AFFECTIVE DISORDERS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
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 ©2004 by ICON Group International, Inc. Copyright ©2004 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., 1960Affective Disorders: 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: 0-597-84323-6 1. Affective Disorders-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.
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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 affective disorders. 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 AFFECTIVE DISORDERS ............................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Affective Disorders........................................................................ 8 E-Journals: PubMed Central ....................................................................................................... 65 The National Library of Medicine: PubMed ................................................................................ 65 CHAPTER 2. NUTRITION AND AFFECTIVE DISORDERS ................................................................. 111 Overview.................................................................................................................................... 111 Finding Nutrition Studies on Affective Disorders .................................................................... 111 Federal Resources on Nutrition ................................................................................................. 117 Additional Web Resources ......................................................................................................... 117 CHAPTER 3. ALTERNATIVE MEDICINE AND AFFECTIVE DISORDERS ........................................... 119 Overview.................................................................................................................................... 119 National Center for Complementary and Alternative Medicine................................................ 119 Additional Web Resources ......................................................................................................... 121 General References ..................................................................................................................... 123 CHAPTER 4. DISSERTATIONS ON AFFECTIVE DISORDERS ............................................................. 125 Overview.................................................................................................................................... 125 Dissertations on Affective Disorders ......................................................................................... 125 Keeping Current ........................................................................................................................ 126 CHAPTER 5. CLINICAL TRIALS AND AFFECTIVE DISORDERS........................................................ 127 Overview.................................................................................................................................... 127 Recent Trials on Affective Disorders ......................................................................................... 127 Keeping Current on Clinical Trials ........................................................................................... 129 CHAPTER 6. PATENTS ON AFFECTIVE DISORDERS ........................................................................ 131 Overview.................................................................................................................................... 131 Patents on Affective Disorders................................................................................................... 131 Patent Applications on Affective Disorders............................................................................... 139 Keeping Current ........................................................................................................................ 154 CHAPTER 7. BOOKS ON AFFECTIVE DISORDERS ........................................................................... 155 Overview.................................................................................................................................... 155 Book Summaries: Federal Agencies............................................................................................ 155 Book Summaries: Online Booksellers......................................................................................... 156 Chapters on Affective Disorders ................................................................................................ 160 CHAPTER 8. PERIODICALS AND NEWS ON AFFECTIVE DISORDERS.............................................. 165 Overview.................................................................................................................................... 165 News Services and Press Releases.............................................................................................. 165 Academic Periodicals covering Affective Disorders................................................................... 168 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 171 Overview.................................................................................................................................... 171 NIH Guidelines.......................................................................................................................... 171 NIH Databases........................................................................................................................... 173 Other Commercial Databases..................................................................................................... 175 The Genome Project and Affective Disorders............................................................................. 175 APPENDIX B. PATIENT RESOURCES ............................................................................................... 179 Overview.................................................................................................................................... 179 Patient Guideline Sources.......................................................................................................... 179 Associations and Affective Disorders......................................................................................... 182 Finding Associations.................................................................................................................. 182 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 185
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Overview.................................................................................................................................... 185 Preparation................................................................................................................................. 185 Finding a Local Medical Library................................................................................................ 185 Medical Libraries in the U.S. and Canada ................................................................................. 185 ONLINE GLOSSARIES................................................................................................................ 191 Online Dictionary Directories ................................................................................................... 191 AFFECTIVE DISORDERS DICTIONARY ............................................................................... 193 INDEX .............................................................................................................................................. 269
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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 affective disorders 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 affective disorders, 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 affective disorders, 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 affective disorders. 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 affective disorders, 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 affective disorders. 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 AFFECTIVE DISORDERS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on affective disorders.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and affective disorders, 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 “affective disorders” (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: •
Assessment of Depression in Dementia Patients: Association of Caregiver Mood With Depression Ratings Source: Gerontologist. 34(2): 231-234. April 1994. Summary: Caregivers typically provide critical diagnostic data on patients with dementia and possible depression. However, their accuracy and the potential influence of their own mood on assessment is unknown. Researchers at the Geriatric and Family Services Clinic at the University of Washington Medical Center in Seattle studied the effects of caregiver mood on the assessment of depression in patients with dementia. Focus was on relationships between caregiver depression and videotape ratings and between caregiver depression and actual patient depression ratings. Forty-one primary caregivers of memory- impaired patients watched two 5-minute videotape analogues in
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which a patient was portrayed as either depressed or nondepressed. Caregivers' ratings of the two videotaped patients were compared to determine the degree to which a caregiver's mood influences his or her ratings of depression. In addition, caregivers rated the level of depression in their own patients. Researchers used the Schedule of Affective Disorders and Schizophrenia and the Hamilton Depression Rating Scale to measure caregiver and patient depression diagnoses. The caregivers correctly identified depression in both the videotaped patients and their own patients. Caregivers' moods were not associated with videotape ratings and only moderately associated with patient ratings. According to the authors, caregiver and patient depression may coexist or occur independently; neither fully explains the existence of the other. The authors support reliance on caregiver input in the diagnosis of depression. 1 table, 29 references. •
Communication and Its Disorders Source: Child and Adolescent Psychiatric Clinics of North America. 8(1): 1-18. January 1999. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: Communication, broadly defined, is the exchange of information between two or more individuals. This introductory article explores communication and its disorders, particularly how a child develops communication and how developmental difficulties in any of the components (production, comprehension, pragmatics) contribute to the development of communicative competence. Topics include the impact of social, affective, and cognitive development on communication; the comorbidity of communication disorders and socioemotional disorders; communication problems associated with social or affective disorders, including autism and selective mutism; communication problems associated with cognitive disorders, such as mental retardation, and acquired brain damage; communicative problems associated with sensory and motor impairment, including hearing impairment, visual impairment, and neuromotor impairment; communicative problems associated with socioeconomic differences, including economic disadvantage and cultural diversity; and specific speech and language disorders. The author concludes that the development of communicative competence is a process that is highly vulnerable to disruptions in social, affective, and cognitive functioning. 80 references.
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Depression With and Without Dementia Source: Hospital Practice. 25(4A): 47-51, 54, 59, 62-63, 66. April 30, 1990. Summary: Generally, illnesses with mixed symptoms involving memory and mood may be termed cognitive-affective disorders, and may be divided into two types. One in which depression is the single diagnosis that accounts for both cognitive and affective symptoms, and in which treatment may alleviate all aspects of the disorder. In the other there are two diagnoses, with depression superimposed on an irreversible dementia, usually Alzheimer's disease or multi-infarct dementia. This journal article illustrates the differentiation between the two types, utilizing a pair of cases, and discusses therapeutic strategies and goals. This journal article also reviews recent trends in the differential diagnosis of dementia and depression, the efficacy of therapy, therapy guidelines, and aspects of excess disability. 5 references.
