apocalypticism in Late Twentieth-century Drama and Theatre (eric Overmyer, Constance Congdon, Craig Lucas) by Freeman, Roger Dee, Phd from The Ohio State University, 1998, 228 pages http://wwwlib.umi.com/dissertations/fullcit/9911192

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The Association between Discepancies in Parent-patient Ratings on Premorbid Adjustment and Symptom Severity in First-episode Schizophrenia by Lieberman, Margeaux Rosette; Psyd from Alliant International University, San Francisco Bay, 2003, 373 pages http://wwwlib.umi.com/dissertations/fullcit/3069765

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The Co-aggregation of Smooth Pursuit, Saccade and Fixation Eye Movement Dysfunction in Schizophrenia Patients and Their First-degree Biological Relatives by Calkins, Monica Elizabeth; Phd from University of Minnesota, 2002, 129 pages http://wwwlib.umi.com/dissertations/fullcit/3058631

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The Correlation between Culture and Reactive Schizophrenia by Davis, Forrest Richard, Phd from University of California, Los Angeles, 1986, 149 pages http://wwwlib.umi.com/dissertations/fullcit/8629884

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The Course of Social Disability in Newly Diagnosed Schizophrenics in Four Countries (germany, Sudan, Turkey, Bulgaria) by Connor, Katherine, Phd from Yale University, 1990, 309 pages http://wwwlib.umi.com/dissertations/fullcit/9121095

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The Critical Moment of Independence: Separation Conflict and Risk Factors in a Sample of Colombian Male Schizophrenics by Colon, Jose Cristobal, Phd from Stanford University, 1981, 178 pages http://wwwlib.umi.com/dissertations/fullcit/8201975

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The Effect of Active Learning Methods with Adult Schizophrenic Inpatients on Attitudes toward Neuroleptic Medications by Berky Beck, Joellyn, Phd from Temple University, 1997, 131 pages http://wwwlib.umi.com/dissertations/fullcit/9724210

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The Effect of Context on Learning Functional Living Skills for a Population of People with Schizophrenia by Duncombe, Linda Werkley; Edd from Boston University, 2002, 122 pages http://wwwlib.umi.com/dissertations/fullcit/3028900

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The Effect of Neighborhood Environments on Schizophrenic Relapse: a Sociocultural Perspective by Kennedy, Marilyn Jean Brennan; Phd from Case Western Reserve University, 2000, 275 pages http://wwwlib.umi.com/dissertations/fullcit/9996316

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The Effects of Acute Tryptophan Depletion on Cigarette Smoking Topography and Psychopathologic Symptoms in Schizophrenia by Hitsman, Brian; Phd from The Herman M. Finch U. of Health Sciences - the Chicago Medical Sch., 2002, 73 pages http://wwwlib.umi.com/dissertations/fullcit/3061534

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The Effects of Auditory Background Interference on Attention and Short-term Memory of Normals and Schizophrenics (memory) by Truhn, Patricia Lynn, Phd from Ball State University, 1989, 76 pages http://wwwlib.umi.com/dissertations/fullcit/9003072

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The Effects of Collaborative Psychoeducational Intervention on Relatives of Schizophrenic Veterans by Lomax, Herbert T., Phd from Saint Louis University, 1992, 204 pages http://wwwlib.umi.com/dissertations/fullcit/9314481

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The Effects of Duration of Untreated Psychosis in Clinical Symptomatology and Cognitive Functioning in Schizophrenia by De Santis, Deborah; Phd from Long Island University, the Brooklyn Center, 2002, 138 pages http://wwwlib.umi.com/dissertations/fullcit/3049627

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The Effects of Pet Facilitated Therapy on Social Self Care Behaviors of Schizophrenics by Barnes, Darlene J., Phd from The University of Toledo, 1985, 290 pages http://wwwlib.umi.com/dissertations/fullcit/8607488

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The Effects of Positive and Negative Assertion Training on Chronic Schizophrenic Outpatients by Buchbauer, Michele Welt, Phd from Seton Hall University, 1986, 203 pages http://wwwlib.umi.com/dissertations/fullcit/8709627

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The Effects of Psychoeducation Intervention with Chronic Schizophrenics (patient Education, Negative/positive Symptoms) by Quinn, Frank Lawrence, Jr., Phd from University of South Carolina, 1986, 95 pages http://wwwlib.umi.com/dissertations/fullcit/8615926

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The Garden and the Map: a Phenomenology of Literary and Cultural Schizophrenia by Vernon, John Edward, Phd from University of California, Davis, 1969, 273 pages http://wwwlib.umi.com/dissertations/fullcit/7021910

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The Historical and Theological Implications in the Treatment of Mental Illness (with Special Reference to Schizophrenia). by Wright, Sargent John, Dmin from School of Theology at Claremont, 1975, 147 pages http://wwwlib.umi.com/dissertations/fullcit/7526899

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The Impact of Activity Scheduling on Activity Level, Negative Symptoms and Selfefficacy for Individuals with Schizophrenia by Lester, Heather Lynne; Phd from Drexel University, 2002, 106 pages http://wwwlib.umi.com/dissertations/fullcit/3070607

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The Impact of Schizophrenia on Family Functioning: a Social Work Perspective by Mojalefa, Susie Ruth; Dphil from University of Pretoria (south Africa), 2002 http://wwwlib.umi.com/dissertations/fullcit/f930561

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The Impact of Schizophrenia on the Family a Voyage Through Turbulence by Geist, Sylvia Sara; Edd from University of Toronto (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL23471

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The Impact of Schizophrenia on the Family: a Voyage Through Turbulence by Geist, Sylvia S., Edd from University of Toronto (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/f1553285

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The Impact of the Introduction of Clozapine on the Utilization of Health Care Services for Schizophrenic Medicaid Enrollees by Brown, Jeffrey Stuart; Phd from Brandeis U., the F. Heller Grad. Sch. for Adv. Stud. in Soc. Wel., 2002, 157 pages http://wwwlib.umi.com/dissertations/fullcit/3052309

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The Impact of Treatment and Treatment Interactions on Employment Outcomes for Individuals with Schizophrenia and Other Severe Mental Disorders by Strutton, David Richards; Phd from The Johns Hopkins University, 2003, 231 pages http://wwwlib.umi.com/dissertations/fullcit/3080772

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The Incidence of Lung Cancer among Schizophrenic Males Versus Nonschizophrenic Males by Breen, Mary Julie, Edd from United States International University, 1981, 100 pages http://wwwlib.umi.com/dissertations/fullcit/8117016

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The Joint Effect of Schizophrenia and Age on Life-skills Learning by Catalano, James A. Phd from Columbia University, 2000, 256 pages http://wwwlib.umi.com/dissertations/fullcit/9985856

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The Meaning of Work for Young Adults with Schizophrenia: a Mixed Method Study by Gioia-hasick, Deborah I. Phd from University of Southern California, 2000, 411 pages http://wwwlib.umi.com/dissertations/fullcit/3041456

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The Predictive Validity of Index Schneiderian First Rank Symptoms: a Long-term Follow-up of Schizophrenic and Nonschizophrenic Psychotic Patients by Riley, Heather Lynn; Phd from University of Hawaii, 2002, 132 pages http://wwwlib.umi.com/dissertations/fullcit/3045439

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The Pure Products of America Go Crazy: the Language of Schizophrenia in the United States during the Early Cold War by Ledes, Richard Chapman, Phd from New York University, 1998, 484 pages http://wwwlib.umi.com/dissertations/fullcit/9831736

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The Quality of Life among Young Adults with Schizophrenia: Two-year Exploratory Study on the Level of Life Satisfaction in a Normative Living Situation in the Community with Good Community Support Programs by Yang, Ok Kyung, Phd from The University of Wisconsin - Madison, 1990, 324 pages http://wwwlib.umi.com/dissertations/fullcit/9020473

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The Relationship between Mental Representations, Premorbid Adjustment, and Symptom Patterns in Schizophrenia by Kimhy, David; Phd from Long Island University, the Brooklyn Center, 2003, 118 pages http://wwwlib.umi.com/dissertations/fullcit/3086803

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The Relationship between Premorbid Social Adjustment and Long-term Outcome in Dsm-iii Schizophrenia by Childers, Susan Elizabeth, Phd from Smith College School for Social Work, 1988, 130 pages http://wwwlib.umi.com/dissertations/fullcit/8822076

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The Relationship of Perceived Social Support, Positive Symptoms, Negative Symptoms, and Self-care Actions in Adults with Schizophrenia Living in the Community by Dato, Carmel A. Phd from New York University, 2002, 191 pages http://wwwlib.umi.com/dissertations/fullcit/3045709

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The Relationship of Unawareness of Illness to Self-representation in a Sample of Patients Diagnosed with Schizophrenia or Schizoaffective Disorder by Laukitis, Daniel Endres; Phd from Columbia University, 2003, 155 pages http://wwwlib.umi.com/dissertations/fullcit/3071399

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The Relative Contributions of Executive Functions and Psychiatric Symptomatology to Psychosocial Competence in Schizophrenia by Harland, Renata Ellen; Phd from University of Cincinnati, 2002, 58 pages http://wwwlib.umi.com/dissertations/fullcit/3041141

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The Role of Attention in Affect Perception: an Examination of Mirsky's Four Factor Model of Attention in Chronic Schizophrenia by Combs, Dennis R. Phd from Louisiana State University and Agricultural & Mechanical College, 2002, 98 pages http://wwwlib.umi.com/dissertations/fullcit/3063050

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The Subject of Schizophrenia: Anamnesis of a Metaphor (robert Frost, Gilles Deleuze, Felix Guattari) by Petersen, Amy Jean, Phd from The University of Iowa, 1998, 253 pages http://wwwlib.umi.com/dissertations/fullcit/9917593

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The Subjective Experience of Negative Symptoms of Schizophrenia by Dintino, Cecilia Ann; Psyd from Rutgers the State University of New Jersey, G.s.a.p.p., 2002, 169 pages http://wwwlib.umi.com/dissertations/fullcit/3062460

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The Symbiotic Relationship with the Mother in Schizophrenia: Evidence of Symbiotic Relational Styles Through Use of the Structural Analysis of Social Behavior Model by Olsen, Kenneth Brent; Psyd from Alliant International University, Fresno, 2002, 144 pages http://wwwlib.umi.com/dissertations/fullcit/3062721

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The Validity of Dsm-iv Paranoid Schizophrenia, Undifferentiated Schizophrenia, and Schizoaffective Disorder by Englund, Nicole Lynn; Phd from University of South Dakota, 2002, 170 pages http://wwwlib.umi.com/dissertations/fullcit/3048760

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Timing and Modulation of Cognitive and Motor Function in Schizophrenia: a Model of Disrupted Cerebellar Circuitry by Marvel, Cherie Lynn; Phd from Georgetown University Medical Center, 2002, 199 pages http://wwwlib.umi.com/dissertations/fullcit/3066281

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Transcultural Studies in Schizophrenia by Rogan, Elaine Newman, Phd from Wayne State University, 1971, 242 pages http://wwwlib.umi.com/dissertations/fullcit/7129785

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Transfer between Clinicians for the Patient with Chronic Schizophrenia in a Clinic: Factors That Predict Smooth Continuation in Treatment by Humphreys, Holly V., Phd from Smith College School for Social Work, 1989, 225 pages http://wwwlib.umi.com/dissertations/fullcit/9005501

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Transformational Distinctions and the Comprehension of Sentences: the Effects of Schizophrenia and Education by Schooler, Nina Harriette, Phd from Columbia University, 1969, 113 pages http://wwwlib.umi.com/dissertations/fullcit/6917615

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Treatment of Aggression in Schizophrenia: a Critical Review of the Literature by Cartagena, Tina; Psyd from Alliant International University, San Diego, 2002, 93 pages http://wwwlib.umi.com/dissertations/fullcit/3018676

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Utilizing Discriminant Analysis to Quantify Treatment Referral Decisions for Adult Schizophrenics by Rudolph, Terry Lee, Phd from Wayne State University, 1984, 187 pages http://wwwlib.umi.com/dissertations/fullcit/8504918

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Variation in Human Eye Movements: Implications for the Evolution and Crosscultural Distribution of Schizophrenia by Allen, John Scott, Phd from University of California, Berkeley, 1989, 240 pages http://wwwlib.umi.com/dissertations/fullcit/9028714

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Vocabularies of Motive and the Social Definition of Schizophrenia: an Exploratory Study by Edgley, Charles Kenneth, Phd from State University of New York at Buffalo, 1970, 236 pages http://wwwlib.umi.com/dissertations/fullcit/7107157

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What Goes Around, Comes Around: the Naive - Schizophrenic - Resurrected Cycle in the Novels of Kurt Vonnegut (social Darwinism) by Leeds, Marc, Phd from State University of New York at Buffalo, 1987, 218 pages http://wwwlib.umi.com/dissertations/fullcit/8718549

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Working Memory Functioning in Schizophrenia Patients and Their First-degree Relatives: Cognitive Functioning Shedding Light on Etiology by Conklin, Heather Marie; Phd from University of Minnesota, 2002, 108 pages http://wwwlib.umi.com/dissertations/fullcit/3056309

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL TRIALS AND SCHIZOPHRENIA Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning schizophrenia.

Recent Trials on Schizophrenia The following is a list of recent trials dedicated to schizophrenia.8 Further information on a trial is available at the Web site indicated. •

5HT3 Antagonism and Auditory Gating in Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: The target groups in this study are brain waves and neurotransmitters (chemical messengers) in the brain. Subjects with diagnosed with schizophrenia will be studied. The study will help understand more about normal brain functioning and how that functioning differs in people with schizophrenia. Another purpose of this study is to determine how the altered brain functioning in schizophrenia contributes the symptoms found in the illness. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018850

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Antidepressant Treatment in Late Life Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH)

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These are listed at www.ClinicalTrials.gov.

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Purpose - Excerpt: The purpose of this study is to evaluate the safety and effectiveness of citalopram (Celexa) for the treatment of depressive symptoms in middle-aged and elderly patients with schizophrenia. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046098 •

Antidepressant Treatment in Older Patients with Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to evaluate the safety and effectiveness of citalopram (Celexa) for the treatment of depressive symptoms in middle-aged and elderly patients with schizophrenia. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047450

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Antipsychotic Response in Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: Motor slowing is a hallmark, clinical sign in mental illness. Slowness can be related to a specific disease process, as in negative schizophrenia or depression or it can be the result of medications used to treat forms of mental illness. Prior research has lead to a novel instrumental approach for distinguishing subtypes of motor slowing - one type related to cognitive processes and another related to parkinsonism. The purpose of this study is to test whether new medications used to treat schizophrenia improve the cognitive or parkinsonian components of motor slowing. Patients will be studied in the laboratory before and 8-weeks after starting a new antipsychotic. The n of this study = 60 patients. The results of this study will improve our understanding of the complex interactions between cognitive processing and motor behavior in patients with psychotic illnesses and how drugs work to treat these problems. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018668

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Brief Hospitalization for Schizophrenia: Strategies to Improve Treatment Outcome Condition(s): Schizophrenia; Schizophrenic Disorder Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service

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Purpose - Excerpt: The goal of this research program is to implement a series of psychoeducational training classes designed to teach individuals with schizophrenia the importance of medication treatment, how to identify and manage medication side effects, and how to make appointments and emergency plans. The skills taught to the research subjects will lead to demonstrable increases (compared to the control group) in adherence to both the prescribed medication regimen and scheduled outpatient appointments and thereby cause a decrease (again compared to the control group) in rehospitalization rates and bed-days during subsequent twelve months following the intervention. A secondary objective of this work is that if the CREP program is successful and/or illness education is effective, the data will be able to disseminated throughout the VISN 22 via the recently awarded Mental Illness Research Education and Clinical Center (MIRECC) program. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018837 •

Clinical Trial of Tolcapone for Cognition in Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to test whether the drug tolcapone improves the memory of patients with schizophrenia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044083

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Clozapine and Risperidone for Treatment of First Episode Schizophrenia and Cannabis Use Disorder Condition(s): Schizophrenia; Marijuana Abuse Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to compare the safety, effectiveness, and tolerability of clozapine and risperidone in patients with first episode schizophrenia and cannabis use disorder. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063349

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Cognitive - Behavioral Therapy Condition(s): Schizophrenia; Schizoaffective Disorder Study Status: This study is currently recruiting patients.

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Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: The purpose of this study is to determine if Cognitive - Behavioral Social Skills Training (CBSST) improves functioning in older patients with schizophrenia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018629 •

Effects of Modafinil on Brain Function in Patients with Schizophrenia Condition(s): Schizophrenia; Schizoaffective Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to test the effect of the drug modafinil on brain functioning in individuals with schizophrenia and in healthy volunteers. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057707

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Efficacy and safety of two atypical antipsychotics vs. placebo in patients with an acute exacerbation of either schizophrenia or schizoaffective disorder Condition(s): Schizophrenia; Schizoaffective Disorder Study Status: This study is currently recruiting patients. Sponsor(s): Janssen Pharmaceutica, L.P. Purpose - Excerpt: A study to evaluate the efficacy and safety of two atypical antipsychotics vs. placebo in patients with an acute exacerbation of either schizophrenia or schizoaffective disorder Phase(s): Phase IV Study Type: Interventional Contact(s): Jennifer Frantz 908-653-1028 [email protected]; Colette KosikGonzalez, MA 609-730-7733 [email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00061802

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Electroconvulsive Therapy in Clozapine Refractory Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will investigate electroconvulsive therapy (ECT) as an additional treatment for patients who have failed to adequately respond to clozapine. Phase(s): Phase I; Phase II

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042224 •

Electrophysiology and Blood Flow in Patients with Schizophrenia and Their Siblings Condition(s): Healthy; Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will explore how the brain works during memory testing in an effort to understand why some patients with schizophrenia have memory difficulties. Patients with schizophrenia and their unaffected family members are eligible for this study. Studying family members may help identify the genes related to the memory deficit in schizophrenia. Normal volunteers will also be studied. Normal volunteers, patients with schizophrenia, and their family members interested in participating in this study will be screened with a complete medical examination and psychiatric assessment, and performance of simple tasks. Study participants will be shown numbers on a screen and asked to recall them after a brief period. This will be done during electroencephalographic (EEG) recording, in which electrodes attached to the scalp measure the brain's electrical activity. The same test will be repeated while the patient has magnetic resonance imaging of the brain. The combined MRI and EEG testing will permit better localization of the brain's electrical activity. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001921

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Enhancing the Outcome of Skills Training for People with Schizophrenia Condition(s): Schizophrenia; Psychotic Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to determine the effectiveness of skills training in people with schizophrenia and to determine the applicability of the acquired skills in the "real world." This study will also determine the effects of deficits in thought processing on treatment response and functional capacity. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069433

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Evaluating Genetic Risk Factors for Childhood-Onset Schizophrenia Condition(s): Healthy; Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to understand the role of genetics in the development of childhood-onset schizophrenia (COS).

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Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001198 •

Eye Blink Response in Healthy Volunteers and Adults with Schizophrenia Condition(s): Healthy; Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to explore how the brain works during particular memory tasks in people with schizophrenia and healthy volunteers. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001920

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Genetic Study of Schizophrenia Condition(s): Psychotic Disorder; Schizoaffective Disorder; Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to understand the role of genetics in the development of schizophrenia by studying heritable traits in families where at least one member has schizophrenia. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001486

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Glycine and D-Cycloserine in Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to compare the effects of D-cycloserine and glycine for treating negative symptoms (such as loss of interest, loss of energy, loss of warmth, and loss of humor) which occur between phases of positive symptoms (marked by hallucinations, delusions, and thought confusions) in schizophrenics. Clozapine is currently the most effective treatment for negative symptoms of schizophrenia. Two other drugs, D-cycloserine and glycine, are being investigated as new treatments. D-cycloserine improves negative symptoms when added to some drugs, but may worsen these symptoms when given with clozapine. Glycine also improves negative symptoms and may still be able to improve these symptoms when given with clozapine. This study gives either D-cycloserine or glycine (or an inactive placebo) with clozapine to determine which is the best combination. Patients will be assigned to 1 of 3 groups. Group 1 will receive D-cycloserine plus clozapine. Group 2 will receive glycine plus clozapine. Group 3 will receive an inactive placebo plus clozapine. Patients will receive these medications for 8 weeks. Negative symptoms of

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schizophrenia will be monitored, and tests will be done on blood and cerebrospinal fluid (CSF) to measure the body's response to the medications. An individual may be eligible for this study if he/she: Is 18 to 65 years old and has been diagnosed with schizophrenia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000372 •

Imaging of Brain Receptors in Healthy Volunteers and in Patients with Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will use single photon emission computed tomography (SPECT) to study brain nicotine receptors (proteins on the surface of brain cells) in healthy subjects and in patients with schizophrenia. Autopsy findings in patients with schizophrenia show changes in their nicotine receptors. This study will use SPECT to look at these receptors in living schizophrenia patients and compare them with those in healthy subjects. The following individuals between 21 and 50 years of age (or between 21 and 80 years of age for Group 1 only) are eligible for this study: healthy non-smokers (Group 1); schizophrenia patients who smoke (Group 2); schizophrenia patients who do not smoke (Group 3); healthy smokers (Group 4); healthy non-smokers (Group 5). Patients with schizophrenia must be taking olanzapine (Zyprexa) or risperidone (Risperdal) for at least 6 months. All candidates will be screened at the first visit. Group 1 participants will have three more visits; Groups 2 through 5 will have two more visits. Visit 1 All participants will be screened with physical and neurological examinations; blood and urine tests; and neuropsychological tests to assess their ability to learn and remember words and numbers, to pay attention, and to quickly perform motor tasks, such as putting pegs into a piece of wood. In addition, they will have an eye movement test and event-related potential testing. For the eye test, the subject sits in a chair and leans forward with the chin on a chin rest. A band is tied around the head and very small amounts of invisible (infrared) light are shined into the eyes. The light is reflected back and measured. Wire electrodes are placed around the area of the eye and cheek to monitor eye blinks and eye movements. Subjects are asked to follow a light with their eyes and to look away from a light. For event- related potential testing, electrodes are placed on the scalp, forehead and cheeks, and brain activity is recorded while the subject identifies particular pictures and sounds. Visit 2 (and Visit 3 for Group 1) Participants will have a SPECT scan. On the night before the scan, the day of the scan, and for 4 days after the scan, subject take an oral dose of potassium iodide to protect the thyroid gland from the radioactive tracer used in the SPECT procedure. (Individuals allergic to potassium iodide will take potassium perchlorate instead.) For the SPECT scan, small radioactive markers containing 99mTc are glued to the subject's head. Two catheters (thin, flexible tubes) are placed in veins in the arms to inject the radioactive tracer [123I]5-I-A-85380 and to draw blood samples. During the scan, the subject lies on a bed with his or her head held still with a headholder. The scans are taken over a 9-hour period after injection of the tracer injection. An electrocardiogram, respiration, and blood pressure measures are taken before injection of [123I]5-I-A-85380, then 5 minutes after the injection, and again 30 to 60 minutes after the injection. Breath samples are

342 Schizophrenia

collected every 60 minutes. Blood and urine samples are collected 5 to 6 hours after starting the scan. Group 1 subjects will have a second SPECT scan within 4 weeks of the first. Visit 3 (Visit 4 for Group 1) Participants will have a magnetic resonance imaging (MRI) scan. For this procedure, the subject lies on a table that slides into a narrow metal cylinder with a strong magnetic field for the scan. The scanner uses a magnetic field and radio waves to produce images that show structural and chemical changes in tissues. The test lasts up to 1 hour. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061789 •

Improving Health Services for Veterans with Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service; University of Maryland Purpose - Excerpt: Schizophrenia is a serious, often chronically disabling mental illness that affects about one percent of the general population and exacts high costs. There is substantial evidence that many patients with schizophrenia, including veterans, do not receive treatment that is consistent with existing, empirically proven treatment technologies. The objectives of this study are: 1) to conduct a field trial of methods for assessing the quality of care (QOC) provided to patients with schizophrenia in a unified system of care, VISN 5; 2) to test hypotheses linking provider adherence with the Patient Outcomes Research Team (PORT) treatment recommendations to: (a) patterns of service utilization; and (b) outcomes, in order to assess the validity of the treatment recommendations as QOC standards; 3) to determine the patient characteristics that correlate with adherence to the PORT treatment recommendations; and 4) to estimate the direct treatment costs associated with adherence and non-adherence to the PORT treatment recommendations. Prospective patterns of service utilization, content of care, and outcomes are being assessed for a ten percent random sample (n=300) of all outpatients in VISN 5 with an Axis I schizophrenia spectrum disorder diagnosis, who will complete baseline and six-month follow up outcome assessments. One-year retrospective and six-month prospective patterns of service utilization and treatment recommendation adherence will also be determined using information obtained from administrative databases, medical record review, and patient report. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012961

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Inpatient Evaluation of Adults with Schizophrenia Condition(s): Psychotic Disorder; Schizophrenia; Schizoaffective; Paranoia; Psychosis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH)

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Purpose - Excerpt: The purpose of this study is to understand the biologic basis of schizophrenia and to determine which symptoms are related to the illness itself and which are related to medications used to treat the illness. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001247 •

Molecular Genetics of Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This NIMH sponsored study will create a DNA collection to permit qualified scientists to search for schizophrenia-related genes. More than 500 families with at least two siblings who have experienced symptoms of schizophrenia are needed for the study. Participants will be interviewed about psychiatric and family history, and will be asked to provide a small blood specimen. The identification of predisposing genes can lead to greater understanding of the brain mechanisms involved in schizophrenia which can in turn lead to the discovery of new treatments. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006418

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Neuropsychiatric Evaluation of Healthy Volunteers and Adults with Schizophrenia Condition(s): Brain Injury; Dementia; Healthy; Mental Disorder; Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: IThe purpose of this study is to evaluate the cognitive processes of participants with schizophrenia, participants with nervous system and mental disorders, and healthy volunteers. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001323

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Olanzapine versus Placebo in the Treatment of Adolescents with Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): Eli Lilly and Company Purpose - Excerpt: This study is to determine the efficacy (how well the drug works), safety, and any side effects of olanzapine compared to placebo in the treatment of schizophrenia in adolescents. Both the potential benefits and side effects of olanzapine will be evaluated throughout this trial. Phase(s): Phase IV

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051298 •

Online Family Support and Education for Schizophrenia Condition(s): Schizophrenia; Schizoaffective Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to evaluate the benefits of providing families of schizophrenia patients the opportunity to interact with each other using the Internet. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046085

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Quetiapine vs Haloperidol Decanoate for the Long Term Treatment of Schizophrenia and Schizoaffective Disorder Condition(s): Schizophrenia; Schizoaffective Disorder Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: The purpose of this research study is to determine whether a new drug for schizophrenia is better for the maintenance treatment than a standard drugs currently prescribed. The new medication is called quetiapine and it will be compared with a standard medication called haloperidol decanoate. The study will determine if quetiapine causes fewer problems than haloperidol with side effects such as stiffness and restlessness and whether it costs the VA more or less to treat patients with quetiapine. In addition, blood samples will be collected every three months to determine if certain chemicals in the blood can influence the outcome of the subjects' illness. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018642

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Randomized Study of Repetitive Magnetic Stimulation of Speech Processing Brain Areas in Schizophrenic Patients Who Hear "Voices" Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Yale University Purpose - Excerpt: Objectives: I. Determine the effect of repetitive transcranial magnetic stimulation on treatment refractory auditory hallucinations of patients with schizophrenia. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004980

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Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to determine whether adding the drug risperidone is more effective than placebo in treating schizophrenic patients who are taking the drug clozapine. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056498

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Safety and efficacy of study drug versus placebo for negative symptoms of schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Purpose - Excerpt: This study is to determine the efficacy (how well the drug works), safety, and side effects of the study medication compared to placebo in the treatment of the negative symptoms of schizophrenia in adults. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063297

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Studies of Frontal Lobe Brain Functioning in Schizophrenia Condition(s): Healthy; Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to use brain imaging technology to investigate the role of the frontal lobe of the brain in the thinking of individuals with schizophrenia and other neuropsychiatric disorders and healthy volunteers. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001258

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The Efficacy and Safety of Risperidone in the Treatment of Adolescents with Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): Johnson & Johnson Pharmaceutical Research and Development, L.L.C.

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Purpose - Excerpt: This is a clinical study of an investigational drug called risperidone which may be effective in the treatment of schizophrenia. The study will include approximately 260 patients in the United States and will be conducted in 15-20 sites. The purpose of this study is to compare the safety and effectiveness of daily doses of liquid risperidone in two different doses in the treatment of adolescents between the ages of 13 and 17 with a diagnosis of schizophrenia. The lower dose within this range may represent an ineffective therapeutic treatment. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034749 •

Treating Drug-Resistant Childhood Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to compare 2 antipsychotic drugs, clozapine and olanzapine (Zyprexa), for the treatment of children and adolescents who have failed standard antipsychotic treatment for schizophrenia. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048828

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Treating Thought Problems in Patients with Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to compare Cognitive Adaptation Training (CAT) to minimal schizophrenia treatment. This study will also determine whether the intensity of CAT can be reduced and still provide benefits to patients with schizophrenia. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051740

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Treatment for First-Episode Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to see if the newest class of antipsychotic medications can improve the course of patients with first-episode schizophrenia.

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Schizophrenia patients generally respond very well to their first round of treatment with antipsychotic medications. However, relapses are common, and the condition can worsen over time. The newest class of antipsychotic medications may be able to prevent this, if begun during the first episode of schizophrenia. Patients will be assigned randomly (like tossing a coin) to 3 years of treatment with 1 of 2 antipsychotic medications: olanzapine or risperidone. Response to medication will be monitored, including symptoms, memory and attention, and any side effects. The effects of longterm treatment will be measured, including any relapses. An individual may be eligible for this study if he/she is 16 to 40 years old and is having his/her first episode of schizophrenia. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000374 •

Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS) Condition(s): Schizophrenia; Psychotic Disorders; Schizophreniform Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to compare the safety, effectiveness, and tolerability of three common antipsychotic medications for the treatment of children and adolescents with schizophrenia, schizophreniform disorder or schizoaffective disorder. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053703

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Treatment Response to Rehabilitation in Patients with Schizophrenia Condition(s): Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to examine the ways in which schizophrenia-related symptoms affect response to a rehabilitation program for people with schizophrenia. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063336

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A Comparison of Study Drug with Placebo and Haloperidol in Patients With Schizophrenia Condition(s): Schizophrenia Study Status: This study is no longer recruiting patients. Sponsor(s): Sumitomo Pharmaceuticals America

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Purpose - Excerpt: The purpose of this study is to evaluate the efficacy of the drug SM13496 compared to a placebo and to haloperidol in patients with schizophrenia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044044 •

CATIE- Schizophrenia Trial Condition(s): Schizophrenia Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The CATIE Schizophrenia Trial is part of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Project. The schizophrenia trial is being conducted to determine the long-term effects and usefulness of antipsychotic medications in persons with schizophrenia. It is designed for people with schizophrenia who may benefit from a medication change. The study involves the newer atypical antipsychotics (olanzapine, quetiapine, risperidone, clozapine, and ziprasidone)and the typical antipsychotics (perphenazine and fluphenazine decanoate). All participants will receive an initial comprehensive medical and psychiatric evaluation and will be closely followed throughout the study. For most participants the study will last up to 18 months. Everyone in the study will be offered an educational program about schizophrenia and family members will be encouraged to participate. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00014001

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Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia Condition(s): Schizophrenia Study Status: This study is no longer recruiting patients. Sponsor(s): Eli Lilly and Company Purpose - Excerpt: The purpose of this study is to determine how Olanzapine compares to an active comparator in the treatment of schizophrenia Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036088

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Safety and Tolerability Study of Drug to Treat Schizophrenia Condition(s): Schizophrenia Study Status: This study is no longer recruiting patients. Sponsor(s): Sumitomo Pharmaceuticals America

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Purpose - Excerpt: The purpose of this study is to evaluate the long-term safety of SM13496 in patients with schizophrenia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044005 •

Schizophrenia Study Condition(s): Schizophrenia Study Status: This study is no longer recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: A Placebo Controlled Study For Patients With Schizophrenia Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049946

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Self-Management Therapy for Youth with Schizophrenia Condition(s): Schizophrenia Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to test the effectiveness of a familycentered, community-based, self-management intervention (Self-Management Therapy) for adolescents with schizophrenia. The study will test the intervention's effectiveness in improving the adolescents' behavior, thinking, mood, and use of substances such as drugs and alcohol. The study also will look at the effects of the patient on the family. The intervention involves training in recognizing symptoms of schizophrenia and in stress management, problem-solving, and social skills. Parents and siblings are included to gain knowledge and skills to support the adolescents. The Self-Management Therapy intervention is administered in small multiple-family groups in 12 sessions over 7-1/2 months. The effects of the intervention on the patient and his/her family are assessed prior to treatment, after 6 sessions, after 12 sessions, and in a follow-up visit 6 months after completion of sessions. A child may be eligible for this study if he/she: Is 15 to 19 years old and has been diagnosed with schizophrenia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000387

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Study of alternate formulation of aripiprazole in agitated patients with schizophrenic disorders Condition(s): Schizophrenia Study Status: This study is no longer recruiting patients.

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Sponsor(s): Bristol-Myers Squibb Purpose - Excerpt: Study to learn if the alternate formulation is effective in agitated schizophrenic patients Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036127 •

The Assessment of a weight-gain agent for the Treatment of Olanzapine-Associated Anti-obesity Agent in Patients with Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder Condition(s): Schizophrenia; Psychotic Disorders; Bipolar Disorder Study Status: This study is no longer recruiting patients. Sponsor(s): Eli Lilly and Company Purpose - Excerpt: Olanzapine is currently marketed for the treatment of schizophrenia and acute manic episodes with bipolar 1 disorder. This Anti-obesity Agent is currently marketed for the management of obesity. In this study, the Anti-obesity Agent is being tested to see if it can treat weight gain that may be associated with taking olanzapine. The purposes of this study are to determine the safety of olanzapine when given in combination with the Anti-obesity Agent and any side effects that might be associated with it and whether weight-gain agent can help treat weight gain that may be associated with taking olanzapine. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044187

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Trial of D-Cycloserine in Schizophrenia Condition(s): Schizophrenia Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: To characterize further the effects of D-cycloserine augmentation of antipsychotic treatment on negative symptoms, performance on neurocognitive tasks, and on markers for glutamatergic, dopaminergic and serotonergic function in serum and cerebrospinal fluid. To determine if negative symptoms and cognitive function improve over time, if these improvements meaningfully impact quality of life factors, if they correlate with markers of neuronal function, and if subpopulations can be identified according to response. Dysfunction of glutamatergic neuronal systems has recently been implicated in the pathophysiology of schizophrenia based on the finding that non-competitive inhibitors of the NMDA receptor can reproduce in normals the positive symptoms, negative symptoms, and cognitive deficits of schizophrenia. Furthermore, glutamatergic dysfunction may alter forebrain dopaminergic neuronal activity, a system central to the antipsychotic action of typical neuroleptics. It is believed that enhancing NMDA receptor function by systemic treatment with D-cycloserine, a partial agonist at the glycine modulatory site of the NMDA receptor, will reduce

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symptoms in schizophrenia. Sixty schizophrenic outpatients with prominent, primary negative symptoms are treated with antipsychotic medication and are randomly assigned to D-cycloserine or placebo for a 6-month, fixed-dose trial. The primary outcome measure is the total score on the Scale for Assessment of Negative Symptoms (SANS). A neuropsychological battery, which emphasizes tests sensitive to prefrontal cortical function, is administered. Blood is obtained at several time points and CSF is obtained at Week 8 for assay of concentrations of D-cycloserine, glutamate, HVA, and 5HIAA. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000371 •

A Multi-Site Study of Strategies for Implementing Schizophrenia Guidelines Condition(s): Schizophrenia Study Status: This study is completed. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service Purpose - Excerpt: Schizophrenia, a chronic psychiatric disorder, is the second most frequent VA discharge diagnosis. Medication management practices for schizophrenia often are not guideline-concordant and place patients at risk for adverse outcomes. This project tests a new strategy to standard implementation for VHA Schizophrenia Guidelines. Research objectives are: (1) to compare the effectiveness of a conceptuallybased, enhanced intervention to that of a basic educational strategy with regard to improving guideline adherence and patient compliance; (2) to compare the effectiveness of the two strategies with regard to improving symptom and side effect outcomes; (3) to determine the effect of the enhanced intervention on service utilization for acute exacerbations of schizophrenia; (4) to determine the extent to which guidelineconcordant medication management improves patient outcomes; and (5) to examine providers' knowledge of and attitudes toward guidelines. Thirteen VA sites were considered for the study, and VistA data were extracted to assess baseline guideline performance. Seven sites were selected and received basic education about schizophrenia guidelines. Three of these sites were randomly selected to receive the enhanced intervention, employing a nurse coordinator to promote providers' guideline adherence and patients' treatment adherence. Subjects with an acute exacerbation of schizophrenia were enrolled and were interviewed at baseline and six months using the Positive and Negative Syndrome Scale, the Schizophrenia Outcomes Module, and the Barnes Akathisia Scale. Data on guideline adherence were collected from medical records and VistA files. When data collection is completed, analyses will be conducted to determine the effectiveness of the enhanced intervention with regard to improving guideline adherence and patient outcomes. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00013000

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Improving Antipsychotic Adherence Among Patients with Schizophrenia Condition(s): Schizophrenia; Schizoaffective Disorder

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Study Status: This study is not yet open for patient recruitment. Sponsor(s): Department of Veterans Affairs Purpose - Excerpt: Anti-psychotic medications are an essential component of the treatment of patients with schizophrenia. Unfortunately, pharmacy data indicate that 40% of VA patients with schizophrenia are poorly adherent with their antipsychotics. These patients are at much greater risk for hospitalization. We will examine the effectiveness of a practical, pharmacy-based intervention for improving adherence among patients with schizophrenia. Specifically, we will examine whether the Pharmacy Based Adherence Facilitation (PBAF) intervention improves medication adherence, increases patient satisfaction with medical care, decreases psychiatric symptoms, and decreases inpatient utilization. We will also determine the relative effectiveness of PBAF intervention among patients with varying: a) degrees of cognitive limitations, b) degrees of insight into their illness, and c) attitudes towards their medications. Using pharmacy and other data from the National VA Psychosis Registry, we will identify approximately 429 patients with schizophrenia and poor antipsychotic adherence in the year preceding study initiation. These patients must have completed at least two outpatient psychiatric visits at one of the study sites (Ann Arbor, Detroit, or San Diego VAs). From this list of patients, we will enroll 174 patients. Patients will be randomized to: 1) usual care; or 2) the Pharmacy Based Adherence Facilitation (PBAF) intervention. The PBAF intervention will consist of usual care plus: 1) "unit-of-use" adherence packaging; 2) a patient education session; 3) refill reminders; and 4) clinician notification of missed fills. Patient assessments will be conducted at baseline, 6 months, 12 months, and 18 months. The primary outcome measure will be medication adherence as measured by the medication possession ratio, and verified by self-report and antipsychotic blood levels. Patients' level of psychiatric symptoms, quality of life, and satisfaction will be secondary measures of outcome. In secondary analyses, we will compare the effectiveness of the PBAF intervention among subgroups of patients who have varying degrees of cognitive limitations, insight into their illness, and attitudes towards antipsychotic medication. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057135 •

Neuroimaging of Dopamine Metabolism in Normal and Psychiatric Patients Condition(s): Healthy; Schizophrenia Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Brain cells communicate with each other by releasing chemicals called neurotransmitters. In order for brain cells to transfer information, one cell will release a neurotransmitter that will be recognized by a receptor located on surface of another cell. One such neurotransmitter is dopamine. Abnormal dopamine transmission has been seen in patients with substance abuse and different neuropsychiatric disorders including schizophrenia. A radioactive drug called IZBM (I-123 iodobenzamide) can also bind to certain dopamine receptors. IZBM can be seen by Single Photon Emission Tomography (SPECT). Therefore, by using IZBM and SPECT scans, researchers can find and "map" the location of dopamine receptors in the brain. Patients participating in this study must also have been selected for other genetic studies being conducted at the NIMH. Patients with schizophrenia will be selected from a NIMH research study titled, "Neurobiological Investigation of Patients with Schizophrenia Spectrum Disorders and

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Their Siblings" (95-M-0150). Normal patient volunteers will be selected from another NIMH study titled, "Inpatient Evaluation of Neuropsychiatric Patients" (89-M-0160). All aspects of clinical care and genetic analysis of these patients will be covered in these studies, while information pertaining to IBZM SPECT scans will be covered in this study. This study will not directly benefit patients participating in it. However, information gathered may contribute to faster and more accurate diagnosis of schizophrenia and eventually better treatment for the disorder. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001320 •

Olanzapine Versus Active Comparator in the Treatment of Depression in Patients with Schizophrenia Condition(s): Depression; Schizophrenia; Schizoaffective Disorder Study Status: This study is completed. Sponsor(s): Eli Lilly and Company Purpose - Excerpt: This is a research study comparing the safety and efficacy of two active study medications Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034801

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To Determine If Olanzapine Is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia Condition(s): Schizophrenia; Schizoaffective Disorder Study Status: This study is completed. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program; Eli Lilly and Company Purpose - Excerpt: Although currently marketed antipsychotic drugs are useful in the treatment of schizophrenia, efficacy and safety profiles need to be improved. Forty to eighty percent of patients either fail to respond or only partially respond to conventional antipsychotic agents. Secondary symptoms may be unimproved even in patients who respond to treatment. A variety of adverse events occur in patients receiving currently available agents. The severity of these events contributes to the poor compliance that is observed in this patient population. Olanzapine is a novel antipsychotic agent with a reduced incidence of extrapyramidal symptoms. Other side effects are minimal. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007774

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Treatment of Schizophrenia Through Internet-Based Psychoeducation Condition(s): Schizophrenia; Schizoaffective Disorder

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Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to assess the effectiveness of a Webbased psychoeducational program in helping people with schizophrenia and their families manage the disease. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051233

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “schizophrenia” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON SCHIZOPHRENIA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “schizophrenia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on schizophrenia, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Schizophrenia By performing a patent search focusing on schizophrenia, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on schizophrenia: •

Benzo-pyrones as a treatment for schizophrenia Inventor(s): Casley-Smith; John R. (97 Seaview Rd., Tennyson, South Australia, AU) Assignee(s): none reported Patent Number: 4,593,041 Date filed: March 14, 1985 Abstract: The invention relates to the treatment of schizophrenia and senile macular degeneration by administering any one of the benzo-pyrone group of drugs. Excerpt(s): This invention relates to the treatment of schizophrenia, and also to the treatment of senile diffuse macular degeneration. Some workers consider that some forms of schizophrenia are associated with high-protein oedema, leading to excess fibrosis in the brain. Hence there follows a general discussion of oedema and the use of benzo-pyrones in the treatment of high-protein oedema. 2. & 3. Colliodal osmotic pressure of the plasma proteins in the blood and tissues. Web site: http://www.delphion.com/details?pn=US04593041__

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Benzoquinoxalines, pharmaceutical compositions containing them and their use in treating schizophrenia Inventor(s): Markstein; Rudolf (Rheinfelden, DE), Gull; Peter (Pfeffingen, CH), Swoboda; Robert (Koniz, CH) Assignee(s): Sandoz Ltd. (Basel, CH) Patent Number: 5,538,971 Date filed: May 27, 1994 Abstract: 6-hydroxy or 6-alkoxy-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinoxalines bearing in position 4 an optionally substituted phenyl group may be used in the treatment of schizophrenia, drug abuse or self-injurious behavior. Excerpt(s): The present invention relates to benzoquinoxalines, their production, their use as pharmaceuticals and pharmaceutical compositions containing them. In particular the present invention provides 6-hydroxy or 6-alkoxy-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoxalines bearing in position 4 an optionally substituted phenyl group, in free base or acid addition salt form. R.sub.3 is hydroxy or (C.sub.1-4)alkoxy, in free base or acid addition salt form. Web site: http://www.delphion.com/details?pn=US05538971__

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Composition for the treatment of schizophrenia Inventor(s): Knoll; Jozsef (Budapest, HU), Frescka; Ede (Budapest, HU), Perenyi; Andras (Budapest, HU), Arato; Mihaly (Budapest, HU), Bela; D. Arpad (Gyongyos, HU), Utpal; Goswami (Calcutta, IN) Assignee(s): Chinoin Gyogyszer- es Vegyeszeti Termekek Gyara Rt. (Budapest, HU) Patent Number: 5,151,419 Date filed: June 18, 1990 Abstract: The present invention is related to a pharmaceutical composition suitable for the treatment of schizophrenia comprising an acid addition salt of (1)-N-(1-phenylisopropyl)-N-methyl-1-propynyl-amine in a therapeutically effective amount and optionally one or more neuroleptica and pharmaceutically acceptable carriers, and other excipients. Excerpt(s): The present invention relates to the treatment of schizophrenia characterized by negative symptoms by selegiline (1-Deprenyl) (-)-N-(1-phenylisopropyl)-N-methylpropynylamine and to a composition for this treatment. Several compounds were tested for the treatment of these patients in order to find an effective drug and in order to be able to send home the patients treated for a long time in mental social homes. It is known that within the nerve system the dopamine hypofunction is in connection with the Parkinson disease (Klin. Wschr. 1960.) leading to the treatment with 1-DOPA (Canad. med. Ass. J. 1969.). But the increase of the dopaminerg tone concerning the whole organism, was accompanied by several side effects (hypertonic crisis, tremor, gastrointestinal disorders etc.). Web site: http://www.delphion.com/details?pn=US05151419__

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Compounds and method of treating psychosis and schizophrenia Inventor(s): Kesten; Suzanne Ross (Ann Arbor, MI), Johnson; Stephen Joseph (Ann Arbor, MI), Connor; David Thomas (Ann Arbor, MI), Miller; Steven Robert (Ann Arbor, MI), Unangst; Paul Charles (Ann Arbor, MI), Wise; Lawrence David (Ann Arbor, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,020,364 Date filed: February 22, 1999 Abstract: This invention relates to compounds that are antagonists of dopamine D4 receptors, and to methods of treating psychosis and schizophrenia using a compound that is an antagonist of dopamine D4 receptors. Excerpt(s): This invention relates to compounds that are antagonists of dopamine D4 receptors and to methods of treating psychosis and schizophrenia using a compound that is an antagonist of dopamine D4 receptors. Dopamine is a neurotransmitter that is found in the brains of animals, including humans, and is essential for proper nerve signal transmission. It is well-known that certain compounds block or inhibit the binding of dopamine to dopamine receptors. Such compounds are called dopamine receptor antagonists. It is also well-known that dopamine receptor antagonists are useful in the treatment of schizophrenia and psychosis. Recently, it has been discovered that more than one type of dopamine receptor exists, and that dopamine receptor antagonists can preferentially inhibit one type of dopamine receptor over another. Two major families of dopamine receptors have been identified and named the D1 and D2

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families. In the D2 family, three distinct receptor subtypes have been identified as D2, D3, and D4. Web site: http://www.delphion.com/details?pn=US06020364__ •

Diagnosing Alzheimer's disease and schizophrenia Inventor(s): Ghanbari; Hossein A. (U.S. MIND Diagnostics, Abbott Laboratories D-9MA, AP20, Abbott Park, IL 60064), Merril; Carl R. (2 Winder Ct., Rockville, MD 20850), Johnson; Ginger (2700 Martin Luther King Ave., SE., Washington, DC 20032) Assignee(s): none reported Patent Number: 5,429,947 Date filed: June 17, 1992 Abstract: A method for detecting elevated levels of the middle isoform of.alpha.-2 haptoglobin,.alpha.-2FS haptoglobin in bodily fluids of subjects with Alzheimer's disease and schizophrenia as compared with the.alpha.-2FS haptoglobin level in normal subjects. Fibrinogen fragments corresponding to proteins 127 and 128 are also found in elevated levels in such subjects. Elevated levels of specific haptoglobin proteins serve as a diagnostic marker for Alzheimer's disease and Schizophrenia. Excerpt(s): This invention relates to methods of diagnosing Alzheimer disease and schizophrenia in subjects by detecting and measuring elevated levels of specific proteins in bodily fluids. The invention also relates to an in vitro diagnostic assay to assist in diagnosis of Alzheimer's disease and schizophrenia. Schizophrenia and Alzheimer's disease are major public health problems. The problems associated with these diseases are compounded by the lack of clinically useful, objective methods of diagnosis. This diagnostic deficiency reflects a lack of understanding of the pathophysiology involved. Many diseases of the central nervous system (CNS), such as Alzheimer's disease and schizophrenia, have few objective physical or biochemical markers useful for diagnostic purposes in the living patient. Alzheimer's disease, the most common form of dementia affecting up to 15% of people over 65 years of age (Pfeffer et al., 1987 Am. J. Epidemiol, 125:420) can only be presumptively diagnosed by pathological examination of brain tissue in conjunction with a clinical history of dementia (Khachaturian 1985 Arch. Neurol., 42:1097). In the diagnosis of schizophrenia, the clinician is limited to aberrations of behavior. No generally accepted laboratory markers for either of these two diseases of the CNS have been found that would allow for diagnosis in a living subject. Cerebrospinal fluid (CSF), which can be obtained by lumbar puncture, provides a source of proteins which may, in part, reflect abnormal CNS metabolism. Web site: http://www.delphion.com/details?pn=US05429947__

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Dopamine and noradrenergic reuptake inhibitors in treatment of schizophrenia Inventor(s): Seibyl; John P. (Branford, CT), Krystal; John H. (New Haven, CT), Charney; Dennis S. (Hamden, CT) Assignee(s): Yale University (New Haven, CT) Patent Number: 5,447,948 Date filed: May 7, 1992

Patents 361

Abstract: Mazindol and other dopamine and/or noradrenergic reuptake inhibitors are effective to treat negative symptoms in schizophrenia. Excerpt(s): This invention relates to methods for treating schizophrenia and/or reducing the symptoms thereof. Schizophrenia is a relatively intractable mental disorder. Although there can be, and often are, psycho-social aspects to the disease, it is well understood to have a clear physiological component. Many medical and psychopharmaceutical treatments have been used in this disorder, with varying degrees of success. However, as yet, there is no true understanding of the cause of the underlying biochemical nature of the disorder, nor any satisfactory long term treatment for it. The manifestations of schizophrenia are numerous and often contradictory. The symptoms can be generally grouped into three groups; positive, or expressive symptomatology; negative, or deficit, symptomatology; and social symptomatology. Many schizophrenic patients are partially or completely refractory to standard antipsychotic drug treatments. Currently, there are no adequate treatments for some symptoms of the disorder, especially negative symptoms which include amotivation, anhedonia, alogia, anergia, and affective impairment. These symptoms have profound effects on psychosocial function and rehabilitation potential. Web site: http://www.delphion.com/details?pn=US05447948__ •

Facilitation of AMPA receptor-mediated synaptic transmission in brain as a treatment for schizophrenia Inventor(s): Larson; John (Costa Mesa, CA), Lynch; Gary (Irvine, CA), Rogers; Gary A. (3056 Foothill Rd., Santa Barbara, CA 93105) Assignee(s): The Regents of the University of California (Oakland, CA), Rogers; Gary A. (Santa Barbara, CA) Patent Number: 5,773,434 Date filed: August 30, 1995 Abstract: Psychotic symptoms are treated by the administration of drugs which amplify the ability of natural stimulators of AMPA receptors to enhance the mediation of excitatory synaptic response. What is previously known about the activity and effectiveness of these drugs is unrelated to the etiology of psychotic symptoms. The invention finds particular utility in the treatment of schizophrenia. Excerpt(s): Schizophrenia is a chronic psychotic mental disorder characterized by both positive symptoms (delusions, hallucinations, and formal thought disorder) and negative symptoms (flattened affect and social withdrawal). The estimated prevalence of schizophrenia among humans is 0.2-2.0% worldwide. Schizophrenia is typically treated with a class of drugs called antipsychotics or neuroleptics that have a common mode of action as antagonists of brain dopamine receptors. The effectiveness of neuroleptics as well as other findings have led to the currently held hypothesis of schizophrenia known as the "dopamine hypothesis." This hypothesis posits that hyperactivity in the dopaminergic projections from the midbrain to limbic and cortical structures is responsible for the clinical symptoms of the disorder. The hypothesis is also supported by the finding that amphetamines, which among other things enhance dopamine release, produce psychotic symptoms in humans and aberrant behaviors in animals. Heretofore, there has been no known connection between psychotic symptoms and stimulators of AMPA receptors. Web site: http://www.delphion.com/details?pn=US05773434__

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Medicament for remedying schizophrenia Inventor(s): Miyamoto; Yoshio (Takarazuka, JA), Inanaga; Kazutoyo (Kurume, JA) Assignee(s): Takeda Chemical Industries, Ltd. (Osaka, JA) Patent Number: 4,088,755 Date filed: May 24, 1976 Abstract: The concomitant administration of L-pyroglutamyl-L-histidyl-L-prolinamide or its physiologically acceptable salt with one or more neuroleptics to patients suffering from schizophrenia can attain remarkable improvement of the overall disease picture of the patients. Excerpt(s): The present invention relates to a medicament for remedying schizophrenia. There are a variety of therapeutic methods which are currently used in the treatment of patients suffering from schizophrenia. These methods include psychotherapy, shock therapy, drug therapy and the like. Drugs used in such drug therapy are so called neuroleptics (called also antipsychotic drugs or major tranquillizers) such as phenothiazines, butyrophenones and thioxanthenes. It has been recognized that neuroleptics currently used are effective in improving accessory symptoms, but at the same time, these drugs are very often not effective enough to cure fundamental symptoms and, thus fundamental symptoms are still marked after the introduction of medication with these neuroleptics. Furthermore, the improvement of symptoms by the administration of neuroleptics has been known to be reversible and symptoms once ameliorated tent to aggravate while the drugs are withdrawn. Therefore, many difficulties accompany the treatment of schizophrenia and novel medicaments which are more effective for the treatment have been long since desired. Web site: http://www.delphion.com/details?pn=US04088755__

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Method and pharmaceutical composition for the treatment of schizophrenia Inventor(s): Kaminski; Ram (Riverdale, NY) Assignee(s): The Mount Sinai School of Medicine of the City University of New York (New York, NY) Patent Number: 5,177,081 Date filed: August 9, 1991 Abstract: Persons suffering from negative symptoms of schizophrenia can be successfully treated using a histamine H.sub.2 -antagonist which crosses the blood-brain barrier so as to interact with histamine-H.sub.2 receptors in the brain. A preferred H.sub.2 -antagonist is famotidine. The H.sub.2 -antagonist may be used alone in patients who are relatively free of positive symptoms or it may be used in combination with known neuroleptics. A pharmaceutical composition containing both an H.sub.2 antagonist and a neuroleptic is part of the present invention. Excerpt(s): This application relates to a method and a pharmaceutical composition for the treatment of schizophrenia. Schizophrenia is a chronic disabling disease which may occur in nearly 1% of the population worldwide. While there remains some dispute as to the proper diagnostic criteria for schizophrenia, it is generally accepted that schizophrenia manifests itself in two distinct sets of symptoms, referred to as positive and negative symptoms. See, e.g. Carpenter et al., Am. J. Psychiatry 145: 578-583 (1988); Morrison et al., J. Nervous and Mental Disease 178: 377-384 (1990). The so-called positive

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symptoms of schizophrenia are typified by delusions, hallucinations and formal thought disorder. These symptoms have proven responsive to treatments with antidopaminergic neuroleptic drugs such as haloperidol, chlorpromazine, thioridazine and others. In contrast, the negative symptoms, which are typified by alogia, anhedonia, asociality, apathy, avolition, and amotivation have not been responsive to drug treatments. Because of this, and the fact that negative symptoms once developed tend to persevere, some authors have characterized this condition is "irreversible." Carpenter, supra at 579. Surprisingly, therefore, a drug therapy which is effective to treat the negative symptoms of schizophrenia has now been found. Web site: http://www.delphion.com/details?pn=US05177081__ •

Method for diagnosing schizophrenia Inventor(s): Mallet; Jacques (Paris, FR), Laurent; Claudine (Saint Cloud, FR), Meloni; Rolando (Paris, FR) Assignee(s): Rhone-Poulenc Rorer S.A. (Antony Cedex, FR) Patent Number: 6,210,879 Date filed: December 22, 1997 Abstract: The present invention relates to a method for diagnosing schizophrenia, said method being based on the detection in vitro of the presence of the allele Ep of the microsatellite HUNTH01 in the gene TH. The invention also relates to the primers used for implementing said method. Excerpt(s): The present invention relates to a method for diagnosing schizophrenia. It relates, more particularly, to a process for detecting variations in a repeated DNA sequence which is present in the TH gene, certain forms of which appear specifically in schizophrenic patients. The invention also relates to primers which can be used for detecting specific alleles of this repeated sequence, which alleles are associated with schizophrenia. The presence of mutations in all classes of repeated DNA sequences is a known phenomenon. However, the functional significance of these mutations is unknown. Thus, microsatellites represent an abundant class of repeated DNA sequences which exhibit a high degree of polymorphism linked to variations in the number of repeated motifs (ref. 1) and/or in the sequence of these motifs. For this reason, these microsatellites have been used as genetic markers for constructing genetic maps and for identifying loci which are involved in pathologies (ref. 2). The size of the different alleles of a microsatellite depends on variations in the number of repeated motifs. Thus, sequencing experiments carried out on repeated dimers have demonstrated a variation in the number of repeated motifs and in their sequence. These variations can correspond, in particular, to "perfect" repeats, that is to say without interruption in the base sequence, or to "imperfect" repeats, which contain one or more interruptions in the sequences of the motifs, which interruption(s) can be (a) deletion(s) or (an) insertion(s) (ref. 3). In the same way, variations in length and/or sequence have also been observed in the repeated trimeric or tetrameric motifs. Thus, variations of this type have been observed in the HUMHPRTB (ref. 4) and HUMTH01 (ref. 5) microsatellites. The Applicant has been interested, more particularly, in searching for genetic alterations which are linked to schizophrenia. To this end, the Applicant has carried out a study of the association between the gene for tyrosine hydroxylase (TH) and schizophrenia, which study has been orientated more particularly towards the HUMTH01 microsatellite. TH is the limiting enzyme in the pathway for biosynthesizing catecholamines. Various genetic studies of psychiatric and neurological pathologies

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have been carried out using markers which are located in the TH gene (refs 6 and 7). However, there has so far been no demonstration in the literature of a genetic association with schizophrenia. Web site: http://www.delphion.com/details?pn=US06210879__ •

Method for the detection of schizophrenia Inventor(s): Gattaz; Wagner F. (Heidelberg, DE) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 5,006,462 Date filed: March 16, 1988 Abstract: The diagnosis of enzyme is disclosed. In this with a test composition to sample can be read and nonschizophrenic controls.

schizophrenia through the detection of a phospholipase invention, a test sample from the patient can be combined measure phospholipase enzyme in the test sample. The the result compared with a scale of values found in

Excerpt(s): This invention relates to a method for the diagnosis of schizophrenia. In particular it relates to the determination of phospholipase-A2 activity or concentration in biological fluids for the diagnosis of schizophrenia. Studies of different neurodiagnostic subgroups indicate the presence of brain dysfunction in at least some schizophrenic patients. These studies have been summarized in reviews that suggest that the brain dysfunction in schizophrenia could occur as the result of a faulty maturation of the central nervous system during infancy and adolescence. Accordingly, one strategy in the biological research of schizophrenia is the investigation of variables that could play a role in the plasticity of the brain. Phospholipase-A2 (hereinafter "PLA2") is a key enzyme in the metabolism of phospholipids, catalyzing the release of fatty acids and highly toxic compounds, such as lysophosphatidylcholine. Extracellular PLA2 is synthesized in the pancreas as a digestive enzyme, whereas intracellular PLA2 controls the phospholipid turnover in the cell membrane, in turn affecting membrane integrity and membrane function. Web site: http://www.delphion.com/details?pn=US05006462__ •

Method for the treatment of schizophrenia Inventor(s): Snorrason; Ernir (Stigahlid 80, 105 Reykjav ik, IS) Assignee(s): none reported Patent Number: 5,633,238 Date filed: June 5, 1995 Abstract: The present invention relates to the use of cholinesterase inhibitors, such as galanthamine, for the preparation of a pharmaceutical composition for counteracting the sedative or hypnotic or respiratory depressive effects of benzodiazepines, substantially without interfering with the anxiolytic, antipsychotic, anticonvulsant, and muscle relaxant activity of benzodiazepines.Expressed in another manner, the invention relates to a method for counteracting the sedative, hypnotic or respiratory depressive effects of benzodiazepines, substantially without interfering with the above-mentioned anxiolytic and other desired properties of benzodiazepines, comprising administering, to a patient

Patents 365

in subjected to benzodiazepine therapy, that is, a patient who receives benzodiazepine, an effective amount of a pharmaceutically acceptable cholinesterase inhibitor.An aspect of the invention relates to the treatment of schizophrenia, in particular affective or schizoaffective type of schizophrenia, by administering, to a patient suffering from such a condition, an effective amount of a cholinesterase inhibitor, such as galanthamine. Excerpt(s): Benzodiazepines have been used for several decades, but have become increasingly popular because of their effects and their low toxicity compared to other drugs of similar actions. antipsychotic. Thus, the benzodiazepines are relevant as drugs in connection with a broad spectrum of diseases. Web site: http://www.delphion.com/details?pn=US05633238__ •

Method for treating schizophrenia Inventor(s): Kinney; Michael J. (Suite 909 - Mt. Huntington, Huntington, WV 25701) Assignee(s): none reported Patent Number: 4,300,551 Date filed: September 4, 1979 Abstract: A method for treating schizophrenia in human patients by hemoperfusion using hemoperfusion of the patient's blood through a charcoal cartridge in a manner for selective removal of molecules is disclosed. The method may use known hemoperfusion cartridges for a heretofore completely unappreciated application and has the advantages of lesser side effects and easier implementation than other known methods of treatment. Excerpt(s): The present invention relates to a new method of treating schizophrenia and is particularly directed to a novel process for the patient's blood chemistry. Schizophrenia is generally considered and is defined by Merriam-Webster's Third International Dictionary as a psychotic disorder of unknown complex etiology that occurs as simple, paranoid, catatonic, or hebephrenic, and is characterized by disturbances in thinking involving a distortion of the usual logical relations between ideas, a separation between the intellect and the emotions so that the patient's feelings or their manifestations seem inappropriate to his life situation, a reduced tolerance for the stress of interpersonal relations, anxiety, delusions, and hallucinations. In the United States at the present time, it is estimated that schizophrenic patients occupy more hospital beds than any other illness and that only 20% of schizophrenic patients are hospitalized. One percent of the entire population of the United States has been labeled schizophrenic. Web site: http://www.delphion.com/details?pn=US04300551__

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Method for treating schizophrenia and medicaments therefor Inventor(s): Harrigan; Stephen E. (Ann Arbor, MI), Weisbach; Jerry A. (Ann Arbor, MI), Heffner; Thomas G. (Ann Arbor, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 4,582,823 Date filed: August 15, 1984

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Abstract: A method for treating schizophrenia without precipitating neurological side effects such as extrapyramidal syndrome and tardive dyskinesia by administering prior to or concomitantly with haloperidol a diphenylalkyladenosine or diphenylalkyl-2amino-adenosine is described as well as pharmaceutical compositions therefor. Excerpt(s): Haloperidol, described in U.S. Pat. No. 3,438,991, is a well-known neuroleptic agent used for treating psychoses, such as schizophrenia. Use of haloperidol causes side effects including acute extrapyramidal syndrome (EPS) which is usually seen soon after antipsychotic therapy is begun as well as the more chronic dystonic syndrome known as tardive dyskinesia which sometimes emerges during long-term antipsychotic use. Attempts at reducing the side effects of haloperidol have been reported. U.S. Pat. No. 3,978,216 describes the use of a gabergic compound administered prior to or with a neuroleptic agent to reduce tardive dyskinesia. Benzodiazepines have been reported to be effective in the reduction of serum prolactin when used with haloperidol, U.S. Pat. No. 4,316,897. Desipramine and imipramine have been reported to reduce Parkinsonlike symptoms in the treatment of schizophrenia with haloperidol in U.S. Pat. No.3,505,451. The present invention has for its object a method of treating psychoses, e.g., schizophrenia, and reducing the side effects of such treatment, such as acute extrapyramidal syndrome and tardive dyskinesia by administering a novel adenosine derivative prior to or concomitant with haloperidol therapy. Web site: http://www.delphion.com/details?pn=US04582823__ •

Method for treating schizophrenia and method and composition for potentiating neuroleptic drugs Inventor(s): Fuxe; Kjell (Sollentuna, SE) Assignee(s): Nelson Research & Development Company (Irvine, CA) Patent Number: 4,138,484 Date filed: July 25, 1977 Abstract: A method for treating schizophrenia and a method and composition for potentiating the beneficial effects and reducing the side effects of neuroleptic drugs. Schizophrenia is treated with a GABA-like compound such as Lioresal. Neuroleptic drugs are potentiated by coadministering to a schizophrenic a neuroleptic drug and a GABA-like drug such as Lioresal. Excerpt(s): Neuroleptic drugs are used to treat schizophrenia. Examples of commom neuroleptic drugs include phenothiazines such as chloropromazine; butyrophenones such as haloperidol and others such as pimocide and clozapine. Side effects of neuroleptic drugs include sedation and tardive dyskinesias. The latter side effect is particularly important because it results in involuntary muscle movements especially of the face and mouth which become irreversible. The onset of this side effect is directly related to the amounts of and length of time which a neuroleptic drug is used in treatment. There has now been discovered a method for treating schizophrenia and a method and composition for potentiating the beneficial effects and for reducing the side effects of neuroleptic drugs. The present invention further relates to a composition comprising a neuroleptic drug and a potentiating amount of a gabergic compound together with a suitable pharmaceutical carrier. Web site: http://www.delphion.com/details?pn=US04138484__

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Method for treating schizophrenia employing an ace inhibitor Inventor(s): Rawlins; John N. P. (Oxford, GB), Sudilovsky; Abraham (Lawrenceville, NJ), Feldon; Joram (Tel Aviv, IL), Weiner; Ina (Patach-Tikva, IL), Smith; A. David (Oxford, GB) Assignee(s): E.R. Squibb & Sons, Inc. (Princeton, NJ) Patent Number: 6,187,752 Date filed: September 12, 1991 Abstract: A method is provided for treating schizophrenia in a mammalian species by administering an ACE inhibitor, such as captopril, alone or with a neuroleptic such as cholecystokinin, fluphenazine or haloperidol. Excerpt(s): The present invention relates to a method for treating schizophrenia in mammalian species by administering an ACE inhibitor, such as captopril, ceronapril, zofenopril or fosinopril, alone or in combination with a neuroleptic or antipsychotic drug. U.S. Pat. Nos. 4,046,889 and 4,105,776 to Ondetti et al disclose proline derivatives which are angiotensin converting enzyme (ACE) inhibitors including captopril. U.S. Pat. No. 4,168,267 to Petrillo discloses phosphinylalkanoyl prolines which are ACE inhibitors. Web site: http://www.delphion.com/details?pn=US06187752__

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Method in the treatment of schizophrenia Inventor(s): Eriksson; Tomas (P.O. Box 71, SE-427 22 Billdal, SE) Assignee(s): none reported Patent Number: 6,468,973 Date filed: June 4, 2001 Abstract: The invention relates to the use of a composition comprising at least one substance within the group GnRH-analogues for producing a drug for treatment of schizophrenia. The invention makes it possible for patients suffering from schizophrenia to obtain partial or total relief of symptoms by treatment with a composition which comprises at least one substance within the group GnRH-analogues. Excerpt(s): The present invention relates to the use of a composition comprising at least one substance within the group GnRH-analogues for treatment of schizophrenia. Schizophrenia is a chronic psychiatric disease in which the main symptoms are delusions, hallucinations and grossly disorganised or catatonic behaviour. The disorder is chronic and often serious enough to make the patient completely or partially unable to work and live a normal life. The disorder is described and defined in detail in The Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) published by the American Psychiatric Association in 1994. Web site: http://www.delphion.com/details?pn=US06468973__

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Method of determining susceptibility to schizophrenia Inventor(s): Gogos; Joseph A. (New York, NY), Karayiorgou; Maria (New York, NY) Assignee(s): The Rockfeller University (New York, NY) Patent Number: 6,395,482 Date filed: March 26, 1999 Abstract: Variations in the DNA sequence of the human proline dehydrogenase gene (PRODH) which correlate to an increased susceptibility to, or presence of schizophrenia or a disease or disorder related thereto, such as obsessive compulsive disorder (OCD), bipolar disorder (BP), or major depressive disorder (MDD) are provided, along with assays to diagnosing schizophrenia or a disease or disorder related thereto, and evaluating potential drugs or agents for using in treating such diseases or disorders. Excerpt(s): The present invention relates to isolated nucleic acid molecules which encode human and murine proline dehydrogenase, and methods for determining susceptibility to, or the presence of schizophrenia or a disease or disorder related thereto, such as obsessive compulsive disorder, bipolar disorder (BP), or major depressive disorder in a subject by determining levels of proline dehydrogenase (PRODH) in a bodily sample. Furthermore, the present invention comprises polymorphisms of the human proline dehydrogenase (PRODH) gene which correlate to a phenotype closely related to schizophrenia or a disease or disorder related thereto. The present invention also relates to various assays for drugs or agents that can treat schizophrenia or a disease or disorder related thereto. It has been posited that the amino acid proline serves as a modulator of synaptic transmission in the mammalian brain, due to the selective expression of a brain specific high affinity proline transporter in a subset of glutamatergic pathways (Fremeau et al., 1996). Proline transporter is modulated by enckephalins, the expression of which may be decreased in the brains of patients with schizophrenia and elevated proline concentration. Furthermore, recent analysis indicates that endogenous extracellular proline may regulate the basal function of some glutamate synapses by maintaining them in a partially potentiated state. Also, elevated proline concentration has also been previously associated with behavioral and neurological effects. Evidence of an association between schizophrenia susceptibility and hemizygous deletions in chromosome 22q11 has been reported. More specifically, three hemizygous cryptic deletions at 22q11 in a sample of 300 unrelated schizophrenic patients have been reported and characterized [Karayiorgou et al., Proc. Natl. Acad. Sci. U.S.A. 92, 7612 (1995); Karayiorgou et al., Amer. J. Med. Genet. 74, 677 (1997)]. The frequency of this microdeletion in the general population is estimated to be approximately 0.02% and no deletions were found in a sample of 200 healthy controls. The identified locus (approximately 1.5 Mb in size) is located in the proximal part of a region at chromosome 22q11 and has been implicated independently in schizophrenia susceptibility through linkage studies [Karayiorgou & Gogos, Neuron 19, 967-979 (1997)]. This locus overlaps with the critical region involved in the etiology of Velocardio-facial (VCFS)/DiGeorge (DGS) syndromes [Driscoll et al. 1993]. Furthermore, it has been shown that approximately 29% VCFS children with 22q11 deletions develop schizophrenia or schizoaffective disorder in adolescence and adulthood [Pulver et al., 1994], an estimate confirmed by a more recent independent study [Murphy and Owen, Am. J. Med. Genet., 74, 660 (1997)]. Deletions in chromosome 22, band q11 (22q11) have been identified among schizophrenia patients of diverse ethnic origins (Chinese, Israeli, British, Danish [L. Y. Chow et al., Am. J. Med. Genet. 74, 677 (1997); D. Gothelf et al., Am. J. Med. Genet. 72, 455 (1997); O. Mors and H. Ewald, Am. J. Med. Genet. 74, 677 (1997); Hodginson et al, Am. J. Med. Genet. 61, 565 (1997)])

Patents 369

and the 22q11 region has been implicated in early-onset schizophrenia [Yan et al., 1998]. In addition, the increased rates of comorbid obsessive compulsive disorder (OCD) or symptoms (OCS) among schizophrenic patients with the 22q11 microdeletion locus [Karayiorgou et al., 1996, 1997; Papolos et al., 1996] and similarly increased rates of anxiety, OCS and OCD in children and adults with the 22q11 microdeletion in the absence of schizophrenia [Papolos et al., 1996], potentially indicate that the 22q11 genomic region may harbor one or more genes predisposing to obsessive compulsive disorder (OCD). Web site: http://www.delphion.com/details?pn=US06395482__ •

Method of pharmacologically treating schizophrenia with alpha-methyl-para-tyrosine Inventor(s): Pozuelo; Jose (1463 Burlington, Cleveland Heights, OH 44118) Assignee(s): none reported Patent Number: 4,165,382 Date filed: October 17, 1977 Abstract: A method of pharmacologically treating schizophrenia which method comprises administering to a human being a therapeutically effective amount of alphamethyl-para-tyrosine and an alkalinizing agent, with the alkalinizing agent being present in an amount sufficient to cause the urine of the human being to have an alkaline pH. Excerpt(s): The present invention relates to a method of treating patients suffering from schizophrenia and to alleviate or abolish the symptoms of the disease. There are two major aspects to consider in the schizophrenic patient: (1) a disturbance of mood and affect and disorganization of the thinking process, and (2) the hallucinations and delusions which render the individual uncapable of dealing effectively with the motivations and decisions of every day living. The biochemical basis of the schizophrenia has been suspected for a long time and the identification of the biochemically altered factors, be they genetically induced or triggered by environmental situations, enzymatic or electrolytic in nature, etc., have been the object of numerous investigations. Even if the etiological agent of all these disturbances is unknown, an abnormality in the mechanism of the neurotransmitters is evidently involved. It is well known that the catecholamines, specifically dopamine and noradrenaline are two fundamental neurotransmitters and it has been speculated that an alteration in the synthesis, release, catabolism or re-uptake of these compounds could be responsible for the symptoms of schizophrenia. Heretofore to accomplish this certain therapeutic agents have been utilized. These agents are the so-called neuroleptics (e.g., chlorpromazine, thioridazine, haloperidol, etc.). Web site: http://www.delphion.com/details?pn=US04165382__

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Method of treating psychosis and schizophrenia Inventor(s): Unangst; Paul Charles (Ann Arbor, MI), Capiris; Thomas (Plymouth, MI), Miller; Steven Robert (Ann Arbor, MI), Wise; Lawrence David (Ann Arbor, MI), Connor; David Thomas (Ann Arbor, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,051,605 Date filed: January 29, 1999 Abstract: This invention relates to compounds that are antagonists of dopamine D4 receptors, and to methods of treating psychosis and schizophrenia using a compound that is an antagonist of dopamine D4 receptors. Excerpt(s): This invention relates to compounds that are antagonists of dopamine D4 receptors and to methods of treating psychosis and schizophrenia using a compound that is an antagonist of dopamine D4 receptors. Dopamine is a neurotransmitter that is found in the brains of animals, including humans, and is essential for proper nerve signal transmission. It is well-known that certain compounds block or inhibit the binding of dopamine to dopamine receptors. Such compounds are called dopamine receptor antagonists. It is also well-known that dopamine receptor antagonists are useful in the treatment of schizophrenia and psychosis. Recently, it has been discovered that more than one type of dopamine receptor exists, and that dopamine receptor antagonists can preferentially inhibit one type of dopamine receptor over another. Two major families of dopamine receptors have been identified and named the D1 and D2 families. In the D2 family, three distinct receptor subtypes have been identified as D2, D3, and D4. Web site: http://www.delphion.com/details?pn=US06051605__

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Method of treating schizophrenia Inventor(s): Fuxe; Kjell (Sollentuna, SW) Assignee(s): Nelson Research and Development Company (Irvine, CA) Patent Number: 4,084,000 Date filed: August 16, 1976 Abstract: A method for treating schizophrenia and a method and composition for potentiating the beneficial effects and reducing the side effects of neuroleptic drugs. Schizophrenia is treated with a GABA-like compound such as Lioresal. Neuroleptic drugs are potentiated by coadministering to a schizophrenic a neuroleptic drug and a GABA-like drug such as Lioresal. Excerpt(s): Neuroleptic drugs are used to treat schizophrenia. Examples of common neuroleptic drugs include phenothiazines such as chloropromazine; butyrophenones such as haloperidol and others such as pimocide and clozapine. Side effects of neuroleptic drugs include sedation and tardive dyskinesias. The latter side effect is particularly important because it results in involuntary muscle movements especially of the face and mouth which become irreversible. The onset of this side effect is directly related to the amounts of and length of time which a neuroleptic drug is used in treatment. There has now been discovered a method for treating schizophrenia and a method and composition for potentiating the beneficial effects and for reducing the side effects of neuroleptic drugs. The present invention further relates to a composition

Patents 371

comprising a neuroleptic drug and a potentiating amount of a gabergic compound together with a suitable pharmaceutical carrier. Web site: http://www.delphion.com/details?pn=US04084000__ •

Method of treating schizophrenia Inventor(s): Shannon; Harlan E. (Carmel, IN), Bymaster; Franklin Porter (Brownsburg, IN) Assignee(s): Novo Nordisk A/S (Bagsvaerd, DK) Patent Number: 5,750,541 Date filed: August 2, 1996 Abstract: The present invention relates to a novel method for treating a mammal suffering from or susceptible to schizophrenia and schizophreniform diseases by administering thiadiazole or oxadiazole compounds. Excerpt(s): This invention provides a novel method for treating a mammal suffering from or susceptible to schizophrenia and schizophreniform diseases, such as schizophrenia (catatonic), schizophrenia (disorganized), schizophrenia (paranoid), schizophrenia (undifferential), schizophrenia (residual), schizophreniform disorder, brief reactive psychosis, schizoaffective disorder, induced psychotic disorder, schizotypal personality disorder, schizoid personality disorder, paranoid personality disorder and delusional (paranoid) disorder. Currently there are many drugs available for the treatment of disorders of the central nervous system. Among such drugs is a category known as antipsychotics for treating serious mental conditions such as schizophrenia and schizophreniform illnesses. The drugs currently available for treating such conditions are often unsatisfactory. The drugs may be associated with serious undesirable side effects which include tardive dyskinesia, movement disorders, and other undesirable extra pyramidal effects. There is a need for better products that control or eliminate the symptoms in a safer and more effective way. Furthermore, many patients do not respond or only partially respond to present drug treatment. Estimates of such partial- or non-responders vary between 40% and 80% of those treated. Web site: http://www.delphion.com/details?pn=US05750541__

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Method of treating schizophrenia by brain stimulation and drug infusion Inventor(s): Rise; Mark T. (Monticello, MN) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 5,975,085 Date filed: May 1, 1997 Abstract: Techniques using one or more drugs and/or electrical stimulation for treating schizophrenia by means of an implantable signal generator and electrode and an implantable pump and catheter. A catheter is surgically implanted in the brain to infuse the drugs, and one or more electrodes are surgically implanted in the brain to provide electrical

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Excerpt(s): This invention relates to nerve tissue stimulation and infusion techniques, and more particularly relates to such techniques for treating schizophrenia. The etiology of schizophrenia is unknown. Many hypotheses have been formulated including infectious (slow virus), genetic, autoimmune or immune dysfunction, environmental and neurotransmitter-mediated. Scans and postmortem studies show abnormalities in schizophrenics, such as enlarged cerebral ventricles and reduced brain size. Brain systems making use of dopamine appear to be particularly involved. Pet scans show that the prefrontal cortex of schizophrenic patients is not properly activated in response to intellectual tasks. Schizophrenia includes disturbances in one or more of three domains of psychopathology. Essentially all patients manifest "positive" symptoms that include delusions and hallucinations. A small majority also have thought disorders. A substantial minority are afflicted with primary, enduring negative symptoms such as flat affect, asociality, anhedonia and intentional impairment. The prevalence of schizophrenia in the U.S. is estimated to be 1.1 million persons with schizophrenia proper and another 2% to 3% of the population suffer schizotypal personality disorder which may simply be a mild form of the disorder. There is a genetic predisposition to schizophrenia. The odds for any person in the general population to suffer from the illness is 1%. The odds that a person will have the illness if they have a parent or sibling with schizophrenia is 15%. And if they have an identical twin with schizophrenia the odds are between 30% and 50% that they will also have it. The cause of schizophrenia is unknown. However, there are several hypotheses that are described above. The structures of the brain that are involved in schizophrenia are suggested by the symptoms that become manifest during the phases of the illness and by the pharmaceutical agents that have an effect on those symptoms. The effectiveness of the neuroleptic drugs (typical antipsychotic) which block the dopamine as a transmitter has led to the hypothesis that schizophrenia is the result of dysfunction of neurons utilizing dopamine as a neurotransmitter. In particular, researchers believe that there is an overactivity in these circuits which utilize dopamine. Web site: http://www.delphion.com/details?pn=US05975085__ •

Method of treating schizophrenia, depression and other neurological conditions Inventor(s): Kelly; John S. (Edinburgh, GB), Marston; Hugh M. (East Lothian, GB) Assignee(s): Fujisawa Pharmaceutical Co., Ltd. (Osaka, JP) Patent Number: 6,284,760 Date filed: June 24, 1999 Abstract: This application relates to the use of aminopiperazine derivatives for the treatment of schizophrenia, depression, and other neurological conditions. Excerpt(s): The aminopiperazine derivatives used in this invention are known as described in PCT International Publication No. WO 91/01979 that said aminopiperazine derivatives possess the potentiation of the cholinergic activity and are useful in the treatment of disorders in the central nervous system for human beings, and more particularly in the treatment of amnesia, dementia, senile dementia and the like. The present invention relates to a new use of aminpiperazine derivatives and pharmaceutically acceptable salts thereof for the treatment and/or prevention of schizophrenia, depression, stroke, head injury, nicotine withdrawal, spinal cord injury, anxiety, pollakiuria, incontinence of urine, myotonic dystrophy, attention deficit hyperactivity disorder, excessive daytime sleepiness (narcolepsy), Parkinson's disease or autism for mammals. Accordingly, this invention is to provide a new use of

Patents 373

aminopiperazine derivatives and pharmaceutically acceptable salts thereof for treating and/or preventing schizophrenia, depression, stroke, head injury, nicotine withdrawal, spinal cord injury, anxiety, pollakiuria, incontinence of urine, myotonic dystrophy, attention deficit hyperactivity disorder, excessive daytime sleepiness (narcolepsy), Parkinson's disease or autism. Web site: http://www.delphion.com/details?pn=US06284760__ •

Method of treating therapy resistant schizophrenia with melperone (R-fluoro-Ymethyl-peperidino-butyrophrenone) Inventor(s): Meltzer; Herbert Y. (Shaker Heights, OH) Assignee(s): Case Western Reserve University (Cleveland, OH) Patent Number: 5,221,679 Date filed: March 16, 1992 Abstract: The invention relates to a method of treating therapy-resistant schizophrenia which includes administering a therapeutically effective amount of melperone (4-fluro.gamma.-(4-methyl-piperidino)-butyrophenone) or an acceptable acid salt thereof. Excerpt(s): This invention relates to the treatment of patients suffering from therapyresistant schizophrenia by administration of the drug melperone (4-fluoro-.gamma.-(4methyl-piperidino) - butyrophenone). The treatment of schizophrenia remains one of the major challenges of modern-day medicine. Even incremental advances in the safe and effective use of currently available treatments can have a major impact on the lives of schizophrenic individuals and their families. Reducing rates of relapse and rehospitalization by as little as 10 percent per year can have enormous public health implications. (J. M. Kane, Special Report: Schizophrenia, 1987, National Institute of Mental Health, in: Schizophrenia Bull., 13:133-156, 1987). It is estimated that about 2 million Americans suffer from classical schizophrenia. Approximately 200,000 to 400,000 (10-20 percent) of these schizophrenic patients do not respond to treatment with traditional neuroleptics (antipsychotic drugs) and are classified as therapy-resistant schizophrenics. Web site: http://www.delphion.com/details?pn=US05221679__

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Method of treating therapy-resistant schizophrenia with amperozide (N-ethyl-4-(4',4'bis(p-fluorophenyl)butyl)-1-piperazine-carboxamide Inventor(s): Bjork; Anders K. (Jagarevagen, SE) Assignee(s): Pharmacia AB (SE) Patent Number: 5,013,735 Date filed: March 1, 1990 Abstract: The present invention relates to a method for treating a patient suffering from therapy-resistant schizophrenia by administering to the patient a therapeutically effective amount of amperozide. Excerpt(s): This invention relates to a method for the treatment of patients suffering from therapy-resistant schizophrenia by administration of the drug amperozide, Nethyl-4-[4',4'-bis(p-flurophenyl)butyl]-l-piperazinecarboxamide. The treatment of

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schizophrenia remains one of the major challenges of modern day medicine. Even incremental advances in the safe and effective use of currently available treatments can have a major impact on the lives of schizophrenic individuals and their families. Reducing rates of relapse and rehospitalization by as little as ten percent per year can have enormous public health implications (J. M. Kane, Special Report: Schizoohrenia, 1987 National Institute of Mental Health). It is estimated that approximately two million Americans suffer from classical schizophrenia. Approximately 200,000 to 400,000 (I0 to 20%) of these schizophrenic patients do not respond to treatment with traditional neuroleptics (antipsychotic drugs) and are classified as therapy-resistant schizophrenics. Web site: http://www.delphion.com/details?pn=US05013735__ •

Methods and materials for the diagnosis and treatment of schizophrenia and related disorders Inventor(s): Deth; Richard C. (Waban, MA) Assignee(s): Northeastern University (Boston, MA) Patent Number: 6,080,549 Date filed: April 8, 1997 Abstract: Methods for detecting schizophrenia or depression based on modifications of the contribution of the D.sub.4 receptor to phospholipid methylation levels are described herein. Individuals with schizophrenia or depression have a deficiency in phospholipid methylation activity compared with normal individuals. Methods for screening therapeutic processes or agents for use in treatment of schizophrenia or related neuropsychiatric disorders are also described. Excerpt(s): Schizophrenia is a devastating neuropsychiatric disorder which affects approximately 1% of the population and results in serious disruption in the lives of afflicted individuals and their families. Common symptoms include delusions, conceptual disorganizations and visual or auditory hallucinations, as well as changes in affective behavior. A number of scales for the rating of symptoms and methods for ascertaining the diagnosis have been developed, including the DSM classification by the American Psychiatric Association (Diagnostic and Statistical Manual of Mental Disorders (4th edition), pp. 273-316, 1994), which have attempted to refine the accuracy of clinical diagnosis. However, it is likely that similar symptoms can result from several underlying abnormalities, and diagnosis relying solely on clinical symptoms is difficult and controversial, as well as subjective, time-consuming and costly. The cause or causes of schizophrenia remain obscure. A defect in dopamine pathways of synaptic neuronal function is a central feature of the most widely held etiopathogenic theory (known as the Dopamine Hypothesis), with recent emphasis on the role of D.sub.4 -type dopamine receptors (Taubes, Science 265:1034-1035, 1994). However, studies to date have failed to identify abnormalities in the basic receptor structure, suggesting that dysfunction may result from an alteration in the dynamic regulation of receptor activity. Dopamine receptors are members of a large superfamily of G protein-coupled receptors which share a high degree of structural similarity while recognizing a widely divergent array of substances which affect cellular function. Recent advances in the study of these receptors have led to the identification of key locations on the receptors which can modulate their function and which therefore may be sites of malfunction in schizophrenia (Samama et al., J. Biol. Chem. 268:4625-4636, 1993). One such critical location or "hot spot" in the dopamine D.sub.4 receptor is a methionine amino acid residue (Van Tol et al., Nature 350:610-614, 1991).

Patents 375

Web site: http://www.delphion.com/details?pn=US06080549__ •

Methods for prevention and treatment of Tourette's syndrome and schizophrenia Inventor(s): Bencherif; Merouane (5437-B Countryside Dr., Winston-Salem, NC 27105), Caldwell; William Scott (1270 Yorkshire Rd., Winston-Salem, NC 27106), Dull; Gary Maurice (1175 Sequoia Dr., Lewsiville, NC 27023), Lippiello; Patrick Michael (1233 Arboretum Dr., Lewisville, NC 27023) Assignee(s): none reported Patent Number: 6,107,298 Date filed: March 12, 1999 Abstract: Patients susceptible to or suffering from Tourette's syndrome or schizophrenia are treated by administering an effective amount of an aryl substituted aliphatic compound, an aryl substituted olefinic amine compound or an aryl substituted acetylenic compound. Exemplary compounds are (E)-4-(5-pyrimidinyl)-3-butene-1amine, (E)-4-[3-(5-methoxypyridin)yl]-3-butene-1-amine, (E)-N-methyly-4-(5pyrimidinyl)-3-butene-1-amine, (E)-N-methyl-4-[3-(5-methoxypyrindin)yl]-3-butene-1amine, (Z)-metanicotine, (E)-metanicotine, N-methyl-(3-pyridinyl)-butane-1-amine, Nmethyl-4-(3-pyridinyl)-3-butyne-1-amine and (E)-N-methyl-4-[3-(6-methylpyrindin)yl]3-butene-1-amine. Excerpt(s): The present invention relates to compounds having pharmaceutical properties, and in particular, to compounds useful for preventing and treating central nervous system (CNS) disorders. The present invention relates to a method for treating patients suffering from or susceptible to such disorders, and in particular, to a method for treating patients suffering from those disorders which are associated with neurotransmitter system dysfunction. The present invention also relates to compositions of matter useful as pharmaceutical compositions in the prevention and treatment of CNS disorders which have been attributed to neurotransmitter system dysfunction. Senile dementia of the Alzheimer's type (SDAT) is a debilitating neurodegenerative disease, mainly afflicting the elderly; characterized by a progressive intellectual and personality decline, as well as a loss of memory, perception, reasoning, orientation and judgment. One feature of the disease is an observed decline in the function of cholinergic systems, and specifically, a severe depletion of cholinergic neurons (i.e., neurons that release acetylcholine, which is believed to be a neurotransmitter involved in learning and memory mechanisms). See, Jones, et al., Intem. J. Neurosci., Vol. 50, p. 147 (1990); Perry, Br. Med. Bull., Vol. 42, p. 63 (1986) and Sitaram. et al., Science, Vol. 201, p. 274 (1978). It has been observed that nicotinic acetylcholine receptors, which bind nicotine and other nucotinic agonists with high affinity, are depleted during the progression of SDAT. See, Giacobini, J. Neurosci. Res., Vol. 27, p. 548 (1990); and Baron, Neurology. Vol. 36, p. 1490 (1986). As such, it would seem desirable to provide therapeutic compounds which either directly activate nicotinic receptors in place of acetylcholine or act to minimize the loss of those nicotinic receptors. Certain attempts have been made to treat SDAT. For example, nicotine has been suggested to possess an ability to activate nicotinic cholinergic receptors upon acute administration, and to elicit an increase in the number of such receptors upon chronic administration to animals. See, Rowell, Adv. Behav. Biol., Vol. 31, p. 191 (1987); and Marks, J. Pharmacol. Exp. Ther., Vol. 226, p. 817 (1983). It also has been proposed that nicotine can act directly to elicit the release of acetylcholine in brain tissue, to improve cognitive functions, and to enhance attention. See, Rowell, et al., J. Neurochem., Vol. 43, p. 1593 (1984); Sherwood, Human

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Psychopharm., Vol. 8, pp. 155-184 (1993); Hodges, et al., Bio. of Nic., Edit. by Lippiello, et al., p. 157 (1991); Sahakian, et al., Br. J. Psych., Vol. 154, p. 797 (1989); and U.S. Pat. No. 4,965,074 to Leeson and U.S. Pat. No. 5,242,935 to Lippiello et al. Other methods for treating SDAT have been proposed, including U.S. Pat. No. 5,212,188 to Caldwell et al. and U.S. Pat. No. 5,227,391 to Caldwell et al. and European Patent Application No. 588,917. Another proposed treatment for SDAT is Cognex, which is a capsule containing tacrine hydrochloride, available from Parke-Davis Division of Warner-Lambert Company, which reportedly preserves existing acetylchloine levels in patients treated therewith. Web site: http://www.delphion.com/details?pn=US06107298__ •

Prophylactic reduction and remediation of schizophrenic impairments through interactive behavioral training Inventor(s): Merzenich; Michael M. (San Francisco, CA), Blake; David T. (San Francisco, CA) Assignee(s): The Regents of the University of California (Oakland, CA), Scientific Learning Corporation (Berkeley, CA) Patent Number: 6,231,344 Date filed: August 14, 1998 Abstract: Computer-implemented perceptual and cognitive training techniques for remediating schizophrenia, either prophylactically prior to the onset of clinically observable schizophrenic behaviors or after the development of schizophrenia symptoms in a person. The computer-implemented behavioral exercises are designed to be sufficiently intensive, both in the number of repetitions and in the attentional focus related to task difficulty, such that permanent changes in neurotransmitter expression are achieved. Excerpt(s): The present invention relates to interactive behavioral training techniques for remediating schizophrenia. More specifically, the present invention relates to perceptual and cognitive training techniques for remediating schizophrenia, either prophylactically prior to the onset of clinically observable schizophrenic behaviors or after the development of schizophrenia symptoms in a person. Evidence suggests that about 1 in 100 individuals is schizophrenic and about 1 in 25 individuals is "at-risk" for schizophrenia onset. Schizophrenia is generally regarded as one of the most devastating of the common forms of mental illness. It generally arises in young adults between about 16 and 30 years of age. Most individuals that develop the illness have behavioral characteristics that identify them as "at risk" for schizophrenia onset from early childhood. Risk is contributed to by inherited factors. At the same time, there is a long history of studies that indicates that onset of the "illness" is modulated by the behavioral experiences of at-risk individuals. Even in the case of identical twins, less than half of their genetically identical siblings develop the illness. At the same time, given underlying genetic factors contributing to the risk of onset of the illness, the historical occurrence of schizophrenia in a family is one simple way of defining "at risk" status for young adults. Web site: http://www.delphion.com/details?pn=US06231344__

Patents 377

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Rat or mouse exhibiting behaviors associated with human schizophrenia Inventor(s): Lipska; Barbara K. (Annandale, VA), Weinberger; Daniel R. (Washington, DC), Jaskiw; George E. (Lyndhurst, OH) Assignee(s): The United States of America as represented by the Secretary of the (Washington, DC) Patent Number: 5,549,884 Date filed: October 28, 1992 Abstract: This invention provides a unique and surprisingly accurate animal model for human schizophrenia. The animals are brain damaged while prepubescent. The brain damage consists of a ventral hippocampus lesion induced by exposure of the hippocampus region to a neurotoxin. When the animal reaches puberty, abnormal behavior and a number of biological phenomena associated with schizophrenic symptoms emerge. These animals are useful for assaying pharmaceutical compounds for anti-schizophrenic activity. Excerpt(s): This invention provides a unique and surprisingly accurate animal model for human schizophrenia. The animals are brain damaged while prepubescent. The brain damage consists of a ventral hippocampus lesion induced by exposure of the hippocampus region to a neurotoxin. When the animal reaches puberty, abnormal behavior and a number of other biological phenomena associated with schizophrenic symptoms emerge. These animals are useful for assaying pharmaceutical compounds for anti-schizophrenic activity. The present invention provides methods of assaying the anti-schizophrenic potential of pharmaceutical compositions. The methods comprise the following steps: (a) inducing or creating a lesion in the ventral hippocampus of a prepubescent mammal, i.e., a mammal which has not yet reached puberty, using a neurotoxin so that the lesion is able to induce abnormal behavior in postpubescent mammals; (b) nurturing or raising the mammal until postpuberty, i.e., until the mammal reaches sexual maturity; (c) administering to the mammal a pharmaceutical composition thought to have anti-schizophrenic properties; and (d) determining the mammal's response to the pharmaceutical composition. The anti-schizophrenic potential of the pharmaceutical composition is assessed by objectively measuring the mammal's behavior following administration of the pharmaceutical composition. The mammal's behavior is measured or monitored using standard tests well-known by those skilled in the art. The behaviors which are measured typically include the following: locomotor activity in a cage, in unfamiliar or novel environments, after injection or administration of drugs (e.g., amphetamines), after mild electric shock, after exposure to sensory stimuli (e.g., noise), in water (swim test), after immobilization, in social interactions, and in various learning and reward paradigms. The present invention also provides methods of assaying the anti-excessive limbic dopamine activity potential of pharmaceutical compositions. The methods comprise the following steps: (a) inducing a lesion in the ventral hippocampus of a prepubescent mammal using a neurotoxin so that the lesion is able to induce excessive limbic dopamine activity in postpubescent mammals; (b) nurturing or raising the mammal until postpuberty; (c) administering a pharmaceutical composition thought to have anti-excessive limbic dopamine activity; and (d) determining the mammal's response to the pharmaceutical composition. The anti-excessive limbic dopamine activity potential of the pharmaceutical composition is assessed by objectively measuring the mammal's behavior following administration of the pharmaceutical composition. The mammal's behavior is measured or monitored using standard tests well-known by those skilled in the art.