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Irritable Bowel Syndrome: A Quick Review of a Common GI Problem Source: IM. Internal Medicine. 19(8): 24-25. August 1998.
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Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Summary: This article briefly brings readers up-to-date on the diagnosis and treatment strategies used for irritable bowel syndrome (IBS). IBS is a functional disorder of the gastrointestinal tract that occurs in 10 to 22 percent of adults. The most common symptoms are abdominal pain and altered bowel habits, including diarrhea or constipation or a combination of the two. The author discusses pathophysiology, the criteria for confirming a diagnosis of IBS, laboratory tests that may contribute to this diagnosis of exclusion, and treatment options. Criteria for confirming a diagnosis require that symptoms be present for at least 3 months. Management begins with the need for the physician to establish a therapeutic relationship. Because of their safety and frequent placebo effect, a trial of fiber supplements is reasonable in all patients with IBS. The author discusses the treatments for patients in whom diarrhea predominates; those in whom pain, gas, and bloating predominate; and those in whom constipation is the primary problem. The author notes that, in all cases of IBS, regardless of the predominating symptom, the use of antidepressants, anxiolytics, and psychotherapy may be indicated for patients with associated affective disorders. 1 figure. 4 references. •
Fibromyalgia: More than Just a Musculoskeletal Disease Source: American Family Physician. 52(3): 843-851, 853-854. September 1, 1995. Summary: This article discusses fibromyalgia, a common condition characterized by diffuse musculoskeletal pain and fatigue. Additionally, people with this syndrome have a high incidence of headaches, ocular and vestibular complaints, paresthesias, esophageal dysmotility, 'allergic' symptoms, irritable bowel syndrome (IBS), genitourinary symptoms, and affective disorders. Recent research has revealed a number of objective biochemical, hormonal, and neurotransmitter abnormalities associated with fibromyalgia, making it a clearly identifiable condition. In discussing the symptoms, the author hopes to clarify the understanding of the pathogenesis and treatment of fibromyalgia. A patient information handout is included for physicians to photocopy and distribute to their patients with fibromyalgia. 2 figures. 3 tables. 33 references. (AA-M).
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Psychiatric Family History and Neurological Disease in Autistic Spectrum Disorders Source: Developmental Medicine and Child Neurology. 36(5): 441-448. May 1994. Summary: This article reports on a study of a clinically accrued group of children with autistic spectrum disorders (ASD) investigated for neurological disease and familial psychopathology, particularly major affective disorder. The study group comprised all of the 40 children and adolescents with ASD evaluated by the authors during a fouryear period at Duke University Medical Center. Neurological evaluation included EEG, MRI, karyotyping and positron emission tomography as indicated. Psychiatric family history data were obtained from family members during long-term follow-up. Twenty probands had positive neurological findings, 18 with negative family history. Fourteen had no neurological findings and positive family histories; they tended to have higher function. Six had neither, and two had both. The segregation of neurological findings and familial affective disorder was highly significant. The authors conclude that their findings suggest that an important subgroup of autistic spectrum disorders may be related etiologically to familial major affective disorders, and may represent the earlylife onset of a severe phenotype of major affective disorder, particularly bipolar disease. 4 tables. 24 references. (AA-M).
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Evolving Concepts in Irritable Bowel Syndrome Source: Current Opinion in Gastroenterology. 15(1): 16-21. January 1999. Contact: Available from Lippincott Williams and Wilkins Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Summary: This article reviews recent research in irritable bowel syndrome (IBS). The authors note that converging evidence from investigations of the peripheral and central aspects of bidirectional brain gut interactions is beginning to shape a pathophysiological model of IBS and related functional gastrointestinal (GI) disorders. This neurobiological model includes alterations in autonomic, neuroendocrine, and pain modulatory mechanisms. The frequent association of IBS and other functional GI disorders with comorbid affective disorders and the temporal association of symptom exacerbation with psychosocial or physical stressors are consistent with alterations in the neurobiological mechanisms underlying the central stress response. The author discusses work in the area of alterations in central nervous system responses of the brain, neuroendocrine responses, autonomic dysfunction, and altered viscerosomatic sensitivity; peripheral modulators of visceral sensitivity; symptom based diagnosis; and affective disorders and psychosocial stressors. Depression and anxiety are the most common comorbid affective disorders in IBS. Classification of functional disorders according to these evolving biological markers holds the promise of a rational treatment design for subgroups of patients in the future. Renewed interest in drug development for IBS treatment has resulted in the development of diagnostic instruments for assessing the impact of symptoms on quality of life and in the development of compounds (drugs) undergoing clinical evaluation. 53 references (16 annotated).
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Depression Among African American Nursing Home Patients With Dementia Source: American Journal of Geriatric Psychiatry. 6(2): 162-175. Spring 1998. Summary: This journal article describes a study of the prevalence, recognition, and treatment of depression among 286 black and white nursing home residents with dementia. The participants were 218 black residents, mean age 80 years, and 68 white residents, mean age 85 years, from 3 nursing homes in Brooklyn, New York. Five scales were used to assess depressive symptoms, and the Core Research Center Modified Schedule for Affective Disorders and Schizophrenia was used to make a diagnosis of depression. Significantly more whites were diagnosed with possible depression, but there were no appreciable racial differences in the diagnoses of probable or definite depression, in depressive symptomatology, or in the clinical, social, or demographic factors associated with depression. There were no significant differences in depressive symptoms or diagnosis between American and Caribbean blacks. Depression was often unrecognized by staff in both racial groups, and was undertreated. Several of the depression scales developed for use in dementia had good reliability and validity among blacks. The authors suggest that factors related to nursing home admission criteria and residents' response to institutionalization may account for the absence of differences between racial groups. 6 tables, 46 references.
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Managing the Neuropsychiatric Symptoms of Parkinson's Disease Source: Neurology. 50(Supplement 6): S33-S38. June 1998. Summary: This journal article discusses the diagnosis and management of neuropsychiatric symptoms in patients with Parkinson's disease (PD). Studies suggest that 27 percent of PD patients may have dementia, and those with dementia are older
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than those who are not. Among PD patients with dementia, 26 percent have a pathology characterized by diffuse Lewy body disease, and 74 percent exhibit the pathologic changes of Alzheimer's disease (some also with cortical Lewy bodies). Because 90 percent of PD patients with dementia have cortical changes, PD dementia should be thought of as a cortical rather than subcortical dementia. The presence of dementia complicates the treatment of PD because antiparkinsonian drugs may superimpose a delirium on the dementia. Inevitably, antiparkinsonian drugs must be decreased or discontinued, resulting in a worsening of the patient's motor symptoms. Although there is no specific treatment for dementia, some patients may benefit from a trial of donepezil or exelon. Other neuropsychiatric symptoms discussed in this article include cognitive impairment without dementia, affective disorders such as depression and anxiety, and delirium. 3 figures, 40 references. •
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 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.