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Web site: http://www.delphion.com/details?pn=US05549884__ •

Schizophrenia Inventor(s): Horrobin; David F. (Guildford, GB2) Assignee(s): Scotia Holdings PLC (GB2) Patent Number: 5,516,800 Date filed: November 19, 1993 Abstract: The negative symptoms of schizophrenia and/or low cell membrane levels of EFAs may be treated with a combination of arachidonic acid and docosahexaenoic acid. Excerpt(s): Essential fatty acids (EFAs) are essential constituents of all cell membranes including those in the brain. There are two series of EFAs, the n-6 derived from linoleic acid and the n-3 derived from alpha-linolenic acid. Their metabolic pathways are shown in Table 1. Whereas in most cell membranes linoleic acid is an important component, this is not true of the brain. In the brain the two most important EFAs by concentration are arachidonic acid (AA) and docosahexaenoic acid (DHA). Dihomo-gamma-linolenic acid (DGLA) and eicosapentaenoic acid (EPA) are also important in the brain, but are present in much lower concentrations than AA and DHA. The other fatty acids of the n3 and n-6 series are minor components but could nevertheless play important functional roles. Schizophrenia is a common and serious psychiatric disorder affecting about 1% of the population. It is diagnosed according to criteria set out in Diagnostic Standards and Methods III--Revised (DSM III R), a manual developed by the American Psychiatric Association and accepted in most countries. Patients classified as schizophrenic under DSM III R may show a wide variety of signs and symptoms. There is discussion as to whether there are two or three separate sub-groups of patients within the overall DSM III R classification. Two of these sub-groups in particular, those with so-called "negative" and those with so-called "positive" symptoms have been much discussed. In the negative groups features of apathy, social withdrawal and a low level or absence of other symptoms predominate. The negative group may be clearly identified by using the negative component scores of standard psychiatric rating scales such as the Brief Psychiatric Rating Scale (BPRS) or by rating scales specifically designed to identify patients with the negative schizophrenia syndrome (sometimes also called the deficit syndrome). One very widely used negative scale is that devised by Andreasen et al. in Arch. Gen. Psychiatry (1982) Volume 39, pages 789-794, although others are available. Web site: http://www.delphion.com/details?pn=US05516800__

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Schizophrenia associated gene, proteins and biallelic markers Inventor(s): Cohen; Daniel (Neuilly-sur-Seine, FR), Essioux; Laurent (Paris, FR), Chumakov; Ilya (Vaux-le-Penil, FR), Blumenfeld; Marta (Paris, FR), Bougueleret; Lydie (Petit Lancy, CH) Assignee(s): Genset S.A. (FR) Patent Number: 6,555,316 Date filed: October 3, 2000 Abstract: The invention concerns the human g35030 gene, polynucleotides, polypeptides biallelic markers, and human chromosome 13q31-q33 biallelic markers. The invention

Patents 379

also concerns the association established between schizophrenia and bipolar disorder and the biallelic markers and the g35030 gene and nucleotide sequences. The invention provides means to identify compounds useful in the treatment of schizophrenia, bipolar disorder and related diseases, means to determine the predisposition of individuals to said disease as well as means for the disease diagnosis and prognosis. Excerpt(s): The invention concerns the human g35030 gene, and g35030 polynucleotides, polypeptides, as well as biallelic markers localized in the g35030 gene and in the human chromosome 13q31-q33 region. The invention also concerns the association established between schizophrenia and bipolar disorder and the biallelic markers and the g35030 gene and nucleotide sequences. The invention provides means to identify compounds useful in the treatment of schizophrenia, bipolar disorder and related diseases, means to determine the predisposition of individuals to said disease as well as means for the disease diagnosis and prognosis. Advances in the technological armamentarium available to basic and clinical investigators have enabled increasingly sophisticated studies of brain and nervous system function in health and disease. Numerous hypotheses both neurobiological and pharmacological have been advanced with respect to the neurochemical and genetic mechanisms involved in central nervous system (CNS) disorders, including psychiatric disorders and neurodegenerative diseases. However, CNS disorders have complex and poorly understood etiologies, as well as symptoms that are overlapping, poorly characterized, and difficult to measure. As a result future treatment regimes and drug development efforts will be required to be more sophisticated and focused on multigenic causes, and will need new assays to segment disease populations, and provide more accurate diagnostic and prognostic information on patients suffering from CNS disorders. Until recently, the identification of genes linked with detectable traits has relied mainly on a statistical approach called linkage analysis. Linkage analysis is based upon establishing a correlation between the transmission of genetic markers and that of a specific trait throughout generations within a family. Linkage analysis involves the study of families with multiple affected individuals and is useful in the detection of inherited-traits, which are caused by a single gene, or possibly a very small number of genes. But, linkage studies have proven difficult when applied to complex genetic traits. Most traits of medical relevance do not follow simple Mendelian monogenic inheritance. However, complex diseases often aggregate in families, which suggests that there is a genetic component to be found. Such complex traits are often due to the combined action of multiple genes as well as environmental factors. Such complex trait, include susceptibilities to heart disease, hypertension, diabetes, cancer and inflammatory diseases. Drug efficacy, response and tolerance/toxicity can also be considered as multifactoral traits involving a genetic component in the same way as complex diseases. Linkage analysis cannot be applied to the study of such traits for which no large informative families are available. Moreover, because of their low penetrance, such complex traits do not segregate in a clear-cut Mendelian manner as they are passed from one generation to the next. Attempts to map such diseases have been plagued by inconclusive results, demonstrating the need for more sophisticated genetic tools. Web site: http://www.delphion.com/details?pn=US06555316__

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Schizophrenia associated genes, proteins and biallelic markers Inventor(s): Chumakov; Ilya (Vaux-le-Penil, FR), Bougueleret; Lydie (Vanves, FR), Blumenfeld; Marta (Paris, FR), Bihain; Bernard (Encinitas, CA), Essioux; Laurent (Paris, FR), Cohen; Daniel (Neuilly-Sue-Seine, FR) Assignee(s): Genset (FR) Patent Number: 6,476,208 Date filed: March 30, 2000 Abstract: The invention concerns the human sbg1, g34665, sbg2, g35017 and g35018 genes, polynucleotides, polypeptides biallelic markers, and human chromosome 13q31q33 biallelic markers. The invention also concerns the association established between schizophrenia and bipolar disorder and the biallelic markers and the sbg1, g34665, sbg2, g35017 and g35018 genes and nucleotide sequences. The invention provides means to identify compounds useful in the treatment of schizophrenia, bipolar disorder and related diseases, means to determine the predisposition of individuals to said disease as well as means for the disease diagnosis and prognosis. Excerpt(s): The invention concerns the human sbg1, g34665, sbg2, g35017 and g35018 genes, polynucleotides, polypeptides biallelic markers, and human chromosome 13q31q33 biallelic markers. The invention also concerns the association established between schizophrenia and bipolar disorder and the biallelic markers and the sbg1, g34665, sbg2, g35017 and g35018 genes and nucleotide sequences. The invention provides means to identify compounds useful in the treatment of schizophrenia, bipolar disorder and related diseases, means to determine the predisposition of individuals to said disease as well as means for the disease diagnosis and prognosis. Advances in the technological armamentarium available to basic and clinical investigators have enabled increasingly sophisticated studies of brain and nervous system function in health and disease. Numerous hypotheses both neurobiological and pharmacological have been advanced with respect to the neurochemical and genetic mechanisms involved in central nervous system (CNS) disorders, including psychiatric disorders and neurodegenerative diseases. However, CNS disorders have complex and poorly understood etiologies, as well as symptoms that are overlapping, poorly characterized, and difficult to measure. As a result future treatment regimes and drug development efforts will be required to be more sophisticated and focused on multigenic causes, and will need new assays to segment disease populations, and provide more accurate diagnostic and prognostic information on patients suffering from CNS disorders. Neurotransmitters serve as signal transmitters throughout the body. Diseases that affect neurotransmission can therefore have serious consequences. For example, for over 30 years the leading theory to explain the biological basis of many psychiatric disorders such as depression has been the monoamine hypothesis. This theory proposes that depression is partially due to a deficiency in one of the three main biogenic monoamines, namely dopamine, norepinephrine and/or serotonin. Web site: http://www.delphion.com/details?pn=US06476208__

Patents 381

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Treating schizophrenia with essential fatty acid compositions Inventor(s): Horrobin; David F. (Guildford, GB2) Assignee(s): Efamol Holdings PLC (Guildford, GB2) Patent Number: 4,977,187 Date filed: June 1, 1989 Abstract: Method of, and preparations of medicaments for, treating schizophrenia and/or associated tardive dyskinesia by combining an essential fatty acid selected from GLA and higher N-6 series acids with an essential fatty acid selected from stearidonic acid and higher n-3 series acids in effective daily amounts of 10 mg and 50 g of each acid. Excerpt(s): The invention relates to essential fatty acid (EFA) compositions and treatments therewith. The acids are in the natural all-cis configuration. In the n-6 series, commonly used names are as follows: for the 18:2 and 18:3 (octadeca di- and trienoic) acids linoleic acid and gamma-linolenic acid (GLA); for the 20:3 and 20:4 (eicosatri- and tetraenoic) acids dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA); and for the 22:4 (docosa-tetraenoic) acid adrenic acid. In the n-3 series only alpha-linolenic acid (18:3) is commonly referred to by a non-systematic name but the name stearidonic acid does exist for the 18:4 n-3 acid. Initials are also used e.g. EPA for the 20:5 (eicosapentaenoic) acid. The brain is exceptionally rich in EFAs which make up over 20% of its dry weight and disorders in EFA metabolism may be expected to be reflected in mental disorders. We have previously discussed, for example in EP-A-0003407, a relation of schizophrenia to a deficit of 1-series prostaglandins (PGs) derived from dihomo-gamma-linolenic acid (DGLA). DGLA can be formed in the body from dietary linoleic acid via gamma-linolenic acid (GLA). Since the conversion of dietary linoleic acid to GLA may be restricted by a variety of factors we proposed that schizophrenia may be treated by GLA or DGLA alone or in combination with a variety of factors which may enhance the formation of 1-series PGs. Web site: http://www.delphion.com/details?pn=US04977187__

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Treatment for schizophrenia and other dopamine system dysfunctions Inventor(s): Nelson; Jodi A. (P.O. Box 200231, Denver, CO 80220) Assignee(s): none reported Patent Number: 6,232,326 Date filed: July 13, 1999 Abstract: Methods and compositions for the treatment of positive and negative symptoms of schizophrenia and tardive dyskinesia are provided. Compositions include 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and its analogs, and/or pyridinium ions thereof, administered in amounts sufficient to reduce dopamine levels in subcortical areas of the brain without causing symptoms of Parkinson's disease. One course of treatment can result in permanent or long-term amelioration of symptoms. Excerpt(s): Schizophrenia is a serious disease affecting one percent of the entire global population including about three million Americans. The annual cost of this disorder to the United Sates alone due to loss of employment, hospitalizations, medications, and the like exceeds 60 billion dollars annually and its toll in human suffering is shown by the ten to thirteen percent suicide rate for people who have the disease (American

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Psychiatric Association Public Information Online [1998] http://www.psych.org). A permanent or long-term cure for this tragic disease would be of tremendous value to the human race. Schizophrenia appears to be genetically transmitted. Concordance rates of monozygous twins has been shown to be 48 percent while for dizygous twins concordance was only 17 percent. Concordance for offspring having two schizophrenic parents was 46 percent, while for those with only one schizophrenic parent, concordance was 17 percent. The "schizophrenic" environment and being raised by a schizophrenic parent or step-parent also increases the likelihood of this illness manifesting in exposed children. (Rosenhan, D., and Seligman, M. [1995], Abnormal Psychology, 3d. Ed., Norton & Co, NY, p. 443). Finding an effective treatment could also decrease the prognosis of schizophrenia in children being raised by someone who suffers from this illness. The symptoms of schizophrenia can be grouped into three separate categories. These are (1) positive symptoms related to hallucinations and reality distortion; (2) disorganized symptoms characterized by attentional impairment and thought disorder; and (3) negative symptoms such as apathy and loss of verbal fluency (O'Donnell, P. O. and Grace, A. A. [1998], "Dysfunctions in multiple interrelated systems as the neurobiological bases of schizophrenic symptom clusters," Schizophrenia Bull., 24(2):267-283). A long history of research has demonstrated the efficacy of D2 receptor antagonism in the alleviation of positive and disorganized symptoms (Gray, J. A. [1998], "Integrating schizophrenia," Schizophrenia Bull., 24(2): 249-266). Persistence of negative symptoms often continues, even following neuroleptic treatment (Arndt, S. et al. [1995], "A longitudinal study of symptom dimensions in schizophrenia," Arch. Gen. Psychiatry, 52:352-359). The stability of negative symptoms has been, by some, attributed to the neuroleptic medications themselves (Carpenter, W. T. [1997], "The risk of medicationfree research," Schizophrenia Bull., 23(1): 11-18). Web site: http://www.delphion.com/details?pn=US06232326__ •

Treatment of negative and cognitive symptoms of schizophrenia with glycine and its precursors Inventor(s): Javitt; Daniel C. (3043 Johnson Ave., Riverdale, NY 10463), Zukin; Stephen R. (10105 Pasture Gate La., Columbia, MD 21044) Assignee(s): Zukin; Stephen R. (Columbia, MD), Javitt; Daniel C. (Riverdale, NY) Patent Number: 5,854,286 Date filed: December 6, 1996 Abstract: The amino acid glycine in an administered amount of above 0.4 g/Kg/day is used for treating symptoms of psychosis and of schizophrenia. Excerpt(s): This application claims benefit of provisional application 60/008,361 filed Dec. 7, 1995. For the past 30 years, the dopamine hypothesis has been the leading neurochemical model of schizophrenia. The dopamine hypothesis is based upon observations that amphetamine-like dopamine releasing agents induce a psychotomimetic state that closely resembles schizophrenia and that agents that block dopamine receptors (e.g., chlorpromazine, haloperidol) are clinically beneficial in the treatment of schizophrenia. The dopamine hypothesis posits that symptoms of schizophrenia reflect functional hyperactivity of brain dopaminergic symptoms, primarily in the mesolimbic and mesocortical brain regions. Despite its heuristic value, however, there are several limitations of the dopamine hypothesis that have contributed to limitations in clinical treatment in schizophrenia. First, amphetamine psychosis provides an accurate model only for the positive symptoms of schizophrenia (e.g.,

Patents 383

hyperactivity, hallucinations). In contrast, amphetamine administration does not lead to the development of negative symptoms (e.g., blunted affect, emotional withdrawal) or cognitive dysfunction similar to that observed in schizophrenia. A significant percentage (20-50%) of schizophrenic patients continue to show prominent negative symptoms and thought disorder despite optimal treatment with dopamine-blocking agents, indicating that new treatment approaches are necessary. Second, for the majority of schizophrenic patients no clear disturbances of dopaminergic neurotransmission have been demonstrated. Thus, to the extent that functional dopaminergic hyperactivity does exist, it may be secondary to a more fundamental disturbance in other neurotransmitter systems. Antidopaminergic treatment, therefore, while controlling symptoms may not address underlying pathophysiology. A potential direction for the development of a new treatment approach first became available in the late 1950's with the development of phencyclidine (PCP, "angel dust"). PCP was initially developed for use as a general anesthetic. In early clinical trials, PCP and related agents (e.g., ketamine) were found to induce psychotic symptoms that closely resembled those of schizophrenia. As opposed to amphetamine psychosis, PCP psychosis incorporated both negative and positive symptoms of schizophrenia. Moreover, PCP uniquely reproduced the type of cognitive dysfunction seen in schizophrenia. Mechanisms underlying PCP-induced psychosis remained largely unknown until the initial description of brain PCP receptors in 1979. Subsequent research in the early 1980s demonstrated that the PCP receptor constitutes a binding site located within the ion channel associated with N-methyl-D-aspartate (NMDA)-type glutamate receptors, and that PCP and related agents induce their psychotogenic effects by blocking NMDA receptor-mediated neurotransmission. This finding led to the suggestion (Reference 15; Reference 5) that endogenous dysfunction or dysregulation of NMDA receptor-mediated neurotransmission might contribute significantly to the etiology of schizophrenia, and, in particular, might lead to the expression of neuroleptic-resistant negative and cognitive symptoms. Further, it raised the possibility that medications that could potentiate NMDA receptor-mediated neurotransmission might be beneficial in the treatment of neuroleptic-resistant signs and symptoms of schizophrenia. Web site: http://www.delphion.com/details?pn=US05854286__ •

Treatment of negative and cognitive symptoms of schizophrenia with glycine uptake antagonists Inventor(s): Javitt; Daniel C. (3043 Johnson Ave., Riverdale, NY 10463) Assignee(s): none reported Patent Number: 5,837,730 Date filed: December 6, 1996 Abstract: A glycine uptake antagonist is administered for augmenting NMDA receptormediated neurotransmission treating symptoms of psychosis and of schizophrenia. Excerpt(s): This application claims benefit of provisional application 60/008,361 filed Dec. 7, 1995. For the past 30 years, the dopamine hypothesis has been the leading neurochemical model of schizophrenia. The dopamine hypothesis is based upon observations that amphetamine-like dopamine releasing agents induce a psychotomimetic state that closely resembles schizophrenia and that agents that block dopamine receptors (e.g., chlorpromazine, haloperidol) are clinically beneficial in the treatment of schizophrenia. The dopamine hypothesis posits that symptoms of schizophrenia reflect functional hyperactivity of brain dopaminergic symptoms,

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primarily in the mesolimbic and mesocortical brain regions. Despite its heuristic value, however, there are several limitations of the dopamine hypothesis that have contributed to limitations in clinical treatment in schizophrenia. First, amphetamine psychosis provides an accurate model only for the positive symptoms of schizophrenia (e.g., hyperactivity, hallucinations). In contrast, amphetamine administration does not lead to the development of negative symptoms (e.g., blunted affect, emotional withdrawal) or cognitive dysfunction similar to that observed in schizophrenia. A significant percentage (20-50%) of schizophrenic patients continue to show prominent negative symptoms and thought disorder despite optimal treatment with dopamine-blocking agents, indicating that new treatment approaches are necessary. Second, for the majority of schizophrenic patients no clear disturbances of dopaminergic neurotransmission have been demonstrated. Thus, to the extent that functional dopaminergic hyperactivity does exist, it may be secondary to a more fundamental disturbance in other neurotransmitter systems. Antidopaminergic treatment, therefore, while controlling symptoms may not address underlying pathophysiology. A potential direction for the development of a new treatment approach first became available in the late 1950's with the development of phencyclidine (PCP, "angel dust"). PCP was initially developed for use as a general anesthetic. In early clinical trials, PCP and related agents (e.g., ketamine) were found to induce psychotic symptoms that closely resembled those of schizophrenia. As opposed to amphetamine psychosis, PCP psychosis incorporated both negative and positive symptoms of schizophrenia. Moreover, PCP uniquely reproduced the type of cognitive dysfunction seen in schizophrenia. Mechanisms underlying PCP-induced psychosis remained largely unknown until the initial description of brain PCP receptors in 1979. Subsequent research in the early 1980s demonstrated that the PCP receptor constitutes a binding site located within the ion channel associated with N-methyl-D-aspartate (NMDA)-type glutamate receptors, and that PCP and related agents induce their psychotogenic effects by blocking NMDA receptor-mediated neurotransmission. This finding led to the suggestion (Reference 14; Reference 5) that endogenous dysfunction or dysregulation of NMDA receptor-mediated neurotransmission might contribute significantly to the etiology of schizophrenia, and, in particular, might lead to the expression of neuroleptic-resistant negative and cognitive symptoms. Further, it raised the possibility that medications that could potentiate NMDA receptor-mediated neurotransmission might be beneficial in the treatment of neuroleptic-resistant signs and symptoms of schizophrenia. Web site: http://www.delphion.com/details?pn=US05837730__ •

Treatment of schizophrenia and psychosis Inventor(s): Sams-Dodd; Frank (Barcelona, ES), Arnt; Jorn (Solrod Strand, DK) Assignee(s): H. Lundbeck A/S (Valby-Copenhagen, DK) Patent Number: 6,297,262 Date filed: January 14, 2000 Abstract: The compound 5-(2-ethyl-2H-tetrazol-5-yl)-1,2,3,6-tetrahydro-1methylpyridine has shown effects on models of psychosis, schizophrenia and schizophreniform diseases and is useful for the manufacture of a pharmaceutical preparation for the treatment of such diseases. Excerpt(s): The present invention relates to the use of 5-(2-ethyl-2H-tetrazol-5-yl)-1,2,3,6tetrahydro-1-methylpyridine for the treatment of psychosis. The structure-activity relationship of this subclass was described by Moltzen et al., J. Med. Chem. 1994, 37,

Patents 385

4085-4099. One of the compounds, i.e. 5-(2-ethyl-2H-tetrazol-5-yl)-1,2,3,6-tetrahydro-1methylpyridine has been reported to be selective for muscarinic receptors with a several fold higher affinity for M.sub.1 than for M.sub.2 and M.sub.3 receptors (Subtypes of Muscarinic Receptors, The Sixth International Symposium, Nov. 9-12, 1994, Fort Lauderdale). Functionally, it has been described to behave as a partial agonist at M.sub.1 receptors and an antagonist at M.sub.2 and M.sub.3 receptors. Furthermore, the only prominent in vivo effect reported was effect on spatial memory acquisition in young and aged rats, respectively. Recently, the compound was disclosed to show relieving effects after traumatic brain injury, WO 97/17074. A class of compounds previously reported to show muscarinic effects were described to be useful in the treatment of schizophrenia, cf. WO 9505174 A1 and WO 95/05379. Web site: http://www.delphion.com/details?pn=US06297262__ •

Treatment of schizophrenia with ampakines and neuroleptics Inventor(s): Lynch; Gary S. (Irvine, CA), Johnson; Steven A. (Costa Mesa, CA), Rogers; Gary A. (Santa Barbara, CA) Assignee(s): Cortex Pharmaceuticals, Inc. (Irvine, CA), The Regents of the University of California (Oakland, CA) Patent Number: 6,166,008 Date filed: October 26, 1998 Abstract: This invention relates to treatment of schizophrenia and related psychotic disorders, including enhancement of receptor functioning in synapses in brain networks responsible for higher order behaviors. In a particular aspect, the invention relates to methods for the use of AMPA receptor up-modulators in conjunction with antipsychotics for the treatment of schizophrenia. Kits containing the compositions in appropriate form for administration are also provided. Excerpt(s): This invention relates to treatment of schizophrenia and other psychotic disorders. This invention especially relates to treatment of schizophrenia and other psychotic disorders by enhancement of receptor functioning in synapses in brain networks responsible for higher order behaviors. In particular, the invention provides methods for the use of AMPA receptor up-modulators in conjunction with antipsychotics for the treatment of schizophrenia. The release of glutamate at synapses at many sites in mammalian forebrain stimulates two classes of postsynaptic receptors. These classes are usually referred to as.alpha.-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/quisqualate and N-methyl-D-aspartic acid (NMDA) receptors. AMPA/quisqualate receptors mediate a voltage-independent fast excitatory postsynaptic current (the fast epsc) whereas NMDA receptors generate a voltage-dependent, slow excitatory current. Studies carried out in slices of hippocampus or cortex indicate that the AMPA receptor-mediated fast epsc is by far the dominant component at most glutamatergic synapses under most circumstances. Schizophrenia is a chronic disease that is characterized by positive (hallucinations, delusions), negative (social withdrawal, flattened affect) and cognitive (formal thought disorder, executive memory dysfunction) symptoms. The dopamine hypothesis, that schizophrenia stems from excessive midbrain dopamine transmission, originated from studies with neuroleptics that revealed correlations between clinical efficacy, effects on dopamine metabolism (Carlsson & Lindqvist, Acta Pharmacol. Toxicol. 20:140-144, 1967) and binding to dopamine receptors (Creese et al., Science 192:481-482, 1976). In addition, drugs that increase synaptic dopamine concentration, (e.g., amphetamines) produce aberrant,

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stereotyped behavior in animals (WT McKinney, in SC Shultz and CA Tamminga (eds) Schizophrenia: Scientific Progress. Oxford University Press, New York, pp 141-154, 1989) and schizophrenia-like symptoms in humans (Snyder, Am. J Psychol. 130:61-67, 1976). Web site: http://www.delphion.com/details?pn=US06166008__ •

Use of a compound for the treatment of schizophrenia Inventor(s): Musch; Bruno (Paris, FR), Maillard; Francoise (La Celle Saint Cloud, FR), Gueremy; Claude (Houilles, FR) Assignee(s): Rhone-Poulenc Sante (Antony, FR) Patent Number: 4,882,345 Date filed: August 22, 1988 Abstract: 2-amino-6-(trifluoromethoxy)benzothiazole or a pharmaceutically accpetable salt thereof is useful for the treatment of schizophrenia, particularly the negative forms thereof. Excerpt(s): The present invention relates to the application of 2-amino-6(trifluoromethoxy)benzothiazole or a pharmaceutically acceptable salt thereof for obtaining a medicinal product intended for the treatment of schizophrenia, and more especially its negative forms. It is known from European Pat. No. 50,551 that 2-amino-6(trifluoromethoxy)benzothiazole is useful as an anticonvulsant, anxiolytic and hypnotic medicinal product. It has now been found that 2-amino-6(trifluoromethoxy)benzothiazole or a pharmaceutically acceptable salt thereof is useful in the treatment of schizophrenia, and more especially the negative forms of schizophrenia. Web site: http://www.delphion.com/details?pn=US04882345__

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Use of NK-1 receptors antagonists for treating schizophrenic disorders Inventor(s): Williams; Brian John (Great Dunmow, GB), Curtis; Neil Roy (Puckeridge, GB), Seward; Eileen May (Bishops Stortford, GB), Kulagowski; Janusz Jozef (Sawbridgeworth, GB), Jackson; Philip Stephen (Harlow, GB), Hollingworth; Gregory John (Basildon, GB), Elliott; Jason Matthew (Felsted, GB), Rupniak; Nadia Melanie (Bishops Stortford, GB), Baker; Raymond (Dursley, GB), Swain; Christopher John (Duxford, GB), Harrison; Timothy (Great Dunmow, GB) Assignee(s): Merck Sharp & Dohme Ltd. (Hoddesdon, GB) Patent Number: 6,100,256 Date filed: June 11, 1998 Abstract: The present invention provides a method for the treatment or prevention of schizophrenic disorders using an orally active, long acting, CNS-penetrant NK-1 receptor antagonist and pharmaceutical compositions comprising such a NK-1 receptor antagonist. Excerpt(s): This invention relates to the treatment or prevention of certain schizophrenic disorders by the administration of a specific class of NK-1 receptor antagonists. The essential features of schizophrenia are a mixture of characteristic signs and symptoms

Patents 387

(both positive and negative) which are present in an individual for a significant portion of time over at least one month. The so-called "active-phase" symptoms include delusions, hallucinations, disorganised speech, disorganised or catatonic behaviour and negative symptoms (e.g. affective flattening, alogia and avolition). Some patients have only a single episode of the illness, but most have either recurrent episodes or chronic illness. The care of schizophrenic patients is a major part of the work of psychiatrists. The long-term care of schizophrenic patients is complicated, however, generally symptoms can at least be kept under control if patients with chronic schizophrenia receive long-term treatment with an antipsychotic drug. Frequently, schizophrenic symptoms cannot be controlled without invoking extrapyramidal side-effects. Consequently, antiparkinsonian drugs may also be prescribed to reduce these sideeffects, however, the use of anticholinergic drugs may actually increase the risk of tardive dyskinesia (a late and sometimes irreversible side-effect of prolonged treatment with antipyschotic drugs). Web site: http://www.delphion.com/details?pn=US06100256__ •

Use of sulbutiamine in the treatment of Parkinson's disease, schizophrenia, alcoholism, and dysthymia Inventor(s): Ollat; Helene (Nesle la Gilberde, FR), Le Ridant; Alain (Neuilly sur Seine, FR), Perret; Laurent (Paris, FR) Assignee(s): Adir et Compagnie (Courbevoie, FR) Patent Number: 5,863,925 Date filed: October 3, 1997 Abstract: The invention relates to the use of sulbutiamine and pharmaceutical compositions thereof for the treatment of Parkinson's Disease, Schizophrenia, alcoholism, and dysthymia. Excerpt(s): The present invention relates to the use of sulbutiamine and pharmaceutical compositions thereof for the treatment of certain psychomotor and psychointellectual disorders, characterized by the delay, the slowing and the depression of behavioral and intellectual responses demanding the strategic mobilization of percepts and mental concepts. These disorders are observed in particular in Parkinson's patients, deficient schizophrenics, alcoholics, major depressives and dysthymics. Sulbutiamine is an active principle which is already known and described in the literature. The special medicament patent 5921 M has described this product as an agent having the activity of vitamin B.sub.1, capable of causing a raised vitamin B.sub.1 blood level and able to exert effects with respect to all the symptoms of B.sub.1 avitaminosis. The special medicament patent 5921 M likewise mentions that for these therapeutic ends, the product is used in the form of tablets containing 5 to 50 mg of product per unit dose. Web site: http://www.delphion.com/details?pn=US05863925__

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Patent Applications on Schizophrenia As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to schizophrenia: •

Animal showing schizophrenia-like abnormality in cognitive behaviors and method of constructing the same Inventor(s): Nawa, Hiroyuki; (Niigata City, JP), Futamura, Takashi; (Niigata City, JP) Correspondence: Oliff & Berridge; PO Box 19928; Alexandria; VA; 22320; US Patent Application Number: 20030056232 Date filed: September 6, 2002 Abstract: To provide a an animal with schizophrenic sensorimotor and behavioral abnormalities, a specific protein factor inhibiting development of brain function is administrated to a juvenile animal in the stage of its development and an animal exhibiting sensorimotor and behavioral abnormalities is prepared. As the sensorimotor and behavioral abnormalities observed in the animal of the present invention is very similar to schizophrenia, the animal is useful for development of an anti-schizophrenic medicine and a diagnostic agent for schizophrenia. Excerpt(s): This invention relates to schizophrenic model animal with sensorimotor and behavioral abnormalities and a method for preparing the same. Schizophrenia is a very serious chronic disease which appears 0.7-1.0% persons of the population. Moreover, in Japan, hundreds of thousand of patients are admitted to a hospital for a long term because of this disease. The main symptom of this disease is accompanied with various psychological disorders, including positive symptoms such as delusion, hallucination and auditory hallucination, in addition to negative symptoms such as withdrawal from society and depression. At present, the cause of occurrence of this disease and the biological pathology of this disease are not elucidated. Schizophrenia occurs from adolescence to manhood with characteristic symptoms in perception, cerebration, emotion and behavior. In many cases, this disease progresses chronically and the patients suffer from various difficulties for adaptation to society. With regard to schizophrenia, there are classifications of positive symptoms (hallucination, delusion, diminished cerebration, tension, curious behavior, etc.) and negative symptoms (flattening in motion, decrease in will and social withdrawal, etc.). Socially, because of the specific pathology of this disease, establishment of a consistent and comprehensive treatment system against this disease, such as detection of occurrence, treatment and social reversion at early stage, and prevention of recurrence, has been desired. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

10

This has been a common practice outside the United States prior to December 2000.

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ANTICONVULSANT DERIVATIVES USEFUL IN TREATING SCHIZOPHRENIA Inventor(s): KAMMEN, DANIEL P. VAN; (NESHANIC STATION, NJ) Correspondence: AUDLEY A CIAMPORCERO JR; ONE JOHNSON & JOHNSON PLAZA; NEW BRUNSWICK; NJ; 089337003 Patent Application Number: 20020006908 Date filed: November 5, 1999 Abstract: Anticonvulsant derivatives useful in treating schizophrenia are disclosed. Excerpt(s): are structurally novel antiepileptic compounds that are highly effective anticonvulsants in animal tests (Maryanoff, B. E, Nortey, S. O., Gardocki, J. F., Shank, R. P. and Dodgson, S. P. J Med. Chem. 30, 880-887, 1987; Maryanoff, B. E., Costanzo, M. J., Shank, R. P., Schupsky, J. J., Ortegon, M. E., and Vaught J. L. Bioorganic & Medicinal Chemistry Letters 3, 2653-2656, 1993). These compounds are covered by U.S. Pat. No. 4,513,006. One of these compounds 2,3:4,5-bis-O-(1-methylethylidene)-.bet- a.-Dfructopyranose sulfamate known as topiramate has been demonstrated in clinical trials of human epilepsy to be effective as adjunctive therapy or as monotherapy in treating simple and complex partial seizures and secondarily generalized seizures (E. FAUGHT, B. J. WILDER, R. E. RAMSEY, R. A. REIFE, L D. KRAMER, G. W. PLEDGER, R. M. KARIM et. al., Epilepsia 36 (S4) 33, 1995; S. K. SACHDEO, R. C. SACHDEO, R. A. REIFE, P. LIM and G. PLEDGER, Epilepsia 36 (S4) 33, 1995), and is currently marketed for the treatment of simple and complex partial seizure epilepsy with or without secondary generalized seizures in approximately twenty countries including the United States, and applications for regulatory approval are presently pending in several additional countries throughout the world. Compounds of Formula I were initially found to possess anticonvulsant activity in the traditional maximal electroshock seizure (MES) test in mice (SHANK, R. P., GARDOCKI, J. F., VAUGHT, J. L., DAVIS, C. B., SCHUPSKY, J. J., RAFFA, R. B., DODGSON, S. J., NORTEY, S. O., and MARYANOFF, B. E., Epilepsia 35 450-460, 1994). Subsequent studies revealed that Compounds of Formula I were also highly effective in the MES test in rats. More recently topiramate was found to effectively block seizures in several rodent models of epilepsy (J. NAKAMURA, S. TAMURA, T. KANDA, A. ISHII, K. ISHIHARA, T. SERIKAWA, J. YAMADA, and M. SASA, Eur. J. Pharmacol. 254 83-89, 1994), and in an animal model of kindled epilepsy (A. WAUQUIER and S. ZHOU, Epilepsy Res. 24, 73-77, 1996). Preclinical studies on topiramate have revealed previously unrecognized pharmacological properties which suggest that topiramate will be effective in treating schizophrenia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Association between schizophrenia and a two-marker haplotype near PILB gene Inventor(s): Sklar, Pamela; (Brookline, MA), Wildenauer, Dieter; (Bonn, DE), Schwab, Sibylle; (Bonn, DE), Lander, Eric S. (Cambridge, MA) Correspondence: HAMILTON, BROOK, SMITH & REYNOLDS, P.C. 530 VIRGINIA ROAD; P.O. BOX 9133; CONCORD; MA; 01742-9133; US Patent Application Number: 20030008301 Date filed: February 1, 2002 Abstract: Methods for diagnosing and treating neuropsychiatric disorders, especially schizophrenia, and methods for identifying compounds for use in the diagnosis and

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treatment of neuropsychiatric disorders are disclosed. Also disclosed are novel compounds and pharmaceutical compositions for use in the diagnosis and treatment of neuropsychiatric disorders such as schizophrenia. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/265,910 filed Feb. 2, 2001, the contents of which are incorporated by reference in their entirety. Neuropsychiatric disorders, such as schizophrenia, attention deficit disorders, schizoaffective disorders, bipolar disorders and unipolar disorders, differ from neurological disorders in that anatomical or biochemical pathologies are readily detectable for the latter but not the former. Largely as a result of this difference, drugs which have been used to treat individuals with neuropsychiatric disorders, including lithium salts, valproic acid and carbamazepine, have not been predictably effective in treatment regimens across a variety of patients. Treatment regimens are further complicated by the fact that clinical diagnosis currently relies on clinical observation and subjective reports. Identification of the anatomical or biochemical defects which result in neuropsychiatric disorders is needed in order to effectively distinguish between disorders and to allow the design and administration of effective therapeutics for these disorders. Accordingly, the invention relates to methods for diagnosing and treating neuropsychiatric disorders, especially schizophrenia, and to methods for identifying compounds for use in the diagnosis and treatment of neuropsychiatric disorders. The invention further relates to novel compounds and pharmaceutical compositions for use in the diagnosis and treatment of neuropsychiatric disorders. In a preferred embodiment, the neuropsychiatric disorder is schizophrenia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods for the diagnosis and treatment of neuropsychiatric disorders, including schizophrenia Inventor(s): Barnes, Glenn T. (Haverhill, MA), Barrington-Martin, Rory; (Wayland, MA), Meyer, Joanne M. (Framingham, MA), Parker, Alexander; (Natick, MA) Correspondence: DARBY & DARBY P.C. 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20030054345 Date filed: January 24, 2001 Abstract: This invention relates to methods and compositions for diagnosing and treating neuropsychiatric disorders, such as schizophrenia, schizoaffective disorder, bipolar affective disorder, unipolar affective disorder and adolescent conduct disorder. In particular, the invention provides novel variants of DISC1 and DISC2 nucleic acid sequences, as well as novel DISC1 polypeptides encoded by these variant nucleic acid sequences. The variant DISC1 and DISC2 nucleic acid sequences provided by this invention, and the variant gene products they encode, are ones that correlate with the presence of a neuropsychiatric disorder in individuals. The invention, therefore, also provides methods and compositions for using the variant nucleic acids and polypeptides to diagnose and treat such neuropsychiatric disorders in individuals. Excerpt(s): Numerous references are cited and discussed in the description of the invention, including patents, patent applications and various publications, as well as biological sequences (e.g., nucleic acid and polypeptide sequences) that are publicly available through various databases such as the GenBank database. The citation and/or discussion of such references is provided merely to clarify the description of the present invention and is not an admission that any such reference is "prior art" to the invention

Patents 391

described herein. All references cited and discussed in this specification are incorporated herein by reference in their entirety and to the same extent as if each reference was individually incorporated by reference. The present invention relates to compositions and methods which may be used to diagnose and treat neuropsychiatric disorders, including schizophrenia, schizoaffective disorder, bipolar disorder, unipolar affective disorder and adolescent conduct disorder. The invention also relates to particular genes, referred to as DISC1 and DISC2, and their gene products. These genes are demonstrated herein to be associated with neuropsychiatric disorders (including schizophrenia, schizoaffective disorder, bipolar disorder, unipolar affective disorder and adolescent conduct disorder) and are therefore useful in the methods of the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Diagnostic kit for schizophrenia Inventor(s): Nawa, Hiroyuki; (Niigata City, JP), Futamura, Takashi; (Niigata City, JP), Asama, Koue; (Sanjo City, JP), Someya, Toshiyuki; (Niigata City, JP) Correspondence: Oliff & Berridge; PO Box 19928; Alexandria; VA; 22320; US Patent Application Number: 20030077678 Date filed: September 9, 2002 Abstract: According to the present invention, a diagnostic kit for schizophrenia was provided and the diagnostic kit comprises measurement of serum epidermal growth factor content using anti-epidermal growth factor antibody. The diagnosis kit according to this invention is useful for objective diagnosis of schizophrenia. Excerpt(s): This invention relates to a diagnostic kit for schizophrenia. More specifically, this invention relates to a diagnostic kit for schizophrenia comprising an antibody against epidermal growth factor (EGF). Schizophrenia appears from adolescence to manhood with characteristic symptoms in perception, cerebration, emotion and behavior. In many cases, the progression of this disease is a chronic process accompanied with various difficulties in social adaptation. With regard to schizophrenia, there are classifications of positive symptoms (hallucination, delusion, diminished cerebration, tension and curious behavior, etc.) and negative symptoms (flattening in emotion, decrease in will and social withdrawal, etc.). As stated above, the present diagnostics of schizophrenia is defined only by psychological symptoms of a patient. Then it is markedly affected by subjective view of a doctor who conducts the diagnosis. Therefore, problems on the objectivity of the diagnosis have been recited many times. Socially, because of the specific pathology of this disease, establishment of a consistent and comprehensive treatment system against this disease, such as early detection of occurrence, treatment and social reversion at early stage, and prevention of recurrence, has been desired. For treatment of schizophrenia, medical therapy (in many cases, long term administration for years) is indispensable. Then, phenothiazine, thioxanthene derivatives, butyrophenone derivatives, benzamide derivatives, and serotonine dopamine antagonists have been administered to patients. If there are some biochemical alterations, which are regulated by genetics, involved in schizophrenia, how it can be proved? In the case of the abnormality in an enzyme existing in the whole body, such as congenital abnormality in amino acid metabolism or carbohydrate metabolism, identification of such enzyme can be performed easily using blood or urine. From the level of the amino acid or the level of its metabolite in blood, the enzyme responsible for the abnormality can be identified. Moreover, using blood cells or

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cultured tissues of skin or using materials from autopsy, this abnormality in the enzyme can be proved in many cases. Plenty of researches have been performed investigations on body fluids of schizophrenic patients, but any apparent abnormality has not yet been found until now. There were some reports describing that a certain substance was specifically found out in blood or urine of schizophrenic patent. However, almost all of them were denied when trace experiments were repeated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Human schizophrenia gene Inventor(s): Andresson, Thorkell; (Reykjavik, IS), Gurney, Mark; (E. Grand Rapids, MI), Stefansson, Hreinn; (Gardabaer, IS), Steinthorsdottir, Valgerdur; (Reykjavik, IS), Gulcher, Jeffrey R. (Chicago, IL) Correspondence: HAMILTON, BROOK, SMITH & REYNOLDS, P.C. 530 VIRGINIA ROAD; P.O. BOX 9133; CONCORD; MA; 01742-9133; US Patent Application Number: 20020165144 Date filed: September 5, 2001 Abstract: Nucleic acids comprising the neuregulin 1 gene (NRG1) and encoding NRG1 polypeptides are disclosed. Also described are related nucleic acids encoding NRG1 polypeptides; NRG1 polypeptides; antibodies that bind to NRG1 polypeptides; methods of diagnosis of susceptibility to schizophrenia; assays for agents that alter the activity of NRG1 polypeptide or which identify NRG1 binding agents, and the agents or binding agents identified by the assays; NRG1 therapeutic agents, including the NRG1 nucleic acids, NRG1 polypeptides, or agents that alter the activity of an NRG1 polypeptides; pharmaceutical compositions comprising the NRG1 therapeutic agents; as well as methods of therapy of schizophrenia. Excerpt(s): This application is a continuation-in-part of International Application No. PCT/US01/06377, which designated the United States and was filed on Feb. 28, 2001, published in English, and is a continuation-in-part of U.S. application Ser. No. 09/795,668 filed Feb. 28, 2001, which is a continuation-in-part of U.S. application Ser. No. 09/515,716, filed Feb. 28, 2000. The entire teachings of the above applications are incorporated herein by reference. Schizophrenia is a devastating form of psychopathology, with a lifetime prevalence worldwide of 0.5%-1%. Twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (see, e.g., Tsuang, M. T. et al., Schizophr. Res. 4(2):157-71 (1991); Tienari, P. J. and Wynne, L. C., Ann. Med. 26(4):233-7 (1994); Franzek, E. and Beckmann, H., Am. J. Psychiatry 155(1):76-83 (1998); Tsuang, M. T., J. Biomed. Sci. 5(1):28-30 (1998)). Among first-degree relatives, the risk has been reported to vary from 6% in parents, to 10% in siblings, and to 13% in children of schizophrenic individuals; if one of the parents is also schizophrenic, the risk to siblings increases to 17%, and children of two schizophrenics have a risk of 46% of developing the illness (McGue, M. and Gottesmann, I. I., Eur. Arch. Psychiatry Clin. Neurosci 240:174-181 (1991); see also, e.g., Lim, L. C. and Sim, L. P., Singapore Med. J. 33(6):645-7 (1992)). The mode of transmission, however, remains uncertain. Reports of suggestive linkage to several loci have been published, including loci on chromosomes 3, 5, 6, 8, 10, 13, 20, 22 and the X chromosome (see, e.g., for chromosomes 3p and 8p, Pulver, A. E., et al., Am. J. Med. Genet. 60(4):252-60 (1995); for chromosomes 5q, 6p and 8p, Kendler, K. S. et al., Am. J. Med. Genet. 88(1):29-33 (1999); for chromosomes 5q, 6p, 8p, 20p and 22q, Hovatta, I. et al., Mol. Psychiatry 3(5):452-7 (1998); for chromosome 6p, Schwab, S. G. et al., Nat. Genet. 11(3):325-7 (1995),

Patents 393

Brzustowicz, L. M. et al., Am. J. Hum. Genet. 61(6):1388-96 (1997) and Cao, Q. et al., Genomics 43(1):1-8 (1997); for chromosomes 6 and 8, Straub, R. E. et al, Cold Spring Harbor Symp. Quant. Biol 61I:823-33 (1996); for chromosome 8, Kendler, K S. et al., Am. J. Psychiatry 153(12):1534-40 (1996); for chromosome 10, Straub, R. E. et al., Am. J. Med. Genet. 81(4):296-301 (1998) and Schwab, S. G. et al, Am. J. Med. Genet. 81(4):302-307 (1998); for chromosome 13, Lin, M. W. et al., Psyciatr. Genet. 5(3):117-26 (1995); Lin, M. W. et al., Hum. Genet. 99(3):417-420 (1997) and Blouin, J. L. et al., Nat. Genet. 20(1):70-73 (1993) (8 and 13); for chromosome 22, Gill, M. et al., Am. J. Med. Genet. 67(1):40-45 (1996) and Bassett, A. S. et al., Am. J. Med. Genet. 81(4):328-37 (1998); and for the X chromosome, Milunsky, J. et al., Clin. Genet. 55(6):455-60 (1999)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for diagnosing schizophrenia using objective indices Inventor(s): Takahashi, Hitoshi; (Niigata-shi, JP), Iritani, Shuji; (Tokyo, JP), Nawa, Hiroyuki; (Niigata-shi, JP) Correspondence: OBLON, SPIVAK, MCCLELLAND, MAIER & NEUSTADT, P.C. 1940 DUKE STREET; ALEXANDRIA; VA; 22314; US Patent Application Number: 20030157548 Date filed: March 17, 2003 Abstract: Provided is a method for diagnosing whether or not a subject suffers from schizophrenia, comprising the steps of taking a sample containing nucleic acid and/or protein from the subject, quantifying nucleic acid and/or protein corresponding to at least one gene selected from the group consisting of genes listed in Table 1 below, fragments thereof, and complementary nucleic acid thereof, and diagnosing whether or not the subject suffers from schizophrenia by using a quantitative value of at least one protein, a fragment thereof or the nucleic acid. Excerpt(s): This application is based upon and claims the benefit of priority from the prior Japanese Patent Application No. 2000-061775, filed Mar. 7, 2000, the entire contents of which are incorporated herein by reference. The present invention relates to a method of objectively diagnosing schizophrenia by using an expression amount of nucleic acid encoding defined protein (index gene) as an index. Schizophrenia is a mental disorder. About 0.8% of the population suffers from schizophrenia during their youth. Once people suffer from schizophrenia, it takes a long time to recover from it. Public loss caused by schizophrenia comes to be immeasurably large. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of simultaneously treating sensory auditory gating deficit and associated psychosis in schizophrenia and bipolar disorder patients with mania Inventor(s): Guidotti, Alessandro; (Chicago, IL), Auta, James; (Chicago, IL), Costa, Erminio; (Chicago, IL), Davis, John M. (Chicago, IL), Tueting, Patricia; (Chicago, IL) Correspondence: LADAS & PARRY; 26 WEST 61ST STREET; NEW YORK; NY; 10023; US Patent Application Number: 20030119821 Date filed: September 20, 2002

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Abstract: Schizophrenia and bipolar disorders with mania may be treated by imidazenil or other benzodiazepine-3-carboxamide derviatives. Excerpt(s): The present invention relates to the treatment of patients suffering from schzophrenia and patients suffering from bipolar disorders with mania. GABAergic inhibition is increasingly considered one of the most important factors in controlling the mode of operation of thalamo-cortical and re-entrant cortico-thalamic pathways as well as of the afferent septal-hippocampus and of the re-entrant hippocampal-septal glutamatergic pathways that are substrates for the regulation of complex brain functions, including normal sensory, gating, cognition, vigilance, spatial orientation, volition, and consciousness. These functions are altered in schizophrenia and bipolar disorder patients with mania. Thus, one may attribute the appearance of psychotic symptoms in these mental disorders to a deficit in GABAergic modulation in critical cortico-thalamic and cortico-hippocampal brain circuits. Indeed, schizophrenia and bipolar disorder patients with mania who manifest an auditory gating deficit and who suffer from other associated problems, such as auditory hallucinations, cognitive impairment, delusions, and defects of volition (lack of motivation, flat affect, and social withdrawal), express downregulation of GABAergic synthesis and function in their cortical, thalamic, septal, and hippocampal circuits (Guidotti et al., 2000). The neuroanatomical and neurochemical abnormalities of the GABAergic system in postmortem brain of patients with schizophrenia and bipolar disorder with mania can be summarized as follows: 1) decreased GABA release and uptake (Reynolds et al., 1990; Sherman et al., 1991; Simpson et al., 1998); 2) increased denervation-dependent GABA.sub.A receptor density measured by 3H-muscimol binding, particularly in layer II of the prefrontal cortex (PFC) and in superficial layers of other adjacent cortical areas (Benes et al., 1992; Benes, 2000); 3) increased expression of the al GABA.sub.A receptor subunit mRNA in the PFC (Impagnatiello et al., 1998); 4) a dorsolateral PFC decrease of presynaptic GABA transporter-1-positive cartridges in GABAergic axon terminals of chandelier cells impinging on the initial segments of pyramidal axons (Woo et al., 1998), and decreased GAD.sub.67 expression (this enzyme is important in the synthesis of GABA and is one of the two molecular forms of glutamic acid decarboxylase expressed in GABAergic neurons, the other being GAD.sub.65) (Akbarian et al., 1995; Impagnatiello et al., 1998; Benes 2000; Bunney and Bunney, 2000; Guidotti et al., 2000; Volk et al., 2000), which taken together suggest that GABAergic function may be downregulated; and 5) an altered cortical distribution of nicotinamide adenine dinucleotide phosphate-positive GABAergic cells (Akbarian et al., 1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of treating schizophrenia Inventor(s): Blech, Stefan M. (Warthausen, DE), Winter, Karin; (Gau-Algesheim, DE), Weiser, Thomas; (Nieder-Olm, DE), Ceci, Angelo; (Biberach, DE) Correspondence: BOEHRINGER INGELHEIM CORPORATION; 900 RIDGEBURY ROAD; P. O. BOX 368; RIDGEFIELD; CT; 06877; US Patent Application Number: 20030158183 Date filed: January 6, 2003 Abstract: A method for treating schizophrenia which comprises administering a compound of general formula (I) 1

Patents 395

Excerpt(s): This application is a division of Ser. No. 09/774,864, filed Jan. 31, 2001, now allowed. The present invention relates to a method of treating schizophrenia by administration of compounds of the Formula I, given below. optionally in the form of the various enantiomers and diastereomers thereof, as well as the pharmacologically acceptable salts thereof. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and compositions for diagnosing and treating neuropsychiatric disorders such as schizophrenia Inventor(s): Meyer, Joanne M. (Framingham, MA), Barrington-Martin, Rory; (Wayland, MA), Parker, Alexander; (Natisk, MA) Correspondence: DARBY & DARBY P.C. POST OFFICE BOX 5257; NEW YORK; NY; 10150-5257; US Patent Application Number: 20030092019 Date filed: April 19, 2002 Abstract: This invention relates to methods and compositions for diagnosing and treating neuropsychiatric disorders, such as schizophrenia, schizoaffective disorder, bipolar affective disorder, unipolar affective disorder and adolescent conduct disorder. In particular, the invention provides novel variants of CADPKL nucleic acid sequences, as well as novel CADPKL polypeptides encoded by these variant sequences. The variant CADPKL nucleic acid sequences provided by this invention, as well as the variant polypeptides they encode are ones that statistically correlate with the presence of a neuropsychiatric disorder in individuals. The invention therefore also provides methods and compositions for using these variant nucleic acids and polypeptides to diagnose and treat such neuropsychiatric disorders. Excerpt(s): This is a divisional of U.S. patent application Ser. No. 09/757,300, filed Jan. 9, 2001 and incorporated herein by reference, in its entirety. The present invention relates to compositions and methods which may be used to diagnose and treat neuropsychiatric disorders, including schizophrenia, schizoaffective disorder, bipolar disorder, unipolar affective disorder and adolescent conduct disorder. In particular, the invention relates to a particular gene, known as the Calcium/Calmodium dependent protein kinase like gene or CADPKL, and its gene products. The CADPKL gene is demonstrated herein to be associated with neuropsychiatric disorders (including schizophrenia, schizoaffective disorder, bipolar disorder, unipolar affective disorder and adolescent conduct disorder). The invention therefore relates to novel use of the CADPKL gene, its gene products and antibodies thereto for diagnosing and treating such disorders. The invention further relates to particular polymorphisms of the CADPKL gene, including particular single nucleotide polynorphisms (SNPs) and microsatellite markers, which co-segregate with neuropsychiatric disorders in individuals. The polymorphisms are useful, therefore, in the methods for treating and diagnosing such disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods and systems for facilitating the diagnosis and treatment of schizophrenia Inventor(s): Nimgaonkar, Vishwajit Laxmikant; (Pittsburgh, PA), Levitt, Pat Ressler; (Pittsburgh, PA), Mirnics, Karoly; (Pittsburgh, PA), Kodavali, Venkata Chowdari; (Pittsburgh, PA) Correspondence: Frederick H. Colen; REED SMITH LLP; P.O. Box 488; Pittsburgh; PA; 15230-0488; US Patent Application Number: 20030113721 Date filed: August 24, 2001 Abstract: A method of diagnosing, assessing susceptibility, and/or treating schizophrenia involving the observation of regulator of G-protein signaling 4 (RGS4) levels in a subject. Embodiments of the present invention include increasing RGS4 expression levels in the cortex, either by chemical means or by genetic complementation (e.g. gene therapy). Excerpt(s): The present invention relates generally to the field of neurological and physiological dysfunctions associated with schizophrenia. The invention further relates to the identification, isolation, and cloning of genes which, when mutated or varied, are associated with schizophrenia. The present invention also relates to methods for diagnosing and detecting carriers of the genes and to diagnosis of schizophrenia. The present invention further relates to the construction of animal models of schizophrenia. Schizophrenia is a serious brain disorder that affects approximately 1% of the human population. The cause of this complex and devastating disease remains elusive, although genetic, nutritional, environmental, and developmental factors have been considered. A combination of clinical, neuroimaging, and postmortem studies have implicated the dorsal prefrontal cortex (PFC) as a prominent site of dysfunction in schizophrenia. Schizophrenia is typically characterized as a disorder of thinking and cognition, as contrasted to other disorders of mental faculties, such as mood, social behavior, and those affecting learning, memory, and intelligence. Schizophrenia is characterized by psychotic episodes during which an individual may lose the ability to test reality or may have hallucinations, delusions, incoherent thinking, and even disordered memory. There are varying forms of schizophrenia differing in severity, from a schizotypal disorder to a catatonic state. A review of schizophrenia can be found in Principles of Neural Science, 3.sup.rd ed., 1991, Kandel, Schwartz, and Jessel (Eds.), Connecticut: Appleton & Lange, pp.853-868; of which Chapter 55 is incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods of determining susceptibility to or presence of schizophrenia, or a disorder related thereto Inventor(s): Gogos, Joseph A. (New York, NY), Karayiorgou, Maria; (New York, NY) Correspondence: KLAUBER & JACKSON; 411 HACKENSACK AVENUE; HACKENSACK; NJ; 07601 Patent Application Number: 20020193581 Date filed: April 10, 2002 Abstract: Variations in the DNA sequence of the human proline dehydrogenase gene (PRODH) which correlate to an increased susceptibility to, or presence of schizophrenia

Patents 397

or a disease or disorder related thereto, such as obsessive compulsive disorder (OCD), bipolar disorder (BP), or major depressive disorder (MDD) are provided, along with assays to diagnosing schizophrenia or a disease or disorder related thereto, and evaluating potential drugs or agents for using in treating such diseases or disorders. Excerpt(s): This Application is a continuation-in-part of copending U.S. application Ser. No. 09/229,530 entitled "Methods of Determining Susceptibility to or presence of schizophrenia, or a disorder related thereto", which is hereby incorporated by reference in its entirety. The present invention relates to isolated nucleic acid molecules which encode human and murine proline dehydrogenase, and methods for determining susceptibility to, or the presence of schizophrenia or a disease or disorder related thereto, such as obsessive compulsive disorder, bipolar disorder (BP), or major depressive disorder in a subject by determining levels of proline dehydrogenase (PRODH) in a bodily sample. Furthermore, the present invention comprises polymorphisms of the human proline dehydrogenase (PRODH) gene which correlate to a phenotype closely related to schizophrenia or a disease or disorder related thereto. The present invention also relates to various assays for drugs or agents that can treat schizophrenia or a disease or disorder related thereto. It has been posited that the amino acid proline serves as a modulator of synaptic transmission in the mammalian brain, due to the selective expression of a brain specific high affinity proline transporter in a subset of glutamatergic pathways (Fremeau et al., 1996). Proline transporter is modulated by enckephalins, the expression of which may be decreased in the brains of patients with schizophrenia and elevated proline concentration. Furthermore, recent analysis indicates that endogenous extracellular proline may regulate the basal function of some glutamate synapses by maintaining them in a partially potentiated state. Also, elevated proline concentration has also been previously associated with behavioral and neurological effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Notch 4 and schizophrenia Inventor(s): Hemmings, Gwynneth; (Bangor, GB), Wei, Jun; (Bangor, GB) Correspondence: JACOBSON HOLMAN PLLC; 400 SEVENTH STREET N.W. SUITE 600; WASHINGTON; DC; 20004; US Patent Application Number: 20030124591 Date filed: November 19, 2002 Abstract: Methods are provided of diagnosing, treating and testing a subject's susceptibility for schizophrenia, based on investigation of the Notch 4 gene or gene(s) associated therewith. Agents which modify the function of the Notch 4 gene are described used in the treatment of schizophrenia. Excerpt(s): Schizophrenia is an illness which causes a great deal of distress to both patients and relatives. Although there are many drugs which modify the symptoms of schizophrenia, their effect sizes are small. On average, the drugs relieve only 15-25% of symptoms as measured by standard rating scales, so leaving 75-85% of symptoms untouched. The drugs have little effect on long term recovery from the illness: long term outcome has not changed over the past 100 years (Hegarty et al, Am J Psychiatry 1994: 151:1409-16). There is therefore a great need for the development of new treatment approaches. For some time attempts have been made to identify the major genes involved in schizophrenia. This is a field where many genes and chromosome regions

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have been identified as possibly involved, only for the results to fail to be replicated by others. Several studies have suggested that there is in the vicinity of the human chromosome 6p a susceptibility locus for schizophrenia. [Wang, S. et al. Nature Genet. 10, 41-46 (1995); Straub, R. E. et al. Nature Genet. 11, 235-236 (1995); Schwab, S. G. et al. Nature Genet. 11, 325-327 (1995); Schizophrenia Linkage Collaborative Group (Schizophrenia Linkage Collaborative Group for Chromosomes 3, 6 and 8) Am. J. Med. Genet. 67, 580-694 (1996). No firm conclusions have been drawn yet. The 6p21 region has now been fully mapped and the complete genomic DNA sequence is in the public domain. The NOTCH family of genes was first identified in Drosophila. These genes encode transmembrane receptor proteins with intracellular segments which are able to interact with signal transduction processes. The Notch genes are involved in differentiation and in cell-cell interactions. They have been implicated in the development of many tissues, including the nervous system. Notch 4 is a gene which has a specific role in regulating capillary and endothelial developments. The gene, and various ways of modulating its function and the functions of its gene products have been described in international patent application no PCT WO 98/57621. The practical applications described in this patent specification are related entirely to the modification of angiogenesis in either an upwards or downwards direction, depending on the nature of the condition to be treated. Modulation of Notch 4 signalling can be used to modulate angiogenesis either positively, by activating Notch signalling to stimulate angiogenesis or negatively, by blocking Notch signalling to block angiogenesis. This induction or inhibition of angiogenesis in vivo can be used as a therapeutic means to treat a variety of diseases including cancer, diabetes, wound repair and arteriosclerosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel primers for screening schizophrenia and a method thereof Inventor(s): Brahmachari, Samir Kumar; (Delhi, IN), Chauhan, Chitra; (Delhi, IN), Quaiser, Salim; (Delhi, IN), Jain, Sanjeev; (Delhi, IN), Verma, Ranjana; (Delhi, IN) Correspondence: John P. White; Cooper & Durham LLP; 1185 Avenue of the Americas; New York; NY; 10036; US Patent Application Number: 20030180730 Date filed: March 21, 2002 Abstract: The present invention relates to novel primers useful for identifying and screening non-sense mutation with codon TGG coding for amino acid tryptophan substituted with TAG a non-sense codon at nucleotide No. 825 in exon 2 of synaptogyrin 1 gene of chromosome 22q11-13, thereby detecting pre-disposition to schizophrenia in a subset of patients and a method thereof. Excerpt(s): Throughout this application various publications are referred to by author(s) and year within parenthesis. The disclosure of these publications, in their entireties, are hereby incorporated by reference into this application in order to more fully describe the state of art to which the invention pertains. The present invention relates to novel primers useful for identifying and screening non-sense mutation with codon TGG coding for amino acid tryptophan substituted with TAG a non-sense codon at nucleotide No. 825 in exon 2 of synaptogyrin 1 gene of chromosome 22q11-13, thereby detecting pre-disposition to schizophrenia in a subset of patients and a method thereof. Schizophrenia is a common and devastating illness afflicting at least 1% of the population worldwide. The characteristic symptoms involve disturbances in perception and inference (hallucinations and delusions), abnormalities in language, behaviour and

Patents 399

motor function (disorganized speech, bizarre behaviour and catatonia) and deficits in emotional capacity and drive (affective flattening, anhedonia and avolition). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Proteins related to schizophrenia and uses thereof Inventor(s): Fraser, Paul E. (Toronto, CA), St. George-Hyslop, Peter H. (Toronto, CA) Correspondence: DARBY & DARBY P.C. 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20020058276 Date filed: August 31, 2001 Abstract: Presenilin Associated Membrane Protein (PAMP), and nucleic acids encoding this protein, are provided. PAMP and PAMP nucleic acids provide diagnostic and therapeutic tools for evaluating and treating or preventing neurodevelopmental and neuropsychiatric disorders. In a specific embodiment, mutations in PAMP are diagnostic for schizophrenia. The invention further relates to screening, particularly using high-throughput screens and transgenic animal models, for compounds that modulate the activity of PAMP and presenilins. Such compounds, or gene therapy with PAMP, can be used in treating neurodevelopmental and neuropsychiatric disorders, particularly schizophrenia. In addition, the invention provides PAMP mutants, nucleic acids encoding for PAMP mutants, and transgenic animals expressing PAMP mutants, which in a preferred aspect result in biochemical, morphological, or neuropsychological changes similar to those associated with schizophrenia. Excerpt(s): This patent application claims the priority of U.S. provisional patent application No. 60/229,889, filed Sep. 1, 2000, which is incorporated herein by reference in its entirety. The present invention relates generally to the field of neurological and physiological dysfunctions associated with neuropsychiatric and neurodevelopmental diseases, especially schizophrenia. More particularly, the invention is concerned with the identification of proteins associated with neuropsychiatric and neurodevelopmental diseases, especially schizophrenia, and relates to methods of diagnosing these diseases, and to methods of screening for candidate compounds which modulate the interaction of a certain protein, specifically Presenilin Associated Membrane Protein ("PAMP"), with presenilin proteins. The origin of and causes for schizophrenia, one of the most serious neuropsychiatric disorders, have long been sought after. A number of studies have suggested that schizophrenia is predominantly genetic, but it has proven difficult to show a significant genetic linkage. However, recently, a novel locus associated with inherited susceptibility to schizophrenia has been mapped to chromosome 1 q21-q22, near the anonymous DNA markers D1S1653, D1S1679, and D1S1677 (Brzustowicz et al., 2000). Furthermore, several lines of evidence, both from morphological and neuropsychological findings, now indicate that schizophrenia may be a disease of central nervous system development (reviewed in Stefan et al, 1997). For example, Falkai et al., 2000, provided quantitative data showing that the positioning of neuron (pre-alpha cell) clusters was abnormal in schizophrenia patients, supporting the theory that schizophrenia derives from impaired brain development. Such abnormal neuron positions could, e.g., arise from failures of neuronal migration during fetal development. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Proteins, genes and their use for diagnosis and treatment of Schizophrenia Inventor(s): Rohlff, Christn; (Oxford, GB), Chandrasiri Herath, Herath Mudiyanselage Athula; (Abingdon, GB), Parekh, Rajesh Bhikhu; (Near Wendlebury, GB) Correspondence: PENNIE AND EDMONDS; 1155 AVENUE OF THE AMERICAS; NEW YORK; NY; 100362711 Patent Application Number: 20020142303 Date filed: February 23, 2001 Abstract: The present invention provides methods and compositions for screening, diagnosis and prognosis of Schizophrenia, for monitoring the effectiveness of Schizophrenia treatment, identifying patients most likely to respond to a particular therapeutic treatment and for drug development. Schizophrenia-Associated Features (SFs), detectable by two-dimensional electrophoresis of cerebrospinal fluid, serum or plasma are described. The invention further provides Schizophrenia-Associated Protein Isoforms (SPIs) detectable in cerebrospinal fluid, serum or plasma, preparations comprising isolated SPIs, antibodies immunospecific for SPIs, and kits comprising the aforesaid. Excerpt(s): The present invention relates to the identification of proteins and protein isoforms that are associated with Schizophrenia and its onset and development, and of genes encoding the same, and to their use for e.g., clinical screening, diagnosis, prognosis, therapy and prophylaxis, as well as for drug screening and drug development. In the majority of psychiatric disorders, little is known about a link between changes at a cellular and/or molecular level and nervous system structure and function. The paucity of detectable neuralgic defects distinguishes neuropsychiatric disorders such as Schizophrenia from neurological disorders, where manifestations of anatomical and biochemical changes have been identified in many cases. Consequently the identification and characterization of cellular and/or molecular causative defects and neuropathologies are necessary for improved treatment of neuropsychiatric disorders. Schizophrenia is characterized by episodes of positive symptoms such as delusions, hallucinations, paranoia and psychosis and/or negative symptoms such as flattened affect, impaired attention, social withdrawal, and cognitive impairments (Ban et al, Psychiatr. Dev. (1984) 2:179-199). It afflicts 1.1% of the U.S. population and imposes a disproportionately large economic burden due to long-term expenditures for hospitalisation, treatment and rehabilitation, and lost productivity. Cost-of-illness studies have estimated that in 1990 the total economic burden of Schizophrenia in the US was $32.5 billion. (Rice J Clin Psychiatry (1999) 60 Suppl 1 4-6). In the UK, the total discounted cost to society attributable to an annual cohort of newly-diagnosed patients with Schizophrenia over the first 5 years following diagnosis has been estimated at.English Pound.-862 million (Guest and Cookson Pharmacoeconomics (1999) 15:597610). Co-morbid substance abuse disorders have emerged as one of the greatest obstacles to the effective treatment of persons with Schizophrenia. Estimates of the prevalence of such co-morbidity vary, but as many as half of persons with Schizophrenia may suffer from a co-morbid drug or alcohol disorder (Dixon Schizophr Res (1999) 35 Suppl:S 93-100). Effective treatments used early in the course of Schizophrenia can help reduce the costs associated with this illness. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 401

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Schizophrenia related gene Inventor(s): Cochran, Susan; (Glasgow, GB), Paterson, Gary; (Glasgow, GB), Ohashi, Yoshitaka; (Tokyo, JP), Pratt, Judith; (Glasgow, GB), Morris, Brian; (Glasgow, GB) Correspondence: Ropes & Gray; One International Place; Boston; MA; 02110-2624; US Patent Application Number: 20030175741 Date filed: April 29, 2003 Abstract: There are provided isolated polynucleotide fragments for use in diagnosing and/or developing treatments for schizophrenia. Further provided is a method for diagnosing schizophrenia using one or more polynucleotides disclosed herein. Also provided is a method for screening a compound which regulates expression of a schizophrenia-related gene. Also provided is a chronic animal model of schizophrenia that mimics the functional deficits observed in patients and methods for producing the animal model comprising the administration of PCP to the animal. Excerpt(s): The present invention relates to the identification of genes postulated to be involved and/or associated with schizophrenia. The present invention also relates to the development of a chronic animal model which mimics functional deficits in schizophrenia and to the use of the model in drug screening and identification of genes/proteins associated with schizophrenia, as well as particular identified genes and their use in therapy/diagnosis of schizophrenia. Schizophrenia is a devastating mental illness which affects 1% of the world population, the aetiology of which remains elusive. To date, there is a poor understanding of the genes involved and no chronic animal models of schizophrenia have been developed which imitate all the characteristics of the disease. One of the goals of modern antipsychotic drug development is to produce a drug which is more effective in ameliorating the negative symptoms and cognitive deficits characteristic of schizophrenia than existing therapies. Although typical and atypical antipsychotic drugs, such as haloperidol and clozapine, are effective in attenuating the positive symptoms, they are ineffective (haloperidol) or minimally effective (clozapine) against the negative symptoms and cognitive dysfunction associated with the disease (Goldberg, T. et al). The development of improved antipsychotic drugs which will have superior action against the negative symptoms and cognitive dysfunction has been severely hampered by the lack of knowledge of which genes are involved and/or associated with schizophrenia, or lack of an animal model which accurately models these symptoms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Schizophrenia related gene and protein Inventor(s): Bougueleret, Lydie; (Petit Lancy, CH), Bihain, Bernard; (Carlsbad, CA), Bour, Barbara; (San Diego, CA) Correspondence: SALIWANCHIK LLOYD & SALIWANCHIK; A PROFESSIONAL ASSOCIATION; 2421 N.W. 41ST STREET; SUITE A-1; GAINESVILLE; FL; 326066669 Patent Application Number: 20030148389 Date filed: February 6, 2002 Abstract: The invention relates to polynucleotides of the PAPAP gene, polypeptides encoded by the PAPAP gene, and antibodies directed specifically against such polypeptides. The invention also concerns methods for the treatment or diagnosis of

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schizophrenia, bipolar disorder or related CNS disorder. The invention also concerns the interaction of PAPAP with schizophrenia candidate gene g34872. Excerpt(s): This application is a continuation-in-part of PCT application PCT/IB01/01891, filed Jul. 26, 2001, which claims priority to U.S. provisional application No. 60/223,482, filed Aug. 7, 2000, both of which are herein incorporated by reference in their entireties. The present invention is directed to polynucleotides of the PAPAP gene, polypeptides encoded by the PAPAP gene, and antibodies directed specifically against such polypeptides. The invention also concerns methods for the treatment or diagnosis of schizophrenia, bipolar disorder or related CNS disorders. The invention also concerns the interaction of PAPAP with schizophrenia candidate gene g34872. Advances in the technological armamentarium available to basic and clinical investigators have enabled increasingly sophisticated studies of brain and nervous system function in health and disease. Numerous hypotheses both neurobiological and pharmacological have been advanced with respect to the neurochemical and genetic mechanisms involved in central nervous system (CNS) disorders, including psychiatric disorders and neurodegenerative diseases. However, CNS disorders have complex and poorly understood etiologies, as well as symptoms that are overlapping, poorly characterized, and difficult to measure. As a result future treatment regimes and drug development efforts will be required to be more sophisticated and focused on multigenic causes, and will need new assays to segment disease populations, and provide more accurate diagnostic and prognostic information on patients suffering from CNS disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Single nucleotide polymorphisms diagnostic for schizophrenia Inventor(s): Kaytes, Paul S. (Kalamazoo, MI), Teng, Chi-Hse; (Portage, MI) Correspondence: PHARMACIA & UPJOHN; 301 HENRIETTA ST; 0228-32-LAW; KALAMAZOO; MI; 49007; US Patent Application Number: 20030170667 Date filed: August 28, 2002 Abstract: The invention provides nucleic acid segments of the human G protein coupled receptor Seq-40 gene including polymorphic sites. Allele specific primers and probes hybridizing to regions flanking these sites are also provided. The invention also provides methods for determining the genetic risk of developing schizophrenia or diagnosing schizophrenia. Excerpt(s): This application claims the benefit of the following provisional application: Application Serial No. 60/315,501 filed Aug. 28, 2001 under 35 U.S.C 119(e)(1). The invention provides nucleic acid segments of a human G-protein coupled receptor Seq-40 including polymorphic sites. The invention also provides methods for determining the genetic risk of developing schizophrenia or for diagnosing schizophrenia. All organisms undergo periodic mutation in the course of their evolution and thus generate variant forms of progenitor sequences (Gusella, Ann. Rev. Biochem. 55, 831-854 (1986)). The variant form may or may not confer an evolutionary advantage relative to a progenitor form. The variant form may be neutral. In some instances, a variant form is lethal and is not transmitted to further generations of the organism. In other instances, a variant form confers an evolutionary advantage to the species and is eventually incorporated into the DNA of many or most members of the species and effectively becomes the progenitor

Patents 403

form. In many instances, both progenitor and variant form(s) survive and co-exist in a species population. This coexistence of multiple forms of a sequence gives rise to polymorphisms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with schizophrenia, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “schizophrenia” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on schizophrenia. You can also use this procedure to view pending patent applications concerning schizophrenia. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON SCHIZOPHRENIA Overview This chapter provides bibliographic book references relating to schizophrenia. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on schizophrenia include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “schizophrenia” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on schizophrenia: •

Mental Health and the Elderly: Service Delivery Issues Source: Cleveland, OH: Western Reserve Geriatric Education Center, Case Western Reserve University School of Medicine. 1989. 66 p. Contact: Western Reserve Geriatric Education Center, Case Western Reserve University School of Medicine. 12200 Fairhill Road, Cleveland, OH 44120. (216) 368-5433. PRICE: $5.00. Summary: This book discusses issues in the delivery of mental health services to elderly persons. The issues are approached from a systemic and policy making perspective. The first chapter reviews research findings on four types of mental disorders commonly seen in the elderly: Alzheimer's disease and other dementias, depression, schizophrenia and anxiety disorders, and substance abuse. The second chapter explores barriers to the delivery of mental health services for the elderly. The barriers include system issues that impede the planning and delivery of services, attitudes toward mental health programs

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held by elderly persons and their families, and the attitudes and levels of knowledge and skills among mental health and aging professionals who work with the elderly. The third chapter presents case studies of state level initiatives in Michigan and Pennsylvania that demonstrate a variety of strategies used to address barriers to mental health care for the elderly. The fourth chapter discusses lessons from these cases concerning collaboration between the aging and mental health systems that are relevant to agencies in other states. 93 references. •

Geriatric Clinical Neuropsychology: An Introduction to the Uses of Neuropsychological Assessment With Older Populations Source: Cleveland, OH: Western Reserve Geriatric Education Center. 1988. 52 p. Contact: Available from Western Reserve Geriatric Education Center. Case Western Reserve University School of Medicine, 12200 Fairhill Road, Cleveland, OH 44120. (216) 368-5433. PRICE: $5.00. Summary: This book focuses on the uses of neuropsychological assessment techniques with elderly persons, including those who display either recently acquired or longstanding psychiatric disorders and those with Alzheimer's disease or Pick's diseaserelated dementias. The neuropsychologist can contribute valuable information to the interdisciplinary treatment team about patients' complaints of mental inefficiency, memory loss, or depression as well as cognitive deficits which arise from both psychiatric and neurological disorders. The book is divided into four chapters with a section devoted to clinical case reports and assessments of patients. The first chapter defines clinical neuropsychology and its usefulness in patient treatment. The second chapter examines when a neuropsychological evaluation should be requested, including discussions about physical disorders, dementia, schizophrenia, affective and systemic disorders. The third chapter discusses the assessment process and areas of assessment. The final chapter examines the functional implications of neuropsychologic deficits as related to behavior, reasoning, sensory and perception, language and visual aspects, and memory. Three case reports are examined at the end of the book, including assessment techniques, summary and recommendations. 67 references.

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Mental Illness: A Homecare Guide Source: New York, NY: John Wiley and Sons, Inc. 1989. 274 p. Contact: Available from John Wiley and Sons, Inc. 605 Third Avenue, New York, NY 10158. (212) 850-6000. PRICE: $12.95. ISBN: 0471611573. Summary: This book is a step-by-step guide for caregivers of people with mental illness, including those with Alzheimer's disease. Based on the authors' belief that a familycentered, loving environment is ultimately a more healing situation than a hospital or other facility, the book provides information that family members need in order to plan home care, ease the transition from hospital to home, and deal with the problems that arise from caring for a mentally ill relative. In nontechnical language, the authors explore various issues such as different types of mental illness, from the schizophrenia to mood and anxiety disorders; diagnosing the problem through differential diagnosis and specialized tests; practical details of basic planning such as consultations with the doctor and the precautions involved in dispensing medications; and what to do when family relationships invariably become strained. In addition, the book provides a comprehensive list of organizations throughout the country that furnish family and individual support including the National Alliance for the Mentally Ill (NAMI), the National Mental Health Association (NMHA), and the National Mental Health

Books 407

Consumer Self-Help Clearinghouse. The chapters discuss: choosing a primary care physician and his or her role, medication, sexuality, behavior in public places, crisis intervention, and community support. •

Geropsychiatric Nursing. Second Edition Source: St. Louis, MO: Mosby. 1995. 420 p. Contact: Available from Mosby. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 426-4545; FAX: (800) 535-9935. Internet: http://www.mosby.com. PRICE: $37.95. ISBN: 0801678110. Summary: This book is designed to teach nurses about the care of older people with mental health and emotional problems. Chapters address the following topics: overview of mental health and older adults; promotion of mental health in older adults; government, financial, and human resources; assessment; psychotropic drugs; depression, suicide, and bereavement; delirium, dementia, and other cognitive disorders; schizophrenia, paranoia, anxiety, and somatoform disorders; substancerelated disorders; inpatient geropsychiatric nursing in a general hospital; mental and behavioral problems in the nursing home; care of the mentally ill older person in the home; and community programs. Chapter seven includes information on the diagnosis of dementia, potentially reversible causes of dementia, Alzheimer's disease and other irreversible dementias, and vascular dementia. The book has a bibliography and eight appendices.

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Principles and Practice of Relapse Prevention Summary: This book provides an up-to-date and comprehensive analysis of current research on relapse prevention. This edited collection presents, with one overall perspective, the diverse applications of relapse prevention. It addresses the conceptual and methodological issues of relapse prevention and offers directions for future research. The book covers relapse prevention strategies for alcohol problems, smoking, obesity, anorexia nervosa, and bulimia. Clinical problems such as depression, schizophrenia, panic disorder and panic disorder with agoraphobia, obsessivecompulsive disorders, and sexual deviance are discussed as well. The book also describes relapse prevention techniques for complaints such as chronic pain, martial problems, social competence, and stuttering.

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Effects of Drugs on Communication Disorders. 2nd ed Source: San Diego, CA: Singular Publishing Group. 1999. 238 p. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 347-7707. Fax (800) 774-8398. E-mail: [email protected]. Website: www.singpub.com. PRICE: $49.95 plus shipping and handling. ISBN: 1565939964. Summary: This handbook gives communication specialists information about prescription drugs and their use with patients who suffer neurogenic or psychogenic communication disorders. The book was designed for communication specialists who work in medical centers, rehabilitation clinics, private practice, public schools, or any setting in which drug therapy may influence a client's communication. Chapter 1 is a discussion of why and how drugs work, the scientific basis of neuropharmacology. Chapter 2 contains general information about drug related issues, including how drugs are administered and arrive at their destination in the body, the procedures for drug

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approval by the Food and Drug Administration (FDA), the influence of age on drug effectiveness, how to evaluate the effectiveness of a drug, and a discussion of dietary supplements and naturally occurring remedies. The authors next discuss the underlying neurologic and psychiatric diseases and conditions most likely to be encountered by speech language pathologists, along with the medicines currently and most commonly used to treat the disorders. Disorders covered include Parkinson disease, myasthenia gravis, amyotrophic lateral sclerosis (ALS), multiple sclerosis, Wilson's disease, cerebral palsy, Huntington's disease, Tourette's syndrome, stroke, epilepsy, neoplasm (brain tumors), dementia, Alzheimer disease, traumatic brain injury (TBI), depression, mania, bipolar disorder, generalized anxiety disorder, schizophrenia, autism, attention deficit hyperactivity disorder (ADHD), stuttering, spasmodic dysphonia, and dysphagia (swallowing disorders). The handbook concludes with a glossary of terms related to medical conditions and management, an appendix of abbreviations and definitions of terms associated with medical management, an appendix of drugs that affect the ear and hearing, and a subject index.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “schizophrenia” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “schizophrenia” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “schizophrenia” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

A Carer's Guide to Schizophrenia by Greg Wilkinson, et al (1999); ISBN: 1853154083; http://www.amazon.com/exec/obidos/ASIN/1853154083/icongroupinterna

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A Clinical Guide for the Treatment of Schizophrenia by Allan S. Bellack (Editor), Alan S. Bellack (1989); ISBN: 0306430649; http://www.amazon.com/exec/obidos/ASIN/0306430649/icongroupinterna

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A Thousand Plateaus: Capitalism and Schizophrenia by Gilles Deleuze, et al (1987); ISBN: 0816614024; http://www.amazon.com/exec/obidos/ASIN/0816614024/icongroupinterna

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A User's Guide to Capitalism and Schizophrenia: Deviations from Deleuze and Guattari by Brian Massumi (Author); ISBN: 0262631431; http://www.amazon.com/exec/obidos/ASIN/0262631431/icongroupinterna

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Adaptation in Schizophrenia: The Theory of Segmental Set by David, Shakow; ISBN: 0471057568; http://www.amazon.com/exec/obidos/ASIN/0471057568/icongroupinterna

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Adjustment of Schizophrenics in the Community by George, Serban; ISBN: 089335063X; http://www.amazon.com/exec/obidos/ASIN/089335063X/icongroupinterna

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Advances in the Neurobiology of Schizophrenia by J. A. den Boer (Editor), et al (1996); ISBN: 0471952877; http://www.amazon.com/exec/obidos/ASIN/0471952877/icongroupinterna

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Affective and Schizophrenic Disorders: New Approaches to Diagnosis and Treatment by Michael Zales (Editor); ISBN: 0876303246; http://www.amazon.com/exec/obidos/ASIN/0876303246/icongroupinterna

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An Atlas of Schizophrenia by Mike Travis (Editor), et al; ISBN: 1850700745; http://www.amazon.com/exec/obidos/ASIN/1850700745/icongroupinterna

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An Inquiry into Schizophrenia and Depression (Animal Models of Psychiatric Disorders, Vol 2) by P. Simon, et al (1988); ISBN: 3805547579; http://www.amazon.com/exec/obidos/ASIN/3805547579/icongroupinterna

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Anti-Oedipus: Capitalism and Schizophrenia by Gilles Deleuze, et al (1985); ISBN: 0816612250; http://www.amazon.com/exec/obidos/ASIN/0816612250/icongroupinterna

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Assessing Schizophrenic Thinking: A Clinical and Research Instrument for Measuring Thought Disorder by Mary Hollis, Johnston; ISBN: 0875894348; http://www.amazon.com/exec/obidos/ASIN/0875894348/icongroupinterna

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Attention and Schizophrenia: Neurobiological Bases by Robert D. Oades; ISBN: 0273084909; http://www.amazon.com/exec/obidos/ASIN/0273084909/icongroupinterna

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Beautiful Minds: Living With Schizophrenia by Abram Hoffer (2002); ISBN: 1550823035; http://www.amazon.com/exec/obidos/ASIN/1550823035/icongroupinterna

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Beyond Symptom Suppression: Improving Long-Term Outcomes of Schizophrenia (Report, No. 134) by Group for The Advancement Of Psychiatry (1992); ISBN: 0873182022; http://www.amazon.com/exec/obidos/ASIN/0873182022/icongroupinterna

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Biochemistry, Schizophrenias and Affective Illnesses by Harold E. Himwich, Irvine H. Page; ISBN: 0882755242; http://www.amazon.com/exec/obidos/ASIN/0882755242/icongroupinterna

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Biological Aspects of Schizophrenia and Addiction by Gwynneth Hemmings (Editor); ISBN: 0471101176; http://www.amazon.com/exec/obidos/ASIN/0471101176/icongroupinterna

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Biological Basis of Schizophrenic Disorders (Taniguchi Symposia on Brain Sciences, Vol 14) by Tsuneyuki Nakazawa (Editor) (1991); ISBN: 3805555032; http://www.amazon.com/exec/obidos/ASIN/3805555032/icongroupinterna

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Biology of Schizophrenia and Affective Disease by Stanley J. Watson (Editor), Association for Research in Nervous and Mental Disease Meeting 1993 N; ISBN: 0880487461; http://www.amazon.com/exec/obidos/ASIN/0880487461/icongroupinterna

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Brain Imaging in Schizophrenia: Insights and Applications by Tonmoy Sharma, Xavier Chitnis (2003); ISBN: 1901346080; http://www.amazon.com/exec/obidos/ASIN/1901346080/icongroupinterna

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Buchner and Madness: Schizophrenia in Georg Buchner's Lenz and Woyzeck (Bristol German Publications, Vol 9) by James Crighton (1998); ISBN: 0773413529; http://www.amazon.com/exec/obidos/ASIN/0773413529/icongroupinterna

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Can a Virus Cause Schizophrenia?: Facts and Hypotheses (Neurobiological Foundation of Aberrant Behaviors, 6) by Bradley D. Pearce (2002); ISBN: 1402073003; http://www.amazon.com/exec/obidos/ASIN/1402073003/icongroupinterna

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Can Schizophrenia Be Localized in the Brain (Progress in Psychiatry Series) by Nancy C. Andreasen (Editor); ISBN: 088048084X; http://www.amazon.com/exec/obidos/ASIN/088048084X/icongroupinterna

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Capitalism and Schizophrenia in the Later Novels of Louis-Ferdinand Céline: D'un. l'autre by Greg Hainge; ISBN: 0820451959; http://www.amazon.com/exec/obidos/ASIN/0820451959/icongroupinterna

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Catecholamines and schizophrenia : [proceedings of the third international Symposium on Catecholamines, Strasbourg, France, May 18-21, 1973]; ISBN: 0080182429; http://www.amazon.com/exec/obidos/ASIN/0080182429/icongroupinterna

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Childhood Schizophrenia by Sheila Cantor; ISBN: 0898627133; http://www.amazon.com/exec/obidos/ASIN/0898627133/icongroupinterna

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Childhood Schizophrenia by W. Goldfarb; ISBN: 0674116003; http://www.amazon.com/exec/obidos/ASIN/0674116003/icongroupinterna

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Children at Risk from Schizophrenia : A Longitudinal Perspective by Norman F. Watt (Editor), et al; ISBN: 0521248884; http://www.amazon.com/exec/obidos/ASIN/0521248884/icongroupinterna

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Chronic schizophrenia by Thomas Freeman (Author); ISBN: B00005VLKC; http://www.amazon.com/exec/obidos/ASIN/B00005VLKC/icongroupinterna

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Chronic Schizophrenia and Adult Autism: Issues in Diagnosis, Assessment, and Psychological Treatment by Johnny L. Matson (Editor); ISBN: 0826160204; http://www.amazon.com/exec/obidos/ASIN/0826160204/icongroupinterna

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Clozapine in Treatment: Resistant Schizophrenia - a Scientific Update: Ascientific Update Edited by Yvon Lapierre, Barry Jones (International Congress and Symposium Series (ICSS)) by Y. Lapierre (Editor), B. Jones (Editor); ISBN: 1853151734; http://www.amazon.com/exec/obidos/ASIN/1853151734/icongroupinterna

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Cognition in Schizophrenia: Impairments, Importance, and Treatment Strategies by Tonmoy Sharma (Editor), Philip D. Harvey (Editor); ISBN: 019262993X; http://www.amazon.com/exec/obidos/ASIN/019262993X/icongroupinterna

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Cognitive Therapy with Schizophrenic Patients by Carlo Perris; ISBN: 0898627370; http://www.amazon.com/exec/obidos/ASIN/0898627370/icongroupinterna

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Cognitive Therapy with Schizophrenic Patients: The Evolution of a New Treatment Approach by Marco C. G., Dr. Merlo (Editor), et al; ISBN: 0889372535; http://www.amazon.com/exec/obidos/ASIN/0889372535/icongroupinterna

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Cognitive-Behavioral Therapy of Schizophrenia by David Kingdon, et al (2002); ISBN: 157230829X; http://www.amazon.com/exec/obidos/ASIN/157230829X/icongroupinterna

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Collected Papers on Schizophrenia and Related Subjects by Harold F. Searles (1966); ISBN: 0823609804; http://www.amazon.com/exec/obidos/ASIN/0823609804/icongroupinterna

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Common Questions on Schizophrenia and the Answers by Abram Hoffer; ISBN: 0879833777; http://www.amazon.com/exec/obidos/ASIN/0879833777/icongroupinterna

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Communication and the Mentally Ill Patient: Developmental and Linguistic Approaches to Schizophrenia by Jenny France (Editor), Niki Muir (Editor) (1997); ISBN: 1853024147; http://www.amazon.com/exec/obidos/ASIN/1853024147/icongroupinterna

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Comprehensive Care of Schizophrenia: a textbook of clinical management by Jeffrey A. Lieberman, Robin M. Murray (2000); ISBN: 1853178934; http://www.amazon.com/exec/obidos/ASIN/1853178934/icongroupinterna

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Comprehensive Treatment of Schizophrenia: Linking Neurobehavioral Findings to Psychosocial Approaches (Keio University International Symposia for Life Sciences and Medicine, 8) by H. Kashima (Editor), et al (2002); ISBN: 4431702989; http://www.amazon.com/exec/obidos/ASIN/4431702989/icongroupinterna

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Conflict and reconciliation; a study in human relations and schizophrenia by Helm Stierlin; ISBN: 0876680252; http://www.amazon.com/exec/obidos/ASIN/0876680252/icongroupinterna

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Contemporary Diagnosis and Management of the Patient with Schizophrenia by Henry A. Nasrallah, Donald J. Smeltzer; ISBN: 1931981027; http://www.amazon.com/exec/obidos/ASIN/1931981027/icongroupinterna

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Contemporary Issues in Schizophrenia by T. Kerr (1986); ISBN: 0880482281; http://www.amazon.com/exec/obidos/ASIN/0880482281/icongroupinterna

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Contemporary Issues in the Treatment of Schizophrenia by Christian L. Shriqui, Henry A. Nasrallah (Editor); ISBN: 0880486813; http://www.amazon.com/exec/obidos/ASIN/0880486813/icongroupinterna

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Contemporary Theories of Schizophrenia: Review of Synthesis by Sue A Shapiro (1979); ISBN: 007056423X; http://www.amazon.com/exec/obidos/ASIN/007056423X/icongroupinterna

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Contributions to the psychopathology of schizophrenia : selected reprints, with new commentaries, from Progress in experimental personality Research by Brendan A. Maher; ISBN: 0124652506; http://www.amazon.com/exec/obidos/ASIN/0124652506/icongroupinterna

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Controversies in Schizophrenia: Changes and Constancies; ISBN: 0898626579; http://www.amazon.com/exec/obidos/ASIN/0898626579/icongroupinterna

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Coping With Schizophrenia by Jacqueline M. Atkinson; ISBN: 0722519907; http://www.amazon.com/exec/obidos/ASIN/0722519907/icongroupinterna

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Coping with Schizophrenia (Overcoming Common Problems) by Frank Tallis, Stephen Jones; ISBN: 0859696790; http://www.amazon.com/exec/obidos/ASIN/0859696790/icongroupinterna

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Coping With Schizophrenia: A Survival Manual for Parents, Relatives and Friends by Mona Wasow; ISBN: 0831400625; http://www.amazon.com/exec/obidos/ASIN/0831400625/icongroupinterna

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Creativity and the Schizophrenia Spectrum (Creativity Research Journal Volume 13, Number 1) by Louis A. Sass (Editor), David Schuldberg (Editor) (2001); ISBN: 0805897399; http://www.amazon.com/exec/obidos/ASIN/0805897399/icongroupinterna

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Cultural Schizophrenia: Islamic Societies Confronting the West (Modern Intellectual and Political History of the Middle East) by Darius Shayegan, et al (1997); ISBN: 0815605072; http://www.amazon.com/exec/obidos/ASIN/0815605072/icongroupinterna

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Current Issues in the Psychopharmacology of Schizophrenia by Alan Breier (Editor), et al; ISBN: 0781724228; http://www.amazon.com/exec/obidos/ASIN/0781724228/icongroupinterna

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Dementia Praecox or the Group of Schizophrenias by Eugen Bleuler, Joseph Zinkin (Translator) (1968); ISBN: 0823611809; http://www.amazon.com/exec/obidos/ASIN/0823611809/icongroupinterna

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Depression and schizophrenia : a contribution on their chemical pathologies by Herman M. van Praag; ISBN: 0893350028; http://www.amazon.com/exec/obidos/ASIN/0893350028/icongroupinterna

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Depression in Schizophrenia (Progress in Psychiatry) by Lynn E. Delisi (Editor); ISBN: 088048196X; http://www.amazon.com/exec/obidos/ASIN/088048196X/icongroupinterna

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Depression in Schizophrenics: Proceedings by Richard Williams, J. Thomas Dalby (Editor) (1989); ISBN: 0306432404; http://www.amazon.com/exec/obidos/ASIN/0306432404/icongroupinterna

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Developmental Neuropathology of Schizophrenia (NATO Asi Series A, Life Sciences, Vol 217) by Sarnoff A. Mednick, Tyrone D. Cannon (Editor) (1992); ISBN: 0306440814; http://www.amazon.com/exec/obidos/ASIN/0306440814/icongroupinterna

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Diagnosis: Schizophrenia by Rachel Miller (Editor), Susan Elizabeth Mason (Editor); ISBN: 0231126255; http://www.amazon.com/exec/obidos/ASIN/0231126255/icongroupinterna

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Diseases Explained: Schizophrenia Wall Chart by Lexi-Comp; ISBN: 193059822X; http://www.amazon.com/exec/obidos/ASIN/193059822X/icongroupinterna

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Disordered Thinking and Schizophrenic Psychopathology by Martin Harrow, Donald M. Quinlan (1985); ISBN: 0898760992; http://www.amazon.com/exec/obidos/ASIN/0898760992/icongroupinterna

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Disordered thought in schizophrenia by Loren J. Chapman; ISBN: 0390184934; http://www.amazon.com/exec/obidos/ASIN/0390184934/icongroupinterna

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Disorders of the Schizophrenic Syndrome by Leopold Bellak (Editor); ISBN: 0465016758; http://www.amazon.com/exec/obidos/ASIN/0465016758/icongroupinterna

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Dopamine in the Pathophysiology and Treatment of Schizophrenia: New Findings by Shitij Kapur, Yves Lecrubier (2003); ISBN: 1841843040; http://www.amazon.com/exec/obidos/ASIN/1841843040/icongroupinterna

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Drug Maintenance Strategies in Schizophrenia by John M. Kane (Editor); ISBN: 0880480548; http://www.amazon.com/exec/obidos/ASIN/0880480548/icongroupinterna

•

Early Clinical Intervention and Prevention in Schizophrenia by William S. Stone (Editor), et al (2004); ISBN: 1588290018; http://www.amazon.com/exec/obidos/ASIN/1588290018/icongroupinterna

Books 413

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Ego Functions in Schizophrenics, Neurotics, and Normals by Leopold Bellak, et al; ISBN: 0471064130; http://www.amazon.com/exec/obidos/ASIN/0471064130/icongroupinterna

•

Environment of Schizophrenia: Innovations in Practice, Policy and Communications by Richard Warner; ISBN: 0415223075; http://www.amazon.com/exec/obidos/ASIN/0415223075/icongroupinterna

•

Essays in Schizophrenia by Bernard H. Shulman (1984); ISBN: 0918560292; http://www.amazon.com/exec/obidos/ASIN/0918560292/icongroupinterna

•

Etiology of Schizophrenia by D. D. Jackson; ISBN: 0465020895; http://www.amazon.com/exec/obidos/ASIN/0465020895/icongroupinterna

•

Etiopathogenetic Hypotheses of Schizophrenia: The Impact of Epidemiological, Biochemical and Neuromorphological Studies by C.L. Cazzulio, et al (1988); ISBN: 0852008430; http://www.amazon.com/exec/obidos/ASIN/0852008430/icongroupinterna

•

Everything You Need to Know About Schizophrenia (Need to Know Library) by Michelle S. Friedman; ISBN: 0823930912; http://www.amazon.com/exec/obidos/ASIN/0823930912/icongroupinterna

•

Experience of Reality in Childhood Schizophrenia by Austin M. Deslauriers; ISBN: 0823618005; http://www.amazon.com/exec/obidos/ASIN/0823618005/icongroupinterna

•

Experiences of Schizophrenia: An Integration of the Personal, Scientific, and Therapeutic by Michael D. Robbins (Author); ISBN: 0898629977; http://www.amazon.com/exec/obidos/ASIN/0898629977/icongroupinterna

•

Families Coping With Schizophrenia: A Practitioner's Guide to Family Groups by Jacqueline M. Atkinson, Denise A. Coia (Contributor); ISBN: 0471941816; http://www.amazon.com/exec/obidos/ASIN/0471941816/icongroupinterna

•

Families Helping Families: Living With Schizophrenia by Families of the Mentally Ill Collective, Families of the Mentally Ill C; ISBN: 0380703548; http://www.amazon.com/exec/obidos/ASIN/0380703548/icongroupinterna

•

Family and Schizophrenia by John G. and Gulrguis, Wajuih Howells, Wahuih Guirguis (1985); ISBN: 0823618501; http://www.amazon.com/exec/obidos/ASIN/0823618501/icongroupinterna

•

Family Care of Schizophrenia: A Problem-solving Approach to the Treatment of Mental Illness; ISBN: 089862049X; http://www.amazon.com/exec/obidos/ASIN/089862049X/icongroupinterna

•

Family Involvement in Schizophrenia by Marion Zucker Goldstein (Author) (1987); ISBN: 0521347076; http://www.amazon.com/exec/obidos/ASIN/0521347076/icongroupinterna

•

Family Involvement in the Treatment of Schizophrenia (Clinical Insights) by Marion Zucker, M.D. Goldstein (Editor); ISBN: 0880480971; http://www.amazon.com/exec/obidos/ASIN/0880480971/icongroupinterna

•

Family Involvement in Treating Schizophrenia: Models, Essential Skills, and Process by James A. Marley (2003); ISBN: 0789012502; http://www.amazon.com/exec/obidos/ASIN/0789012502/icongroupinterna

414 Schizophrenia

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Family Management of Schizophrenia: A Study of Clinical, Social, Family, and Economic Benefits by Ian R. H. Falloon; ISBN: 080182429X; http://www.amazon.com/exec/obidos/ASIN/080182429X/icongroupinterna

•

Family Processes and Schizophrenia by Mishler. Elliot G., et al (1983); ISBN: 0876687117; http://www.amazon.com/exec/obidos/ASIN/0876687117/icongroupinterna

•

Family Therapy in Schizophrenia by William R. McFarlane (Editor); ISBN: 0898620422; http://www.amazon.com/exec/obidos/ASIN/0898620422/icongroupinterna

•

Family Work for Schizophrenia by Julian Leff, et al; ISBN: 1901242773; http://www.amazon.com/exec/obidos/ASIN/1901242773/icongroupinterna

•

Family Work for Schizophrenia: A Practical Guide by Liz Kuipers (Editor), et al; ISBN: 0902241494; http://www.amazon.com/exec/obidos/ASIN/0902241494/icongroupinterna

•

Fetal Neural Development and Adult Schizophrenia by Sarnoff A. Mednick (Editor), et al (1991); ISBN: 052139158X; http://www.amazon.com/exec/obidos/ASIN/052139158X/icongroupinterna

•

Five Lost Years: A Personal Exploration of Schizophrenia by Christina Alexandra, John Paul Brady (2000); ISBN: 1883938465; http://www.amazon.com/exec/obidos/ASIN/1883938465/icongroupinterna

•

Getting Your Life Back Together When You Have Schizophrenia by Roberta Temes; ISBN: 1572242736; http://www.amazon.com/exec/obidos/ASIN/1572242736/icongroupinterna

•

Group Therapy for Schizophrenic Patients (Clinical Practice, No 39)(8172) by Nick Kanas (1996); ISBN: 0880481722; http://www.amazon.com/exec/obidos/ASIN/0880481722/icongroupinterna

•

Growth and Change of Schizophrenic Children: A Longitudinal Study. by William, Goldfarb; ISBN: 0470311029; http://www.amazon.com/exec/obidos/ASIN/0470311029/icongroupinterna

•

Guide to Assessment Scales in Schizophrenia by McEvoy, et al (2000); ISBN: 1858733995; http://www.amazon.com/exec/obidos/ASIN/1858733995/icongroupinterna

•

Guidelines for Neuroleptic Relapse Prevention in Schizophrenia: Proceedings of a Consensus Conference Held April 19-20, 1989, in Bruges, Belgium by Werner Kissling (Editor); ISBN: 0387539859; http://www.amazon.com/exec/obidos/ASIN/0387539859/icongroupinterna

•

Handbook of Psychopharmacology, Section III: Human Psychopharmacology, Volume 10: Neuroleptics and Schizophrenia by Leslie L. Iversen, et al (1978); ISBN: 0306389304; http://www.amazon.com/exec/obidos/ASIN/0306389304/icongroupinterna

•

Handbook of Social Functioning in Schizophrenia by Kim T. Mueser (Author), Nicholas Tarrier (Author); ISBN: 0205164447; http://www.amazon.com/exec/obidos/ASIN/0205164447/icongroupinterna

•

Handbook of Studies on Schizophrenia, Part 2: Management and Research by Graham D. Burrows, et al; ISBN: 0444807268; http://www.amazon.com/exec/obidos/ASIN/0444807268/icongroupinterna

Books 415

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Handbook of Studies on Schizophrenia, Part I: Epidemiology, Aetiology and Clinical Features by G.D. Burrows (Editor); ISBN: 0444807160; http://www.amazon.com/exec/obidos/ASIN/0444807160/icongroupinterna

•

How to Become a Schizophrenic by John Modrow; ISBN: 0963262629; http://www.amazon.com/exec/obidos/ASIN/0963262629/icongroupinterna

•

How to Live With Schizophrenia by Abram Hoffer, et al (1997); ISBN: 0806513829; http://www.amazon.com/exec/obidos/ASIN/0806513829/icongroupinterna

•

In Search of Madness: Schizophrenia and Neuroscience by R. Walter Heinrichs (2001); ISBN: 0195122194; http://www.amazon.com/exec/obidos/ASIN/0195122194/icongroupinterna

•

Intellectual Schizophrenia by Rousas J. Rushdoony; ISBN: 0875524117; http://www.amazon.com/exec/obidos/ASIN/0875524117/icongroupinterna

•

Interaction in Families: An Experimental Study of Family Processes and Schizophrenia by Elliot George, Mishler, Nancy Waxler-Morrison; ISBN: 0471609404; http://www.amazon.com/exec/obidos/ASIN/0471609404/icongroupinterna

•

Interpretation of Schizophrenia by Silvano Arieti; ISBN: 0465034292; http://www.amazon.com/exec/obidos/ASIN/0465034292/icongroupinterna

•

Iraos: Interview for the Retrospective Assessment of the Onset and Course of Schizophrenia and Other Psychoses by Heinz Hafner (2003); ISBN: 0889372705; http://www.amazon.com/exec/obidos/ASIN/0889372705/icongroupinterna

•

Issues and Controversies in the Psychotherapy of Schizophrenia (The Master Work Series) by John G. Gunderson, Loren R. Mosher (Editor) (1995); ISBN: 1568213972; http://www.amazon.com/exec/obidos/ASIN/1568213972/icongroupinterna

•

Jewish Schizophrenia in the Land of Israel: In the Land of Israel by David J. Forman; ISBN: 9652292613; http://www.amazon.com/exec/obidos/ASIN/9652292613/icongroupinterna

•

Lafayette Clinic Studies on schizophrenia; ISBN: 0814314317; http://www.amazon.com/exec/obidos/ASIN/0814314317/icongroupinterna

•

Language and Cognition in Schizophrenia by Hal, Steven Schwartz; ISBN: 047099343X; http://www.amazon.com/exec/obidos/ASIN/047099343X/icongroupinterna

•

Language and Thought in Schizophrenia by Kasanin Js; ISBN: 0393002527; http://www.amazon.com/exec/obidos/ASIN/0393002527/icongroupinterna

•

Late Onset Schizophrenia by Robert Howard (Editor), et al; ISBN: 1871816394; http://www.amazon.com/exec/obidos/ASIN/1871816394/icongroupinterna