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Recent Developments in Geriatric Psychopharmacotherapy Source: Canadian Journal of Psychiatry. 39(8 Supplement 1): S9-S18. October 1994. Summary: This paper highlights recent advances in the pharmacological management of geriatric affective disorders and dementia. The paper focuses on the treatment of unipolar depression, bipolar disorder, and the cognitive and psychiatric symptoms of Alzheimer's disease (AD). The author discusses the current roles of tricyclic antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors in the treatment of depression in old age. He discusses recent findings pertaining to continuation and maintenance of antidepressant treatment. The treatment of bipolar disorder in old age has received very little study. A number of issues relating to efficacy, side effects and optimal blood levels of lithium, carbamazepine, and valproate in bipolar disorder remain unresolved and await further study. The paper reviews drug treatment of the cognitive impairment and psychiatric complications of AD. To date, with the possible exception of tacrine, no medication has been shown to have any clinically meaningful benefit in improving cognition in AD. 94 references. (AA- M).
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Depression in Alzheimer's Disease Patients: Caregivers As Surrogate Reporters Source: Journal of the American Geriatrics Society. 43(2): 150-155. February 1995. Summary: This study evaluated the use of caregivers as surrogate reporters of depressive symptoms in patients with Alzheimer's disease (AD) on five depression measures. Researchers compared scale characteristics, including means, ranges, internal consistency, sensitivity, and item content of modified self-report questionnaires and depression interviews. Participants were 76 patients diagnosed with both depression and AD, and their family caregivers. All subjects were community-residing participants in an outcome investigation of behavioral treatment for depression. Researchers completed a Schedule for Affective Disorders and Schizophrenia (SADS) interview on all subjects to establish a diagnosis of depression. Caregivers then completed three additional questionnaires about their patients: the Beck Depression Inventory, the Geriatric Depression Scale, and the Center for Epidemiological Studies-Depression Scale, all modified to provide a surrogate report of their patient's depressive symptoms. In addition, two interview measures were completed based on interviews with the caregiver and patient: the Hamilton Depression Rating Scale (HDRS) and the Cornell Scale for Depression in Dementia (CSDD). Mean scores were above the recommended cutoff score for mild levels of depression on all measures. Coefficient alpha levels were comparable to levels reported for the traditional self-report formats. Sensitivity varied among the measures, with the CSDD most sensitive and the HDRS least sensitive. Based on these results, the study suggests that caregivers are able to act as surrogate reporters of depression in AD patients. The modification of self-report questionnaires did not decrease their internal consistency, and they remained highly correlated with each other, supporting their validity when used in this manner. The authors recommend a two-step process of evaluating patients with AD for depression: first, a surrogate report questionnaire completed by caregivers to screen patients, eliminating those who are unlikely to be depressed, and then a more extensive interview with those patients who appear likely to be depressed and their caregivers. 4 tables, 35 references. (AA-M).
Federally Funded Research on Affective Disorders The U.S. Government supports a variety of research studies relating to affective disorders. 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 affective disorders. 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 affective disorders. The following is typical of the type of information found when searching the CRISP database for affective disorders: 2 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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Project Title: 5HT PRESYNAPTIC INHIBITION OF RETINAL INPUT TO THE SCN Principal Investigator & Institution: Pickard, Gary E.; Professor; Health and Exercise Science; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2002; Project Start 21-AUG-1997; Project End 30-JUN-2004 Summary: (applicant's abstract): The goal of this research is to furnish an understanding of the complex neural substrates underlying the regulation of the circadian oscillator located in the hypothalamic suprachiasmatic nucleus (SCN), which functions as our biological clock. Increased knowledge of the functional organization of the hypothalamus and the circadian timing system is relevant to major public health concerns such as sleep disorders, sleep disruption (as in jet lag or shift work), and serious affective disorders. Photic information essential for the daily resetting of the SCN circadian clock is conveyed directly to the SCN from the retina via the retinohypothalamic tract. The SCN also receives a dense serotonergic innervation arising from the midbrain raphe and additional afferents from the intergeniculate leaflet (IGL). In recent years, multiple serotonin (5-HT) receptor subtypes have been described and grouped into several families: 5-HT1 - 5-HT7. In this proposal, we will test the hypotheses that 5-HT1B receptors are located on the terminals of IGL afferents in the SCN and that 5-HT7 receptors are present on SCN neurons and on GABAergic terminals in the SCN. Moreover, we will test the hypothesis that 5-HT1B receptors are not located on a subset of retinal ganglion cells that send axonal branches to the SCN and IGL. Electron microscopic immunocytochemical techniques will be used to test the hypotheses that 5-HT1B receptors are presynaptic on IGL terminals in the SCN and that 5-HT7 receptors are located on neurons and presynaptically on GABA terminals in the SCN. In situ hybridization will be used to test the hypothesis that IGL neurons express 5-HT1B receptor mRNA. Using whole-cell patch-clamp techniques, we will test the hypothesis that 5-HT7 receptor agonists inhibit optic nerve stimulation-evoked EPSCs in SCN neurons in vitro in wild-type and in 5-HTlA receptor knock-out mice and that these same agonists inhibit GABA release in the SCN via a presynaptic mechanism. Behavioral pharmacological analyses of circadian wheel-running activity will be used to complement the in vitro analysis. The use of behavioral, pharmacological, morphological, and electrophysiological approaches will provide an integrated analysis of 5-HT receptor subtype function in the SCN and on afferents to the SCN that regulate clock function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: A NEUROBEHAVIORAL PROBE OF HUMAN REWARD FUNCTION Principal Investigator & Institution: Knutson, Brian D.; Assistant Professor; Psychology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: The proposed research aims to evaluate the hypothesis that reward anticipation selectively recruits the nucleus accumbens (NAcc) of the ventral striatum by eliciting a positive activated (PA) affective state. Study 1 will examine whether a functional magnetic resonance imaging (FMRI) probe of NAcc response during anticipation of monetary rewards of different magnitudes reliably indexes individual differences in reward sensitivity, as measured by affective reactions to reward cues. Study 2 will examine whether increasing anticipated reward probability will also increase NAcc activation and PA. A reliable neurobehavioral probe of reward responsiveness may have applications in assessing the severity of some affective