•

Lectures in Psychiatry: The Functional Psychoses: The Schizophrenias and Major Affective Disorders by Ken Reed (1985); ISBN: 0875273394; http://www.amazon.com/exec/obidos/ASIN/0875273394/icongroupinterna

•

Levels of Schizophrenia by Albert E. Scheflen; ISBN: 0876302525; http://www.amazon.com/exec/obidos/ASIN/0876302525/icongroupinterna

•

Little Voices : A True Paranoid Schizophrenic Adventure by Rodney St. Michael; ISBN: 0738823279; http://www.amazon.com/exec/obidos/ASIN/0738823279/icongroupinterna

416 Schizophrenia

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Living and Working With Schizophrenia by E. Plummer, et al (1990); ISBN: 0802067816; http://www.amazon.com/exec/obidos/ASIN/0802067816/icongroupinterna

•

Living Outside Mental Illness: Qualitative Studies of Recovery in Schizophrenia (Qualitative Studies in Psychology Series) by Larry Davidson (2003); ISBN: 0814719430; http://www.amazon.com/exec/obidos/ASIN/0814719430/icongroupinterna

•

Living With Schizophrenia by Stuart Emmons (Editor), et al; ISBN: 1560325569; http://www.amazon.com/exec/obidos/ASIN/1560325569/icongroupinterna

•

Living with Schizophrenia by Monkey See Productions (Producer) (2003); ISBN: 1572309520; http://www.amazon.com/exec/obidos/ASIN/1572309520/icongroupinterna

•

Living With Schizophrenia by Alexander Hyde; ISBN: 0809252627; http://www.amazon.com/exec/obidos/ASIN/0809252627/icongroupinterna

•

Living with Schizophrenia: A Positive Guide for Sufferers and Carers by Brenda Linter (1996); ISBN: 0091813409; http://www.amazon.com/exec/obidos/ASIN/0091813409/icongroupinterna

•

Madwives: Schizophrenic Women in the 1950s by Carol A.B. Warren; ISBN: 0813512255; http://www.amazon.com/exec/obidos/ASIN/0813512255/icongroupinterna

•

Magic and Schizophrenia by G. Roheim; ISBN: 0253200342; http://www.amazon.com/exec/obidos/ASIN/0253200342/icongroupinterna

•

Management Issues in Schizophrenia: pocketbook (2000); ISBN: 185317940X; http://www.amazon.com/exec/obidos/ASIN/185317940X/icongroupinterna

•

Management of Chronic Schizophrenia by Carol L. M. Caton; ISBN: 0195033469; http://www.amazon.com/exec/obidos/ASIN/0195033469/icongroupinterna

•

Managing Relapse in Schizophrenia by M. J. Travis, et al; ISBN: 1858733154; http://www.amazon.com/exec/obidos/ASIN/1858733154/icongroupinterna

•

Managing Schizophrenia by Gordon Mallarkey (Editor), Matthews; ISBN: 0864710593; http://www.amazon.com/exec/obidos/ASIN/0864710593/icongroupinterna

•

Managing Side Effects of Drug Therapy in Schizophrenia by Kane (1999); ISBN: 1858733499; http://www.amazon.com/exec/obidos/ASIN/1858733499/icongroupinterna

•

Masked Schizophrenia, Diagnosis and a Unified Method of Treatment by Margaret O. Strahl; ISBN: 0826128203; http://www.amazon.com/exec/obidos/ASIN/0826128203/icongroupinterna

•

Medical Illness and Schizophrenia (62106) by Jonathan M. Meyer (Editor), Henry A. Nasrallah (Editor) (2003); ISBN: 1585621064; http://www.amazon.com/exec/obidos/ASIN/1585621064/icongroupinterna

•

Medicating Schizophrenia: A History by Sheldon Gelman (1999); ISBN: 0813526434; http://www.amazon.com/exec/obidos/ASIN/0813526434/icongroupinterna

•

Mental Disorders in Urban Areas: An Ecological Study of Schizophrenia and Other Psychoses by Robert E.L. Faris, Warren H. Dunham; ISBN: 0226238164; http://www.amazon.com/exec/obidos/ASIN/0226238164/icongroupinterna

Books 417

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Mental Health Disorders Sourcebook: Basic Consumer Health Information About Anxiety Disrders, Depression and Other Mood Disorders, Eating Disorders, Personality Disorders, Schizophrenia (Health Reference Series) by Karen Bellenir (Editor) (2000); ISBN: 0780802403; http://www.amazon.com/exec/obidos/ASIN/0780802403/icongroupinterna

•

Mental Health Disorders Sourcebook: Basic Information About Schizophrenia, Depression, Bipolar Disorder, Panic Disorder, Obsessive-Compulsive Disorder, Phobias and Other Anxiety disorder (Health Reference Series, Vol 9) by Karen Bellenir (Editor) (1997); ISBN: 0780800400; http://www.amazon.com/exec/obidos/ASIN/0780800400/icongroupinterna

•

Models of Madness: Psychological, Social and Biological Approaches to Schizophrenia by John Read (Editor), et al (2004); ISBN: 1583919066; http://www.amazon.com/exec/obidos/ASIN/1583919066/icongroupinterna

•

Modern Psychoanalysis of the Schizophrenic Patient: Theory of the Technique by Hyman Spotnitz; ISBN: 0898852501; http://www.amazon.com/exec/obidos/ASIN/0898852501/icongroupinterna

•

My Mother's Keeper: A Daughter's Memoir of Growing Up in the Shadow of Schizophrenia by Tara Elgin Holley, Joe Holley (Contributor); ISBN: 0688133681; http://www.amazon.com/exec/obidos/ASIN/0688133681/icongroupinterna

•

Mythology of the soul: a research into the unconscious from schizophrenic dreams and drawings by H. G. Baynes; ISBN: 0090987403; http://www.amazon.com/exec/obidos/ASIN/0090987403/icongroupinterna

•

Natural Healing for Schizophrenia & Other Common Mental Disorders: And Other Common Mental Disorders by Eva Edelman; ISBN: 0965097668; http://www.amazon.com/exec/obidos/ASIN/0965097668/icongroupinterna

•

Natural Healing for Schizophrenia: And Other Common Mental Disorders by Eva Edelman; ISBN: 0965097676; http://www.amazon.com/exec/obidos/ASIN/0965097676/icongroupinterna

•

Natural Medicine Guide to Schizophrenia by Stephanie Marohn (2003); ISBN: 1571742891; http://www.amazon.com/exec/obidos/ASIN/1571742891/icongroupinterna

•

Nebraska Symposium on Motivation, 1983: Theories of Schizophrenia & Psychosis (Current Theory and Research in Motivation, Vol 31) by William D. Spaulding (Editor), James K. Cole (Editor); ISBN: 0803241488; http://www.amazon.com/exec/obidos/ASIN/0803241488/icongroupinterna

•

Negative Symptom and Cognitive Deficit Treatment Response in Schizophrenia by Richard S. E., Ph.D. Keefe (Editor), Joseph P. McEvoy (Editor); ISBN: 0880487852; http://www.amazon.com/exec/obidos/ASIN/0880487852/icongroupinterna

•

Neurochemical and immunologic components in schizophrenia : proceedings of a conference held at the University of Texas Medical Branch, October 28-31, 1976; ISBN: 0845110195; http://www.amazon.com/exec/obidos/ASIN/0845110195/icongroupinterna

•

Neurochemistry and Neuropharmacology of Schizophrenia (Handbook of Schizophrenia, Vol 2) by Fritz A. Henn, Lyn Delisi (Editor); ISBN: 0444904360; http://www.amazon.com/exec/obidos/ASIN/0444904360/icongroupinterna

418 Schizophrenia

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Neurology of Schizophrenia (Handbook of Schizophrenia, Vol 1) by Daniel R. Weinberger (Editor), Henry A. Nasrallah; ISBN: 0444904158; http://www.amazon.com/exec/obidos/ASIN/0444904158/icongroupinterna

•

Neuropsychology, Psychophysiology & Information Processing Vol. 5: Handbook of Schizophrenia by J. H. Gruzelier (Editor), et al (1991); ISBN: 0444904379; http://www.amazon.com/exec/obidos/ASIN/0444904379/icongroupinterna

•

New Biological Vistas on Schizophrenia (Clinical and Experimental Psychiatry Monograph, No 6) by Jean-Pierre Lindenmayer, Stanley R. Kay (Editor); ISBN: 0876306547; http://www.amazon.com/exec/obidos/ASIN/0876306547/icongroupinterna

•

New Developments in Interventions With Families of Schizophrenics. Ed by Michael J. Goldstein (New Directions for Mental Health Services, No 12) by Michael J. Goldstein; ISBN: 0875898491; http://www.amazon.com/exec/obidos/ASIN/0875898491/icongroupinterna

•

New perspectives in schizophrenia; ISBN: 0443012474; http://www.amazon.com/exec/obidos/ASIN/0443012474/icongroupinterna

•

Nightmare: A Schizophrenia Narrative by Wendell Williamson; ISBN: 0971222908; http://www.amazon.com/exec/obidos/ASIN/0971222908/icongroupinterna

•

Nosology, Epidemiology, and Genetics of Schizophrenia (Handbook of Schizophrenia, Vol 3) by Ming T. Tsuang, John C, Simpson (Editor); ISBN: 0444904662; http://www.amazon.com/exec/obidos/ASIN/0444904662/icongroupinterna

•

Occupational Therapy Practice Guidelines for Adults With Schizophrenia (2001); ISBN: 1569001537; http://www.amazon.com/exec/obidos/ASIN/1569001537/icongroupinterna

•

Occupational Therapy Practice Guidelines for Adults With Schizophrenia (The Aota Practice Guidelines Series: Adults With Schizophrenia) by Aota Staff (Editor) (1999); ISBN: 156900126X; http://www.amazon.com/exec/obidos/ASIN/156900126X/icongroupinterna

•

Office Treatment of Schizophrenia by Mary V. Seeman (Author), Stanley E. Greben (Author) (1990); ISBN: 0521384923; http://www.amazon.com/exec/obidos/ASIN/0521384923/icongroupinterna

•

On Schizophrenia, Phobias Depression, Psychotherapy and the Farther Shores of Psychiatry: Selected Papers of Silvano Arieti by Silvano Arieti; ISBN: 0876301618; http://www.amazon.com/exec/obidos/ASIN/0876301618/icongroupinterna

•

Operators and Things: The Inner Life of a Schizophrenic by Barbara, Pseud. O'Brien; ISBN: 0498016641; http://www.amazon.com/exec/obidos/ASIN/0498016641/icongroupinterna

•

Options for Improving Patient Care in Schizophrenia: Proceedings of a Round Table Meeting Held at the Royal Society of Medicine in London on 30th April 1996 (Round Table Series (RTS)) by Hugh Freeman (Editor); ISBN: 1853152889; http://www.amazon.com/exec/obidos/ASIN/1853152889/icongroupinterna

•

Origins and Development of Schizophrenia: Advances in Experimental Psychopathology by Mark F. Lenzenweger (Editor), Robert H. Dworkin (Editor) (1998); ISBN: 1557984972; http://www.amazon.com/exec/obidos/ASIN/1557984972/icongroupinterna

Books 419

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Orthomolecular Psychiatry: Treatment of Schizophrenia by David Hawkins, Linus Pauling; ISBN: 0716708981; http://www.amazon.com/exec/obidos/ASIN/0716708981/icongroupinterna

•

Orthomolecular Treatment for Schizophrenia: Megavitamin Supplements and Nutritional Strategies for Healing and Recovery (Good Health Guides) by Abram Hoffer (1999); ISBN: 0879839104; http://www.amazon.com/exec/obidos/ASIN/0879839104/icongroupinterna

•

Outcome and Innovation in Psychological Treatment of Schizophrenia by Til Wykes (Editor), et al; ISBN: 0471978426; http://www.amazon.com/exec/obidos/ASIN/0471978426/icongroupinterna

•

Overcoming Addictions: Skills Training for People with Schizophrenia by Lisa J. Roberts, et al; ISBN: 0393702995; http://www.amazon.com/exec/obidos/ASIN/0393702995/icongroupinterna

•

Overcoming Ocd and Schizophrenia With God in My Life by Chip F. Correll (2000); ISBN: 0595121470; http://www.amazon.com/exec/obidos/ASIN/0595121470/icongroupinterna

•

Personal Therapy for Schizophrenia and Related Disorders: A Guide to Individualized Treatment by Gerard E. Hogarty (Author); ISBN: 157230782X; http://www.amazon.com/exec/obidos/ASIN/157230782X/icongroupinterna

•

Perspectives in schizophrenia research; ISBN: 0890044902; http://www.amazon.com/exec/obidos/ASIN/0890044902/icongroupinterna

•

Pharmacologic Treatment of Schizophrenia by Robert Conley, Deanna Kelly (2000); ISBN: 1884735568; http://www.amazon.com/exec/obidos/ASIN/1884735568/icongroupinterna

•

Pharmacological and Psychosocial Treatments in Schizophrenia by David Castle, et al; ISBN: 1841842680; http://www.amazon.com/exec/obidos/ASIN/1841842680/icongroupinterna

•

Phenomenology and treatment of schizophrenia; ISBN: 089335032X; http://www.amazon.com/exec/obidos/ASIN/089335032X/icongroupinterna

•

Phenomology & Lacan on Schizophrenia, After the Decade of the Brain (Figures of the Unconscious, 2) by Alphonse De Waelhens, Wilfried Ver Eecke (2001); ISBN: 9058671607; http://www.amazon.com/exec/obidos/ASIN/9058671607/icongroupinterna

•

Poems of the Lost Souls in Life: Poetry of Dementia, Schizophrenia, Megolamania, and Love for the Death of the World by Demien Blackthorne (2000); ISBN: 0595165664; http://www.amazon.com/exec/obidos/ASIN/0595165664/icongroupinterna

•

Positive and Negative Syndromes in Schizophrenia: Assessment and Research (Clinical and Experimental Psychiatry, Monograph No 5) by Stanley R. Kay (1991); ISBN: 0876306083; http://www.amazon.com/exec/obidos/ASIN/0876306083/icongroupinterna

•

Positron-Emission Tomography in Schizophrenia Research (Progress in Psychiatry, No. 33) by Nora D. Volkow, Alfred P. Wolf (Editor); ISBN: 0880481951; http://www.amazon.com/exec/obidos/ASIN/0880481951/icongroupinterna

•

Practice Guidelines for the Treatment of Patients with Schizophrenia by American Psychiatric Association, APA; ISBN: 0890423091; http://www.amazon.com/exec/obidos/ASIN/0890423091/icongroupinterna

420 Schizophrenia

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Predictors of Relapse in Schizophrenia (Clinical Insights) by Jeffrey A. Lieberman, John M. Kane (Editor); ISBN: 0880481250; http://www.amazon.com/exec/obidos/ASIN/0880481250/icongroupinterna

•

Prenatal Exposures in Schizophrenia by Ezra S. Susser (Editor), et al; ISBN: 0880484993; http://www.amazon.com/exec/obidos/ASIN/0880484993/icongroupinterna

•

Propranolol and schizophrenia : proceedings of a conference sponsored by the Kroc Foundation, held December 1976, at its headquarters in the Santa Ynez Valley, California; ISBN: 0845103008; http://www.amazon.com/exec/obidos/ASIN/0845103008/icongroupinterna

•

Psychoanalytic Treatment of Schizophrenic Borderline and Characterological Disorders by Peter Giovachinni, et al (1980); ISBN: 0876684088; http://www.amazon.com/exec/obidos/ASIN/0876684088/icongroupinterna

•

Psychobiology of Schizophrenia by M. Namba; ISBN: 0080280072; http://www.amazon.com/exec/obidos/ASIN/0080280072/icongroupinterna

•

Psychodiagnosis in Schizophrenia by Irving B. Weiner (1997); ISBN: 0805825789; http://www.amazon.com/exec/obidos/ASIN/0805825789/icongroupinterna

•

Psychoeducational Groups for Patients With Schizophrenia: A Guide for Practitioners by Haya Ascher-Svanum, Audrey A. Krause (1991); ISBN: 0834201976; http://www.amazon.com/exec/obidos/ASIN/0834201976/icongroupinterna

•

Psychoneurosis and Schizophrenia by G. L. Usdin; ISBN: 0397590148; http://www.amazon.com/exec/obidos/ASIN/0397590148/icongroupinterna

•

Psychoses of the Schizophrenic Spectrum in Twins: A Discussion of the NatureNurture Debate in the Etiology of "Endogenous" Psychoses by Ernst Franzek, et al (1999); ISBN: 321183298X; http://www.amazon.com/exec/obidos/ASIN/321183298X/icongroupinterna

•

Psychosocial Interventions for People with Schizophrenia: A Practical Guide for Mental Health Workers by Neil Harris (Editor), et al; ISBN: 0333777395; http://www.amazon.com/exec/obidos/ASIN/0333777395/icongroupinterna

•

Psychosocial Interventions in Schizophrenia: An International View by H. Stierlin, et al; ISBN: 0387121951; http://www.amazon.com/exec/obidos/ASIN/0387121951/icongroupinterna

•

Psychosocial Interventions in Schizophrenia: An International View; ISBN: 3540121951; http://www.amazon.com/exec/obidos/ASIN/3540121951/icongroupinterna

•

Psychosocial Treatment of Schizophrenia (Handbook of Schizophrenia, Vol 4) by S.J. Keith, et al; ISBN: 0444812504; http://www.amazon.com/exec/obidos/ASIN/0444812504/icongroupinterna

•

Psychotherapeutic Intervention in Schizophrenia by Lewis B. Hill; ISBN: 0226336492; http://www.amazon.com/exec/obidos/ASIN/0226336492/icongroupinterna

•

Psychotherapy of Preoedipal Conditions: Schizophrenia and Sever Character Disorders by Hyman, MD Spotnitz (1996); ISBN: 1568216335; http://www.amazon.com/exec/obidos/ASIN/1568216335/icongroupinterna

•

Psychotherapy of Schizophrenia; ISBN: 0876682085; http://www.amazon.com/exec/obidos/ASIN/0876682085/icongroupinterna

Books 421

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Psychotherapy of Schizophrenia (Master Work Series) by Gaetano Benedetti (1996); ISBN: 1568217560; http://www.amazon.com/exec/obidos/ASIN/1568217560/icongroupinterna

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Punishing The Patient: How Psychiatrists Misunderstand and Mistreat Schizophrenia by Richard, Ph.D. Gosden; ISBN: 0908011520; http://www.amazon.com/exec/obidos/ASIN/0908011520/icongroupinterna

•

Recent advances in schizophrenia; ISBN: 0387972218; http://www.amazon.com/exec/obidos/ASIN/0387972218/icongroupinterna

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Recent Advances in Schizophrenia (International Perspectives Series: Psychiatry, Psychology, and neurosciencEs) by Anthony Kales (Editor), et al; ISBN: 038797024X; http://www.amazon.com/exec/obidos/ASIN/038797024X/icongroupinterna

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Recent advances in the biology of schizophrenia by Thomas A. Ban; ISBN: 0398025711; http://www.amazon.com/exec/obidos/ASIN/0398025711/icongroupinterna

•

Recovery from Schizophrenia: An International Perspective by Kim Hopper (Editor), et al (2004); ISBN: 1887841393; http://www.amazon.com/exec/obidos/ASIN/1887841393/icongroupinterna

•

Recovery from Schizophrenia: Psychiatry and Political Economy by Richard Warner (2004); ISBN: 0415212669; http://www.amazon.com/exec/obidos/ASIN/0415212669/icongroupinterna

•

Recovery from Schizophrenia: Psychiatry and Political Economy by Richard Warner; ISBN: 0415212677; http://www.amazon.com/exec/obidos/ASIN/0415212677/icongroupinterna

•

Recovery from Schizophrenia: Psychiatry and Political Economy by Richard Warner (1985); ISBN: 0710099797; http://www.amazon.com/exec/obidos/ASIN/0710099797/icongroupinterna

•

Reparenting Schizophrenics the Cathexis Experience by Elaine Childs-Gowell (1979); ISBN: 0815803729; http://www.amazon.com/exec/obidos/ASIN/0815803729/icongroupinterna

•

Research in the Schizophrenic Disorders: The Stanley R. Dean Award Lectures by Robert Cancro, Stanley R Dean (Editor); ISBN: 089335211X; http://www.amazon.com/exec/obidos/ASIN/089335211X/icongroupinterna

•

Return from Madness: Psychotherapy With People Taking the New Antipsychotic Medications and Emerging from Severe, Lifelong, and Disabling Schizophrenia by Kathleen, Md Degen, Ellen Nasper (Contributor) (1996); ISBN: 1568216254; http://www.amazon.com/exec/obidos/ASIN/1568216254/icongroupinterna

•

Risk and Protective Factors in Schizophrenia: Towards a Conceptual Model of the Disease Process by Heinz Hafner (Editor), et al (2003); ISBN: 3798513651; http://www.amazon.com/exec/obidos/ASIN/3798513651/icongroupinterna

•

Sampling Normal and Schizophrenic Inner Experience (Emotions, Personality and Psychotherapy) by Russell T. Hurlburt (1990); ISBN: 0306432846; http://www.amazon.com/exec/obidos/ASIN/0306432846/icongroupinterna

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Sanity Plea: Schizophrenia in the Novels of Kurt Vonnegut by Lawrence R. Broer (1994); ISBN: 0817307524; http://www.amazon.com/exec/obidos/ASIN/0817307524/icongroupinterna

422 Schizophrenia

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Save Me!: A Young Woman's Journey Through Schizophrenia to Health by Judy. Lee; ISBN: 0385151012; http://www.amazon.com/exec/obidos/ASIN/0385151012/icongroupinterna

•

Schizophrenia by Vaughn Bode (2001); ISBN: 1560973714; http://www.amazon.com/exec/obidos/ASIN/1560973714/icongroupinterna

•

Schizophrenia by John S. Strauss (1981); ISBN: 0306407043; http://www.amazon.com/exec/obidos/ASIN/0306407043/icongroupinterna

•

Schizophrenia by Mario Maj (Editor), Norman Sartorius (Editor) (2003); ISBN: 0470849649; http://www.amazon.com/exec/obidos/ASIN/0470849649/icongroupinterna

•

Schizophrenia by John M. Neale, Thomas F. Oltmanns; ISBN: 0471630861; http://www.amazon.com/exec/obidos/ASIN/0471630861/icongroupinterna

•

Schizophrenia by Steven R. Hirsch (Editor), et al (2003); ISBN: 0632063882; http://www.amazon.com/exec/obidos/ASIN/0632063882/icongroupinterna

•

Schizophrenia by Peter B. Jones, Peter F. Buckley (2003); ISBN: 072343316X; http://www.amazon.com/exec/obidos/ASIN/072343316X/icongroupinterna

•

Schizophrenia by Chris Jackson, Max J. Birchwood; ISBN: 0863775535; http://www.amazon.com/exec/obidos/ASIN/0863775535/icongroupinterna

•

Schizophrenia by Sophia, M.D. Frangou, Robin M, Md, Dsc, Frcpsych, Frcp Murray; ISBN: 1853179205; http://www.amazon.com/exec/obidos/ASIN/1853179205/icongroupinterna

•

Schizophrenia (A Venture Book) by Douglas W. Smith; ISBN: 0531125149; http://www.amazon.com/exec/obidos/ASIN/0531125149/icongroupinterna

•

Schizophrenia (Contemporary Issues Companions) by Scott Barbour (Editor) (2001); ISBN: 0737706368; http://www.amazon.com/exec/obidos/ASIN/0737706368/icongroupinterna

•

Schizophrenia (Diseases and Disorders) by Melissa Abramovitz, Mimi Abramovitz (2002); ISBN: 1560069082; http://www.amazon.com/exec/obidos/ASIN/1560069082/icongroupinterna

•

Schizophrenia (Diseases and People) by Jane E. Phillips, et al; ISBN: 0766018962; http://www.amazon.com/exec/obidos/ASIN/0766018962/icongroupinterna

•

Schizophrenia (Fast Facts Series) by Shon W. Lewis, Robert W. Buchanan (2002); ISBN: 190373424X; http://www.amazon.com/exec/obidos/ASIN/190373424X/icongroupinterna

•

Schizophrenia (The Infinite Mind) by Lichtenstein Creative Media Inc; ISBN: 1888064439; http://www.amazon.com/exec/obidos/ASIN/1888064439/icongroupinterna

•

Schizophrenia : a disease or some ways of being human?; ISBN: 1850754012; http://www.amazon.com/exec/obidos/ASIN/1850754012/icongroupinterna

•

Schizophrenia : pharmacotherapy and psychotherapy by Lester Grinspoon; ISBN: 0882756036; http://www.amazon.com/exec/obidos/ASIN/0882756036/icongroupinterna

Books 423

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Schizophrenia and Affective Disorders: Biology and Drug Treatment by Arthur Rifkin (Editor); ISBN: 0723670544; http://www.amazon.com/exec/obidos/ASIN/0723670544/icongroupinterna

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Schizophrenia and Aging: Schizophrenia, Paranoia, and Schizophreniform Disorders in Later Life by Nancy Miller, Gene Cohen (Editor); ISBN: 089862228X; http://www.amazon.com/exec/obidos/ASIN/089862228X/icongroupinterna

•

Schizophrenia and Civilization by E. Fuller Torrey (1979); ISBN: 0876683804; http://www.amazon.com/exec/obidos/ASIN/0876683804/icongroupinterna

•

Schizophrenia and Comorbid Conditions: Diagnosis & Treatment by Michael Y., Md. Hwang (Editor), Paul C., Md. Bermanzohn (Editor); ISBN: 0880487712; http://www.amazon.com/exec/obidos/ASIN/0880487712/icongroupinterna

•

Schizophrenia and genetics; a twin study vantage point by Irving I. Gottesman; ISBN: 0122934504; http://www.amazon.com/exec/obidos/ASIN/0122934504/icongroupinterna

•

Schizophrenia and Human Value by Peter Barham; ISBN: 0631134743; http://www.amazon.com/exec/obidos/ASIN/0631134743/icongroupinterna

•

Schizophrenia and Human Value: Chronic Schizophrenia, Science and Society by Peter Barham; ISBN: 0631150161; http://www.amazon.com/exec/obidos/ASIN/0631150161/icongroupinterna

•

Schizophrenia and Madness by Andrew C. Smith (1983); ISBN: 0041570081; http://www.amazon.com/exec/obidos/ASIN/0041570081/icongroupinterna

•

Schizophrenia and Manic-Depressive Disorder: The Biological Roots of Mental Illness As Revealed by the Landmark Study of Identical Twins by E. Fuller Torrey, et al (1995); ISBN: 0465072852; http://www.amazon.com/exec/obidos/ASIN/0465072852/icongroupinterna

•

Schizophrenia and Mood Disorders: The New Drug Therapies in Clinical Practice by Peter F. Buckley (Editor), John L. Waddington (Editor); ISBN: 0750640960; http://www.amazon.com/exec/obidos/ASIN/0750640960/icongroupinterna

•

Schizophrenia and Parenting by Michael Ferriter (1999); ISBN: 1859723896; http://www.amazon.com/exec/obidos/ASIN/1859723896/icongroupinterna

•

Schizophrenia and the Family: A Practitioner's Guide to Psychoeducation and Management by Gerard E. Hogarty, et al; ISBN: 0898620651; http://www.amazon.com/exec/obidos/ASIN/0898620651/icongroupinterna

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Schizophrenia and the Need-Fear Dilemma by Donald L. Burnham; ISBN: 0823659801; http://www.amazon.com/exec/obidos/ASIN/0823659801/icongroupinterna

•

Schizophrenia As a Brain Disease by Fritz A. Henn (Editor), Henry A. Nasrallah (Photographer); ISBN: 0195030885; http://www.amazon.com/exec/obidos/ASIN/0195030885/icongroupinterna

•

Schizophrenia As a Human Process by Harry Stack Sullivan, Helen Swick Perry (Introduction); ISBN: 0393007219; http://www.amazon.com/exec/obidos/ASIN/0393007219/icongroupinterna

•

Schizophrenia As a Life Style by Arthur, Burton; ISBN: 0826115705; http://www.amazon.com/exec/obidos/ASIN/0826115705/icongroupinterna

424 Schizophrenia

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Schizophrenia at Home: A Guide to Helping the Family by Jacqueline M. Atkinson; ISBN: 0814705863; http://www.amazon.com/exec/obidos/ASIN/0814705863/icongroupinterna

•

Schizophrenia Biological and Psychological Perspectives by Gene Usdin; ISBN: 0876301103; http://www.amazon.com/exec/obidos/ASIN/0876301103/icongroupinterna

•

Schizophrenia from a Neurocognitive Perspective: Probing the Impenetrable Darkness by Michael Foster Green (Author); ISBN: 0205184774; http://www.amazon.com/exec/obidos/ASIN/0205184774/icongroupinterna

•

Schizophrenia Genesis: The Origins of Madness by Irving I. Gottesman, Dorothea L. Wolfgram (Contributor) (1990); ISBN: 0716721473; http://www.amazon.com/exec/obidos/ASIN/0716721473/icongroupinterna

•

Schizophrenia in A Molecular Age by Carol A. Tamminga (Editor); ISBN: 0880489618; http://www.amazon.com/exec/obidos/ASIN/0880489618/icongroupinterna

•

Schizophrenia in Focus: Guidelines for Treatment and Rehabilitation by David Dawson; ISBN: 0898850967; http://www.amazon.com/exec/obidos/ASIN/0898850967/icongroupinterna

•

Schizophrenia into Later Life: Treatment, Research, and Policy by Carl I. Cohen (Editor) (2003); ISBN: 1585620378; http://www.amazon.com/exec/obidos/ASIN/1585620378/icongroupinterna

•

Schizophrenia Research (Advances in Neuropsychiatry and Psychopharmacology, Vol 1) by Carol A. Tamminga, S. Charles Schulz (Editor); ISBN: 0881676756; http://www.amazon.com/exec/obidos/ASIN/0881676756/icongroupinterna

•

Schizophrenia Revealed: From Neurons to Social Interactions by Michael Foster Green; ISBN: 0393703347; http://www.amazon.com/exec/obidos/ASIN/0393703347/icongroupinterna

•

Schizophrenia Simplified (1991); ISBN: 3456815972; http://www.amazon.com/exec/obidos/ASIN/3456815972/icongroupinterna

•

Schizophrenia Simplified: A Field Guide to Schizophrenia for Frontline Workers, Families, and Professionals by J.F. Thornton, M.V. Seeman (Editor) (1991); ISBN: 0920887171; http://www.amazon.com/exec/obidos/ASIN/0920887171/icongroupinterna

•

Schizophrenia Today by Capri, 1975. Schizophrenia Workshop, D. Kemali (1976); ISBN: 0080209289; http://www.amazon.com/exec/obidos/ASIN/0080209289/icongroupinterna

•

Schizophrenia Towards an New Synthesis by J Wing; ISBN: 0808911406; http://www.amazon.com/exec/obidos/ASIN/0808911406/icongroupinterna

•

Schizophrenia, a Source of Social Insight by Brian W., Grant; ISBN: 0664207227; http://www.amazon.com/exec/obidos/ASIN/0664207227/icongroupinterna

•

Schizophrenia, Culture, and Subjectivity : The Edge of Experience by Janis H. Jenkins (Editor), Robert J. Barrett (Editor) (2003); ISBN: 0521829550; http://www.amazon.com/exec/obidos/ASIN/0521829550/icongroupinterna

•

Schizophrenia, Medical Diagnosis or Moral Verdict? by Theodore R. Sarbin; ISBN: 0080246133; http://www.amazon.com/exec/obidos/ASIN/0080246133/icongroupinterna

Books 425

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Schizophrenia, theory, diagnosis, and treatment : [proceedings]; ISBN: 082476711X; http://www.amazon.com/exec/obidos/ASIN/082476711X/icongroupinterna

•

Schizophrenia, Volume 3 (2001); ISBN: 0815337558; http://www.amazon.com/exec/obidos/ASIN/0815337558/icongroupinterna

•

Schizophrenia: A Biopsychological Perspective by Andrew Crider; ISBN: 0470268336; http://www.amazon.com/exec/obidos/ASIN/0470268336/icongroupinterna

•

Schizophrenia: A Developmental Analysis by Sidney J. Blatt, Cynthia Wild; ISBN: 0121050505; http://www.amazon.com/exec/obidos/ASIN/0121050505/icongroupinterna

•

Schizophrenia: A Guide for Sufferers and Their Families by Jacqueline M. Atkinson; ISBN: 0855002166; http://www.amazon.com/exec/obidos/ASIN/0855002166/icongroupinterna

•

Schizophrenia: A Life-Course Developmental Perspective (Personality, Psychopathology, and Psychotherapy Series) by Elaine F. Walker (Editor); ISBN: 0127320806; http://www.amazon.com/exec/obidos/ASIN/0127320806/icongroupinterna

•

Schizophrenia: A Mother's Story by Georgina Wakefield (2002); ISBN: 1903877032; http://www.amazon.com/exec/obidos/ASIN/1903877032/icongroupinterna

•

Schizophrenia: A New Guide for Clinicians (Medical Psychiatry, Volume 16) by John G. Csernansky (Editor) (2002); ISBN: 0824706420; http://www.amazon.com/exec/obidos/ASIN/0824706420/icongroupinterna

•

Schizophrenia: A Philosophical Reflection on Lacan's Structuralist Interpretation by Alphonse De. Waelhens; ISBN: 0391006584; http://www.amazon.com/exec/obidos/ASIN/0391006584/icongroupinterna

•

Schizophrenia: A Scientific Delusion? by Mary Boyle (2003); ISBN: 0415227186; http://www.amazon.com/exec/obidos/ASIN/0415227186/icongroupinterna

•

Schizophrenia: A Very Short Introduction (Very Short Introductions) by Christopher Donald Frith, Eve C. Johnstone (2003); ISBN: 0192802216; http://www.amazon.com/exec/obidos/ASIN/0192802216/icongroupinterna

•

Schizophrenia: A Workbook for Healthcare Professionals by Peter Thompson (Editor) (2000); ISBN: 1857754611; http://www.amazon.com/exec/obidos/ASIN/1857754611/icongroupinterna

•

Schizophrenia: An Integrated Approach to Research and Treatment by Max J. Birchwood, et al (1992); ISBN: 0814711812; http://www.amazon.com/exec/obidos/ASIN/0814711812/icongroupinterna

•

Schizophrenia: An Introduction to Research and Theory by Glenn Shean; ISBN: 0876267975; http://www.amazon.com/exec/obidos/ASIN/0876267975/icongroupinterna

•

Schizophrenia: Behavioral Aspects(Approaches to Behavior Pathology) by Kurt Salzinger; ISBN: 0471750905; http://www.amazon.com/exec/obidos/ASIN/0471750905/icongroupinterna

•

Schizophrenia: Breaking Down the Barriers by Stephen G. Holliday (Editor), et al; ISBN: 0471967033; http://www.amazon.com/exec/obidos/ASIN/0471967033/icongroupinterna

426 Schizophrenia

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Schizophrenia: Comprehensive Treatment and Management by Marvin I. Herz, Stephen R. Marder (2002); ISBN: 0683307096; http://www.amazon.com/exec/obidos/ASIN/0683307096/icongroupinterna

•

Schizophrenia: Concepts and Clinical Management by Eve C. Johnstone (Author), et al; ISBN: 0521580846; http://www.amazon.com/exec/obidos/ASIN/0521580846/icongroupinterna

•

Schizophrenia: Conditional Reflex Studies by Christian Astrup; ISBN: 039800062X; http://www.amazon.com/exec/obidos/ASIN/039800062X/icongroupinterna

•

Schizophrenia: Exploring the Spectrum of Psychosis by J Higgenbottam (Editor), et al; ISBN: 0471952559; http://www.amazon.com/exec/obidos/ASIN/0471952559/icongroupinterna

•

Schizophrenia: From Mind to Molecule (American Psychopathological Association) by Nancy C. Andreasen (Editor) (1994); ISBN: 0880489502; http://www.amazon.com/exec/obidos/ASIN/0880489502/icongroupinterna

•

Schizophrenia: Handbook for Clinical Care by Judy A. Malone (Editor); ISBN: 1556422008; http://www.amazon.com/exec/obidos/ASIN/1556422008/icongroupinterna

•

Schizophrenia: Its Origins and Need-Adapted Treatment by Yrjo O. Alanen, SirkkaLiisa Leinonem (Translator); ISBN: 1855751569; http://www.amazon.com/exec/obidos/ASIN/1855751569/icongroupinterna

•

Schizophrenia: Losing Touch With Reality (Encyclopedia of Psychological Disorders Series) by Daniel E. Harmon, et al (1999); ISBN: 0791049531; http://www.amazon.com/exec/obidos/ASIN/0791049531/icongroupinterna

•

Schizophrenia: New Directions for Clinical Research and Treatment by Charles A. Kaufmann (1998); ISBN: 0913113743; http://www.amazon.com/exec/obidos/ASIN/0913113743/icongroupinterna

•

Schizophrenia: New Medical Therapies by Lisa Henderson; ISBN: 1930624174; http://www.amazon.com/exec/obidos/ASIN/1930624174/icongroupinterna

•

Schizophrenia: Origins, Processes, Treatment, and Outcome by Rue L. Cromwell (Editor), et al; ISBN: 0195069226; http://www.amazon.com/exec/obidos/ASIN/0195069226/icongroupinterna

•

Schizophrenia: Pathophysiological Mechanisms by Goran Sedvall (Editor), L. Y. Terenius (Editor); ISBN: 0444503153; http://www.amazon.com/exec/obidos/ASIN/0444503153/icongroupinterna

•

Schizophrenia: Positive and Negative Symptoms and Syndromes (Modern Problems of Pharmacopsychiatry, Vol. 24) by Nancy C. Andreasen (Editor) (1990); ISBN: 3805550502; http://www.amazon.com/exec/obidos/ASIN/3805550502/icongroupinterna

•

Schizophrenia: Psychological Disorders and Their Treatment (The Encyclopedia of Health) by Patrick Young; ISBN: 0791000524; http://www.amazon.com/exec/obidos/ASIN/0791000524/icongroupinterna

•

Schizophrenia: Science and Practice by John C. Shershow (Editor) (1978); ISBN: 0674791126; http://www.amazon.com/exec/obidos/ASIN/0674791126/icongroupinterna

Books 427

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Schizophrenia: Scientific Progress by S. Charles Schulz (Editor), Carol A. Tamminga (Editor); ISBN: 0195055276; http://www.amazon.com/exec/obidos/ASIN/0195055276/icongroupinterna

•

Schizophrenia: Selected Papers by David Shakow (1977); ISBN: 0823660028; http://www.amazon.com/exec/obidos/ASIN/0823660028/icongroupinterna

•

Schizophrenia: Straight Talk for Family and Friends by Maryellen Walsh; ISBN: 0688041787; http://www.amazon.com/exec/obidos/ASIN/0688041787/icongroupinterna

•

Schizophrenia: Symptoms, Causes, Treatments by Kayla F. Bernheim, Richard R. Lewine (1979); ISBN: 0393090175; http://www.amazon.com/exec/obidos/ASIN/0393090175/icongroupinterna

•

Schizophrenia: the divided mind by Joyce Emerson; ISBN: 090022102X; http://www.amazon.com/exec/obidos/ASIN/090022102X/icongroupinterna

•

Schizophrenia: The Epigenetic Puzzle by Irving I. Gottesman (Author), James Shields (Author); ISBN: 0521295599; http://www.amazon.com/exec/obidos/ASIN/0521295599/icongroupinterna

•

Schizophrenia: The Experience and Its Treatment by Werner M. Mendel; ISBN: 0875892965; http://www.amazon.com/exec/obidos/ASIN/0875892965/icongroupinterna

•

Schizophrenia: The Facts by Ming T. Tsuang; ISBN: 0192613367; http://www.amazon.com/exec/obidos/ASIN/0192613367/icongroupinterna

•

Schizophrenia: the first ten Dean award lectures by Stanley R. Dean; ISBN: 0842271155; http://www.amazon.com/exec/obidos/ASIN/0842271155/icongroupinterna

•

Schizophrenia: The Meanings of Madness by Alexander Ross Kerr. Mitchell; ISBN: 0800870026; http://www.amazon.com/exec/obidos/ASIN/0800870026/icongroupinterna

•

Schizophrenia: The Positive Perspective: In Search of Dignity for Schizophrenic People by Peter K. Chadwick (1997); ISBN: 0415142881; http://www.amazon.com/exec/obidos/ASIN/0415142881/icongroupinterna

•

Schizophrenia: The Sacred Symbol of Psychiatry by Thomas Szasz (1988); ISBN: 0815602243; http://www.amazon.com/exec/obidos/ASIN/0815602243/icongroupinterna

•

Schizophrenia: Treatment of Acute Psychotic Episodes by Steven T. Levy, Philip T. Ninan (Editor) (1990); ISBN: 0880481641; http://www.amazon.com/exec/obidos/ASIN/0880481641/icongroupinterna

•

Schizophrenia: Treatment Process and Outcome by Thomas H. McGlashan, Christopher, J. Keats (1989); ISBN: 0880482818; http://www.amazon.com/exec/obidos/ASIN/0880482818/icongroupinterna

•

Schizophrenia: Understanding and Coping with the Illness (Thorsons Health Series) by Anne Charlish, John Cutting; ISBN: 0722531222; http://www.amazon.com/exec/obidos/ASIN/0722531222/icongroupinterna

•

Schizophrenia: Voices of an Illness by Lichtenstein Creative Media Inc. ISBN: 1888064021; http://www.amazon.com/exec/obidos/ASIN/1888064021/icongroupinterna

428 Schizophrenia

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Schizophrenia: Your Questions Answered by Trevor H. Turner (2004); ISBN: 0443073473; http://www.amazon.com/exec/obidos/ASIN/0443073473/icongroupinterna

•

Schizophrenia; a psychopharmacological approach by Thomas A. Ban; ISBN: 0398022224; http://www.amazon.com/exec/obidos/ASIN/0398022224/icongroupinterna

•

Schizophrenia? Huh: Stories for Children by Richard W. Carlson (2002); ISBN: 0595263240; http://www.amazon.com/exec/obidos/ASIN/0595263240/icongroupinterna

•

Schizophrenias (Directions in Psychiatry Monograph Series, No 4) by Frederic Flach (Editor); ISBN: 0393700623; http://www.amazon.com/exec/obidos/ASIN/0393700623/icongroupinterna

•

Schizophrenia--treatment, management, and rehabilitation; ISBN: 0808916408; http://www.amazon.com/exec/obidos/ASIN/0808916408/icongroupinterna

•

Schizophrenic Disorders: Sense and Nonsense in Conceptualization, Assessment, and Treatment (Perspectives on Individual Differences) by Leighton C. Whitaker (1992); ISBN: 030644156X; http://www.amazon.com/exec/obidos/ASIN/030644156X/icongroupinterna

•

Schizophrenic Disorders: Theory and Treatment from a Psychodynamic Point of View by Ping-Nie Pao (1979); ISBN: 0823659909; http://www.amazon.com/exec/obidos/ASIN/0823659909/icongroupinterna

•

Search for the Causes of Schizophrenia, Volume 4: Balance of the Century by Wagner F. Gattaz, Heinz Hafner; ISBN: 3798511721; http://www.amazon.com/exec/obidos/ASIN/3798511721/icongroupinterna

•

Searching for the Causes of Schizophrenia (Oxford Psychiatry, No 2) by Eve C. Johnstone, et al; ISBN: 019262296X; http://www.amazon.com/exec/obidos/ASIN/019262296X/icongroupinterna

•

Separating Parents and Adolescents: A Perspective on Running Away, Schizophrenia, and Waywardness by Helm Stierlin; ISBN: 0876684770; http://www.amazon.com/exec/obidos/ASIN/0876684770/icongroupinterna

•

Sepultura: Schizophrenia by Sepultura; ISBN: 0895248743; http://www.amazon.com/exec/obidos/ASIN/0895248743/icongroupinterna

•

Sex, Violence, and Schizophrenia by B. W. Miller (2002); ISBN: 1401059570; http://www.amazon.com/exec/obidos/ASIN/1401059570/icongroupinterna

•

Sexuality, War and Schizophrenia: Collected Psychoanalytic Papers by Victor Tausk (1991); ISBN: 0887383653; http://www.amazon.com/exec/obidos/ASIN/0887383653/icongroupinterna

•

Shattered--Married to an Ill Person: How Mental Illness and Paranoia Schizophrenia Ruined my Marriage: A Memoir [DOWNLOAD: MICROSOFT READER] by John Moreland (2002); ISBN: B00006JMCV; http://www.amazon.com/exec/obidos/ASIN/B00006JMCV/icongroupinterna

•

Social Cognition and Schizophrenia by Patrick W. Corrigan (Editor), David L. Penn (Editor) (2001); ISBN: 1557987742; http://www.amazon.com/exec/obidos/ASIN/1557987742/icongroupinterna

Books 429

•

Social Skills Training for Schizophrenia, Second Edition : A Step-by-Step Guide by Alan S. Bellack (Author), et al; ISBN: 157230846X; http://www.amazon.com/exec/obidos/ASIN/157230846X/icongroupinterna

•

Social Skills Training for Schizophrenia: A Step-by-Step Guide by Alan S. Bellack (Author), et al; ISBN: 1572301775; http://www.amazon.com/exec/obidos/ASIN/1572301775/icongroupinterna

•

Social Systems and Schizophrenia: Selected Papers by H. Warren Dunham (Author); ISBN: 0275904725; http://www.amazon.com/exec/obidos/ASIN/0275904725/icongroupinterna

•

Soothing the Troubled Mind: Acupuncture and Moxibustion in the Treatment and Prevention of Schizophrenia by Baiceng Lou, et al (2000); ISBN: 0912111607; http://www.amazon.com/exec/obidos/ASIN/0912111607/icongroupinterna

•

Specific Techniques for the Psychotherapy of Schizophrenic Patients by Andrew Lotterman (1996); ISBN: 082366130X; http://www.amazon.com/exec/obidos/ASIN/082366130X/icongroupinterna

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Strategic intervention in schizophrenia; current developments in treatment; ISBN: 087705133X; http://www.amazon.com/exec/obidos/ASIN/087705133X/icongroupinterna

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Surviving Schizophrenia: A Family Manual by E. Fuller Torrey; ISBN: 0060962496; http://www.amazon.com/exec/obidos/ASIN/0060962496/icongroupinterna

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Surviving Schizophrenia: A Manual for Families, Consumers, and Providers (4th Edition) by E. Fuller Torrey (Author); ISBN: 0060959193; http://www.amazon.com/exec/obidos/ASIN/0060959193/icongroupinterna

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Symbolic Realization: A New Method of Psychotherapy Applied to a Case of Schizophrenia (Monography Series on Schizophrenia, No 2) by M. A. Sechehaye; ISBN: 0823663000; http://www.amazon.com/exec/obidos/ASIN/0823663000/icongroupinterna

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Symptoms of Schizophrenia by Charles G. Costello (Editor) (1993); ISBN: 0471548758; http://www.amazon.com/exec/obidos/ASIN/0471548758/icongroupinterna

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Temporal Lobe Epilepsy, Mania and Schizophrenia and the Limbic System. by W. P. Koella (Editor), M. R. Trimble (Editor) (1982); ISBN: 3805534949; http://www.amazon.com/exec/obidos/ASIN/3805534949/icongroupinterna

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The Biological basis of schizophrenia; ISBN: 0839113293; http://www.amazon.com/exec/obidos/ASIN/0839113293/icongroupinterna

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The Biological Basis of Schizophrenia by G. Hemmings (Editor); ISBN: 0852002335; http://www.amazon.com/exec/obidos/ASIN/0852002335/icongroupinterna

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The chronic schizophrenias by Christian Astrup; ISBN: 8200018105; http://www.amazon.com/exec/obidos/ASIN/8200018105/icongroupinterna

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The Clinical Roots of the Schizophrenia Concept : Translations of Seminal European Contributions on Schizophrenia by John Cutting (Editor), Michael Shepherd (Editor); ISBN: 0521266351; http://www.amazon.com/exec/obidos/ASIN/0521266351/icongroupinterna

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The Cognitive Neuropsychology Of Schizophrenia (Essays in Cognitive Psychology) by Christopher Donald Frith, Christopher Firth; ISBN: 0863773346; http://www.amazon.com/exec/obidos/ASIN/0863773346/icongroupinterna

430 Schizophrenia

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The Dialectics of Schizophrenia by Philip Thomas (1997); ISBN: 1853433616; http://www.amazon.com/exec/obidos/ASIN/1853433616/icongroupinterna

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The Disordered Mind: What We Know About Schizophrenia by Patrick O'Brien; ISBN: 0132164655; http://www.amazon.com/exec/obidos/ASIN/0132164655/icongroupinterna

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The Early Stages of Schizophrenia by Robert B. Zipursky (Editor), et al; ISBN: 0880488409; http://www.amazon.com/exec/obidos/ASIN/0880488409/icongroupinterna

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The Encyclopedia of Schizophrenia and Other Psychotic Disorders (Facts on File Library of Health and Living) by Richard Noll; ISBN: 0816040702; http://www.amazon.com/exec/obidos/ASIN/0816040702/icongroupinterna

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The Encyclopedia of Schizophrenia and the Psychotic Disorders by Richard Noll; ISBN: 0816022402; http://www.amazon.com/exec/obidos/ASIN/0816022402/icongroupinterna

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The Epidemiology of Schizophrenia by Robin M. Murray (Editor), et al (2003); ISBN: 052177540X; http://www.amazon.com/exec/obidos/ASIN/052177540X/icongroupinterna

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The Family Face of Schizophrenia: The Practical Counsel from America's Leading Experts by Patricia Backlar, Nancy Andreasen (Introduction); ISBN: 0874777488; http://www.amazon.com/exec/obidos/ASIN/0874777488/icongroupinterna

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The Family Face of Schizophrenia: True Stories of Mental Illness With Practical Advice from America's Leading Experts by Patricia Backlar, Nancy C. Andreasen (Introduction) (1995); ISBN: 0874777909; http://www.amazon.com/exec/obidos/ASIN/0874777909/icongroupinterna

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The Family Shadow: Sources of Suicide and Schizophrenia by David K. Reynolds; ISBN: 0520042131; http://www.amazon.com/exec/obidos/ASIN/0520042131/icongroupinterna

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The Garden and the Map: Schizophrenia in Twentieth-Century Literature and Culture. by John, Vernon; ISBN: 0252002563; http://www.amazon.com/exec/obidos/ASIN/0252002563/icongroupinterna

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The Human Body as Symbol: Psychotherapy of Schizophrenia Through Existential Dialectics by Thorsten Herner, Torsten Herner (1990); ISBN: 9122013237; http://www.amazon.com/exec/obidos/ASIN/9122013237/icongroupinterna

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The Infantile Psychotic Self and Its Fates: Understanding and Treating Schizophrenics and Other Difficult Patients by Vamik D. Volkan (1995); ISBN: 1568213794; http://www.amazon.com/exec/obidos/ASIN/1568213794/icongroupinterna

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The Madness of Adam and Eve: How Schizophrenia Shaped Humanity by David F. Horrobin (2002); ISBN: 0593046498; http://www.amazon.com/exec/obidos/ASIN/0593046498/icongroupinterna

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The Meaning of Madness: Symptomatology, Sociology, Biology, and Therapy of the Schizophrenias by C. Peter, Rosenbaum; ISBN: 0876680287; http://www.amazon.com/exec/obidos/ASIN/0876680287/icongroupinterna

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The Natural History of Mania, Depression, and Schizophrenia by George Winokur (Editor), Ming T. Tsuang (Editor) (1996); ISBN: 0880487267; http://www.amazon.com/exec/obidos/ASIN/0880487267/icongroupinterna

Books 431

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The Nature of Schizophrenia: New Approaches to Research and Treatment by Lyman C. Wynne, et al; ISBN: 0471022098; http://www.amazon.com/exec/obidos/ASIN/0471022098/icongroupinterna

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The Neuropathology of Schizophrenia: Progress and Interpretation by P. J. Harrison (Editor), Gareth W. Roberts (Editor); ISBN: 0192629077; http://www.amazon.com/exec/obidos/ASIN/0192629077/icongroupinterna

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The New Pharmacotherapy of Schizophrenia (Clinical Practice Series, No 36) by Alan Breier (Editor) (1996); ISBN: 0880484918; http://www.amazon.com/exec/obidos/ASIN/0880484918/icongroupinterna

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The Origin and Treatment of Schizophrenic Disorders by Theodore Lidz; ISBN: 0465053378; http://www.amazon.com/exec/obidos/ASIN/0465053378/icongroupinterna

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The Paradoxes of Delusion: Wittgenstein, Schreber, and the Schizophrenic Mind by Louis A. Sass (1993); ISBN: 0801422108; http://www.amazon.com/exec/obidos/ASIN/0801422108/icongroupinterna

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The Pathophysiology of Schizophrenia (Medical Intelligence Unit) by Ray S. Greenberg; ISBN: 1570590532; http://www.amazon.com/exec/obidos/ASIN/1570590532/icongroupinterna

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The Physiology of Psychological Disorders: Schizophrenia, Depression, Anxiety, and Substance Abuse (Plenum Series in Behavioral Psychophysiology and) by James G. Hollandsworth (1990); ISBN: 0306433532; http://www.amazon.com/exec/obidos/ASIN/0306433532/icongroupinterna

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The Psyche and Schizophrenia: The Bond Between Affect and Logic by Luc Ciompi, Deborah L. Schneider (Translator) (1988); ISBN: 0674719905; http://www.amazon.com/exec/obidos/ASIN/0674719905/icongroupinterna

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The Psychiatric Team and the Social Definition of Schizophrenia : An Anthropological Study of Person and Illness by Rob Barrett (Author) (1996); ISBN: 0521416531; http://www.amazon.com/exec/obidos/ASIN/0521416531/icongroupinterna

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The psychology of dementia praecox by C. G. Jung; ISBN: 0691018006; http://www.amazon.com/exec/obidos/ASIN/0691018006/icongroupinterna

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The Psychology of Schizophrenia by John C. Cutting; ISBN: 0443026637; http://www.amazon.com/exec/obidos/ASIN/0443026637/icongroupinterna

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The Psychopharmacology and Treatment of Schizophrenia (British Association for Psychopharmacology Monograph, No 8) by Hirsch S.R. (Editor), et al; ISBN: 0192612603; http://www.amazon.com/exec/obidos/ASIN/0192612603/icongroupinterna

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The Psychopharmacology of Schizophrenia by Michael A. Reveley (Editor), J. F. William Deakin (Editor); ISBN: 0340759127; http://www.amazon.com/exec/obidos/ASIN/0340759127/icongroupinterna

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The Psychotherapy of Schizophrenia by Strauss (1980); ISBN: 0306404974; http://www.amazon.com/exec/obidos/ASIN/0306404974/icongroupinterna

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The Schizophrenias (1988); ISBN: 0515021784; http://www.amazon.com/exec/obidos/ASIN/0515021784/icongroupinterna

432 Schizophrenia

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The Schizophrenias: A Biological Approach to the Schizophrenia Spectrum Disorders (Springer Series on Psychiatry) by Mary Coleman, Christopher Gillberg; ISBN: 0826192904; http://www.amazon.com/exec/obidos/ASIN/0826192904/icongroupinterna

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The Schizophrenic Child: A Primer for Parents and Professionals by Sheila Cantor; ISBN: 0920792138; http://www.amazon.com/exec/obidos/ASIN/0920792138/icongroupinterna

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The Schizophrenic Disorders: Patient Long-Term and Family Studies by Manfred Bleuler; ISBN: 0300016638; http://www.amazon.com/exec/obidos/ASIN/0300016638/icongroupinterna

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The schizophrenic reactions: a critique of the concept, hospital treatment, and current research; the proceedings; ISBN: 0876300220; http://www.amazon.com/exec/obidos/ASIN/0876300220/icongroupinterna

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The Severed Soul: A Psychoanalyst's Heroic Battle to Heal the Mind of a Schizophrenic by Lucy Freeman (Contributor), Herbert S. Strean; ISBN: 0312039301; http://www.amazon.com/exec/obidos/ASIN/0312039301/icongroupinterna

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The Split Brain II: Alternative Research and Voices of Schizophrenia by Aurealia N. Nelson (2002); ISBN: 0595256759; http://www.amazon.com/exec/obidos/ASIN/0595256759/icongroupinterna

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The Split Brain: An Analysis of Schizophrenia by Aurealia N. Nelson; ISBN: 059518314X; http://www.amazon.com/exec/obidos/ASIN/059518314X/icongroupinterna

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The Story of Barbara: My Daughter's Battle With Schizophrenia by Katherine Homer Fryer, Katharine Homer Fryer; ISBN: 0944957684; http://www.amazon.com/exec/obidos/ASIN/0944957684/icongroupinterna

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The Telephone Book: Technology, Schizophrenia, Electric Speech by Avital Ronell (1991); ISBN: 0803289383; http://www.amazon.com/exec/obidos/ASIN/0803289383/icongroupinterna

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The Therapeutic Relationship and Its Impact : A Study of Psychotherapy with Schizophrenics by Carl Ransom Rogers (Author), -- (Author) (1976); ISBN: 0837183588; http://www.amazon.com/exec/obidos/ASIN/0837183588/icongroupinterna

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The Treatment of Schizophrenia: A Holistic Approach: Based on the Readings of Edgar Cayce by David, M.A. McMillin; ISBN: 0876043848; http://www.amazon.com/exec/obidos/ASIN/0876043848/icongroupinterna

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The Treatment of Schizophrenia: Status and Emerging Trends by H. D. Brenner (Editor), et al; ISBN: 0889371954; http://www.amazon.com/exec/obidos/ASIN/0889371954/icongroupinterna

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The Year in Schizophrenia 2003 by Juan Romeu Bes (Editor), T. Crow (Editor) (2004); ISBN: 1904392040; http://www.amazon.com/exec/obidos/ASIN/1904392040/icongroupinterna

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Theories of Schizophrenia by Arnold H. and Buss, Edith H. Buss; ISBN: 0883114003; http://www.amazon.com/exec/obidos/ASIN/0883114003/icongroupinterna

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Theories of Schizophrenia and Psychosis: Nebraska Symposium on Motivation 1983 by William D. Spaulding (Editor), James K. Cole (Editor) (1984); ISBN: 0803291450; http://www.amazon.com/exec/obidos/ASIN/0803291450/icongroupinterna

Books 433

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Towards A Comprehensive Therapy for Schizophrenia by H. D. Brenner (Editor), et al; ISBN: 088937175X; http://www.amazon.com/exec/obidos/ASIN/088937175X/icongroupinterna

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Towards a Sociology of Schizophrenia: Humanistic Reflections by Keith Doubt (1996); ISBN: 0802008453; http://www.amazon.com/exec/obidos/ASIN/0802008453/icongroupinterna

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Towards Need-Specific Treatment of Schizophrenic Psychoses: A Study of the Development and the Results of a Global Psychotherapeutic Approach to Psyc by Yrjo O. Alanen; ISBN: 0387166424; http://www.amazon.com/exec/obidos/ASIN/0387166424/icongroupinterna

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Towards Need-Specific Treatment of Schizophrenic Psychoses: A Study of the Development and the Results of a Global Psychotherapeutic Approach to Psychoses of the Schizophrenia Group in Turku, Finland; ISBN: 3540166424; http://www.amazon.com/exec/obidos/ASIN/3540166424/icongroupinterna

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Trapped: Families and Schizophrenia by Lloyd H. Rogler, August B. Hollingshead; ISBN: 0943862280; http://www.amazon.com/exec/obidos/ASIN/0943862280/icongroupinterna

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Treating Schizophrenia (Jossey-Bass Social and Behavioral Science Series) by Werner M. Mendel; ISBN: 1555421512; http://www.amazon.com/exec/obidos/ASIN/1555421512/icongroupinterna

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Treating Schizophrenic Patients: A Clinical-Analytic Approach by Michael H. Stone; ISBN: 0070019177; http://www.amazon.com/exec/obidos/ASIN/0070019177/icongroupinterna

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Treating the treatment failures; the challenge of chronic schizophrenia by Arnold M. Ludwig; ISBN: 0808907077; http://www.amazon.com/exec/obidos/ASIN/0808907077/icongroupinterna

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Treatment of Schizophrenia: Progress and Prospects by L.J. West, D.E. Finn; ISBN: 0808909703; http://www.amazon.com/exec/obidos/ASIN/0808909703/icongroupinterna

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Treatment of schizophrenia; a comparative study of five treatment methods by Philip R. A. May (Author); ISBN: B00005X09Z; http://www.amazon.com/exec/obidos/ASIN/B00005X09Z/icongroupinterna

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Understanding and Helping the Schizophrenic: A Guide for Family and Friends by Silvano Arieti; ISBN: 0465088554; http://www.amazon.com/exec/obidos/ASIN/0465088554/icongroupinterna

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Understanding and Treating Cognition in Schizophrenia: A Clinician's Handbook by Philip D., Ph.D. Harvey, et al; ISBN: 1841841331; http://www.amazon.com/exec/obidos/ASIN/1841841331/icongroupinterna

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Understanding and Treating Schizophrenia: Contemporary Research, Theory, and Practice by Glenn Shean (2003); ISBN: 0789018888; http://www.amazon.com/exec/obidos/ASIN/0789018888/icongroupinterna

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Understanding Schizophrenia: A Guide to the New Research on Causes and Treatment by Richard S.E. Keefe, Philip D. Harvey (Contributor) (1994); ISBN: 0029172470; http://www.amazon.com/exec/obidos/ASIN/0029172470/icongroupinterna

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Welcome, Silence: My Triumph over Schizophrenia by Carol S., M.D. North; ISBN: 0671528343; http://www.amazon.com/exec/obidos/ASIN/0671528343/icongroupinterna

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What Is Schizophrenia? by Daniel R. Miller, et al; ISBN: 0387976426; http://www.amazon.com/exec/obidos/ASIN/0387976426/icongroupinterna

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When the Music's over: My Journey into Schizophrenia by Ross David Burke, et al; ISBN: 0465091415; http://www.amazon.com/exec/obidos/ASIN/0465091415/icongroupinterna

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Why Does Schizophrenia Develop at Late Adolescence? : A Cognitive-developmental Approach to Psychosis by Chris Harrop (Author), Peter Trower (Author) (2003); ISBN: 0470848774; http://www.amazon.com/exec/obidos/ASIN/0470848774/icongroupinterna

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Women and Schizophrenia by David J. Castle (Editor), et al; ISBN: 0521786177; http://www.amazon.com/exec/obidos/ASIN/0521786177/icongroupinterna

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Working With Schizophrenia: A Needs Based Approach by Gwen Howe (1995); ISBN: 185302242X; http://www.amazon.com/exec/obidos/ASIN/185302242X/icongroupinterna

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Working With the Person With Schizophrenia: The Treatment Alliance by Michael A. Selzer, Timothy B. Sullivan (1989); ISBN: 0814778917; http://www.amazon.com/exec/obidos/ASIN/0814778917/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “schizophrenia” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

A clinical and genetico-statistical study of schizophrenia and low-grade mental deficiency in a large Swedish rural population, by Bertil Hallgren and Torsten Sjögren. Author: Hallgren, Bertil.; Year: 2002; Copenhagen, Munksgaard, 1959

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A follow-op [sic] study of 255 patients with acute schizophrenia and schizophreniform psychoses, by R. Holmboe and C. Astrup. Author: Holmboe, R.; Year: 1984; Copenhagen, Munksgaard, 1957

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A study of schizophrenia in the male; a psychiatric and social study based on 138 cases with follow up. Author: Johanson, Eva.; Year: 1965; Göteborg, 1958

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

Books 435

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Annotated bibliography on childhood schizophrenia, 1955-1964 [by] James R. Tilton [et al.]. Author: Tilton, James R.; Year: 1964; New York, Grune; Stratton [c1966]

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Collected papers on schizophrenia and related subjects. Author: Searles, Harold F. (Harold Frederic),; Year: 1964; London, Hogarth, 1965

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Community and schizophrenia; an epidemiological analysis. Author: Dunham, H. Warren (Henry Warren),; Year: 1963; Detroit, Wayne State Univ. Press, 1965

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Drug and social therapy in chronic schizophrenia. Ed. by Milton Greenblatt [et al.]Contributing authors: Dexter M. Bullard, Jr. [et al.]. Author: Greenblatt, Milton.; Year: 1953; Springfield, Ill., Thomas [c1965]

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Generalizing ability in schizophrenia; an inquiry into the disorders of problem thinking in schizophrenia, by Henry J. Wegrocki. Author: Wegrocki, Henry Joseph,; Year: 1964; New York, 1940

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How to live with schizophrenia, by Abram Hoffer and Humphry Osmond. Author: Hoffer, Abram,; Year: 1964; New Hyde Park, N. Y., University Books [c1966]

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Living outside mental illness: qualitative studies of recovery in schizophrenia Author: Davidson, Larry.; Year: 1956; New York: New York University Press, c2003; ISBN: 0814719422 http://www.amazon.com/exec/obidos/ASIN/0814719422/icongroupinterna

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Portrait of a schizophrenic nurse. Author: Wallace, Clare Marc.; Year: 1965; London, Hammond, Hammond [1965]

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Psychoneurosis & schizophrenia. Author: Usdin, Gene Leonard,; Year: 1942; Philadelphia, Lippincott [c1966]

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Psychopathology of schizophrenia, ed. by Paul H. Hoch and Joseph Zubin. Author: Hoch, Paul H.,; Year: 1964; New York, Grune; Stratton, 1966

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Psychotherapy for the whole family; case histories, techniques, and concepts of family therapy of schizophrenia in the home and clinic [by] Alfred S. Friedman [et al.]. Author: Friedman, Alfred S.; Year: 1965; New York, Springer [c1965]

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Psychotherapy of schizophrenic and manic-depressive states. Contributions of basic sciences to psychiatry; definitive statements and future problems, ed. by Hassan Azima [and] Bernard C. Glueck, Jr. Author: Azima, Hassan,; Year: 1957; [Washington] American Psychiatric Assn., 1963

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Recent research on schizophrenia. Ed. by Philip Solomon and Bernard C. Glueck. Author: Solomon, Philip,; Year: 1962; [Washington] American Psychiatric Assn., 1964

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Schizophrenia ed. by Lawrence C. Kolb. [et al.]. Author: Kolb, Lawrence Coleman,; Year: 2003; Boston, Little, Brown, 1964

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Schizophrenic women; studies in marital crisis [by] Harold Sampson [et al.] with the collaboration of David Ross [et al.]. Author: Sampson, Harold.; Year: 2003; New York, Atherton Press, 1964

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Screening and treatment of adolescents with schizophrenia Author: Bolhuis, P. A.; Year: 1954; The Hague: Health Council of the Netherlands, [1999]; ISBN: 9055493295

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The biologic basis of schizophrenia. Author: Karlsson, Jon L. (Jon Love),; Year: 1965; Springfield, Ill., Thomas [c1966]

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The industrial rehabilitation of long-stay schizophrenic patients; a study of 45 patients at an industrial rehabilitation unit [by] J. K. Wing [et al.]. Author: Wing, J. K. (John Kenneth),; Year: 1964; London, H. M. Stationery Off., 1964

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The prognosis in schizophrenia. Author: Langfeldt, Gabriel,; Year: 1973; Copenhagen, Munksgaard, 1956

436 Schizophrenia

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The role of institutionalization in the natural history of schizophrenia, by Gilbert Honigfeld and Roderic Gillis. Author: Honigfeld, Gilbert.; Year: 1964; Perry Point, Md., Central Neuropsychiatric Research Laboratory, 1966

Chapters on Schizophrenia In order to find chapters that specifically relate to schizophrenia, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and schizophrenia using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “schizophrenia” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on schizophrenia: •

Behavioral and Psychiatric Disorders Source: in Little, J.W., et al. Dental Management of the Medically Compromised Patient. 5th ed. St. Louis, MO: Mosby, Inc. 1997. p. 546-575. Contact: Available from Harcourt Health Sciences. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177. Fax (800) 874-6418. Website: www.harcourthealth.com. PRICE: $48.00 plus shipping and handling. ISBN: 0815156340. Summary: A working knowledge of the multitude of compromised health states is essential for dental professionals, as the majority of medically compromised patients need or want oral health care. This chapter on behavioral and psychiatric disorders is from a text that provides the dental practitioner with an up to date reference work describing the dental management of patients with selected medical problems. In this chapter, the authors discuss problems encountered in dental practice that stem from a patient's behavioral patterns rather than from physical conditions. The authors stress that both patients with emotional factors that contribute to oral or systemic problems and patients with more serious mental disorders can be managed in an understanding, safe, and empathetic manner. The authors discuss incidence and prevalence of anxiety disorders, mood disorders, and somatoform disorders; psychologic factors affecting physical conditions, including substance abuse, schizophrenia, and organic mental syndromes (dementia, Alzheimer's disease, delirium); etiology; pathophysiology and complications; signs and symptoms (clinical presentation and laboratory findings); drugs used to treat psychiatric disorders; and the dental management of this population, including patient attitude toward the dentist, the psychologic significance of the oral cavity, and behavior toward illness; and management of specific patients, including those with depression bipolar disorder, somatoform disorder, psychophysiologic disorder, a cocaine habit, schizophrenia, Alzheimer's disease, and suicidal patients. The chapter concludes with a section on drug interactions and side effects in patients with mental disorders, including tricyclic antidepressants, monoamine oxidase inhibitors, antianxiety drugs, and antipsychotic drugs. 3 figures. 25 tables. 40 references.

•

Frequently Asked Questions Source: in Attwood, T. Asperger's Syndrome: A Guide for Parents and Professionals. London, England: Jessica Kingsley Publishers. 1998. p. 141-185.

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Contact: Available from Future Horizons. 721 West Abram Street, Arlington, TX 76013. (800) 489-0727. Fax (817) 277-2270. Website: www.futurehorizons-autism.com. PRICE: $19.95 plus shipping and handling. ISBN: 1853025771. Summary: Asperger's syndrome is characterized by a lack of social skills, limited ability to have a reciprocal conversation, and an intense interest in a particular subject. This chapter is from a book for parents and professionals written to assist in the identification and treatment of children and adults with Asperger's syndrome. The book provides a description and analysis of the unusual characteristics of the syndrome, and practical strategies to reduce those that are most conspicuous or debilitating. Included are numerous quotations from people with Asperger's syndrome. In this chapter, the author answers frequently asked questions on topics include the inheritance of Asperger's syndrome, prenatal or perinatal conditions that may contribute to the syndrome, brain physiology and pathophysiology, family dynamics, Asperger's that occurs in parallel with another syndrome, determining whether a syndrome is present or the child is exhibiting the normal range of abilities and personality, language disorders, attention deficit disorder (ADD), schizophrenia, high functioning autism, different expressions of the syndrome in girls compared to boys, strategies to reduce the person's level of anxiety, the role of depression in Asperger's, coping with temper and anger, changes during adolescence, developing normal relationships, educational methods or settings, the advantages of having a label for the condition, how to tell others about Asperger's, suitable careers for people with Asperger's syndrome, and the long term outcomes of Asperger's syndrome. •

Evaluation of Olfactory Deficits by Medical Imaging Source: in Doty, R.L., ed. Handbook of Olfaction and Gustation. New York, NY: Marcel Dekker, Inc. 1995. p. 395-419. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (800) 228-1160 or (212) 696-9000; Fax (212) 685-4540. PRICE: $225.00 plus shipping and handling. ISBN: 0824792521. Summary: In this chapter, from a medical text on olfaction and gustation, the authors review the literature on the evaluation of olfactory deficits by medical imaging. Topics covered include imaging modalities and techniques, including plain radiographs, conventional tomography, computer tomography, magnetic resonance imaging, nuclear medicine, and angiography; the basic anatomy and physiology of the olfactory system; peripheral causes of olfactory disturbance, including sinonasal infectious disease, tumors of the nasal cavity and paranasal sinuses, allergic rhinitis, congenital or developmental abnormalities, and substance abuse; and central causes of olfactory diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, Korsakoff's psychosis, schizophrenia, congenital anosmia, head trauma, brain tumors, and AIDS. The authors conclude that in assessing the peripheral causes of olfactory deficits, medical imaging studies can reveal anatomical information and structural changes, suggest differential diagnosis, and provide guidelines for surgical intervention. In the evaluation of central causes, imaging studies can provide information elucidating the links between olfactory dysfunction and the structural or functional changes in the living brain. 5 figures. 152 references. (AA-M).

•

Treatment of the Elderly Neuropsychiatric Patient: Pharmacologic Considerations Source: in Maletta, G.J. and Pirozzolo, F.J., eds. Assessment and Treatment of the Elderly Neuropsychiatric Patient. New York, NY: Praeger Publishers. 1986. p. 40-58.

438 Schizophrenia

Contact: Available from Greenwood Publishing Group. 88 Post Road West, PO Box 5007, Westport, CT 06881. (203) 226-3571. PRICE: $65.00. ISBN: 0275921123. Summary: This book chapter argues that the skilled use of anti-psychotic medication will help significantly in reducing the functional disability associated with acute and chronic psychotic symptoms of mental illness in the elderly. Specific attention is focused on: diagnostic considerations; neuroleptic-responsive disorders in the elderly (dementia; delirium; late-life paraphrenia; chronic schizophrenia; mania) and their treatment; and guidelines for using anti-psychotic drugs in the elderly. Several case studies are discussed. 63 references. •

Syndromes of Altered Mental State Source: in Hazzard, W.R., et al., eds. Principles of Geriatric Medicine and Gerontology. 2nd ed. New York, NY: McGraw-Hill, Inc. 1990. p. 1089-1101. Contact: Available from McGraw-Hill. PO Box 548, Blacklick, OH 43004. (800) 262-4729; FAX (614) 578-3641. Internet access: http://www.books.mcgraw-hill.com. PRICE: $115.00. ISBN: 0070275009. Summary: This chapter emphasizes a psychiatric approach to the patient with an altered mental state. Standard procedures for psychiatric examination usually covered in medical school courses are repeated here, since there is sufficient evidence that many physicians in medical inpatient/outpatient settings do not routinely assess mental state and, thus, fail to recognize altered mental states. Specific attention is given to: (1) diagnostic procedures (psychiatric history taking, disability assessment, mental state examinations); and (2) cognitive syndromes (delirium, dementia, focal cognitive syndromes, schizophrenia, mental retardation, emotional syndromes, reactive syndromes, affective disorders, secondary/symptomatic depression). It is concluded that an elderly patient who presents to a physician with an altered mental state is likely to have either a cognitive syndrome (usually a delirium or a dementia) or an emotional disorder (usually, depression). A diagnosis can usually be reached by evaluating information obtained from taking a medical and personal history, laboratory tests, and longitudinal follow-up. 42 references, 1 figure.

•

Psychiatric Disorders Source: in Vogel, D. Carter, J.E. Carter, P.B. Effects of Drugs on Communication Disorders. 2nd ed. San Diego, CA: Singular Publishing Group, Inc. 1999. p. 145-187. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 347-7707. Fax (800) 774-8398. E-mail: [email protected]. Website: www.singpub.com. PRICE: $49.95 plus shipping and handling. ISBN: 1565939964. Summary: This chapter on psychiatric disorders is from a handbook that gives communication specialists information about prescription drugs and their use with patients who suffer neurogenic or psychogenic communication disorders. The book was designed for communication specialists who work in medical centers, rehabilitation clinics, private practice, public schools, or any setting in which drug therapy may influence a client's communication. This chapter covers psychiatric disorders that may affect language. For each disorder, the authors provide a definition and cause; discuss the general features, symptoms, and signs; describe the features, symptoms, and signs of language impairment associated with each disorder; list pharmacologic (drug) treatment for each disorder; and discuss the influence that drug treatment may have on

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communication. Each section also lists references for additional information. Disorders covered are depression, mania, manic depressive illness (bipolar disorder), generalized anxiety disorder, schizophrenia, autism, and attention deficit hyperactivity disorder (ADHD). 11 tables. 38 references. •

Schizoid Personality in Childhood and Asperger Syndrome Source: in Klin, A. Volkmar, F.R. Sparrow, S.S., eds. Asperger Syndrome. New York, NY: Guilford Press. 2000. p. 278-305. Contact: Available from Guilford Publications. 72 Spring Street, New York, NY 10012. (800) 365-7006. Fax (212) 966-6708. E-mail: [email protected]. Website: www.guilford.com. PRICE: $45.00 plus shipping and handling. ISBN: 1572305347. Summary: This chapter on schizoid personality in childhood and Asperger syndrome (AS) is from a comprehensive text on this autistic spectrum disorder. This chapter focuses on the clinical picture of a group of children, seen in child psychiatric practice since the 1960s, who were followed up into adult life. They were diagnosed as having a schizoid personality disorder because they resembled descriptions of this disorder in the psychiatric literature. This group of schizoid young people were, as a group, much less impaired socially both in childhood and adult life, than groups of patients described more recently as having AS. The chapter begins with an account of the childhood picture, followed by a description of two prognostic validation studies. Some changes in diagnostic nomenclature over the years are then discussed, as well as the relationships between schizoid personality in childhood, as the authors have used the term, and pervasive developmental disorders of childhood, including AS, pervasive developmental disorder not otherwise specified (PDD NOS), and multiplex developmental disorder. The chapter then provides results of two records surveys, exploring the association of schizoid personality in childhood with psychiatric morbidity, including schizophrenia, in later life; and with adult criminality. A section on helpful treatment interventions is followed by a discussion of schizoid personality in relation to the justice system. The chapter ends with speculations about the genetic causes of the syndrome, in particular a possible link between schizoid personality traits and childhood autism on the one hand, schizophrenia on the other. 85 references.

•

Neurological Disorders Source: in Clinician's Guide to Treatment of Medically Compromised Patients. Baltimore, MD: American Academy of Oral Medicine (AAOM). 1995. p. 57-63. Contact: Available from American Academy of Oral Medicine (AAOM). 2910 Lightfoot Drive, Baltimore, MD 21209-1452. (410) 602-8585. Website: www.aaom.com. PRICE: $21.00 plus shipping and handling. Summary: This chapter, from a guide for dentists on managing problems of medically compromised dental patients, discusses patients with neurological disorders. The authors cover seizures disorders; multiple sclerosis; Parkinson's disease; myasthenia gravis; psychiatric disorders; manic-depressive disorder; schizophrenia; and dementia. For each condition covered, topics covered include a definition, the etiology, clinical findings and symptoms, drug therapy, and dental management considerations. The majority of the information is presented in chart format.

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Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to schizophrenia have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:12 •

Georgia Mental Health Sourcebook Source: Atlanta, GA: Care Solutions, Inc. 1994. 177 p. Contact: Available from Care Solutions, Inc. 8302 Dunwoody Place, Suite 352, Atlanta, GA 30350. (404) 642-6722; (800) 227-3410; FAX (404) 640-6073. PRICE: $24.95 plus $3.00 shipping and handling. ISBN: 0963193961. Summary: This guide for consumers and professionals provides basic definitions of mental illness, information about the types of mental health services available, and where to call for help within Georgia. Resources are organized by category and geographic area. Some of the more common mental difficulties and disorders are briefly described and include mood and anxiety disorders; schizophrenia; dementia, including Alzheimer's disease; substance abuse; and eating, sleeping, and sexual disorders. Topics include information about where to start in seeking help; mental health issues involving children; special issues such as older adults and mental health, family relationship, homelessness, suicide, and AIDS; violence, aggression, and emotional crises; health insurance and financial options; and legal and ethical issues. Among the community resources listed are residential and day treatment services, counseling and outpatient services, supportive living programs, advocacy and support groups, multicultural programs, substance abuse programs, psychiatric hospitals, and children and adolescent programs. Over 1,700 providers are listed.

12

You will need to limit your search to “Directory” and “schizophrenia” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “schizophrenia” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.

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CHAPTER 8. MULTIMEDIA ON SCHIZOPHRENIA Overview In this chapter, we show you how to keep current on multimedia sources of information on schizophrenia. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Bibliography: Multimedia on Schizophrenia The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in schizophrenia (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on schizophrenia: •

[Diagnosis of childhood schizophrenia] [motion picture] Source: an Affiliated Film production; Year: 1957; Format: Diagnosis of childhood schizophrenia; United States: [New York State Mental Health Authority, 1957]

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Activity for schizophrenia [motion picture]: technique for corrective therapy Source: produced for the Department of Medicine and Surgery by Presentation Division; [United World Films; presented by] the Veterans Administration; Year: 1951; Format: Motion picture; [United States]: The Administration, [1951]

•

Acute schizophrenic episode: differential diagnosis [videorecording]: migraine, neutropenia, secondary to unknown drugs Source: [University of Mississippi Medical Center, Dept. of Psychiatry]; Year: 1969; Format: Videorecording; [Jackson, Miss.: The University, 1969]

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Acute undifferentiated schizophrenia [videorecording] Source: [University of Mississippi Medical Center, Dept. of Psychiatry]; Year: 1969; Format: Videorecording; Jackson, Miss.: The University, [1969]

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Catatonic schizophrenia [motion picture] Source: Departments of Neurology and Psychiatry, University of Texas Medical Branch at Galveston; Year: 1971; Format:

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Motion picture; San Antonio, Tex.: Univ. of Texas at San Antonio, Dept. of Anatomy, 1971 •

Childhood schizophrenia [motion picture] Source: University of Michigan School of Medicine, Dept. of Psychiatry; Year: 1969; Format: Motion picture; [Ann Arbor, Mich.]: The Univ.: [for loan by Sandoz Pharmaceuticals, Medical Film Library, 196-?]

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Genetic and environmental factors in schizophrenia [videorecording] Source: Social Psychiatry Research Institute; Year: 1978; Format: Videorecording; [New York]: The Institute, [1978]

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Hemodialysis for the treatment of schizophrenia [sound recording] Source: Huxley Institute for Biosocial Research; Year: 1978; Format: Sound recording; New York: The Institute, [1978]

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New discussions in the treatment of schizophrenia [videorecording]: what clinicians should know about "naturalistic" studies Source: Interactive Medical Networks; [HSTN]; Year: 2003; Format: Videorecording; Carrollton, TX: PRIMEDIA Workplace Learning, c2003

•

Paranoid schizophrenia: delusional systems [videorecording] Source: Depts, of Neurology and Psychiatry, Columbia University College of Physicians and Surgeons; [made by] New York State Psychiatric Institute; Year: 1972; Format: Videorecording; New York: The Institute, [1972]

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Paranoid schizophrenia [videorecording] Source: [University of Mississippi Medical Center, Dept. of Psychiatry]; Year: 1969; Format: Videorecording; [Jackson, Miss.: The University, 1969]

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Prefrontal lobotomy in chronic schizophrenia [motion picture] Source: from the Psychiatric Department of the Bishop Clarkson Memorial Hospital; Year: 1944; Format: Motion picture; [Pennsylvania]: Psychological Cinema Register of the Pennsylvania State College, c1944

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Schizophrenia [filmstrip] Source: Trainex Corporation; Year: 1973; Format: Filmstrip; [Garden Grove, Calif.]: Trainex, c1973

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Schizophrenia [filmstrip] Source: Medical Electronic Educational Services; Year: 1975; Format: Filmstrip; Tucson, Ariz.: The Services, c1975

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Schizophrenia is a family affair [sound recording] Source: Huxley Institute for Biosocial Research; Year: 1978; Format: Sound recording; New York: The Institute, [1978]

•

Schizophrenia, paranoid type: differential diagnosis [videorecording]: hysterical neurosis, conversion type: schizophrenia, schizo-affective type Source: University of Mississippi Medical Center, Dept. of Psychiatry; Year: 1969; Format: Videorecording; [Jackson, Miss.: The University, 1969?]

•

Schizophrenic reaction, acute undifferentiated type [videorecording] Source: [University of Mississippi Medical Center, Dept. of Psychiatry]; Year: 1969; Format: Videorecording; [Jackson, Miss.: The University, 1969]

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Symptoms in schizophrenia [motion picture] Source: [produced by Psychological Cinema Register of the Pennsylvania State College]; Year: 1938; Format: Motion picture; University Park, Pa.: Psychological Cinema Register of the Pennsylvania State College, 1938

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The Clinical significance of blood histamine with & without schizophrenia [sound recording] Source: Huxley Institute for Biosocial Research; Year: 1978; Format: Sound recording; New York: The Institute, [1978]

•

The magic mirror of Aloyse [motion picture]: the artistic work of a schizophrenic patient Source: produced by the Center for the Study of Plastic Expression, Psychiatric

Multimedia 443

Clinic, University of Lausanne; [presented by] the Center for Mass Communication; Year: 1964; Format: Motion picture; [United States]: Center for Mass Communication, [1964]

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CHAPTER 9. PERIODICALS AND NEWS ON SCHIZOPHRENIA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover schizophrenia.

News Services and Press Releases One of the simplest ways of tracking press releases on schizophrenia is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “schizophrenia” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to schizophrenia. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “schizophrenia” (or synonyms). The following was recently listed in this archive for schizophrenia: •

Olfactory discrimination deficit precedes schizophrenia onset Source: Reuters Medical News Date: October 16, 2003

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Stimulating environment may curb schizophrenia Source: Reuters Health eLine Date: October 10, 2003

446 Schizophrenia

•

Stimulating childhood environment may help prevent schizophrenia Source: Reuters Medical News Date: October 10, 2003

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Late-onset schizophrenia sometimes a prelude to dementia Source: Reuters Medical News Date: September 29, 2003

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Late-onset schizophrenia can lead to dementia Source: Reuters Health eLine Date: September 29, 2003

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Abnormal gene expression similar in schizophrenia and bipolar disorder Source: Reuters Medical News Date: September 04, 2003

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Risperidone may increase osteoporosis risk in premenopausal schizophrenics Source: Reuters Medical News Date: August 20, 2003

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Doctors link social drive, smell in schizophrenia Source: Reuters Health eLine Date: June 09, 2003

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UK patients denied new schizophrenia drugs: charity Source: Reuters Health eLine Date: June 05, 2003

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UK patients denied new drugs for schizophrenia, group says Source: Reuters Medical News Date: June 05, 2003

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Patients with schizophrenia tolerate switch from Clozaril to generic clozapine: study Source: Reuters Medical News Date: May 21, 2003

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Mental risk high in children of schizophrenic mom Source: Reuters Health eLine Date: May 13, 2003

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Diuretics for maternal hypertension may increase schizophrenia risk in offspring Source: Reuters Medical News Date: March 14, 2003

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Magnet therapy may quiet "voices" in schizophrenia Source: Reuters Health eLine Date: January 30, 2003

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Community care in India improves outcomes of chronic schizophrenia Source: Reuters Medical News Date: January 29, 2003

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Maternal-fetal RhD genotype incompatibility increases schizophrenia risk Source: Reuters Medical News Date: December 25, 2002

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Dopamine receptor-interacting protein elevated in schizophrenic and bipolar patients Source: Reuters Medical News Date: December 16, 2002

Periodicals and News 447

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Australia scientists identify schizophrenia genes Source: Reuters Health eLine Date: November 26, 2002

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Marijuana smoking tied to depression, schizophrenia Source: Reuters Health eLine Date: November 22, 2002

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Rh incompatibility could up schizophrenia risk Source: Reuters Health eLine Date: November 19, 2002

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FDA approves aripiprazole for schizophrenia Source: Reuters Medical News Date: November 19, 2002

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Schizophrenia medication linked to heart risk Source: Reuters Health eLine Date: November 08, 2002

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FDA advisors back Novartis' Clozaril for suicide prevention in schizophrenics Source: Reuters Medical News Date: November 04, 2002

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Older fathers' kids face higher schizophrenia risk Source: Reuters Health eLine Date: September 06, 2002

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Advanced paternal age again linked to increases schizophrenia risk in offspring Source: Reuters Medical News Date: September 06, 2002

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FDA gives conditional approval for aripiprazole for schizophrenia Source: Reuters Medical News Date: September 03, 2002

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Key regulator of dopaminergic neurons decreased in brains of schizophrenics Source: Reuters Medical News Date: August 26, 2002

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Puzzling particles found in schizophrenia patients Source: Reuters Health eLine Date: August 23, 2002

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Micron-sized particles in cerebrospinal fluid may be a marker of schizophrenia Source: Reuters Medical News Date: August 23, 2002

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Clues to brain changes behind schizophrenia Source: Reuters Health eLine Date: August 16, 2002

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Brainwave finding differs in chronic and first-episode schizophrenics Source: Reuters Medical News Date: August 16, 2002

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Celecoxib hastens response to risperidone in patients with schizophrenia Source: Reuters Medical News Date: June 14, 2002

448 Schizophrenia

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UK health body backs newer schizophrenia drugs Source: Reuters Health eLine Date: June 06, 2002

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Japanese society updates term for schizophrenia Source: Reuters Health eLine Date: May 28, 2002

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CORRECTION: US FDA investigates schizophrenia drug tampering Source: Reuters Health eLine Date: May 09, 2002

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US FDA investigates schizophrenia drug tampering Source: Reuters Health eLine Date: May 08, 2002

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Company defends schizophrenia drug Source: Reuters Health eLine Date: May 07, 2002

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Britain alerts doctors over schizophrenia drug Source: Reuters Health eLine Date: May 03, 2002

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Schizophrenia impacts women differently than men Source: Reuters Health eLine Date: April 16, 2002

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FDA approves Risperdal for relapsing schizophrenia Source: Reuters Medical News Date: March 14, 2002

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Gene activity linked to schizophrenia: studies Source: Reuters Health eLine Date: March 12, 2002

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Loci on chromosome 22 linked to schizophrenia susceptibility Source: Reuters Medical News Date: March 11, 2002

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Company strengthens warning on schizophrenia drug Source: Reuters Health eLine Date: February 21, 2002

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Minor physical anomalies linked to schizophrenia spectrum disorders Source: Reuters Medical News Date: February 11, 2002

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Prefrontal cortical activity and dopaminergic function linked in schizophrenia Source: Reuters Medical News Date: January 30, 2002

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Risperidone superior to haloperidol in preventing relapse in schizophrenics Source: Reuters Industry Breifing Date: January 03, 2002

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Drug helps prevent relapse in schizophrenia Source: Reuters Health eLine Date: January 02, 2002

Periodicals and News 449

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Isolation of minorities ups schizophrenia risk Source: Reuters Health eLine Date: December 13, 2001

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Urban upbringing tied to risk of schizophrenia Source: Reuters Health eLine Date: November 20, 2001

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Urban upbringing linked with increased schizophrenia risk Source: Reuters Medical News Date: November 20, 2001 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “schizophrenia” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “schizophrenia” (or synonyms). If you know the name of a company that is relevant to schizophrenia, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “schizophrenia” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “schizophrenia” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on schizophrenia: •

Medications and Their Effects on the Voice Source: Voice Foundation Newsletter. 5(2): 1, 5-6. April 1999. Contact: Available from Voice Foundation. 1721 Pine Street, Philadelphia, PA 19103. (215) 735-7999. Fax (215) 735-9293. E-mail: [email protected]. Summary: This newsletter article, the third in a series of three, summarizes the vocal consequences of many common types of psychoactive medications. The author reviews the vocal impact of antidepressant drugs, anticonvulsant agents, antianxiety drugs, and antipsychotic drugs (primarily for schizophrenia). For each type of drug, the author discusses the indications, the side effects that may be encountered, and the different specific drugs in that category. The author concludes with a brief discussion of the ongoing psychiatric treatment of singers and of any patients with voice disorders, focusing on the need for a careful evaluation of current and prior psychoactive drug therapy. In addition, numerous psychoactive substances are used in the medical management of various neurological conditions, pain syndromes, and vertigo. The laryngologist, singing teacher, and psychological professional on the voice team must collaborate to help identify symptoms which may be causally related to drug side effects and to avoid drug interactions.

Academic Periodicals covering Schizophrenia Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to schizophrenia. In addition to these sources, you can search for articles covering schizophrenia that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles.

Periodicals and News 451

At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for schizophrenia. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with schizophrenia. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

454 Schizophrenia

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to schizophrenia: Amantadine •

Systemic - U.S. Brands: Symmetrel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202024.html

Amphetamines •

Systemic - U.S. Brands: Adderall; Desoxyn; Desoxyn Gradumet; Dexedrine; Dexedrine Spansule; DextroStat http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202031.html

Barbiturates •

Systemic - U.S. Brands: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202031.html

Carbamazepine •

Systemic - U.S. Brands: Atretol; Carbatrol; Epitol; Tegretol; Tegretol-XR http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202111.html

Clozapine •

Systemic - U.S. Brands: Clozaril http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202157.html

Haloperidol •

Systemic - U.S. Brands: Haldol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202278.html

Lithium •

Systemic - U.S. Brands: Cibalith-S; Eskalith; Lithane; Lithobid; Lithonate; Lithotabs http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202330.html

Olanzapine •

Systemic - U.S. Brands: Zyprexa http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203492.html

Phenothiazines •

Systemic - U.S. Brands: Chlorpromazine Hydrochloride Intensol; Compazine; Compazine Spansule; Mellaril; Mellaril Concentrate; Mellaril-S; Permitil; Permitil Concentrate; Prolixin; Prolixin Concentrate; Prolixin Decanoate; Prolixin Enanthate; Serentil; Serentil Concentrate; Ste http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202457.html

Pimozide •

Systemic - U.S. Brands: Orap http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202466.html

Researching Medications 455

Quetiapine •

Systemic - U.S. Brands: Seroquel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203124.html

Risperidone •

Systemic - U.S. Brands: Risperdal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202769.html

Ziprasidone •

Systemic - U.S. Brands: Geodon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500283.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute13: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

13

These publications are typically written by one or more of the various NIH Institutes.

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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.14 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:15 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

14

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 15 See http://www.nlm.nih.gov/databases/databases.html.

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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway16 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “schizophrenia” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 61166 2133 147 127 80 63653

HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.20 Simply search by “schizophrenia” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

16

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

17

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 18 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 19 20

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists21 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.22 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Schizophrenia In the following section, we will discuss databases and references which relate to the Genome Project and schizophrenia. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).24 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 21 Adapted 22

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 23 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 24 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “schizophrenia” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for schizophrenia: •

Disrupted in Schizophrenia 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605210

•

Disrupted in Schizophrenia 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606271

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Schizophrenia Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?181500

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Schizophrenia 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?181510

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Schizophrenia 10 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605419

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Schizophrenia 11 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?608078

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Schizophrenia 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603342

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Schizophrenia 3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600511

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Schizophrenia 4 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600850

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Schizophrenia 5 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603175

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Schizophrenia 6 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603013

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Schizophrenia 7 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603176

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Schizophrenia 8 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603206

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Schizophrenia 9 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604906 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed:

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•

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “schizophrenia” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database25 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html.

25

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.

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The Genome Database26 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “schizophrenia” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

26

Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

469

APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on schizophrenia can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to schizophrenia. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to schizophrenia. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “schizophrenia”:

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Other guides Bipolar Disorder http://www.nlm.nih.gov/medlineplus/bipolardisorder.html Child Mental Health http://www.nlm.nih.gov/medlineplus/childmentalhealth.html Hepatitis C http://www.nlm.nih.gov/medlineplus/hepatitisc.html Mental Health http://www.nlm.nih.gov/medlineplus/mentalhealth.html Movement Disorders http://www.nlm.nih.gov/medlineplus/movementdisorders.html Multiple Sclerosis http://www.nlm.nih.gov/medlineplus/multiplesclerosis.html Post-Traumatic Stress Disorder http://www.nlm.nih.gov/medlineplus/posttraumaticstressdisorder.html Schizophrenia http://www.nlm.nih.gov/medlineplus/schizophrenia.html Suicide http://www.nlm.nih.gov/medlineplus/suicide.html

Within the health topic page dedicated to schizophrenia, the following was listed: •

Diagnosis/Symptoms Schizophrenia: First Warning Signs http://www.world-schizophrenia.org/publications/20-warnings.html

•

Treatment FDA Approves Clozaril to Reduce the Risk of Suicidal Behavior in Patients with Schizophrenia or Schizoaffective Disorder Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01184.html Medications Source: National Institute of Mental Health http://www.nimh.nih.gov/publicat/medicate.cfm Mental Health Providers: Making the Right Choice Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=MH00008

•

Coping Maintaining Your Own Health: For Family Members of People with Brain Disorders Source: World Fellowship for Schizophrenia and Allied Disorders http://www.world-schizophrenia.org/publications/07-health.html

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Schizophrenia: How Should One Behave? Source: World Fellowship for Schizophrenia and Allied Disorders http://www.world-schizophrenia.org/publications/17a-behave.html •

Specific Conditions/Aspects Schizophrenia and Suicide Source: World Fellowship for Schizophrenia and Allied Disorders http://www.world-schizophrenia.org/publications/23-suicide.html Schizophrenia: Schizoaffective Disorder Source: National Mental Health Association http://www.nmha.org/infoctr/factsheets/52.cfm

•

Children Childhood-Onset Schizophrenia: An Update Source: National Institute of Mental Health http://www.nimh.nih.gov/publicat/schizkids.cfm

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Latest News Late-Onset Schizophrenia Can Lead to Dementia Source: 09/29/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14123 .html Stimulating Environment May Curb Schizophrenia Source: 10/10/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14256 .html

•

Organizations National Alliance for the Mentally Ill http://www.nami.org/ National Institute of Mental Health http://www.nimh.nih.gov/ National Mental Health Association http://www.nmha.org/ World Fellowship for Schizophrenia and Allied Disorders http://www.world-schizophrenia.org/

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.

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The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on schizophrenia. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Asperger's Disorder Source: Bethesda, MD: Autism Society of America. 199x. 8 p. Contact: Available from Autism Society of America. 7910 Woodmont Avenue, Suite 300, Bethesda, MD 20814-3067. (800) 328-8476 or (301) 657-0881. Fax (301) 657-0869. Website: www.autism-society.org. PRICE: $7.00 for members; $10.00 for non-members, plus shipping and handling. Also available for free at www.autismsociety.org/packages/packages.html. Summary: This fact sheet, from the Autism Society of America (ASA), gives parents an overview of Asperger's disorder. The diagnostic criteria for Asperger's disorder includes qualitative impairment in social interaction; restricted repetitive and stereotyped patterns of behavior, interests and activities; clinically significant impairment in social, occupational, or other important areas of functioning; no clinically significant general delay in language; no clinically significant delay in cognitive development or in the development of age appropriate self help skills, adaptive behavior (other than in social interaction) and curiosity about the environment in childhood; and criteria are not met for another specific pervasive developmental disorder (PDD) or schizophrenia. The fact sheet notes that controversy still exists about whether or not Asperger's is a type of autism. Topics covered include how the diagnosis of Asperger's differs from autism, effective strategies for working with an individual with Asperger's, and the support functions of the ASA. The second half of the fact sheet lists resources for additional information, including periodicals, audio cassettes (mostly conference proceedings), web sites (particularly places to order related books), and the mailing addresses of related organizations and publishers. Each page of the fact sheet includes the contact information for the Society (www.autism-society.org).

•

Glossary of symptoms and mental illnesses affecting teenagers Source: American Academy of Child and Adolescent Psychiatry. 1997. 2 pp. Contact: Available from American Academy of Child and Adolescent Psychiatry, 3615 Wisconsin Avenue, N.W, Washington, DC 20016. Telephone: (202) 966-7300 / fax: (202) 966-2891 / e-mail: [email protected] / Web site: http://www.aacap.org. Available at no charge. Summary: This glossary, written for health professionals, educators, parents, and adolescents, provides information about various mental health issues that affect many adolescents. Included in this list are: alcohol and drug use, anorexia nervosa, anxiety, attention deficit/hyperactivity disorder, bipolar disorder (manic depression), bulimia nervosa, conduct disorder, depression, learning disorder, obsessive-compulsive disorders, physical abuse, post-traumatic stress disorder, psychosis, schizophrenia, sexual abuse, suicide, and Tourette's syndrome. A definition and list of symptoms are included for each of the disorders listed in the glossary.