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disorders (e.g., anhedonic unipolar depression), the likelihood of recovery, and efficacy of pharmacotherapeutic or psychotherapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: A NEW DRUG FOR DEPRESSION Principal Investigator & Institution: Simon, Neal G.; Chair; Serenix Pharmaceuticals, Inc. 111 Research Dr, B217 Bethlehem, Pa 18015 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-AUG-2003 Summary: (provided by applicant): Long Term Goals: Serenix Pharmaceuticals (SP) will develop drugs for the treatment of CNS disorders. Strategy: SP acquired a series of vasopressin receptor antagonists from Eli Lilly and Company and has refined these molecules through manipulations of various structural zones. A subset of these antagonists (LEAD SERIES) exhibit reasonable affinity for the vasopressin receptor subtype involved in depression and stress-related affective disorders. The LEAD SERIES requires refinement to optimize affinity (less than 5.0 nM) and early stage testing to demonstrate biological activity. The platform molecule has four essential structural zones; two of these will be the focus of the proposed research. Phase I objectives are (i) utilize classical and combinatorial chemistry to modify structural zones on the LEAD SERIES to generate ca. 200 compounds, (ii) screen these for target receptor affinity and focus on those with Kds less than 5 nM, and (iii) test the high affinity compounds for in vitro biological activity. The findings, combined with considerations related to affinity, structural diversity, structural attractiveness, and QSAR models, will identify promising compounds for testing in Phase II for oral absorption, stability, metabolism, toxicity, and efficacy. PROPOSED COMMERCIAL APPLICATION: SP will focus on the development of a novel drug for the treatment of depression and stressrelated affective disorders. In 1999, the NIMH reported that depression affects over 19,000,000 adults in the United States, making it the most common serious CNS disease. The proposed drug represents a novel pharmacological approach that differs from the tricyclics, SSRIs, and NRIs currently used for these disorders. It therefore may capture significant market share. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ACUTE CORTICOSTERIOD ACTIONS IN THE HYPOTHALAMUS Principal Investigator & Institution: Tasker, Jeffrey G.; Professor; Cellular and Molecular Biology; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Stress is associated with activation of the hypothalamic-pituitary-adrenal (HPA) axis and increased levels of circulating adrenal corticosteroids. Glucocorticoids feed back onto the hypothalamus to inhibit not only corticotropin releasing hormone (CRH) secretion and HPA activation, but also many other hypothalamic neuroendocrine systems. The negative feedback regulation by glucocorticoids occurs in two stages: an acute inhibition of the release of CRH, and a slower down-regulation of CRH and vasopressin synthesis in neurons of the hypothalamic paraventricular nucleus (PVN). To date, it is not known where in the brain glucocorticoids exert their negative feedback regulation of hypothalamic neurosecretion, and what the cellular mechanisms of this feedback are. These questions have profound significance for the treatment of widespread affective disorders, including stress, depression, and eating disorders, that impact large numbers of people. The overall purpose of this proposal is to determine whether acute negative
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glucocorticoid regulation of PVN neuroendocrine systems occurs directly at the hormone-secreting neurons in the PVN, and to characterize the cellular mechanisms of this regulation. We have preliminary evidence for rapid inhibitory glucocorticoid effects in the PVN mediated by membrane receptor activation and the release of a retrograde endocannabinoid messenger that suppresses excitatory and facilitates inhibitory inputs to PVN neurons. Based on these findings, we propose to conduct whole-cell patchclamp recordings in acute rat hypothalamic slices to test the following specific hypotheses: 1. glucocorticoids inhibit PVN neurons directly by stimulating an endocannabinoid-mediated suppression of glutamate release and facilitation of GABA release; 2. glucocorticoids elicit retrograde endocannabinoid release from PVN neurons by activation of a postsynaptic G protein-coupled receptor and lipid messenger signaling cascade; 3. the endocannabinoid-mediated changes in glutamate and GABA release in the PVN are mediated by presynaptic, G protein- and protein kinasedependent signaling mechanisms. These studies will reveal for the first time the site and physiological mechanisms of fast glucocorticoid actions in the hypothalamus. Fast glucocorticoid feedback in the hypothalamus plays a critical role in the organism's holistic response to stress, and understanding the mechanisms of glucocorticoid actions in the hypothalamus will provide important cellular targets for the treatment of HPArelated pathologies. Furthermore, the glucocorticoid-endocannabinoid link opens interesting possibilities for interactions between hypothalamic function and the cannabinoids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AFFECTIVE NEUROSCIENCE OF TASTE REACTIVITY Principal Investigator & Institution: Berridge, Kent C.; Psychology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Little is known about how brain mechanisms cause positive affective reactions to natural stimuli. This project aims to identify neural circuits in the shell of the nucleus accumbens that are uniquiely capable of causing increased positive affective reactions to the taste of food. Objective behavioral affective reactions, based on the taste reactivity paradigm (taste-elicted reactions of human infants, other primates, and rats [in this study]) will be studied to assess the effect of brain manipulations on affective reactions.Neurochemical receptor identity: We will identify the neurochemical identity of the opioid receptor subtype(s) in nucleus accumbens responsible for causing positive affective reactions to tastes. We will make microinjections of selective opioid agonists into a region of accumbens shell where we've shown morphine enhances positive affective reactions to the taste of sucrose. Then blockade by microinjection selective opioid antagonists will be used to confirm receptor subtype identity. Then opioid effects will be compared to GABA, DA, and glutamate neurotransmitter effects in accumbens. We expect to find that accumbens opioid receptor activation plays a unique role in causing increased positive affective reactions (contributing to increased food intake).Neuroanatomical identity: We will identify the neuroanatomical boundary of the accumbens site that causes increased positive affective reactions with a combination of excitotoxin lesion mapping and microinjection mapping techniques. We expect based on preliminary results that a caudal medial region of the shell of the nuclues accumbens will be the chief site.Circuit interactions: Finally, we will examine the larger neural system in which accumbens is embedded, specifically the role of efferent projections to target structures in positive affective reaction. This will begin to clarify the neural circuits underlying generation of
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positive affective reactions, which may be involved in human affective disorders that involve specific deficits of positive affect. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SUBSTRATES
AFFECTIVE
STYLE--SOCIAL
AND
PSYCHOBIOLOGICAL
Principal Investigator & Institution: Davidson, Richard J.; Vilas Professor; Psychology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 30-SEP-1993; Project End 31-AUG-2003 Summary: This is a competitive renewal of the CBSR that established the Wisconsin Center for Affective Science. Our Center is focused on the social and psychobiological contributions to affective style. Affective style refers to a brad range of individual difference in emotion-related processes. Such individual differences are hypothesized to play a key role in governing vulnerability to psychopathology. The distal and proximal influences on the development of internalizing disorders and behavioral inhibition are central features of our research, long with a focus on the underlying neural circuitry associated with these characteristics, with a particular emphasis on prefrontal cortex, the amygdala and the HPA axis. An important component of affective style is the time course of affective responding, particularly the recovery function following a negative event. This we have described as affective chronometry and a number of proposed studies will further develop this concept and explore its neural substrates and behavioral correlates. Common measures are included in very Center project to facilitate comparisons across studies. Our center will consist of four projects that are supported by three cores. In Project (Davidson) we will examine the neural circuitry underlying individual differences in affective chronometry