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The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “schizophrenia” (or synonyms). The following was recently posted: •

Practice parameter for the assessment and treatment of children and adolescents with schizophrenia Source: American Academy of Child and Adolescent Psychiatry - Medical Specialty Society; 2000 June 6; 40 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3017&nbr=2243&a mp;string=schizophrenia

•

Psychosocial interventions in the management of schizophrenia. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1998 October; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2904&nbr=2130&a mp;string=schizophrenia Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Schizophrenia Summary: Current research-based information is provided for people with schizophrenia, their family members, friends, and the general public about the symptoms and diagnosis of schizophrenia, possible causes, Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=160

•

Schizophrenia: Real Lives Ravaged by Imaginary Terror: Drugs, Therapy Can Turn Life Around for Some Summary: This consumer health information article discusses the devastation caused to families and patients by schizophrenia and how drugs and therapy can help. Source: U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3586

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•

When Someone Has Schizophrenia Summary: This 3-page factsheet describes schizophrenia, research being conducted about the disease, and its treatment. Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6634 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to schizophrenia. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources

A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Associations and Schizophrenia The following is a list of associations that provide information on and resources relating to schizophrenia: •

Bazelon Center for Mental Health Law Telephone: (202) 467-5730 Fax: (202) 223-0409 Email: [email protected] Web Site: http://www.bazelon.org Background: The Bazelon Center for Mental Health Law is a national not-for-profit organization that uses litigation and federal policy reform to define and uphold the legal

Patient Resources 475

rights of children, adults, and elderly individuals with mental disabilities and to create approaches to meeting their needs that will assure them choice and dignity. Staff attorneys provide training and technical assistance to legal services, protection and advocacy, state ombudsman programs, and other advocates for low income individuals and families. The Center was formed in 1972 as the Mental Health Law Project; however, its name was changed in 1993 to honor the late Chief Justice of the U.S. Court of Appeals of the District of Columbia Circuit, David L. Bazelon. The Center publishes issue papers, booklets, manuals, and periodic newsletters explaining and interpreting major federal laws and regulations that protect the rights of and make resources available to children and adults with disabilities. Relevant area(s) of interest: Schizophrenia •

Dana Alliance for Brain Initiatives Telephone: (212) 223-4040 Fax: (212) 593-7623 Email: [email protected] Web Site: http://www.dana.org Background: The Dana Alliance for Brain Initiatives, a nonprofit organization supported by the Charles A. Dana Foundation, was established as an alliance of neuroscientists dedicated to providing information and promoting understanding concerning the personal and public benefits of brain research. (The Charles A. Dana Foundation is a private philanthropic foundation with grant programs in health and education.) According to the Alliance, approximately one in five Americans is affected by a brain disease or disorder, ranging from learning disabilities to Parkinson s Disease from epilepsy to spinal cord injuries. The Dana Alliance for Brain Initiatives is dedicated to answering questions concerning brain-related research and providing information concerning new developments. The Alliance offers a variety of periodicals, newsletters, reports, reference works, and books. Relevant area(s) of interest: Schizophrenia

•

Harvard Brain Tissue Resource Center Telephone: (617) 855-2400 Toll-free: (800) 272-4622 Fax: (617) 855-3199 Email: [email protected] Web Site: http://www.brainbank.mclean.org:8080 Background: The Harvard Brain Tissue Resource Center is a federally funded, not-forprofit organization, dedicated to serving as a national resource for the collection and distribution of postmortem brain tissues for medical research into the causes of neurological and psychiatric disorders. The Brain Bank is interested in the study of Huntington s, Alzheimer s, and Parkinson s diseases, progressive supranuclear palsy (PSP), amyotrophic lateral sclerosis (ALS), Tourette and Rett syndromes, and autism, as well as schizophrenia and manic depressive illnesses. The Center distributes brain tissue samples, at no charge, to qualified investigators in the United States who are involved in studying the neurobiology of these disorders. Relevant area(s) of interest: Schizophrenia

476 Schizophrenia

•

National Alliance for the Mentally Ill Telephone: (703) 524-7600 Toll-free: (800) 950-6264 Fax: (703) 524-9094 Email: [email protected] Web Site: http://www.nami.org Background: The National Alliance for the Mentally Ill (NAMI) is a not-for-profit voluntary health organization dedicated to providing mutual support, education, advocacy, and research funding for people affected by mental illness, their families, and friends. The organization also serves those who have been diagnosed with schizophrenic depression and other related disorders. Established in 1979, this self-help organization refers individuals to nationwide support groups, services, and outreach programs. Educational materials produced by the organization include a database, directories, annual reports, informational brochures, pamphlets, a bimonthly newsletter entitled 'The Advocate,' and 'The Decade of the Brain,' NAMI's quarterly publication for presenting research, clinical practices and advances, and policy updates relevant to serious brain disorders. Relevant area(s) of interest: Schizophrenia

•

National Mental Health Association Telephone: (703) 684-7722 Toll-free: (800) 969-6642 Fax: (703) 684-5968 Email: [email protected] Web Site: http://www.nmha.org Background: Established in 1909, the National Mental Health Association (NMHA) is a not-for-profit voluntary organization that addresses the mental health needs of individuals throughout the United States. The Association, which has over 300 affiliates in 35 states, has a network of volunteers across the country that work to meet the mental health needs of their communities. Activities include support groups, community outreach and education, information and referral programs, patient advocacy, and a wide array of other services. Nationally, the Association works with the media to keep the public informed about mental health and mental illness and with the Federal government to promote research and services for people with mental health problems. The Association also works with other major organizations to ensure that the nation s mental health needs are understood and addressed. Services include fact sheet and pamphlet distribution; buddy and companion programs; client services and case management; education and training programs; referral services; and social and recreational programs, workshops, and seminars. Educational materials distributed by the Association include quarterly newsletters entitled 'Prevention Update' and 'The Bell.'. Relevant area(s) of interest: Schizophrenia

•

New Directions for People with Disabilities, Inc Telephone: (805) 967-2841 Toll-free: (888) 967-2841 Fax: (805) 964-7344 Email: [email protected]

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Web Site: NewDirectionsTravel.com Background: New Directions for People with Disabilities, Inc., a not-for-profit organization established in 1985, is dedicated to providing local, national, and international travel and foreign exchange programs for people with disabilities. The purpose of the programs is to promote the understanding, acceptance, and appreciation of people with disabilities as important and contributing members of our society as well as to promote a sense of accomplishment, belonging, and self-worth for participants by providing a wide range of challenging activities. Such activities include skiing, river rafting, biking tours, and hot air ballooning. The Tour Guides/Chaperones are special educational instructors, recreation therapists, residential counselors, nurses, nurses aides, vocational and independent living skill counselors, and other professional staff who have been trained to work with people with disabilities. Each year, New Directions serves over 350 children, adults, and seniors who have developmental, emotional, and physical disabilities such as cerebral palsy, Down Syndrome, autism, schizophrenia, blindness, hearing impairment, and mental retardation. Participants live in state hospitals, board and care homes, residential treatment centers, and nursing homes. Most have not previously had a vacation, and many have not been away from their facilities or treatment centers for 10 or more years. New Directions annually sponsors trips in the United States and abroad to locations including Hawaii, Washington D.C., New York City, Las Vegas, Disneyland, the Grand Canyon, Australia, Ireland, Japan, and Mexico. Relevant area(s) of interest: Schizophrenia •

SANE Australia Telephone: 61 3 9682 5933 Toll-free: 1800 688 382 Fax: 61 3 9682 5944 Email: [email protected] Web Site: http://www.sane.org Background: SANE Australia is a national voluntary organization dedicated to improving the well-being of Australians affected by mental illness. Established in 1986, the organization is committed to promoting and conducting research, developing innovative resources for affected individuals and families, and campaigning for improved awareness, attitudes, and services. SANE Australia works to fulfill its mission and objectives by offering an information and referral helpline for Australian callers who are concerned about mental illness; conducting research into the effects of mental illness; promoting public awareness through media campaigns, sponsorships, and other activities; and having an informational network of over 100 community organizations across Australia that are dedicated to working with people affected by mental illness. The organization also develops a wide range of print and multimedia resources that explain mental illness and related issues in understandable language, including fact sheets, booklets, educational software, videotapes, audiotapes, a magazine entitled 'SANE News,' and a series entitled 'SANE Blueprints' that focuses on helping individuals affected by mental illness live in the community. Relevant area(s) of interest: Schizophrenia

•

Schizophrenia Society of Canada Telephone: (905) 415-2007 Toll-free: (888) 772-4673 Fax: (905) 415-2337 Email: [email protected]

478 Schizophrenia

Web Site: http://www.schizophrenia.ca Background: Founded in 1979, the Schizophrenia Society of Canada (SSC) is a national registered charity whose mission is to alleviate the suffering caused by schizophrenia and related mental disorders. SSC works with 10 provincial societies and their more than 100 chapters and branches to help affected individuals and their families have a better quality of life, while also searching for a cure. SSC is committed to: raising awarness and educating the public to help reduce stigma and discrimination; supporting families and individuals with formation and educational materials; advocating for legislative change and improved treatment and services; and supporting research through the SSC Foundation and other independent efforts.

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to schizophrenia. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with schizophrenia. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about schizophrenia. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “schizophrenia” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information.

Patient Resources 479

The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “schizophrenia”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “schizophrenia” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “schizophrenia” (or a synonym) into the search box, and click “Submit Query.”

481

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.27

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

27

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

482 Schizophrenia

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)28: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

28

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries 483

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

484 Schizophrenia

•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries 485

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

486 Schizophrenia

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

487

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on schizophrenia: •

Basic Guidelines for Schizophrenia Autism Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001526.htm Schizophrenia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000928.htm Schizophrenia - disorganized (hebephrenic) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000937.htm Schizophrenia - paranoid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000936.htm

•

Signs & Symptoms for Schizophrenia Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm

488 Schizophrenia

Excitement Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Hallucinations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003258.htm Hyperactivity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003256.htm Stupor Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm •

Diagnostics and Tests for Schizophrenia CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Ceruloplasmin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003662.htm Chest X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm EEG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003931.htm Lumbar puncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003428.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Porphobilinogen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003596.htm Sedimentation rate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003638.htm Toxicology screen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003578.htm Urinalysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003579.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm

Online Glossaries 489

•

Background Topics for Schizophrenia Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm LSD Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001945.htm Stimulus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002309.htm Substance abuse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001945.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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SCHIZOPHRENIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH]

ACE Inhibitor: A type of drug used to lower blood pressure. Studies indicate that it may also help prevent or slow the progression of kidney disease in people with diabetes. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH]

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Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aetiology: Study of the causes of disease. [EU] Affective Symptoms: Mood or emotional responses dissonant with or inappropriate to the behavior and/or stimulus. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH]

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Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha Cell: A type of cell in the pancreas (in areas called the islets of Langerhans). Alpha cells make and release a hormone called glucagon, which raises the level of glucose (sugar) in the blood. [NIH] Alpha-Linolenic Acid: A fatty acid that is found in plants and involved in the formation of prostaglandins. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical

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compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analeptic: A drug which acts as a restorative, such as caffeine, amphetamine, pentylenetetrazol, etc. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast

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cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Annual Reports: Annual statements concerning the administrative and operational functions of an institution or organization. [NIH] Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]

Anosmia: Absence of the sense of smell; called also anosphrasia and olfactory anaesthesia. [EU]

Anoxia: Clinical manifestation of respiratory distress consisting of a relatively complete absence of oxygen. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH]

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Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]

Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Anthropology: The science devoted to the comparative study of man. [NIH] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidepressive Agents: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several monoamine oxidase inhibitors are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents also appear to act through brain catecholamine systems. A third group (antidepressive agents, secondgeneration) is a diverse group of drugs including some that act specifically on serotonergic systems. [NIH] Antidopaminergic: Preventing or counteracting (the effects of) dopamine. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antiepileptic: An agent that combats epilepsy. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU]

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Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipsychotic Agents: Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in schizophrenia, senile dementia, transient psychosis following surgery or myocardial infarction, etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. [NIH] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [NIH]

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Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Artifacts: Any visible result of a procedure which is caused by the procedure itself and not by the entity being analyzed. Common examples include histological structures introduced by tissue processing, radiographic images of structures that are not naturally present in living tissue, and products of chemical reactions that occur during analysis. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements.

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This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audition: The sense of hearing. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Auditory Cortex: Area of the temporal lobe concerned with hearing. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autopsy: Postmortem examination of the body. [NIH] Autoreceptors: Transmitter receptors on or near presynaptic terminals (or varicosities) which are sensitive to the transmitter(s) released by the terminal itself. Receptors for the hormones released by hormone-releasing cells are also included. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease;

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neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Binaural: Used of the two ears functioning together. [NIH] Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU]

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Biochemical Phenomena: Biochemical functions, activities, and processes at organic and molecular levels in humans, animals, microorganisms, and plants. [NIH] Biogenic Monoamines: Biogenic amines having only one amine moiety. Included in this group are all natural monoamines formed by the enzymatic decarboxylation of natural amino acids. [NIH] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological Phenomena: Biological functions and activities at the organic and molecular levels in humans, animals, microorganisms, and plants. For biochemical and metabolic processes, biochemical phenomena is available. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Birth Rate: The number of births in a given population per year or other unit of time. [NIH] Bladder: The organ that stores urine. [NIH] Blinking: Brief closing of the eyelids by involuntary normal periodic closing, as a protective measure, or by voluntary action. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a

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network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinesia: Abnormal slowness of movement; sluggishness of physical and mental responses. [EU] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broadband: A wide frequency range. Sound whose energy is distributed over a broad range of frequency (generally, more than one octave). [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be

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found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins or activator proteins. [NIH] Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency, or other output. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Cannabis: The hemp plant Cannabis sativa. Products prepared from the dried flowering tops of the plant include marijuana, hashish, bhang, and ganja. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU]

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Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and

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secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and

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the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH]

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Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Choroid Plexus: A villous structure of tangled masses of blood vessels contained within the third, lateral, and fourth ventricles of the brain. It regulates part of the production and composition of cerebrospinal fluid. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]

Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which

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causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzymes: Substances that are necessary for the action or enhancement of action of an enzyme. Many vitamins are coenzymes. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH]

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Competency: The capacity of the bacterium to take up DNA from its surroundings. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Compulsion: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray

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machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Contrast Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of this visual function are used to evaluate visual acuity and to detect eye disease. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH]

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Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cribriform: Pierced with small holes as in a sieve. Refers to the appearance of a tumor when viewed under a microscope. The tumor appears to have open spaces or small holes inside. [NIH]

Criterion: A standard by which something may be judged. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used

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with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Custom-made: Any active implantable medical device specifically made in accordance with a medical specialist's written prescription which gives, under his responsibility, specific design characteristics and is intended to be used only for an individually named patient. [NIH]

Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cycloserine: Antibiotic substance produced by Streptomyces garyphalus. It may be used in the treatment of resistant tuberculosis as part of a multi-drug regimen. It has also been used in urinary tract infections. [NIH] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU]

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Delusion: A false belief, not susceptible to argument or reason, and determined, pathologically, by some form of mental disorder. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demyelinating Diseases: Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH]

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Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diathesis: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the person more than usually susceptible to certain diseases. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of

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the environment, or lightheadedness. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Antagonists: Drugs that bind to but do not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (antipsychotic agents) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as antiemetics, in the treatment of Tourette syndrome, and for hiccup. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dosage schedule: A scheme set up to determine and regulate size, frequency and number of doses. [EU] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Dreams: A series of thoughts, images, or emotions occurring during sleep which are dissociated from the usual stream of consciousness of the waking state. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Approval: Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH]

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Duodenum: The first part of the small intestine. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysphagia: Difficulty in swallowing. [EU] Dysphonia: Difficulty or pain in speaking; impairment of the voice. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electric Conductivity: The ability of a substrate to allow the passage of electrons. [NIH] Electric shock: A dangerous patho-physiological effect resulting from an electric current passing through the body of a human or animal. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU]

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Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Electroshock: Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

Emetic: An agent that causes vomiting. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium,

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vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH]

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Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH]

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Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Factor V: Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Relations: Behavioral, psychological, and social relations among various members of the nuclear family and the extended family. [NIH] Family Therapy: A form of group psychotherapy. It involves treatment of more than one member of the family simultaneously in the same session. [NIH] Famotidine: A competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect is the inhibition of gastric secretion. [NIH] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetal Development: Morphologic and physiologic growth and development of the

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mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Financial Management: The obtaining and management of funds for institutional needs and responsibility for fiscal affairs. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Fluphenazine: A phenothiazine used in the treatment of psychoses. Its properties and uses are generally similar to those of chlorpromazine. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH]

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Fornix: A bundle of nerves connected to the hippocampus. [NIH] Fosinopril: A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that is converted to its active metabolite fosinoprilat. [NIH] Fossa: A cavity, depression, or pit. [NIH] Free Association: Spontaneous verbalization of whatever comes to mind. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [NIH] Galactosemia: Buildup of galactose in the blood. Caused by lack of one of the enzymes needed to break down galactose into glucose. [NIH] Galanthamine: A cholinesterase inhibitor. It has been used to reverse the muscular effects of gallamine and tubocurarine and has been studied as a treatment for Alzheimer's disease and other central nervous system disorders. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as

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a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genes, pol: DNA sequences that form the coding region for retroviral enzymes including reverse transcriptase, protease, and endonuclease/integrase. "pol" is short for polymerase, the enzyme class of reverse transcriptase. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Geniculate Bodies: Part of the diencephalon inferior to the caudal end of the dorsal thalamus. Includes the lateral geniculate body which relays visual impulses from the optic tract to the calcarine cortex, and the medial geniculate body which relays auditory impulses from the lateral lemniscus to the auditory cortex. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric Psychiatry: A subspecialty of psychiatry concerned with the mental health of the aged. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH]

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Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamate Dehydrogenase: An enzyme that catalyzes the conversion of L-glutamate and water to 2-oxoglutarate and NH3 in the presence of NAD+. (From Enzyme Nomenclature, 1992) EC 1.4.1.2. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are

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different for each type of cancer. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guideline Adherence: Conformity in fulfilling or following official, recognized, or institutional requirements, guidelines, recommendations, protocols, pathways, or other standards. [NIH] Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of the limbic system. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Habituation: Decline in response of an organism to environmental or other stimuli with repeated or maintained exposure. [NIH] Hallucination: A sense perception without a source in the external world; a perception of an external stimulus object in the absence of such an object. [EU] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [NIH] Handedness: Preference for using right or left hand. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]

Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors

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influencing life style are socioeconomic, educational, and cultural. [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemoperfusion: Removal of toxins or metabolites from the circulation by the passing of blood, within a suitable extracorporeal circuit, over semipermeable microcapsules containing adsorbents (e.g., activated charcoal) or enzymes, other enzyme preparations (e.g., gel-entrapped microsomes, membrane-free enzymes bound to artificial carriers), or other adsorbents (e.g., various resins, albumin-conjugated agarose). [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring.

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2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH]

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Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypomania: An abnormality of mood resembling mania (persistent elevated or expansive mood, hyperactivity, inflated self-esteem, etc.) but of lesser intensity. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Ibotenic Acid: Neurotoxic isoxazole substance found in Amanita muscaria and A. pantherina. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [NIH] Ileus: Obstruction of the intestines. [EU]

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Illusion: A false interpretation of a genuine percept. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]

Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantable pump: A small device installed under the skin to administer a steady dose of drugs. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in

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walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infuse: To pour (a liquid) into something. [EU] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Institutionalization: The caring for individuals in institutions and their adaptation to routines characteristic of the institutional environment, and/or their loss of adaptation to life outside the institution. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH]

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Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrase: An enzyme that inserts DNA into the host genome. It is encoded by the pol gene of retroviruses and also by temperate bacteriophages, the best known being bacteriophage lambda. EC 2.7.7.-. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Capsule: White matter pathway, flanked by nuclear masses, consisting of both afferent and efferent fibers projecting between the cerebral cortex and the brainstem. It consists of three distinct parts: an anterior limb, posterior limb, and genu. [NIH] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interpersonal Relations: The reciprocal interaction of two or more persons. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH]

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Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isopropyl: A gene mutation inducer. [NIH] Jealousy: An irrational reaction compounded of grief, loss of self-esteem, enmity against the rival and self criticism. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lactation: The period of the secretion of milk. [EU] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called

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colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lateral Ventricles: Cavity in each of the cerebral hemispheres derived from the cavity of the embryonic neural tube. They are separated from each other by the septum pellucidum, and each communicates with the third ventricle by the foramen of Monro, through which also the choroid plexuses of the lateral ventricles become continuous with that of the third ventricle. [NIH] Laterality: Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lenticular: 1. Pertaining to or shaped like a lens. 2. Pertaining to the crystalline lens. 3. Pertaining to the lenticular nucleus. [EU] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH]

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Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Lod: The lowest analyte content which, if actually present, will be detected with reasonable

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statistical certainty and can be identified according to the identification criteria of the method. If both accuracy and precision are constant over a concentration range. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] Loxapine: An antipsychotic agent used in schizophrenia. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumbar puncture: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a spinal tap. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH]

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Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Magnetoencephalography: The measurement of magnetic fields over the head generated by electric currents in the brain. As in any electrical conductor, electric fields in the brain are accompanied by orthogonal magnetic fields. The measurement of these fields provides information about the localization of brain activity which is complementary to that provided by electroencephalography. Magnetoencephalography may be used alone or together with electroencephalography, for measurement of spontaneous or evoked activity, and for research or clinical purposes. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH]

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Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Maternal Deprivation: Prolonged separation of the offspring from the mother. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] Mediodorsal Thalamic Nucleus: The largest of the medial nuclei of the thalamus. It makes extensive connections with most of the other thalamic nuclei. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some

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primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Health Services: Organized services to provide mental health care. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular

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animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat, especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Mode of Transmission: Hepatitis A [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the

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same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Monogenic: A human disease caused by a mutation in a single gene. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Perception: The real or apparent movement of objects through the visual field. [NIH] Motivations: The most compelling inner determinants of human behavior; also called drives, urges, impulses, needs, wants, tensions, and willful cravings. [NIH] Motor Cortex: Area of the frontal lobe concerned with primary motor control. It lies anterior to the central sulcus. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat

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(lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Muscimol: Neurotoxic isoxazole isolated from Amanita muscaria and A. phalloides and also obtained by decarboxylation of ibotenic acid. It is a potent agonist at GABA-A receptors and is used mainly as an experimental tool in animal and tissue studies. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelin Sheath: The lipid-rich sheath investing many axons in both the central and peripheral nervous systems. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (Schwann cells in the peripheral and oligodendroglia in the central nervous system). Deterioration of the sheath in demyelinating diseases is a serious clinical problem. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable

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tendency to fall asleep. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Natural Language Processing: Computer processing of a language with rules that reflect and describe current usage rather than prescribed usage. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needs Assessment: Systematic identification of a population's needs or the assessment of individuals to determine the proper level of services needed. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU]

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Neuregulin-1: A peptide factor originally identified by its ability to stimulate the phosphorylation the erbB-2 receptor. It is a ligand for the erbB-3 receptor and the erbB-4 receptor. Variant forms of neuregulin-1 occur through alternative splicing of its mRNA. [NIH]

Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]

Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuropil: A dense intricate feltwork of interwoven fine glial processes, fibrils, synaptic

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terminals, axons, and dendrites interspersed among the nerve cells in the gray matter of the central nervous system. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neurosciences: The scientific disciplines concerned with the embryology, anatomy, physiology, biochemistry, pharmacology, etc., of the nervous sytem. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotensin: A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]

Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

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Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Family: A family composed of spouses and their children. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH]

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Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Olfaction: Function of the olfactory apparatus to perceive and discriminate between the molecules that reach it, in gas form from an external environment, directly or indirectly via the nose. [NIH] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Olfactory Nerve: The 1st cranial nerve. The olfactory nerve conveys the sense of smell. It is formed by the axons of olfactory receptor neurons which project from the olfactory epithelium (in the nasal epithelium) to the olfactory bulb. [NIH] Oligodendroglia: A class of neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal satellite cells according to their location. The most important recognized function of these cells is the formation of the insulating myelin sheaths of axons in the central nervous system. [NIH] Oligodendroglial: A cell that lays down myelin. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Orofacial: Of or relating to the mouth and face. [EU] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more

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concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in

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different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Paranoia: A psychotic disorder marked by persistent delusions of persecution or delusional jealousy and behaviour like that of the paranoid personality, such as suspiciousness, mistrust, and combativeness. It differs from paranoid schizophrenia, in which hallucinations or formal thought disorder are present, in that the delusions are logically consistent and that there are no other psychotic features. The designation in DSM III-R is delusional (paranoid) disorders, with five types : persecutory, jealous, erotomanic, somatic, and grandiose. [EU] Paranoid Personality Disorder: A personality disorder characterized by the avoidance of accepting deserved blame and an unwarranted view of others as malevolent. The latter is expressed as suspiciousness, hypersensitivity, and mistrust. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Paternal Age: Age of the father. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be

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used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Peduncle: A narrow supporting part, a stem. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perazine: A phenothiazine antipsychotic with actions and uses similar to those of chlorpromazine. Extrapyramidal symptoms may be more common than other side effects. [NIH]

Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perennial: Lasting through the year of for several years. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Perivascular: Situated around a vessel. [EU] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Perphenazine: An antipsychotic phenothiazine derivative with actions and uses similar to those of chlorpromazine. [NIH] Personality Development: Growth of habitual patterns of behavior in childhood and adolescence. [NIH] Personality Disorders: A major deviation from normal patterns of behavior. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [NIH]

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Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-Daspartate). As a drug of abuse, it is known as PCP and Angel Dust. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

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Pilot study: The initial study examining a new method or treatment. [NIH] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Policy Making: The decision process by which individuals, groups or institutions establish policies pertaining to plans, programs or procedures. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polydipsia: Chronic excessive thirst, as in diabetes mellitus or diabetes insipidus. [EU] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand

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as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Polyuria: Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [NIH] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of

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health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predictive factor: A situation or condition that may increase a person's risk of developing a certain disease or disorder. [NIH] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Preventive Medicine: A medical specialty primarily concerned with prevention of disease and the promotion and preservation of health in the individual. [NIH] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [NIH] Private Practice: Practice of a health profession by an individual, offering services on a person-to-person basis, as opposed to group or partnership practice. [NIH] Private Sector: That distinct portion of the institutional, industrial, or economic structure of a country that is controlled or owned by non-governmental, private interests. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] Procyclidine: A muscarinic antagonist that crosses the blood-brain barrier and is used in the treatment of drug-induced extrapyramidal disorders and in parkinsonism. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not

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itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Proneness: Susceptibility to accidents due to human factors. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proprioception: The mechanism involved in the self-regulation of posture and movement through stimuli originating in the receptors imbedded in the joints, tendons, muscles, and labyrinth. [NIH] Prosencephalon: The part of the brain developed from the most rostral of the three primary vesicles of the embryonic neural tube and consisting of the diencephalon and telencephalon. [NIH]

Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests

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upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoacoustics: The science pertaining to the interrelationship of psychologic phenomena and the individual's response to the physical properties of sound. [NIH] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychoanalysis: The separation or resolution of the psyche into its constituent elements. The term has two separate meanings: 1. a procedure devised by Sigmund Freud, for investigating mental processes by means of free association, dream interpretation and interpretation of resistance and transference manifestations; and 2. a theory of psychology

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developed by Freud from his clinical experience with hysterical patients. (From Campbell, Psychiatric Dictionary, 1996). [NIH] Psychoanalytic Theory: Conceptual system developed by Freud and his followers in which unconscious motivations are considered to shape normal and abnormal personality development and behavior. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psycholinguistics: A discipline concerned with relations between messages and the characteristics of individuals who select and interpret them; it deals directly with the processes of encoding (phonetics) and decoding (psychoacoustics) as they relate states of messages to states of communicators. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychology, Clinical: The branch of psychology concerned with psychological methods of recognizing and treating behavior disorders. [NIH] Psychometrics: Assessment of psychological variables by the application of mathematical procedures. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychopharmacology: The study of the effects of drugs on mental and behavioral activity. [NIH]

Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH]

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Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Public Sector: The area of a nation's economy that is tax-supported and under government control. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pulvinar: Large mass of nuclei forming the most caudal portion of the thalamus and overhanging the geniculate bodies and the dorsolateral surface of the midbrain. It is divided into four parts: the lateral, medial, inferior, and oral pulvinar nuclei. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [NIH] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Raclopride: A substituted benzamide that has antipsychotic properties. It is a dopamine D2 receptor antagonist. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency)

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waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive

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error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Rehabilitative: Instruction of incapacitated individuals or of those affected with some mental disorder, so that some or all of their lost ability may be regained. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Research Personnel: Those individuals engaged in research. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which

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contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH]

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Rod: A reception for vision, located in the retina. [NIH] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Saccades: An abrupt voluntary shift in ocular fixation from one point to another, as occurs in reading. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizoid Personality Disorder: A personality disorder manifested by a profound defect in the ability to form social relationships, no desire for social involvement, and an indifference to praise or criticism. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizophrenic Language: The artificial language of schizophrenic patients - neologisms (words of the patient's own making with new meanings). [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU]

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Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selegiline: A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Self-Injurious Behavior: Behavior in which persons hurt or harm themselves without the motive of suicide or of sexual deviation. [NIH] Semantics: The relationships between symbols and their meanings. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Senile Plaques: Spherical masses consisting of amyloid fibrils and neuronal processes. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression.

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[NIH]

Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of

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tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Class: A stratum of people with similar position and prestige; includes social stratification. Social class is measured by criteria such as education, occupation, and income. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Isolation: The separation of individuals or groups resulting in the lack of or minimizing of social contact and/or communication. This separation may be accomplished by physical separation, by social barriers and by psychological mechanisms. In the latter, there may be interaction but no real communication. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and

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the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal tap: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a lumbar puncture. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Stereotyped Behavior: Relatively invariant mode of behavior elicited or determined by a particular situation; may be verbal, postural, or expressive. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other

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excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strained: A stretched condition of a ligament. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [NIH] Striate: Recurrent branch of the anterior cerebral artery which supplies the anterior limb of the internal capsule. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Strychnine: An alkaloid found in the seeds of nux vomica. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU]

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Subthalamus: A transition zone in the anterior part of the diencephalon interposed between the thalamus, hypothalamus, and tegmentum of the mesencephalon. Components of the subthalamus include the subthalamic nucleus, zona incerta, nucleus of field H, and the nucleus of ansa lenticularis. The latter contains the entopeduncular nucleus. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH]

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Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamic Nuclei: Several groups of nuclei in the thalamus that serve as the major relay centers for sensory impulses in the brain. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active

Dictionary 569

form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness. [NIH]

Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonal: Based on special tests used for a topographic diagnosis of perceptive deafness (damage of the Corti organ, peripheral or central damage, i. e. the auditive cortex). [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH]

570 Schizophrenia

Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Tranquilizing Agents: A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the anti-anxiety agents (minor tranquilizers), antimanic agents, and the antipsychotic agents (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy,

Dictionary 571

effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triad: Trivalent. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubocurarine: A neuromuscular blocker and active ingredient in curare; plant based alkaloid of Menispermaceae. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

572 Schizophrenia

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venter: Belly. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventral Tegmental Area: A region in the mesencephalon which is dorsomedial to the substantia nigra and ventral to the red nucleus. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the nucleus accumbens. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of schizophrenia. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or

Dictionary 573

viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Visual Pathways: Set of cell bodies and nerve fibers conducting impulses from the eyes to the cerebral cortex. It includes the retina, optic nerve, optic tract, and geniculocalcarine tract. [NIH]

Visual Perception: The selecting and organizing of visual stimuli based on the individual's past experience. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voice Disorders: Disorders of voice pitch, loudness, or quality. Dysphonia refers to impaired utterance of sounds by the vocal folds. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Vomeronasal Organ: A specialized part of the olfactory system located anteriorly in the nasal cavity within the nasal septum. Chemosensitive cells of the vomeronasal organ project via the vomeronasal nerve to the accessory olfactory bulb. The primary function of this organ appears to be in sensing pheromones which regulate reproductive and other social behaviors. While the structure has been thought absent in higher primate adults, data now suggests it may be present in adult humans. [NIH] Vomica: The profuse and sudden expectoration of pus and putrescent matter. An abnormal cavity in an organ especially in the lung, caused by suppuration and the breaking down of tissue. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] War: Hostile conflict between organized groups of people. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH]

574 Schizophrenia

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

575

INDEX 1 1-Methyl-4-phenyl-1,2,3,6tetrahydropyridine, 381, 491 A Abdominal, 491, 492, 547, 549 Aberrant, 49, 50, 62, 83, 93, 129, 237, 361, 385, 410, 491 Abortion, 491, 553 Abscess, 491, 562 ACE, 367, 491 ACE Inhibitor, 367, 491 Acetylcholine, 44, 197, 259, 375, 491, 506, 544 Acidity, 491, 549 Acne, 491, 560 Acoustic, 18, 117, 292, 296, 300, 308, 491 Actin, 491, 541, 543 Activities of Daily Living, 196, 491 Adaptation, 53, 327, 346, 388, 391, 408, 491, 506, 530, 551 Adenine, 394, 491, 557 Adenosine, 265, 366, 491, 550 Adipocytes, 492, 533 Adjunctive Therapy, 389, 492 Adjustment, 44, 70, 117, 121, 136, 199, 317, 323, 326, 329, 331, 408, 491, 492 Adolescence, 47, 50, 68, 106, 364, 368, 388, 391, 434, 437, 492, 549 Adrenal Cortex, 492, 511, 554, 559 Adrenal Medulla, 492, 504, 518, 519, 545 Adrenergic, 82, 87, 492, 496, 497, 515, 519, 567, 571 Adverse Effect, 176, 243, 492, 497, 507, 550, 563 Aetiology, 103, 401, 415, 492 Affective Symptoms, 99, 117, 492 Afferent, 54, 394, 492, 531, 533, 553, 562 Affinity, 105, 368, 375, 385, 397, 492, 498, 507, 564 Agarose, 492, 526 Age Groups, 35, 492 Age of Onset, 68, 82, 103, 302, 492 Aged, 80 and Over, 492 Agonist, 37, 75, 87, 105, 174, 350, 385, 492, 497, 515, 528, 541, 544 Agoraphobia, 407, 492, 529, 547 Akathisia, 12, 159, 351, 493, 497 Albumin, 493, 526, 551

Algorithms, 13, 16, 120, 127, 493, 501 Alkaline, 369, 493, 494, 503 Alkaloid, 493, 499, 508, 540, 544, 566, 571 Alleles, 66, 104, 363, 493, 527, 534 Allergic Rhinitis, 437, 493, 525 Allylamine, 493, 494 Alpha Cell, 399, 493 Alpha-Linolenic Acid, 378, 381, 493 Alternative medicine, 449, 493 Alternative Splicing, 493, 543, 555 Ameliorated, 362, 493 Ameliorating, 70, 111, 401, 493 Amenorrhea, 493, 495 Amine, 359, 375, 493, 501, 527 Amino Acid Sequence, 494, 496, 520, 523 Ammonia, 494, 524 Amnesia, 372, 494 Amnestic, 60, 494 Amphetamine, 63, 82, 105, 140, 382, 383, 494, 513 Amputation, 265, 494 Amygdala, 54, 163, 251, 253, 300, 494, 499, 534, 562, 568 Amyloid, 146, 494, 562 Anaesthesia, 494, 495, 529 Anal, 4, 32, 38, 99, 226, 433, 494, 518, 521, 535, 541 Analeptic, 494, 566 Analogous, 15, 58, 494, 570 Analysis of Variance, 60, 494 Anaphylatoxins, 494, 509 Anatomical, 22, 66, 77, 82, 99, 120, 123, 390, 400, 437, 495, 499, 506, 529, 539, 543, 561 Anemia, 66, 465, 495, 521 Anesthesia, 495, 496, 511, 532 Anesthetics, 5, 495, 519 Angiogenesis, 398, 495 Angiography, 437, 495 Anions, 46, 493, 495, 532, 563, 567 Anisotropy, 13, 90, 130, 199, 241, 495 Annual Reports, 476, 495 Anode, 495 Anomalies, 89, 107, 108, 118, 125, 212, 213, 231, 448, 495 Anorexia, 407, 472, 495 Anorexia Nervosa, 407, 472, 495 Anosmia, 437, 495

576 Schizophrenia

Anoxia, 92, 495 Antagonism, 247, 335, 382, 495, 507 Antecedent, 38, 496 Anterior Cerebral Artery, 496, 566 Anthropology, 39, 496 Anti-Anxiety Agents, 496, 556, 570 Antibacterial, 496, 565 Antibiotic, 495, 496, 512, 549, 565 Antibodies, 62, 150, 197, 232, 392, 395, 400, 401, 402, 496, 525, 526, 527, 529, 535, 551 Antibody, 62, 391, 492, 496, 497, 509, 512, 519, 525, 527, 529, 530, 537, 557, 558, 564 Anticholinergic, 5, 387, 496 Anticoagulant, 496, 555 Anticonvulsant, 364, 386, 389, 450, 496, 504, 550, 572 Antidepressant, 14, 26, 335, 336, 450, 496, 502, 507, 521, 529 Antidepressive Agents, 496, 556 Antidopaminergic, 58, 363, 383, 384, 496 Antiemetic, 496, 497, 506 Antiepileptic, 389, 496 Antigen, 75, 195, 492, 496, 497, 509, 527, 528, 529, 530, 537, 539, 558 Antigen-Antibody Complex, 497, 509 Anti-inflammatory, 497, 505, 524 Anti-Inflammatory Agents, 497, 505 Antioxidant, 206, 278, 301, 497 Antipsychotic Agents, 28, 222, 353, 497, 515, 570 Antiseptic, 497, 504 Anus, 494, 497, 502, 508 Anxiety Disorders, 235, 289, 405, 406, 436, 440, 497, 547 Anxiolytic, 85, 364, 386, 497 Aorta, 497, 572 Apathy, 12, 363, 378, 382, 497, 543 Aphasia, 494, 497 Apomorphine, 276, 497 Applicability, 24, 84, 106, 228, 339, 498 Aqueous, 498, 500, 512, 528, 533 Arachidonic Acid, 378, 381, 498, 533, 554 Arginine, 203, 494, 498, 544 Arterial, 493, 498, 504, 528, 555, 568 Arteries, 497, 498, 501, 502, 511, 538, 569 Arterioles, 498, 502, 503 Arteriolosclerosis, 498 Arteriosclerosis, 398, 498 Artery, 496, 498, 511, 557, 561 Artifacts, 123, 498 Aspartate, 75, 86, 88, 95, 140, 149, 164, 224, 232, 323, 383, 384, 498, 532, 550

Aspartic, 385, 498 Aspartic Acid, 385, 498 Assay, 33, 104, 351, 360, 498, 558 Astringent, 498, 504 Astrocytes, 498, 539, 540 Ataxia, 24, 247, 465, 498, 505, 528, 568 Atrial, 499, 567 Atrium, 499, 572 Atrophy, 65, 152, 465, 499, 543 Atropine, 5, 499, 500 Attenuation, 299, 499 Audition, 16, 499 Auditory Cortex, 16, 17, 499, 523 Autoimmune disease, 499, 540 Autoimmunity, 195, 499 Autonomic, 204, 279, 319, 491, 497, 499, 500, 545, 549 Autopsy, 59, 341, 392, 499 Autoreceptors, 111, 499 Axonal, 13, 107, 131, 499 Axons, 13, 75, 394, 499, 513, 531, 541, 542, 544, 546, 553, 557 B Bacteria, 496, 499, 500, 518, 526, 539, 565, 570, 571, 572 Bacterial Physiology, 491, 499 Bacterium, 499, 509 Basal Ganglia, 32, 53, 216, 319, 497, 499, 507, 528, 534, 545 Basal Ganglia Diseases, 499, 507, 528 Base, 26, 58, 118, 358, 363, 491, 500, 512, 513, 519, 523, 532, 551, 557, 568 Base Sequence, 363, 500, 523 Basophils, 500, 525, 533 Belladonna, 499, 500 Benign, 279, 498, 500, 525, 542, 561 Benzene, 500 Benzodiazepines, 152, 364, 365, 366, 500 Bereavement, 407, 500 Bilateral, 35, 500 Bile, 23, 500, 522, 527, 534, 565 Bile Acids, 500, 565 Bile Acids and Salts, 500 Binaural, 21, 500 Binding agent, 392, 500 Binding Sites, 59, 500 Bioavailability, 60, 500 Bioavailable, 12, 500 Biochemical, 33, 88, 119, 121, 360, 361, 369, 390, 391, 399, 400, 413, 493, 500, 501, 562 Biochemical Phenomena, 501 Biogenic Monoamines, 380, 501

Index 577

Biological Markers, 84, 98, 501 Biological Phenomena, 377, 501 Biological response modifier, 501, 531 Biological therapy, 501, 525 Biotechnology, 135, 142, 434, 449, 461, 463, 464, 465, 466, 501 Biotransformation, 501, 549 Birth Rate, 207, 501 Bladder, 501, 506, 509, 529, 540, 543, 554, 571, 572 Blinking, 5, 501 Blood Coagulation, 501, 503, 520, 569 Blood Platelets, 113, 501, 562 Blood pressure, 341, 491, 501, 504, 506, 528, 540, 564 Blood-Brain Barrier, 362, 502, 533, 553, 568 Body Fluids, 392, 502, 564 Bone Marrow, 500, 502, 523, 535, 540, 564 Bone scan, 502, 561 Bowel, 494, 502, 514, 532, 566 Bowel Movement, 502, 514, 566 Bradykinesia, 223, 502 Bradykinin, 502, 544, 551 Brain Stem, 502, 505, 543 Branch, 417, 441, 485, 502, 516, 535, 543, 544, 548, 549, 556, 564, 566, 567, 568 Breakdown, 68, 248, 502, 514, 522, 546 Broadband, 52, 502 Bronchi, 502, 519, 570 Bronchial, 502, 527 Bulimia, 303, 407, 472, 502 Bupropion, 94, 125, 502 Butyric Acid, 95, 314, 502 C Calcification, 498, 502 Calcineurin, 162, 178, 503 Calcium, 66, 124, 163, 221, 250, 395, 502, 503, 509, 520, 555, 563 Calcium-Binding Proteins, 221, 250, 503 Calibration, 52, 503 Callus, 503, 517 Calmodulin, 503 Candidiasis, 5, 503 Candidosis, 503 Cannabidiol, 503 Cannabinoids, 25, 503 Cannabinol, 503 Cannabis, 25, 29, 45, 85, 140, 155, 275, 285, 287, 298, 337, 503, 568 Capillary, 398, 502, 503, 572 Captopril, 367, 504 Carbamazepine, 275, 287, 390, 454, 504

Carbohydrate, 391, 504, 524, 552 Carbon Dioxide, 504, 512, 521, 560 Carboxy, 75, 504 Carcinogenic, 500, 504, 530, 554, 565 Carcinogens, 504, 546 Cardiac, 205, 493, 504, 516, 517, 519, 520, 541, 565, 567 Cardiovascular, 139, 230, 246, 494, 504, 533, 562 Cardiovascular disease, 246, 504 Carotene, 314, 504, 560 Carrier Proteins, 504, 551, 558 Case report, 113, 167, 197, 235, 249, 406, 504, 507 Case series, 504, 507 Catabolism, 369, 504 Catechol, 155, 180, 184, 275, 276, 504 Catecholamine, 496, 504, 515, 550 Catheter, 371, 505 Cations, 505, 532 Caudal, 505, 514, 523, 528, 545, 552, 557 Caudate Nucleus, 64, 119, 496, 499, 505, 542, 545 Causal, 40, 66, 78, 106, 125, 141, 230, 319, 505, 518, 526, 531 Celecoxib, 151, 447, 505 Cell Count, 121, 505 Cell Differentiation, 505, 563 Cell Division, 465, 499, 505, 525, 537, 551, 554, 562 Cell membrane, 23, 305, 364, 378, 504, 505, 513, 522, 541, 550, 564 Cell proliferation, 498, 505, 563 Cell Respiration, 505, 560 Cell Survival, 505, 525 Cerebellar, 25, 140, 143, 198, 236, 245, 332, 499, 505, 558, 571 Cerebellar Diseases, 499, 505, 571 Cerebellum, 21, 24, 75, 329, 505, 511, 552, 558 Cerebral Cortex, 13, 16, 150, 221, 240, 499, 505, 519, 521, 531, 542, 557, 573 Cerebral hemispheres, 499, 502, 505, 506, 533, 568 Cerebral Palsy, 408, 477, 506 Cerebrospinal, 62, 139, 156, 176, 212, 341, 350, 360, 400, 447, 506, 507, 535, 563, 565 Cerebrospinal fluid, 62, 139, 156, 176, 212, 341, 350, 360, 400, 447, 506, 507, 535, 563, 565 Cerebrovascular, 499, 504, 506, 568 Cerebrum, 505, 506, 511, 568, 571

578 Schizophrenia

Cervical, 506, 561 Character, 256, 420, 506, 512 Chemoreceptor, 497, 506 Chemotactic Factors, 506, 509 Chin, 310, 341, 506, 538 Chlorpromazine, 150, 157, 363, 369, 382, 383, 454, 506, 521, 549 Cholecystokinin, 135, 367, 506 Cholesterol, 9, 156, 500, 506, 511, 537, 565 Cholinergic, 49, 57, 87, 372, 375, 497, 506, 544, 562 Cholinesterase Inhibitors, 364, 506, 515 Chorea, 497, 507 Choroid, 507, 533, 560 Choroid Plexus, 507, 533 Chromosomal, 12, 33, 47, 50, 54, 275, 507, 561 Chronic Disease, 385, 388, 507 Chronic renal, 148, 507, 522, 551 CIS, 381, 507, 560 Citalopram, 14, 26, 336, 507 Clamp, 77, 507 Clinical study, 41, 43, 92, 346, 507, 511 Cloning, 12, 62, 75, 396, 501, 507 Coagulation, 501, 507, 526, 551 Coca, 508 Cocaine, 106, 227, 246, 318, 436, 508 Codon, 398, 508, 523 Coenzymes, 508, 544 Cofactor, 508, 555, 569 Cognitive restructuring, 508, 566 Collagen, 494, 508, 521, 522, 551, 554 Collapse, 217, 502, 508, 563 Colloidal, 493, 508, 516, 563 Colon, 329, 465, 508, 532 Combination Therapy, 240, 508 Communication Disorders, 355, 407, 438, 460, 508 Comorbidity, 14, 26, 81, 126, 160, 161, 165, 173, 210, 254, 265, 508 Competency, 197, 509 Complement, 94, 494, 509, 523, 536, 551 Complementary and alternative medicine, 283, 316, 509 Complementary medicine, 283, 509 Complementation, 396, 509 Complete remission, 509, 559 Compliance, 5, 65, 78, 126, 141, 210, 322, 325, 353, 509 Compulsion, 509, 573 Computational Biology, 461, 463, 509

Computed tomography, 136, 291, 341, 509, 510, 561 Computer Simulation, 56, 70, 73, 510 Computerized tomography, 510 Conception, 491, 510, 521, 553 Concomitant, 362, 366, 510 Conduction, 510, 541 Cones, 510, 560 Confounding, 27, 66, 213, 510 Congestion, 497, 510 Conjugated, 500, 510, 526 Conjunctiva, 510, 530 Connective Tissue, 502, 508, 510, 513, 521, 522, 535, 538 Consciousness, 117, 196, 394, 496, 510, 512, 513, 514, 515, 555 Constipation, 497, 510 Constitutional, 510, 541 Consultation, 4, 30, 51, 63, 94, 510 Continuum, 102, 152, 510 Contraindications, ii, 510 Contralateral, 510, 538, 558 Contrast medium, 495, 510 Contrast Sensitivity, 256, 510 Control group, 6, 27, 53, 61, 68, 337, 510 Controlled clinical trial, 150, 305, 511 Controlled study, 14, 26, 173, 201, 228, 244, 292, 303, 511 Convulsions, 496, 511, 516, 528 Convulsive, 511, 517 Coordination, 22, 55, 162, 505, 511, 540 Coronary, 504, 511, 538 Coronary heart disease, 504, 511 Coronary Thrombosis, 511, 538 Corpus, 84, 511, 535, 542, 554, 562, 568, 573 Corpuscle, 511, 519 Cortices, 23, 83, 139, 140, 184, 511, 526 Corticosteroids, 85, 511, 524 Cortisol, 85, 274, 493, 511 Cranial, 505, 511, 519, 525, 545, 546, 547, 549, 565 Cribriform, 511, 546 Criterion, 266, 511 Crossing-over, 511, 558 Cues, 290, 511 Curare, 511, 541, 571 Curative, 512, 544, 568 Custom-made, 83, 512 Cutaneous, 503, 512 Cyclic, 24, 503, 512, 525, 544 Cycloserine, 340, 350, 512

Index 579

Cytokines, 114, 195, 512, 539 Cytomegalovirus, 300, 512 Cytoplasm, 500, 505, 512, 518, 540, 543, 544, 560 Cytoskeleton, 71, 102, 512, 539 Cytotoxic, 512, 563 D Data Collection, 56, 72, 125, 351, 512 Deamination, 512, 540 Decarboxylation, 501, 512, 527, 541 Degenerative, 7, 99, 170, 512, 526, 536, 540 Deletion, 363, 512 Delirium, 407, 436, 438, 497, 512 Delusion, 388, 391, 425, 431, 513 Demyelinating Diseases, 130, 513, 541 Dendrites, 60, 513, 543, 544, 546, 557 Dendritic, 14, 36, 45, 60, 102, 107, 513, 537 Density, 13, 14, 27, 36, 45, 55, 99, 103, 104, 125, 153, 246, 253, 263, 285, 291, 394, 513, 546 Dental Care, 3, 6, 513 Dentate Gyrus, 513, 527 Dentists, 4, 439, 513 Depersonalization, 513, 547, 561 Depolarization, 513, 563 Depressive Disorder, 179, 194, 210, 211, 263, 368, 397, 423, 439, 513, 534 Derealization, 513, 547 Dermis, 513, 560, 570 Dextroamphetamine, 494, 513, 538 Diabetes Insipidus, 513, 551 Diabetes Mellitus, 514, 526, 551 Diagnostic procedure, 103, 357, 438, 449, 514 Diastolic, 514, 528 Diathesis, 42, 56, 88, 123, 514 Diencephalon, 22, 514, 519, 523, 528, 543, 553, 554, 567, 568 Digestion, 500, 502, 514, 532, 534, 566 Digestive system, 355, 514 Digestive tract, 514, 563 Dihydroxy, 93, 514 Dilatation, 491, 514, 553 Diploid, 509, 514, 551 Direct, iii, 20, 24, 40, 43, 54, 57, 65, 72, 73, 77, 84, 99, 102, 107, 342, 453, 514, 515, 528, 558, 567 Discrete, 59, 87, 186, 514, 535 Discrimination, 4, 80, 86, 98, 116, 129, 197, 445, 478, 514 Disorientation, 512, 514 Disparity, 251, 514