in both normal individuals and patients with affective disorders using a variety of techniques including quantitative brain electric activity measures, positron emission tomography and functional magnetic resonance imaging. In Project (Kalin) we will characterize the detailed circuitry underlying fearful temperaments in rhesus monkeys using reversible inactivation techniques to examine the contribution of the amygdala to this behavior. The roles of glutamate and GABA in the amygdala will be explore with intra-amygdaloid infusions of agonists and antagonists. In Project (Goldsmith), we will examine a batter of central and autonomic psychophysiological measures related to affective style in monozygotic (MZ) and dizygotic (DZ) twin children. A second component of this project will involve more intensive study of a sample of MZ and DZ twins selected to be at-risk for internalizing disorders. Project (Essex) will continue to be carried out in conjunction with the Wisconsin family and Work Project, a study that began in 1989 with 570 families This project will examine early individual measures of temperament during the preschool years. Relations between these early social factors and individual child characteristics and biological measures will also be examined. These projects will be supported by an Administrative Core, a Behavioral Assessment Core and a Biological Measures Core. This Center will continue to significantly advance our understanding of the social, psychological and biological bases of individual differences in affective style and will yield important new information that will facilitate our understanding of emotion disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AMYGDALAR NEUROPEPTIDES AND ANXIETY Principal Investigator & Institution: Wilson, Marlene A.; Professor; Pharmacology, Physiology and Neuroscience; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The amygdala is a brain structure that plays a crucial role in fear and anxiety, and the actions of anxiety-reducing compounds. The opioid peptide has also been shown to modulate anxiety-related responses within the amygdala. Using herpes virus-mediated gene transfer, we have demonstrated that overexpression of enkephalin in the amygdala enhances the anxiety-reducing influences of the benzodiazepine diazepam (Valium) in rats. These initial results demonstrate that herpes virus-mediated gene transfer can transiently alter expression of neuropeptides in confined brain sites of adult rats, and that these changes can modify behavioral responses. The present studies continue to utilize this powerful technique to examine the role of amygdalar enkephalin in regulating anxiety-related behaviors and the actions of anxiolytic drugs. Both decreases and cell-targeted increases in peptide expression will be examined in several animal models of anxiety. Aim 1 will verify the ability of virusmediated gene transfer to decrease and cell-specifically increase expression of enkephalin in select areas of amygdala. Anatomical and quantitative methods will assess changes in mRNA expression, while peptide changes will be assessed with immunohistochemistry and radioimmunoassay. AIM 2 examines if altered enkephalin expression in central amygdala modifies anxiety-related behaviors in additional animal tests of anxiety behaviors and/or the effectiveness of other anxiolytics in these tests. These studies 1) compare decreases with cell-specific increases in enkephalin expression, 2) test the activity of other anxiolytics (alcohol, the serotonergic compound buspirone), and 3) tests effects in several models of anxiety. AIM 3 assesses the effects of pharmacological modulation of enkephalin activity in amygdala. Using more traditional techniques selective opioid receptor (mu, delta) agonists and antagonists will be locally applied in amygdala, and the effect of these compounds on responses to anxiolytic drugs will be tested. These studies will lead to a better understanding of the role of amygdala and enkephalin in anxiety and anxiolytic responses, as well as elucidate the differences between animal models of anxiety. This understanding may also suggest novel, avenues for development of treatments for anxiety or affective disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANIMAL MODELS OF DEPRESSION Principal Investigator & Institution: Weiss, Jay M.; Professor; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 11-AUG-2003; Project End 30-JUN-2008 Summary: The proposed project will examine effects of a number of drugs supplied by GlaxoSmithKline, assessing these drugs for their potential antidepressant capability. Assessment will be made primarily using two new animal models. One of these is a new screening technique for effective antidepressant treatments that appears to be more selective for detecting effective antidepressant drugs than is previously-developed screening techniques. This model uses a selectively-bred line of rats, the Swim-test Susceptible rat (or Susceptible rat), that shows heightened vulnerability to having its active behavior in a swim test reduced when it is exposed to a mild stress situation prior to the swim test. Chronic treatment with antidepressant drugs has been found to block this vulnerability; chronic treatment with other psychoactive drugs is without effect.
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Thus, this test appears usable to detect antidepressant drugs, and to discriminate these from other psychoactive drugs. The second model is a new rodent model of depression in which the animals show long-lasting symptoms of depression (i.e., 20-35 days duration) following a single exposure to a stressful situation. In previously-existing rodent models, depression-like symptoms have been transitory (i.e., lasted 2-4 days); thus, previous models did not allow drugs to be administered after onset of depressive symptoms so that recovery could be observed as it occurs in humans. This new model permits this to be done. The model in which long-lasting symptoms occur uses another selectively-bred rat- the Hyperactive rat. In addition to testing of drugs in these models, drugs also will be tested in a standard Porsolt swim test. Finally, additional development of animal models is proposed. In this regard, we will (a) attempt to further perfect the Hyperactive rat as a potential model for study of bipolar disorder, and (b) subject our selectively-bred rats to maternal separation as a possible means of producing improved models of affective disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL, ERP AND EEG ASYMMETRY IN AFFECTIVE DISORDERS Principal Investigator & Institution: Bruder, Gerard E.; Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 28-SEP-1982; Project End 30-JUN-2007 Summary: (provided by applicant): Converging evidence from perceptual asymmetry, electrophysiologic, and neuroimaging studies support the hypothesis that depressive disorders involve both left prefrontal and right temporoparietal hypoactivation. Perceptual and electrophysiologic asymmetries are related to important clinical features of depression, i.e., diagnostic subtype, comorbidity with anxiety, and responsiveness to antidepressants. The major focus of the next project period will be on development and evaluation of behavioral, EEG and event-related potential (ERP) measures for predicting clinical response to antidepressants. One aim is to evaluate hypothesized differences in hemispheric asymmetry between patients who respond to a selective serotonin reuptake inhibitor (SSRI) and those who do not. ERPs will be recorded during continuous recognition memory tests with word and face stimuli to provide physiologic measures of lateralized medial temporal and frontal function. Regional measures Df EEG hemispheric asymmetry will be examined not only in a resting state but also during psychometrically matched verbal and spatial tasks. We will also continue to use dichotic word and complex tone tests for assessing perceptual asymmetries. A second aim is to evaluate alternative hypotheses relating antidepressant response to bilateral frontal lobe function, particularly to dorsolateral and medial frontal function. For this purpose ERPs will be recorded during a novelty oddball paradigm, which provides a physiologic probe of frontal function, i.e., the novelty P3. Neuropsychological tests will be independently performed to assess frontal lobe function. Testing a large sample of depressed patients will