Disposition, 398, 514 Dissection, 8, 9, 514 Dissociation, 31, 492, 514 Dissociative Disorders, 514 Distal, 499, 514, 516, 553, 555 Dizziness, 514, 547, 572 Dominance, 210, 515, 533 Donepezil, 151, 170, 515 Dopamine Antagonists, 95, 391, 515 Dorsal, 63, 97, 396, 515, 519, 523, 552, 562 Dosage schedule, 127, 515 Dosimetry, 105, 515 Dreams, 321, 417, 515 Drive, ii, vi, 3, 5, 228, 273, 399, 407, 436, 439, 446, 515 Drug Approval, 408, 453, 515 Drug Interactions, 436, 450, 455, 515 Drug Tolerance, 515, 569 Duodenum, 500, 516, 544, 566 Dyskinesia, 12, 34, 114, 218, 232, 239, 252, 313, 366, 371, 381, 387, 497, 507, 516 Dysphagia, 5, 408, 516 Dysphonia, 408, 516, 573 Dysphoric, 308, 513, 516 Dysplasia, 465, 516 Dyspnea, 516, 547 Dystonia, 497, 516 Dystrophy, 373, 465, 516 E Edema, 516, 522, 546 Effector, 491, 509, 516 Efferent, 45, 516, 531, 540, 562 Elasticity, 498, 516 Elective, 140, 250, 516 Electric Conductivity, 495, 516 Electric shock, 377, 516 Electrocardiogram, 341, 516 Electroconvulsive Therapy, 142, 175, 338, 516 Electrode, 99, 371, 495, 516 Electroencephalography, 516, 536 Electrolysis, 495, 505, 516, 517 Electrolyte, 176, 512, 516, 552, 564 Electrophoresis, 400, 516 Electrophysiological, 67, 69, 77, 86, 95, 96, 102, 129, 176, 244, 516 Electroplating, 504, 517 Electroshock, 389, 517 Elementary Particles, 517, 536, 555 Embryo, 491, 505, 517, 521, 529, 553, 565 Embryo Transfer, 517, 553 Embryogenesis, 22, 517

580 Schizophrenia

Embryology, 517, 544 Emesis, 497, 517 Emetic, 497, 517 Empirical, 14, 19, 27, 29, 39, 73, 112, 120, 269, 325, 517 Endemic, 517, 565 Endocarditis, 503, 517 Endocrine System, 517, 543 Endogenous, 25, 63, 75, 90, 105, 111, 368, 383, 384, 397, 420, 515, 517, 518 Endometrium, 517, 537 Endorphins, 517, 544 Endothelial cell, 502, 517, 569 Endothelium, 517, 518, 544 Endothelium-derived, 518, 544 Endotoxin, 518, 571 End-stage renal, 507, 518, 551 Energy balance, 518, 533 Enhancer, 151, 518 Enkephalins, 518, 544 Entorhinal Cortex, 45, 186, 222, 518, 527 Environmental Exposure, 501, 518, 546 Environmental Health, 460, 462, 518 Enzymatic, 75, 369, 494, 501, 503, 504, 509, 518, 527, 537, 560 Enzyme Inhibitors, 518, 551 Eosinophils, 518, 525, 533 Epidemic, 105, 518, 565 Epidemiologic Studies, 501, 518 Epidemiological, 25, 47, 50, 181, 274, 413, 435, 518 Epidermal, 391, 518, 537 Epidermal Growth Factor, 391, 518 Epidermis, 513, 518 Epidural, 276, 519 Epigastric, 519, 547 Epinephrine, 5, 492, 515, 519, 544, 545, 571 Epithalamus, 514, 519, 534 Epithelial, 518, 519, 526 Epithelial Cells, 518, 519, 526 Epithelium, 98, 517, 519, 546 Epitope, 62, 519 Erythrocyte Membrane, 254, 304, 519 Erythrocytes, 23, 495, 502, 519, 526, 558 Esophagus, 514, 519, 550, 566 Essential Tremor, 465, 519 Estrogen, 174, 226, 261, 276, 519, 554 Ethanol, 507, 519 Ethmoid, 519, 546, 547 Ethnic Groups, 294, 519 Eukaryotic Cells, 519, 529, 571 Evoke, 519, 565

Excipients, 359, 519 Excitability, 215, 520 Excitation, 46, 58, 506, 520, 544 Excitatory, 20, 36, 111, 124, 361, 385, 520, 524, 528 Exhaustion, 495, 520 Exocrine, 506, 520, 547 Exogenous, 501, 504, 515, 517, 520, 523 Exon, 66, 154, 171, 398, 493, 520 Expiration, 520, 559 Extracellular, 90, 364, 368, 397, 494, 498, 510, 520, 521, 539, 564 Extracellular Space, 520, 539 Extracorporeal, 520, 526 Extrapyramidal, 12, 65, 127, 147, 217, 229, 280, 353, 366, 387, 493, 497, 515, 520, 549, 553 Extremity, 80, 265, 520 Eye Movements, 49, 69, 79, 97, 124, 164, 165, 171, 179, 333, 341, 520 F Facial, 11, 184, 244, 245, 268, 368, 520 Facial Expression, 11, 520 Factor V, 47, 520 Family Planning, 461, 520 Family Relations, 406, 440, 520 Family Therapy, 414, 435, 520 Famotidine, 362, 520 Fat, 209, 274, 277, 278, 296, 492, 498, 500, 502, 504, 511, 520, 533, 534, 540, 546, 552, 571 Fathers, 11, 447, 520 Fatty acids, 293, 294, 304, 364, 378, 493, 520, 524, 534, 554 Fertilization in Vitro, 520, 553 Fetal Development, 399, 520 Fetus, 43, 491, 521, 553, 565, 572 Fibrinogen, 360, 521, 551, 569 Fibroblasts, 521, 531 Fibrosis, 358, 465, 493, 521, 561 Financial Management, 53, 521 Fissure, 513, 521, 553 Fixation, 329, 521, 561 Flatus, 521, 522 Fluoxetine, 228, 521 Fluphenazine, 309, 348, 367, 521 Folate, 75, 521 Fold, 385, 521 Folic Acid, 282, 521 Foramen, 506, 521, 533, 549 Forearm, 501, 521 Fornix, 37, 522, 562

Index 581

Fosinopril, 367, 522 Fossa, 505, 522 Free Association, 522, 555 Free Radicals, 497, 514, 522 Frontal Lobe, 17, 31, 129, 137, 225, 258, 322, 328, 345, 496, 522, 540, 553 Functional magnetic resonance imaging, 17, 25, 48, 49, 52, 62, 86, 89, 108, 120, 132, 133, 134, 284, 522 Fungus, 503, 522 Furosemide, 46, 522 G Galactosemia, 160, 522 Galanthamine, 364, 522 Gallbladder, 491, 506, 514, 522 Ganglia, 151, 491, 499, 522, 542, 549 Gap Junctions, 522, 567 Gas, 92, 494, 504, 521, 522, 528, 544, 545, 546, 572 Gastric, 518, 520, 522, 527 Gastrin, 522, 527 Gastrointestinal, 359, 502, 506, 519, 522, 533, 562, 566 Gastrointestinal tract, 506, 519, 522, 533, 562 Gelatin, 522, 524, 569 Gene Expression, 27, 51, 59, 61, 82, 83, 102, 103, 119, 212, 446, 466, 523 Gene Targeting, 50, 523 Gene Therapy, 396, 399, 523 Generator, 371, 523 Genes, pol, 380, 523 Genetic Code, 523, 545 Genetic Engineering, 501, 507, 523 Genetic Markers, 9, 10, 19, 67, 363, 379, 523 Geniculate Bodies, 523, 557 Genotype, 13, 28, 72, 104, 137, 148, 245, 446, 523, 550 Geriatric Psychiatry, 51, 133, 185, 256, 258, 523 Gestation, 34, 66, 523, 549, 565 Ginkgo biloba, 283, 294, 309, 310, 523 Gland, 492, 524, 535, 547, 554, 561, 565, 566, 569 Glomeruli, 71, 524, 546 Glomerulus, 524 Glucocorticoid, 191, 242, 524 Glucose, 86, 123, 156, 166, 191, 196, 277, 465, 493, 514, 522, 524, 526, 528, 530, 531 Glucose tolerance, 166, 196, 524 Glucose Tolerance Test, 524

Glutamate, 12, 45, 57, 58, 59, 71, 75, 86, 90, 93, 95, 96, 192, 202, 212, 214, 280, 351, 368, 383, 384, 385, 397, 524, 538 Glutamate Dehydrogenase, 192, 524 Glutamic Acid, 394, 521, 524, 544, 554 Glutamine, 192, 314, 524 Glycerol, 502, 524, 550 Glycerophospholipids, 524, 550 Glycine, 59, 75, 90, 95, 192, 274, 277, 314, 340, 350, 382, 383, 494, 500, 524, 544, 562, 566 Glycoprotein, 520, 521, 524, 569, 571 Governing Board, 524, 552 Grade, 434, 524 Granulocyte, 525, 531 Gravis, 408, 439, 525 Growth factors, 141, 525, 539 Guanylate Cyclase, 525, 544 Guideline Adherence, 351, 525 Gyrus Cinguli, 496, 525, 534 H Habitual, 138, 506, 525, 549 Habituation, 15, 37, 290, 308, 525 Hallucination, 388, 391, 525 Hallucinogen, 525, 550 Handedness, 65, 131, 225, 525 Haplotypes, 168, 525 Haptens, 492, 525, 558 Hay Fever, 493, 525 Headache, 525, 528, 530 Health Behavior, 78, 525 Health Policy, 12, 107, 240, 526 Health Services, 10, 342, 351, 405, 526 Health Status, 78, 193, 525, 526 Hearing Disorders, 508, 526 Heart attack, 504, 526 Heart failure, 526, 546 Heartbeat, 526, 567 Hemoglobin, 495, 519, 526 Hemoglobinopathies, 523, 526 Hemoglobinuria, 465, 526 Hemolysis, 519, 526 Hemoperfusion, 365, 526 Hemorrhage, 525, 526, 566 Hemostasis, 526, 562 Hepatic, 493, 512, 524, 526, 540 Hepatitis, 235, 470, 526, 539 Hepatocytes, 526 Hereditary, 66, 526, 540, 543, 560 Heredity, 66, 182, 523, 526 Herpes, 150, 527 Herpes Zoster, 527

582 Schizophrenia

Heterogeneity, 31, 32, 47, 57, 69, 70, 122, 187, 193, 266, 492, 527 Heterozygotes, 515, 527 Hiccup, 506, 515, 527 Histamine, 277, 362, 442, 495, 497, 520, 527 Histidine, 527 Histology, 527, 543 Homeostasis, 46, 527 Homogeneous, 45, 104, 149, 236, 498, 510, 527 Homologous, 493, 511, 523, 527, 562, 567 Hormonal, 499, 527 Hormone, 276, 493, 499, 501, 511, 519, 522, 527, 530, 533, 554, 563, 569 Humoral, 156, 527 Humour, 527 Hybrid, 527 Hybridization, 61, 66, 527 Hybridomas, 527, 531 Hydrogen, 491, 494, 500, 504, 528, 540, 545, 547, 549, 555, 567 Hydrogen Peroxide, 528, 567 Hydrogenation, 500, 528 Hydrolysis, 75, 498, 501, 528, 550, 555 Hydroxyproline, 494, 508, 528 Hyperglycemia, 264, 528 Hypersensitivity, 528, 533, 548 Hypertension, 5, 169, 379, 446, 498, 504, 522, 525, 528 Hypnotic, 364, 386, 528 Hypoglycaemia, 512, 528 Hypokinesia, 528, 548 Hypomania, 239, 528 Hypotension, 497, 511, 528, 544 Hypothalamic, 85, 528 Hypothalamus, 514, 528, 534, 544, 562, 567, 568 Hypoxia, 182, 512, 528, 568 I Ibotenic Acid, 528, 541 Id, 166, 281, 312, 470, 473, 474, 484, 486, 528 Idiopathic, 8, 528 Ileum, 528, 544 Ileus, 276, 528 Illusion, 529, 572 Imipramine, 366, 529 Immune function, 310, 529 Immune response, 62, 195, 199, 496, 499, 525, 529, 536, 566, 573 Immune system, 156, 499, 501, 529, 533, 535, 536, 540, 541, 572, 573

Immunity, 114, 195, 529, 535, 546 Immunodeficiency, 465, 529 Immunogenic, 529, 558 Immunoglobulins, 529, 551 Immunohistochemistry, 25, 83, 529 Immunologic, 417, 506, 529, 536 Immunology, 492, 529 Immunophilin, 503, 529 Immunosuppressive, 503, 524, 529 Implantable pump, 371, 529 In situ, 61, 75, 83, 529 In Situ Hybridization, 61, 75, 83, 529 In vitro, 23, 88, 95, 360, 363, 517, 523, 529 In vivo, 13, 18, 23, 41, 45, 54, 95, 105, 130, 197, 297, 385, 398, 523, 529, 534, 539, 569 Incision, 529, 532 Incontinence, 372, 529 Indicative, 40, 129, 408, 529, 548, 572 Induction, 66, 71, 398, 497, 517, 529, 532, 554 Infancy, 364, 529 Infant, Newborn, 492, 530 Infarction, 497, 511, 530, 538 Infection, 88, 199, 491, 501, 503, 506, 512, 525, 529, 530, 535, 549, 566, 569, 573 Inflammation, 491, 493, 497, 521, 526, 527, 530, 533, 551, 572 Influenza, 234, 530 Informed Consent, 64, 112, 530 Infuse, 371, 530 Infusion, 37, 371, 372, 530 Ingestion, 524, 530, 551 Initiation, 22, 56, 69, 79, 352, 530 Inositol, 530, 538 Inotropic, 515, 530 Inpatients, 6, 32, 121, 201, 233, 246, 266, 309, 328, 329, 530 Insight, 54, 60, 83, 118, 195, 200, 201, 215, 323, 325, 352, 424, 530 Institutionalization, 436, 530 Insulator, 530, 541 Insulin, 86, 524, 530, 531 Insulin-dependent diabetes mellitus, 530, 531 Integrase, 523, 531 Interferon, 114, 197, 531 Interferon-alpha, 531 Interleukin-1, 150, 201, 531 Interleukin-2, 114, 531 Interleukin-4, 232, 531 Interleukin-6, 176, 531 Intermediate Filaments, 531, 543

Index 583

Intermittent, 117, 531, 535 Internal Capsule, 496, 531, 566 Interneurons, 43, 107, 531 Interpersonal Relations, 201, 365, 531 Interstitial, 140, 169, 520, 531, 559 Intervention Studies, 121, 144, 531 Intestinal, 504, 506, 524, 531, 532, 536 Intestinal Mucosa, 506, 532 Intestine, 500, 502, 532 Intoxication, 25, 512, 532, 574 Intracellular, 24, 46, 54, 111, 364, 398, 530, 532, 537, 538, 544, 552, 558, 563 Intravenous, 60, 530, 532 Intrinsic, 18, 36, 97, 492, 532 Invasive, 65, 529, 532, 536 Involuntary, 366, 370, 499, 501, 507, 519, 532, 541, 558, 564 Ion Channels, 498, 532, 550, 567 Ions, 381, 491, 500, 503, 514, 516, 528, 532, 539, 555, 564 Ischemia, 499, 532 Isopropyl, 359, 532 J Jealousy, 532, 548 Joint, 19, 331, 532, 567 K Kb, 50, 214, 460, 532 Ketamine, 60, 75, 87, 383, 384, 532, 550 Kidney Disease, 355, 460, 465, 491, 532 Kinetics, 254, 532 L Labile, 509, 520, 532 Labyrinth, 532, 554 Lactation, 532, 554 Language Disorders, 437, 508, 532 Large Intestine, 514, 532, 558, 563 Latency, 67, 244, 533 Latent, 18, 118, 204, 293, 318, 323, 533, 553 Lateral Ventricles, 43, 533, 562, 568 Laterality, 80, 100, 278, 298, 533 Least-Squares Analysis, 533, 559 Length of Stay, 169, 533 Lens, 533, 573 Lenticular, 218, 533 Leptin, 269, 533 Lethal, 402, 533 Leukemia, 465, 523, 533 Leukocytes, 27, 500, 502, 506, 512, 518, 531, 533, 540, 544, 571 Leukotrienes, 498, 533 Levodopa, 533, 562 Library Services, 484, 533

Ligament, 533, 554, 566 Ligands, 63, 533 Likelihood Functions, 534, 559 Limbic System, 54, 99, 100, 429, 494, 525, 534, 553 Linear Models, 534, 559 Linkage Disequilibrium, 47, 55, 103, 116, 149, 233, 534 Lipid, 177, 206, 254, 275, 277, 278, 294, 298, 304, 498, 524, 530, 534, 541, 571 Lipid Peroxides, 254, 304, 534 Lithium, 206, 315, 390, 454, 497, 534 Liver, 246, 491, 493, 498, 500, 512, 514, 521, 522, 524, 526, 534, 540, 559, 561 Liver scan, 534, 561 Lobe, 21, 91, 534 Localization, 8, 9, 42, 45, 55, 61, 62, 80, 93, 99, 339, 529, 534, 536 Localized, 25, 45, 61, 114, 379, 410, 521, 530, 534, 540, 546, 551 Locomotion, 534, 551 Locomotor, 377, 534 Lod, 116, 534 Logistic Models, 535, 559 Longitudinal Studies, 107, 109, 535 Longitudinal study, 11, 91, 110, 207, 382, 535 Long-Term Care, 52, 53, 101, 127, 387, 535 Long-Term Potentiation, 71, 87, 535 Loxapine, 137, 172, 535 Lumbar, 360, 488, 535, 565 Lumbar puncture, 360, 488, 535, 565 Lutein Cells, 535, 554 Lymph, 506, 511, 517, 518, 527, 535, 561, 566 Lymph node, 506, 535, 561 Lymphatic, 518, 530, 535, 538, 546, 561, 564, 565 Lymphatic system, 535, 561, 564, 565 Lymphocyte, 136, 496, 535, 536, 537 Lymphoid, 496, 511, 535, 536 Lymphokines, 535, 536 Lymphoma, 465, 536 M Macrophage, 114, 531, 536 Macrophage Activation, 114, 536 Macula, 536 Macula Lutea, 536 Macular Degeneration, 358, 536 Magnetic Resonance Spectroscopy, 41, 74, 88, 131, 218, 237, 322, 536 Magnetoencephalography, 83, 536

584 Schizophrenia

Maintenance therapy, 127, 536 Major Histocompatibility Complex, 525, 531, 536 Malabsorption, 465, 536 Malignant, 220, 233, 465, 498, 536, 542 Malnutrition, 493, 499, 536, 541 Mandible, 506, 536 Mania, 20, 146, 310, 320, 393, 394, 408, 429, 430, 438, 439, 528, 536 Manic-depressive psychosis, 209, 274, 277, 278, 296, 536, 556 Manifest, 5, 11, 22, 41, 56, 372, 394, 499, 537 Man-made, 504, 537 Maternal Deprivation, 88, 537 Maxillary, 22, 537, 547 Mediate, 36, 67, 102, 106, 128, 232, 385, 515, 537 Mediator, 506, 531, 537, 562 Medical Records, 7, 76, 103, 351, 537 Medicament, 362, 387, 537 Mediodorsal Thalamic Nucleus, 123, 537 MEDLINE, 461, 463, 465, 537 Meiosis, 537, 567 Melanin, 537, 550, 571 Melanocytes, 537 Melanoma, 465, 537 Membrane Lipids, 537, 550 Memory, 4, 12, 16, 19, 20, 21, 31, 34, 41, 43, 47, 48, 49, 57, 58, 60, 69, 80, 82, 83, 84, 86, 89, 92, 94, 97, 98, 100, 102, 104, 106, 120, 122, 125, 129, 132, 133, 134, 137, 138, 140, 146, 153, 170, 178, 187, 193, 196, 201, 204, 211, 222, 234, 240, 244, 252, 260, 264, 268, 270, 277, 287, 300, 312, 320, 323, 324, 330, 333, 337, 339, 340, 347, 375, 385, 396, 406, 494, 495, 512, 513, 535, 537 Meninges, 505, 537 Menopause, 537, 552, 553 Menstrual Cycle, 145, 537, 554 Menstruation, 493, 537, 538 Mental deficiency, 434, 538 Mental Health Services, iv, 8, 128, 256, 296, 320, 405, 418, 440, 462, 538 Mental Processes, 49, 514, 538, 555, 556 Mental Retardation, 11, 19, 172, 438, 466, 477, 508, 538 Mentors, 10, 16, 83, 538 Mesencephalic, 22, 538, 558 Mesenchymal, 518, 538 Mesolimbic, 63, 85, 382, 384, 497, 538, 572

Meta-Analysis, 7, 144, 154, 189, 190, 200, 238, 243, 250, 538 Metabolite, 391, 501, 522, 538, 553 Metabotropic, 71, 212, 538 Metastasis, 538 Metastatic, 75, 538 Methamphetamine, 165, 538 Methionine, 374, 538, 567 Methyltransferase, 155, 180, 184, 275, 276, 538 MI, 59, 88, 96, 113, 138, 194, 359, 365, 370, 392, 402, 489, 538 Microbe, 538, 570 Microbiology, 491, 499, 539 Microdialysis, 18, 539 Microglia, 498, 539, 540 Microorganism, 508, 539, 573 Microscopy, 58, 539 Microtubule-Associated Proteins, 135, 539, 543 Microtubules, 531, 539, 543 Microwaves, 539, 557 Migration, 130, 212, 399, 536, 539 Mobility, 130, 539 Mobilization, 387, 539 Mode of Transmission, 116, 392, 539 Modeling, 30, 129, 146, 539 Modification, 66, 294, 398, 494, 523, 539, 557 Modulator, 368, 397, 539 Molecular Structure, 119, 539, 571 Monitor, 341, 540, 545 Monoamine, 380, 436, 494, 496, 513, 540, 562, 571 Monoamine Oxidase, 436, 494, 496, 513, 540, 562, 571 Monocytes, 531, 533, 540 Monogenic, 379, 540 Mononuclear, 137, 540, 571 Monotherapy, 389, 540 Mood Disorders, 7, 55, 85, 137, 160, 242, 417, 423, 436, 540 Morphine, 497, 540, 542 Morphological, 24, 36, 95, 130, 399, 517, 522, 537, 540 Morphology, 13, 24, 31, 36, 89, 93, 136, 154, 187, 199, 214, 229, 230, 264, 536, 540 Motility, 540, 562 Motion Perception, 79, 540 Motivations, 369, 540, 556 Motor Cortex, 65, 540, 558 Motor nerve, 540, 541, 545

Index 585

Movement Disorders, 223, 371, 470, 497, 540, 568 Mucosa, 540, 542, 554 Multicenter study, 194, 540 Multiple sclerosis, 138, 408, 439, 540 Multivariate Analysis, 57, 122, 541 Muscimol, 394, 541 Muscle Fibers, 541 Muscle relaxant, 364, 496, 541, 550, 568 Muscle tension, 541 Muscular Atrophy, 465, 541 Muscular Dystrophies, 516, 541 Myalgia, 530, 541 Myasthenia, 408, 439, 541 Myelin, 13, 130, 131, 269, 513, 540, 541, 546 Myelin Sheath, 130, 131, 541, 546 Myocardium, 538, 541 Myosin, 503, 541 Myotonic Dystrophy, 372, 465, 541 N Naive, 27, 62, 74, 98, 100, 104, 150, 154, 196, 212, 220, 263, 290, 296, 307, 333, 541 Naloxone, 541 Naltrexone, 81, 541 Narcolepsy, 217, 372, 513, 541 Narcotic, 540, 541, 542 Nasal Cavity, 437, 542, 547, 573 Nasal Mucosa, 530, 542 Nasal Septum, 542, 573 Natural Language Processing, 84, 542 Nausea, 496, 497, 542, 547 NCI, 1, 354, 459, 507, 542 Needs Assessment, 229, 542 Neocortex, 14, 24, 36, 59, 60, 82, 542, 543 Neonatal, 43, 46, 66, 93, 300, 323, 542 Neonatal period, 43, 542 Neoplasia, 465, 542 Neoplasm, 408, 542 Neoplastic, 527, 536, 542 Neostriatum, 505, 542 Nephropathy, 532, 542 Nerve, 359, 370, 372, 492, 495, 499, 506, 511, 513, 516, 537, 540, 541, 542, 544, 545, 546, 552, 560, 561, 565, 570, 573 Nerve Fibers, 542, 573 Networks, 18, 20, 25, 33, 53, 68, 126, 128, 234, 328, 385, 442, 542 Neuregulin-1, 248, 543 Neuroanatomy, 49, 52, 66, 67, 89, 131, 184, 218, 534, 543 Neurodegenerative Diseases, 379, 380, 402, 500, 543

Neuroendocrine, 85, 88, 220, 543 Neuroendocrinology, 87, 543 Neurofibrillary Tangles, 7, 8, 543 Neurofilaments, 543 Neurogenic, 407, 438, 543 Neurologic, 408, 496, 543 Neuromuscular, 491, 543, 571 Neuromuscular Junction, 491, 543 Neurons, 13, 14, 24, 36, 41, 46, 54, 60, 61, 66, 77, 92, 107, 121, 124, 141, 169, 186, 194, 215, 240, 250, 251, 264, 277, 281, 372, 375, 394, 424, 447, 508, 513, 520, 522, 531, 533, 541, 542, 543, 544, 546, 557, 567 Neuropeptide, 149, 543 Neuropharmacology, 24, 90, 92, 145, 151, 174, 194, 258, 297, 407, 417, 543 Neurophysiology, 62, 75, 91, 218, 286, 292, 302, 305, 306, 310, 513, 543 Neuropil, 50, 543 Neuropsychological Tests, 246, 258, 341, 544 Neurosis, 442, 544 Neurotensin, 18, 222, 544 Neurotic, 117, 496, 544 Neurotoxic, 54, 95, 491, 528, 541, 544 Neurotoxicity, 95, 544 Neurotoxin, 377, 544 Neutrophils, 525, 533, 544 Niacin, 198, 544, 571 Nicotine, 49, 94, 125, 223, 257, 279, 341, 372, 375, 544 Nitric Oxide, 163, 203, 544 Nitrogen, 492, 493, 521, 524, 545, 571 Nonverbal Communication, 508, 545, 556 Norepinephrine, 380, 492, 515, 544, 545 Nuclear, 23, 24, 121, 304, 437, 499, 519, 520, 531, 534, 537, 545, 568 Nuclear Family, 520, 545 Nuclear Medicine, 304, 437, 545 Nuclei, 121, 494, 519, 523, 536, 537, 545, 546, 551, 555, 557, 561, 562, 568 Nucleic Acid Hybridization, 527, 545 Nucleus Accumbens, 37, 54, 102, 545, 572 O Obsessive-Compulsive Disorder, 182, 215, 228, 251, 258, 407, 417, 472, 545 Occipital Lobe, 545, 573 Ocular, 48, 53, 96, 545, 561 Oculomotor, 79, 80, 97, 538, 545 Odds Ratio, 545, 559 Oedema, 358, 546

586 Schizophrenia

Olfaction, 4, 98, 99, 100, 228, 437, 546 Olfactory Bulb, 98, 99, 207, 546, 573 Olfactory Nerve, 546 Oligodendroglia, 130, 541, 546 Oligodendroglial, 13, 130, 546 Omega-3 fatty acid, 74, 279, 282, 284, 305, 308, 546 Oncogene, 465, 546 Opacity, 513, 546 Opsin, 546, 560 Optic Nerve, 546, 560, 573 Oral Health, 3, 5, 6, 436, 546 Oral Hygiene, 4, 5, 6, 546 Orbit, 546 Orbital, 37, 546 Orofacial, 4, 5, 6, 546 Orthostatic, 497, 546 Osmosis, 546, 547 Osmotic, 220, 358, 493, 547, 563 Osteoporosis, 446, 547 Outpatient, 32, 128, 145, 149, 182, 183, 257, 264, 268, 325, 337, 352, 438, 440, 547 Overexpress, 24, 547 Ovum, 523, 547, 554 Oxidation, 497, 501, 534, 547 Oxygen Consumption, 547, 560 Oxygenation, 53, 547 P Palliative, 547, 568 Palsy, 475, 547 Pancreas, 364, 491, 493, 514, 530, 547 Pancreatic, 465, 506, 547 Pancreatic cancer, 465, 547 Panic, 407, 417, 529, 547 Panic Disorder, 407, 417, 529, 547 Paradoxical, 185, 547 Paralysis, 511, 538, 547 Paranasal Sinuses, 437, 547 Paranoia, 322, 342, 400, 407, 423, 428, 548 Paranoid Personality Disorder, 371, 548 Paresthesias, 547, 548 Parietal, 80, 92, 97, 134, 140, 184, 234, 496, 548, 551 Parietal Lobe, 80, 496, 548 Parkinsonism, 12, 336, 497, 533, 548, 553 Paroxysmal, 465, 548 Partial remission, 548, 559 Partnership Practice, 548, 553 Parturition, 548, 554 Patch, 548, 570 Paternal Age, 447, 548

Pathogenesis, 14, 46, 67, 89, 99, 140, 177, 203, 224, 230, 277, 548 Pathologic, 17, 107, 503, 511, 528, 548, 555, 572 Pathologies, 363, 390, 412, 548 Patient Advocacy, 476, 548 Patient Compliance, 351, 548 Patient Education, 325, 352, 472, 482, 484, 489, 548 Patient Satisfaction, 352, 548 Pedigree, 56, 76, 77, 216, 548 Peduncle, 143, 549, 558 Pelvic, 549, 554 Pelvis, 535, 549, 572 Penicillin, 495, 549 Peptide, 18, 62, 494, 506, 533, 543, 549, 555 Perazine, 202, 549 Perennial, 549, 571 Perfusion, 528, 549 Perinatal, 34, 66, 88, 139, 437, 549 Peripheral blood, 27, 531, 549 Peripheral Nervous System, 513, 518, 541, 543, 544, 547, 549, 553, 566 Peritoneal, 546, 549 Peritoneal Cavity, 546, 549 Perivascular, 539, 546, 549 Peroxide, 177, 549 Perphenazine, 315, 348, 549 Personality Development, 549, 556 Personality Disorders, 47, 118, 417, 549 PH, 136, 147, 171, 200, 217, 218, 230, 231, 237, 251, 268, 291, 341, 549 Pharmacogenetics, 28, 549 Pharmacokinetic, 183, 550 Pharmacologic, 18, 94, 145, 419, 437, 438, 495, 550, 570 Pharmacotherapy, 18, 46, 51, 81, 154, 209, 222, 238, 260, 291, 422, 431, 550 Pharynx, 530, 542, 550 Phencyclidine, 46, 90, 95, 306, 383, 384, 550 Phenotype, 13, 18, 24, 42, 44, 47, 53, 79, 116, 144, 154, 368, 397, 501, 509, 550 Phenyl, 358, 359, 550 Phenylalanine, 315, 550, 571 Phenytoin, 504, 550 Phorbol, 163, 550 Phospholipases, 550, 563 Phospholipids, 364, 520, 530, 537, 550 Phosphorus, 322, 503, 550 Phosphorylation, 543, 550

Index 587

Physiologic, 91, 134, 231, 492, 520, 528, 537, 538, 550, 558, 567, 571 Physiology, 46, 66, 77, 108, 130, 147, 196, 277, 278, 431, 437, 501, 516, 543, 544, 550 Pigments, 504, 550, 560 Pilot study, 10, 28, 84, 123, 126, 144, 145, 171, 174, 175, 246, 305, 551 Pitch, 551, 573 Plants, 493, 498, 499, 500, 501, 504, 508, 524, 540, 545, 550, 551, 552, 570, 571 Plasma cells, 496, 551 Plasma protein, 358, 493, 551, 555, 563 Plasticity, 71, 102, 364, 551 Platelet Activation, 551, 563 Platelet Aggregation, 495, 544, 551, 569 Platelets, 23, 252, 544, 551, 569 Pleomorphic, 545, 551 Pleural, 546, 551 Pleural cavity, 546, 551 Pneumonia, 510, 551 Point Mutation, 67, 551 Poisoning, 497, 512, 532, 542, 551 Policy Making, 405, 551 Polycystic, 465, 551 Polydipsia, 176, 551 Polymerase, 71, 523, 551 Polymorphic, 9, 10, 66, 116, 402, 513, 552 Polysaccharide, 492, 496, 552 Polyunsaturated fat, 73, 177, 279, 302, 552, 569 Polyuria, 147, 552 Pons, 173, 502, 552 Posterior, 22, 45, 92, 97, 134, 234, 494, 499, 505, 507, 515, 519, 531, 545, 547, 552, 565 Postmenopausal, 547, 552 Postnatal, 36, 88, 552 Postoperative, 276, 552 Postsynaptic, 105, 111, 146, 240, 385, 552, 563, 567 Post-synaptic, 71, 102, 105, 385, 552 Post-traumatic, 472, 540, 552 Post-traumatic stress disorder, 472, 552 Postural, 552, 565 Potassium, 46, 66, 166, 341, 552 Potentiate, 95, 111, 118, 383, 384, 552 Potentiating, 366, 370, 552 Potentiation, 372, 506, 535, 552, 563 Practicability, 552, 571 Practice Guidelines, 261, 280, 418, 419, 462, 473, 552 Preclinical, 41, 60, 87, 90, 92, 96, 104, 107, 233, 389, 553

Precursor, 498, 515, 516, 517, 518, 533, 545, 550, 553, 554, 555, 571 Predictive factor, 69, 553 Predisposition, 96, 103, 125, 263, 372, 379, 380, 553, 568 Pregnancy Outcome, 270, 553 Premenopausal, 246, 446, 553 Prenatal, 34, 40, 43, 66, 72, 74, 88, 96, 139, 234, 235, 326, 420, 437, 517, 553 Presynaptic, 105, 111, 394, 499, 544, 553, 567 Presynaptic Terminals, 499, 553 Prevalence, 94, 95, 125, 128, 235, 291, 361, 372, 392, 400, 436, 545, 553 Preventive Medicine, 16, 483, 553 Prion, 221, 553 Private Practice, 407, 438, 553 Private Sector, 4, 553 Probe, 11, 20, 79, 99, 100, 105, 268, 539, 553 Problem Solving, 44, 553 Procyclidine, 292, 553 Prodrug, 522, 553 Progesterone, 554, 565 Prognostic factor, 117, 554 Progression, 26, 52, 91, 110, 262, 375, 391, 491, 495, 554, 562 Projection, 36, 37, 45, 531, 545, 546, 553, 554, 557, 558, 572 Prolactin, 153, 176, 236, 258, 274, 366, 554 Proline, 367, 368, 396, 397, 508, 528, 554 Promoter, 67, 149, 201, 232, 296, 554 Prone, 118, 554 Proneness, 118, 170, 180, 229, 554 Prophase, 554, 567 Prophylaxis, 400, 554, 560 Proprioception, 5, 554 Prosencephalon, 514, 554, 568 Prospective Studies, 19, 554 Prospective study, 47, 121, 203, 535, 554 Prostaglandins, 277, 381, 493, 498, 554 Prostate, 75, 465, 554 Protease, 508, 523, 555 Protein C, 33, 393, 402, 493, 494, 508, 555 Protein Isoforms, 400, 493, 555 Protein S, 33, 103, 131, 396, 434, 465, 466, 501, 523, 555, 560 Proteolytic, 509, 521, 555 Prothrombin, 520, 555, 569 Protocol, 28, 52, 53, 76, 555 Protons, 528, 536, 555, 557 Proximal, 9, 79, 104, 368, 514, 542, 553, 555, 562

588 Schizophrenia

Pruritus, 497, 555 Psoriasis, 555, 560 Psychic, 318, 538, 544, 555, 556, 562 Psychoacoustics, 555, 556 Psychoactive, 450, 555, 568, 574 Psychoanalysis, 260, 261, 417, 555 Psychoanalytic Theory, 261, 521, 556 Psychogenic, 85, 407, 438, 556 Psycholinguistics, 67, 556 Psychology, Clinical, 22, 556 Psychometrics, 62, 556 Psychomotor, 231, 387, 504, 512, 543, 556 Psychotomimetic, 382, 383, 494, 513, 556 Psychotropic, 148, 407, 556 Psychotropic Drugs, 407, 556 Puberty, 377, 556 Public Health, 12, 14, 27, 28, 73, 85, 87, 94, 119, 126, 274, 308, 360, 373, 374, 462, 556 Public Policy, 147, 461, 557 Public Sector, 45, 557 Pulmonary, 501, 533, 557, 572 Pulmonary Artery, 501, 557, 572 Pulse, 131, 540, 557 Pulvinar, 123, 207, 557 Purines, 500, 557, 562 Pyramidal Cells, 17, 104, 513, 557 Pyramidal Tracts, 520, 557 Pyrimidines, 500, 557, 562 R Race, 85, 118, 120, 382, 539, 557 Raclopride, 63, 105, 557 Radiation, 515, 517, 518, 522, 537, 557, 558, 561, 574 Radiation therapy, 515, 557 Radio Waves, 342, 539, 557 Radioactive, 341, 352, 502, 528, 534, 537, 545, 557, 558, 561 Radioimmunoassay, 290, 558 Radioisotope, 558, 570 Radiological, 198, 558 Radiology, 5, 23, 545, 558 Radiopharmaceutical, 523, 558 Rape, 552, 558 Reaction Time, 20, 210, 284, 319, 326, 558 Reality Testing, 556, 558 Receptors, Serotonin, 558, 562 Recombinant, 62, 558 Recombination, 103, 523, 558 Rectum, 497, 502, 508, 514, 521, 522, 529, 532, 555, 558 Recurrence, 116, 388, 391, 501, 536, 558 Red blood cells, 74, 519, 558

Red Nucleus, 499, 558, 572 Refer, 1, 68, 509, 514, 517, 521, 523, 527, 531, 534, 536, 541, 543, 556, 558, 562, 570 Reflex, 108, 123, 293, 308, 426, 520, 558 Refraction, 495, 558, 565 Refractory, 16, 28, 32, 131, 149, 175, 194, 196, 227, 294, 310, 338, 344, 361, 559 Regimen, 3, 28, 337, 512, 516, 548, 550, 559 Regression Analysis, 136, 559 Rehabilitative, 19, 42, 559 Relapse, 100, 108, 126, 171, 210, 243, 319, 326, 329, 373, 374, 407, 414, 416, 420, 448, 559 Relative risk, 116, 559 Relaxant, 550, 559 Reliability, 35, 63, 127, 172, 257, 261, 304, 559 Remission, 106, 147, 278, 279, 293, 298, 304, 501, 536, 558, 559 Renal failure, 512, 559 Renin, 504, 559 Renin-Angiotensin System, 504, 559 Reproduction Techniques, 553, 559 Research Design, 38, 115, 127, 132, 559 Research Personnel, 115, 559 Respiration, 341, 504, 506, 512, 540, 559 Reticular, 109, 121, 560 Retina, 79, 507, 510, 533, 536, 546, 560, 561, 573 Retinal, 79, 97, 305, 514, 546, 560, 573 Retinoblastoma, 465, 560 Retinoids, 141, 560 Retinol, 560 Retrograde, 77, 560 Retrospective, 26, 85, 133, 292, 342, 415, 560 Retroviral vector, 523, 560 Reversion, 388, 391, 560 Rhodopsin, 546, 560 Ribose, 491, 560 Ribosome, 560, 570 Rigidity, 80, 223, 548, 551, 560 Risk factor, 8, 9, 43, 66, 98, 139, 140, 157, 187, 212, 234, 518, 535, 554, 559, 560 Risk patient, 26, 560 Rod, 499, 507, 561 Rubella, 34, 561 Rural Population, 434, 561 S Saccades, 159, 561 Salivary, 512, 514, 547, 561, 566, 574 Salivary glands, 512, 514, 561

Index 589

Satellite, 546, 561 Scans, 56, 65, 90, 116, 123, 124, 131, 190, 191, 211, 341, 352, 372, 561 Schizoid, 371, 439, 561, 574 Schizoid Personality Disorder, 371, 439, 561 Schizophrenic Language, 84, 561 Schizotypal Personality Disorder, 68, 129, 371, 372, 513, 561, 574 Sclerosis, 408, 465, 470, 475, 498, 540, 561 Screening, 66, 76, 77, 139, 216, 230, 250, 374, 398, 399, 400, 401, 435, 507, 561 Secretion, 274, 518, 520, 527, 531, 532, 539, 561, 562 Secretory, 561, 567 Sedative, 364, 529, 561 Segmentation, 91, 562 Segregation, 558, 562 Seizures, 389, 439, 504, 512, 548, 550, 562 Selegiline, 359, 562 Self Care, 6, 330, 491, 562 Self-Injurious Behavior, 358, 562 Semantics, 67, 562 Semen, 554, 562 Senile, 7, 358, 372, 375, 497, 547, 562 Senile Plaques, 7, 562 Septal, 37, 111, 394, 496, 534, 562 Septal Nuclei, 496, 534, 562 Septum, 533, 562 Septum Pellucidum, 533, 562 Sequencing, 156, 197, 363, 562, 567 Serine, 75, 94, 95, 164, 562 Sertraline, 28, 228, 562 Serum, 62, 92, 114, 150, 164, 263, 269, 304, 350, 366, 391, 400, 493, 494, 509, 558, 563, 571 Serum Albumin, 164, 558, 563 Sex Characteristics, 492, 556, 563 Sex Determination, 465, 563 Shock, 62, 362, 517, 563, 570 Shunt, 275, 563 Signal Transduction, 398, 503, 530, 563 Signs and Symptoms, 116, 378, 383, 384, 386, 436, 559, 563 Skeletal, 506, 507, 511, 541, 563, 564 Skeleton, 491, 532, 563 Skull, 65, 546, 563, 568 Sleep apnea, 563, 566 Small intestine, 75, 516, 527, 528, 532, 563 Smoking Cessation, 94, 125, 328, 502, 563 Smooth muscle, 493, 494, 527, 540, 559, 564, 566

Social Behavior, 240, 332, 396, 564, 573 Social Class, 137, 328, 564 Social Environment, 155, 201, 557, 564 Social Isolation, 63, 561, 564 Social Support, 85, 101, 118, 126, 327, 328, 331, 564, 566 Sodium, 564, 572 Sodium Channels, 564, 572 Solid tumor, 495, 564 Solvent, 23, 500, 519, 524, 547, 564 Soma, 557, 564 Somatic, 285, 492, 517, 527, 534, 537, 548, 549, 553, 564 Soybean Oil, 552, 564 Spasm, 511, 527, 538, 564 Spasmodic, 408, 564 Specialist, 229, 478, 512, 564 Specificity, 23, 26, 42, 69, 98, 102, 156, 162, 166, 169, 221, 242, 270, 492, 564 Spectroscopic, 277, 536, 565 Sperm, 507, 565 Sphenoid, 547, 565 Spinal cord, 372, 475, 498, 502, 505, 506, 519, 537, 542, 549, 557, 558, 565 Spinal tap, 535, 565 Spleen, 512, 535, 565 Spontaneous Abortion, 553, 565 Sporadic, 138, 140, 543, 560, 565 Stabilization, 14, 26, 550, 565 Staging, 561, 565 Stasis, 280, 311, 565 Steady state, 91, 565 Steel, 507, 565 Stereotactic, 48, 565 Stereotyped Behavior, 386, 565 Steroid, 500, 511, 565 Stillbirth, 553, 565 Stimulant, 494, 513, 527, 538, 565, 568 Stomach, 491, 514, 519, 522, 524, 527, 542, 549, 550, 563, 565, 566 Stool, 508, 529, 532, 566 Strained, 406, 566 Strand, 384, 551, 566 Stress management, 349, 566 Striate, 114, 566 Striatum, 41, 63, 279, 542, 545, 566 Stroke, 355, 372, 408, 460, 504, 566 Structure-Activity Relationship, 384, 566 Strychnine, 59, 566 Subacute, 530, 566 Subclinical, 530, 562, 566 Subcutaneous, 492, 516, 546, 566

590 Schizophrenia

Subiculum, 45, 54, 60, 527, 566 Submaxillary, 518, 566 Subspecies, 564, 566 Substance P, 512, 538, 561, 566 Substrate, 60, 72, 85, 99, 254, 516, 518, 566, 571 Subthalamus, 514, 567 Sudden death, 246, 567 Sulfur, 538, 567 Superoxide, 176, 256, 309, 310, 567 Superoxide Dismutase, 176, 256, 309, 310, 567 Supplementation, 73, 276, 284, 298, 301, 302, 308, 567 Support group, 53, 310, 440, 476, 567 Suppression, 57, 122, 295, 300, 302, 305, 409, 567 Sympathomimetic, 494, 513, 515, 519, 538, 545, 567, 571 Symphysis, 506, 554, 567 Symptomatic, 21, 106, 108, 173, 232, 438, 496, 567 Symptomatology, 25, 32, 57, 86, 104, 183, 230, 250, 252, 255, 267, 275, 324, 330, 332, 361, 430, 567 Synapse, 58, 59, 99, 184, 492, 543, 553, 567, 570 Synapsis, 567 Synaptic Transmission, 111, 361, 368, 397, 544, 567 Synchrony, 145, 567 Synergistic, 554, 567 Systolic, 528, 568 T Tacrine, 376, 568 Tardive, 12, 34, 218, 232, 239, 313, 366, 370, 371, 381, 387, 497, 507, 568 Telangiectasia, 465, 568 Telencephalon, 499, 505, 554, 568 Temperament, 45, 256, 568 Temporal Lobe, 17, 21, 47, 91, 131, 147, 197, 238, 241, 298, 429, 494, 499, 568 Terminator, 508, 568 Tetrahydrocannabinol, 503, 568 Thalamic, 22, 25, 32, 121, 123, 131, 140, 269, 309, 394, 499, 519, 537, 568 Thalamic Diseases, 499, 568 Thalamic Nuclei, 22, 121, 269, 519, 537, 568 Therapeutics, 46, 92, 119, 144, 166, 214, 230, 306, 390, 455, 540, 568 Thermal, 495, 514, 568

Third Ventricle, 519, 528, 533, 568 Thorax, 535, 568 Threonine, 562, 568 Threshold, 4, 61, 65, 98, 100, 520, 528, 569 Thrombin, 520, 521, 551, 555, 569 Thrombocytes, 551, 569 Thrombomodulin, 555, 569 Thrombosis, 555, 566, 569 Thromboxanes, 498, 569 Thrush, 158, 211, 266, 503, 569 Thyroid, 262, 341, 569, 571 Thyroid Gland, 341, 569 Thyroid Hormones, 569, 571 Ticks, 140, 569 Time Management, 566, 569 Tolerance, 127, 365, 379, 524, 569 Tomography, 41, 80, 89, 132, 140, 284, 322, 352, 419, 437, 510, 536, 561, 569 Tonal, 298, 569 Tone, 21, 286, 359, 546, 569 Tonic, 54, 569 Tonus, 569 Tooth Preparation, 491, 569 Toxic, iv, 364, 499, 500, 511, 518, 529, 534, 544, 570 Toxicity, 365, 379, 515, 570 Toxicology, 25, 46, 96, 110, 462, 488, 570 Toxin, 518, 569, 570 Tracer, 78, 341, 570 Trachea, 502, 550, 569, 570 Traction, 202, 507, 570 Tranquilizing Agents, 556, 570 Transcriptase, 523, 570 Transdermal, 125, 570 Transduction, 563, 570 Transfection, 501, 523, 570 Translation, 92, 494, 570 Translational, 15, 36, 93, 134, 570 Translocation, 245, 570 Transmitter, 111, 372, 491, 498, 499, 515, 532, 537, 545, 570, 571 Transplantation, 193, 507, 517, 536, 570 Trauma, 38, 262, 437, 500, 512, 525, 568, 570 Treatment Failure, 433, 570 Treatment Outcome, 31, 321, 336, 570 Trees, 156, 571 Tremor, 359, 538, 548, 571 Triad, 13, 55, 571 Tricyclic, 436, 496, 507, 529, 571 Trigger zone, 497, 571 Triglyceride, 269, 571

Index 591

Trophic, 124, 571 Tryptophan, 330, 398, 508, 562, 571 Tubercle, 545, 571 Tuberous Sclerosis, 465, 571 Tubocurarine, 522, 571 Tumor Necrosis Factor, 197, 224, 571 Tyramine, 540, 571 Tyrosine, 179, 268, 363, 369, 515, 571 U Ubiquitin, 543, 571 Unconscious, 417, 419, 495, 528, 556, 571 Urethra, 554, 571, 572 Urinary, 506, 512, 529, 552, 571 Urinary tract, 512, 571 Urinary tract infection, 512, 571 Urine, 341, 369, 372, 391, 501, 513, 518, 526, 529, 552, 571, 572 Uterus, 491, 506, 511, 517, 538, 544, 554, 572 V Vaccine, 555, 572 Vagina, 503, 538, 572 Vaginal, 66, 572 Vaginitis, 503, 572 Valproic Acid, 280, 390, 572 Vascular, 119, 407, 493, 507, 513, 518, 530, 544, 546, 569, 572 Vasoconstriction, 519, 572 Vasodilator, 502, 515, 527, 572 VE, 147, 204, 206, 214, 342, 572 Vein, 532, 545, 561, 572 Venous, 546, 555, 572 Venter, 572 Ventral, 31, 37, 54, 63, 135, 214, 300, 377, 528, 545, 552, 572 Ventral Tegmental Area, 54, 572 Ventricle, 32, 43, 494, 505, 527, 533, 545, 557, 568, 572 Ventricular, 238, 567, 572 Venules, 502, 503, 572 Vertebrae, 565, 572

Vertigo, 450, 572 Veterinary Medicine, 461, 572 Viral, 88, 156, 530, 570, 572 Virulence, 570, 572 Virus, 137, 150, 235, 372, 410, 518, 523, 531, 560, 561, 570, 572, 573 Visceral, 534, 573 Visual Acuity, 510, 573 Visual Cortex, 61, 573 Visual field, 540, 573 Visual Pathways, 129, 573 Visual Perception, 245, 573 Vitreous, 533, 560, 573 Vitreous Body, 560, 573 Vitro, 23, 202, 322, 573 Vivo, 13, 23, 45, 105, 130, 322, 573 Voice Disorders, 450, 573 Volition, 394, 532, 573 Vomeronasal Organ, 546, 573 Vomica, 566, 573 W Wakefulness, 244, 512, 573 War, 331, 428, 552, 573 Weight Gain, 28, 94, 127, 160, 179, 228, 258, 350, 573 White blood cell, 27, 496, 525, 533, 535, 536, 551, 573 Windpipe, 550, 569, 573 Withdrawal, 12, 82, 112, 125, 173, 361, 372, 378, 383, 384, 385, 388, 391, 394, 400, 512, 574 X Xenograft, 495, 574 Xerostomia, 4, 5, 574 X-ray, 66, 488, 509, 510, 537, 545, 557, 558, 561, 565, 574 Y Yeasts, 503, 522, 550, 574 Z Zymogen, 555, 574

592 Schizophrenia

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