allow further evaluation of these behavioral and electrophysiologic tests as predictors of therapeutic response to antidepressants and will provide a more definitive determination of gender effects. We will also take advantage of ongoing crossover studies to begin to examine the potential of these tests for predicting response to alternative treatments for SSRI non-responders. These aims contribute to the long range goal of identifying more homogeneous subtypes of depression with distinctive clinical features and characteristic alterations of regional brain asymmetry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BORNA DISEASE VIRUS AND NEUROPSYCHIATRIC DISEASE Principal Investigator & Institution: Lipkin, W Ian.; Professor; Epidemiology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: The basis of schizophrenia and affective disorders remains unknown. Although a genetic component is likely, discordance for disease in monozygotic twin studies and epidemiology suggest the presence of cofactors. One candidate risk factor is brain infection. Although no linkage has been established between any infectious agent and either affective disorders or schizophrenia, a potential role in their pathogenesis has been suggested for Borna disease virus (BDV). BDV is a neurotropic RNA virus, worldwide in distribution, that causes movement and behavior disturbances in warmblooded animal hosts ranging from birds to primates. It is not lytic in vitro or in vivo, replicates at lower levels than most known viruses and is dissimilar in nucleic acid and protein sequence to other infectious agents. Sensitive, specific methods for detection of BDV infection were established only recently. Based on serology and RT-PCR analysis of peripheral blood mononuclear cells (PBMC), groups in North America, Europe and Asia have reported evidence of BDV infection in patients with affective disorders and schizophrenia as well as in domesticated animals that could serve as vectors for virus transmission. The prevalence estimates of BDV infection in patients and controls differ between research groups. To date there has been no blinded multicenter analysis of sera and PBMC samples from well characterized patients and controls using standardized methods for diagnosis of psychiatric illness and BDV infection. Thus, the significance of BDV for pathogenesis of neuropsychiatric disease remains controversial. Four clinical centers and a core laboratory will join in a united effort to rigorously address the epidemiology of BDV in human populations. Specific aims will be: (1) establish a multicenter group to investigate potential linkages between Borna disease virus infection and neuropsychiatric disease; (2) determine the prevalence of serum antibodies to Borna disease virus proteins in subjects with schizophrenia, affective disorders, and normal controls; and (3) determine the prevalence of Borna disease virus nucleic acids in PBMC of subjects with schizophrenia, affective disorders, and normal controls. Interpretation of previous RT-PCR analyses of human materials was complex because samples were processed in laboratories working with other BDV isolates and putative human sequences were sufficiently similar to known isolates that contamination could not be excluded. This study will be the first to collect and process human sera and PBMC samples in clinical laboratories with no history of BDV research and dispense aliquots to a central laboratory for randomized, blinded analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BRAINSTEM MECHANISMS OF STRESS REGULATION Principal Investigator & Institution: Herman, James P.; Professor; Psychiatry; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): Inappropriate processing of psychological stress is a major causal or complicating factor in affective disorders. Stress dysfunction takes the form of behavioral hyperreactivity and glucocorticoid hypersecretion, mediated by amygdalar and hypothalamic effector circuits, respectively. Previous work has suggested that psychogenic stressors are predominantly processed in the forebrain, relayed to the effector neurons by descending corticolimbic inputs. Our group has recent findings that challenge this view, and thereby offer a potential new approach to
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treatment of stress-related disorders. Our results indicate that glucagon-like peptide-1 (GLP-I), a neuropeptide synthesized only in the brainstem, plays a major role in promoting both neuroendocrine and behavioral responses to psychogenic stressors. This has led us to hypothesize that the brainstem GLP-1 system may comprise a general coordinator of stress responses. To test this hypothesis, we propose four Specific Aims. In Aim 1, we will perform anatomical studies to evaluate the hypothesis that the GLP- 1 system selectively targets corticotropin-releasing hormone effector neurons in hypothalamic and amygdalar circuits, and determine whether GLP-1 neurons have collateral projections to both regions. Aim 2 will test the hypothesis that GLP-1 neurons are activated by psychogenic, interoceptive and conditioned stressors, and thus occupy a central role in generalized stress integration. Specific experiments will assess Fos expression in GLP-1 neurons as a measure of neuronal activation, address potential signaling pathways affecting GLP-1 neuronal activation, and demonstrate stress effects on transcription of the preproglucagon gene expression. Aim 3 will test the hypothesis that GLP-1 systems are persistently activated by chronic stress or glucocorticoids, providing a mechanism whereby prolonged stimulation can promote inappropriate behavioral and neuroendocrine responses. Finally, Aim 4 will test whether GLP-1 systems are necessary and sufficient for chronic stress-induced pathologies, testing the ability of exogenous GLP- 1 or a GLP- 1 receptor antagonist to cause or block, respectively, behavioral and endocrine changes characteristic of chronic stress. The results of these studies are expected to establish a major role for GLP-1 systems in stress regulation, and identify the GLP-1 system as a target for future therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CNS CIRCUITS MEDIATING VISCEROMOTOR RESPONSES TO STRESS Principal Investigator & Institution: Sawchenko, Paul E.; Professor and Director; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099 Timing: Fiscal Year 2002; Project Start 23-SEP-1985; Project End 30-JUN-2003 Summary: Alterations in the expression of genes encoding hypothalamic neuroendocrine and autonomic effector peptides, and certain immediate- early gene markers of neuronal activation, will be followed, in situ, in response to various combinations of stress, central ablations, pharmacological manipulations, or perturbations in the steroid hormone environment, in order to clarify the neural circuits and mechanisms through which categorically different stressors come to elicit integrated and appropriately adaptive hypothalamic responses. An initial series of experiments will explore the mechanisms through the immune system mediator, interleukin-1 (IL-1), exerts its powerful stimulatory influence on stress-related hypothalamic mechanisms. Previous work supports the hypothesis that paracrine effects of prostaglandin E2 released from perivascular cells in the medulla as a consequence of IL-1 stimulation, and acting on a prostanoid receptor or near local catecholaminergic neurons that project to the hypothalamus, underlies the stimulatory effects of increased circulating IL-1 on stress-related hypothalamic effector neurons. This will be tested by determining whether the requisite molecules are expressed in the medulla, and by assessing whether medullary administration of. prostanoid agonists can mimic, and synthesis inhibitors block, IL-1 effects at the level of the hypothalamus. The specific involvement of medullary catecholaminergic neurons will be probed by assessing the ability of neurotoxin lesions at the level of the brainstem or delivery of adrenoceptor antagonists at the level of the hypothalamus to block hypothalamic responses to a systemic IL-1
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challenge. The generality of the mechanism will be explored by determining whether disruption of ascending aminergic projections mitigates hypothalamic responses to more strenuous immune insults. A second major goal will be to employ an IEG- guided ablation strategy to identify the pathways through which ostensibly more complex, emotional or neurogenic, stress paradigms come to invoke integrated hypothalamic responses and the manner in which hypothalamic output may be modified as a consequence of repeated exposure to emotional stress. A final set of experiments will seek to characterize the neurotransmitter systems and receptor mechanisms mediating transcriptional activation of genes encoding peptides that govern pituitary-adrenal responses to stress, and the manner in which they are modulated tonically and phasically by the steroid hormone environment. The neural and neuroendocrine systems under scrutiny here play essential physiologic roles, dysfunction of which has been linked to such diverse pathologies as autoimmune disease, hypertension and agerelated deficits in learning and memory, and have been implicated in the etiology of affective disorders, including anorexia nervosa and major depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COCAINE-BINDING DOPAMINE TRANSPORTER: MOLECULAR BIOLOGY Principal Investigator & Institution: Bannon, Michael J.; Professor; Psychiatry & Behav Neuroscis; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 01-APR-1990; Project End 31-JAN-2008 Summary: (provided by applicant): Neurons utilizing dopamine (DA) as a neurotransmitter constitute a rare neurochemical phenotype but nevertheless play an important role in regulating locomotion, motivation, cognition and hormone release. The DA transporter (DAT) is a plasma membrane transport protein that controls the spatio-temporal domains of DA neurotransmission by rapidly reaccumulating DA that has been released into the extracellular space. A wide spectrum of neurological and psychiatric disorders, including drug abuse, Parkinson's disease, schizophrenia, affective disorders, and attention deficit hyperactivity disorder is thought to involve DA systems and the DAT. The DAT is an important target for therapeutic and illicit drugs (e.g. methylphenidate, buproprion, amphetamine, and cocaine), and serves as the point of entry for DA-specific neurotoxins. DAT radioligand binding provides an in vivo measure of DA cell integrity and can be used to monitor the efficacy of therapeutic interventions in neurodegenerative disease. The Aims of this project are to identify the silencing element(s) and cognate transcription factor(s) that repress transcription of the human dopamine transporter gene in non-dopaminergic cells, as well the mechanism by which the transcription factor nurrl activates human dopamine transporter gene transcription in dopamine neurons. It is likely that a greater understanding of the regulation of the DAT expression will impact the diagnosis and treatment of a number of neuropsychiatric disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COGNITIVE-BEHAVIORAL TREATMENT OF PTSD IN SMI CLIENTS Principal Investigator & Institution: Mueser, Kim T.; Professor of Psychiatry; Psychiatry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2004
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Summary: (provided by applicant): There is ample evidence documenting that persons with severe mental illness (SMI) are at increased risk for exposure to trauma and the development of posttraumatic stress disorder (PTSD). However, despite research showing that trauma and PTSD are related to worse functioning and a more severe course of SMI, no standardized interventions have been empirically validated for the treatment of PTSD in this population. The proposed research will be a randomized controlled trial of an individual cognitive-behavior therapy (CBT) program for PTSD designed for clients with SMI. The CBT intervention is 12-16 weeks long, has been manualized, and a pilot study supports its feasibility and suggests clinical benefits. A total of 88 clients with SMI (44 with major affective disorders, 44 with schizophrenia or schizoaffective disorder) and PTSD will be randomly assigned to either CBT or treatment as usual (TAU), with assessments conducted at baseline, posttreatment, and 3and 6-month follow-ups. Primary hypotheses will focus on evaluating whether CBT is superior to TAU in improving PTSD diagnoses and symptoms, quality of life, selfperceived health, knowledge of PTSD, and distorted perceptions of the world. Secondary analyses will explore whether changes in PTSD are associated with improved outcomes for clients with SMI, as suggested by our interactive model of trauma, PTSD, and course of SMI. If our CBT program is effective at improving PTSD and associated outcomes, clinicians will have a valuable new tool for treating this common and distressing comorbid disorder in the SMI population, and potentially for improving the course of SMI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COLLABORATIVE DEPRESSION STUDY Principal Investigator & Institution: Rice, John P.; Professor; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUL-1977; Project End 30-JUN-2004 Summary: Results from the NIMH Collaborative Depression Study (CDS) have clearly shown that affective illness is a lifetime disorder and that long-term observation will be necessary to adequately characterize it. Follow-up so far shows high rates of recovery, recurrence, changes in inter- episode psychosocial functioning, co-morbid alcoholism, minor affective syndromes, mortality and suicide. Recoveries are likely even after lengthy periods of illness, the distribution of episode length is relatively constant and unimpaired psychosocial functioning appears to require a complete absence of symptoms. It is essential that this follow-up continue, especially as the probands enter their sixth an seventh decades of life. This application seeks to extend the prospective annual follow-up of the CDS proband sample to at least 22 years for all subjects. The genera aim in doing this is to describe the long-term cause of the affective disorders. The specific aims are to collect data that will describe more fully: 1.) the cumulative probability of recovery and recurrence, and the changes in polarity, severity, and episode and cycle lengths; 2.) the predictors of long-term course and diagnostic change; 3.) the eventual level of psychosocial functioning, physical health, likelihood of suicide and mental health service utilization; 4.) the influence of naturalistically applied treatments as a mediating variable; 5.) the cause and outcomes of subsyndromal stages of affective disorders; and 6.) the long-term inter-relationships of the affective disorders and other chronic and recurrent disorders such as alcohol and drug use disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COLLABORATIVE DEPRESSION STUDY Principal Investigator & Institution: Fawcett, Jan A.; Professor and Chairman; RushPresbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-AUG-1977; Project End 31-MAY-2004 Summary: (Applicant's Abstract): Results from the NIMH Collaborative Depression Study (CDS) have clearly show that affective illness is a lifetime disorder and the longterm observation will be necessary to adequately characterize it. Follow-up so far shows high rates of recovery, recurrence, changes in inter-episode psychosocial functioning, comorbid alcoholism, minor affective syndromes, mortality and suicide. Recoveries are likely even after lengthy periods of illness, the distribution of episode length is relatively constant and unimpaired psychosocial functioning appears to require a complete absence of symptoms. It is essential that this follow-up continue, especially as the probands enter their sixth and seventh decades of life. This application seeks to extend the prospective annual follow-up of the CDS proband sample to at least 22 years for all subjects. The general aim in doing this is to describe the long-term course of the affective disorders. The specific aims are to collect data that will describe more fully: 1) the cumulative probability of recovery and recurrence, and the changes in polarity, severity, and episode and cycle lengths; 2) the predictors of long-term course and diagnostic change; 3) the eventual level of psychosocial functioning, physical health likelihood of suicide and mental health services utilization; 4) the influence of naturalistically applied treatments as a mediating variable; 5) the course and outcomes of subsyndromal states of affective disorders; and 6) the long-term inter-relationships of the affective disorders and other chronic and recurrent disorders such as alcohol and drug us disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COMPUTATIONAL ASPECTS OF PRIMATE MEMORY Principal Investigator & Institution: Fuster, Joaquin M.; Professor; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 30-APR-2005 Summary: Active short-term memory plays a critical role in the temporal organization of behavior, reasoning, and language. It is impaired in a variety of mental disorders, notably in the psychoses, major affective disorders and syndromes resulting from pathological aging of the brain. Recent experimental evidence indicates that active shortterm memory consists in the sustained activation of an extensive network of interconnected neuronal assemblies of the cerebral cortex. Memory networks are widely distributed, extending beyond the boundaries of anatomically defined cortical areas. The mechanisms of active memory are believed to include the sustained circulation of neuronal impulses within one such network. This research will attempt to substantiate the distributed nature of active short-term memory and the reentry of neural impulses presumed to be the basis of short-term memory retention. Experiments with that objective will be conducted in nonhuman primates trained to perform auditory, tactile, and cross-modal memory tasks. Fields potentials and cell discharge will be recorded from frontal and parietal regions of the cortex during performance-and also to some extent during learning-of those tasks. Frequency and pattern of cell discharge will be analyzed for evidence of neuronal interactions within and between those cortical regions during the short-term memorization of sensory information. Special computational methods of time-series analysis will be used to explore those interactions. Some of the interactions will be further explored by reversible functional depression (by
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Affective Disorders
local cooling) of frontal cortex and the study of its effects on parietal cell discharge and the animal's performance of haptic memory tasks. The results of these studies are expected to shed light on the functional architecture of cortical memory networks and on the mechanisms of encoding, retention, and retrieval of memory. A better understanding of the neural dynamics of memory may help us better understand the pathogenesis of memory disorders in the mentally ill and thus lead to better treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CULTURE, SCHIZOPHRENIA, AND ATYPICAL ANTIPSYCHOTICS Principal Investigator & Institution: Jenkins, Janis H.; Professor; Anthropology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 31-MAY-2004 Summary: This anthropological study investigates the subjective experience of schizophrenia and schizo-affective disorders under treatment conditions characterized by medication with atypical antipsychotics. There are two specific aims: (1) to examine a series of hypotheses concerning (a) how subjects perceive the effects of atypical antipsychotics on symptomatic improvement or worsening; socio-emotional comfort or vulnerability; and medication side effects; (b) features of sociocultural context, specifically sex and ethnicity, that may mediate illness experience during treatment with atypical antipsychotics, as well as features, specifically gender identity and household composition, that may modify illness experience; and (2) to provide an ethnographic account of the subjective experience of schizophrenic illness under specific treatment conditions in clinic and home settings, brining to bear recent developments in culture theory. The overall goal of this research is the identification of cultural and psychosocial factors that may affect the phenomenology and meaning (i.e., subjective experience) of schizophrenic disorders during treatment with atypical antipsychotic drugs. The subjective experience of schizophrenia will be studied with a sample of 120 psychiatric outpatients from the Psychobiology Clinic of greater Cleveland though use of convergent, complementary methods (ethnographic interviewing and observations, administered questionnaires, and self-report). In addition, a sub-sample of 32 patients will be studied on a monthly basis for one year through ethnographic home visits. The final product will be a comprehensive account of the experience of patients undergoing treatment with atypical antipsychotics. It is anticipated that the findings will contribute to the literature on culture, gender, ethnicity and psychopathology and to treatment strategies for optimal illness management through state-of-the-art medications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CYSTEINE STRING PROTEINS: CELLULAR & MOLECULAR FUNCTION Principal Investigator & Institution: Umbach, Joy A.; Associate Professor; Molecular & Med Pharmacology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 27-JUL-1993; Project End 31-JUL-2005 Summary: This application has two long-range goals. The first is to advance our understanding of cellular and molecular functions of cysteine string proteins (csps). Csps are a family of proteins associated with secretory organelles in nerve cells and elsewhere. The second is to pursue recent findings which indicate that lithium (Li) ions modulate csp gene expression in vitro and in vivo. While the first goal entails basic investigations of the role of csps in secretion, the latter goal is likely to have more-
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immediate clinical relevance. This is because Li, which is used in the management of bipolar-affective disorders, remains a mechanistic enigma. Thus, further study of the LIcsp link may afford insights into the therapeutic role of Li, as well as into the cause and improved treatment of bipolar syndromes. To approach these long-term goals, the current proposal has three specific aims: First, we will study regulatory, and functional/anatomical correlates of Li's effect on csp gene expression. These investigations will illuminate the signaling pathways that mediate this effect of Li, and also suggest whether Li is likely to modify the secretory behavior of discrete populations of neurons in the brain. Second, we propose to characterize further the secretory functions of a unique relative of csp. It is our hypothesis that this protein substitutes for csp in csp null mutant fruit flies. Using genetic, biochemical and physiological strategies, we plan to evaluate the role of this "csp substitute" in wild type and csp mutant Drosophila, as well as in vertebrates. Finally, we plan to exhibit calciumion independent regulated secretion of cortical granules. Perturbation of csp function in this system will afford insight into molecular contributions of csps to regulated secretion. Taken together, these aims constitute substantial progress toward resolving the role of csps in normal and pathological circumstances. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPRESSION DIAGNOSIS AND TREATMENT IN PARKINSON DISEASE Principal Investigator & Institution: Weintraub, Daniel; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by candidate): This grant application on behalf of Daniel Weintraub, MD, Assistant Professor of Psychiatry at the University of Pennsylvania, is for the Mentored Patient-Oriented Research Career Development Award,(K23). The focus of this award is to enable Dr. Weintraub (PI) to acquire the academic and research expertise to achieve his career goal of becoming an independent researcher in the assessment and treatment of the psychiatric complications of Parkinson's disease (PD), an area in which there is an urgent need for clinical research due to a lack of consensus over phenomenology and the lack of empirical evidence to support current treatment practice. The research plan for this award will in part involve conducting a depression screening and assessment process in two PD specialty care settings in order to determine demographic, psychiatric, neurologic, and cognitive correlates of depression and to propose modified criteria for affective disorders in PD. In conjunction with this, the PI will conduct an open-label antidepressant study using escitalopram to determine response rates under treatment as a function of different diagnostic criteria and to identify moderators of response under treatment. The impact of antidepressant treatment on comorbid psychiatric and cognitive symptoms, motor symptoms, quality of life, and caregiver burden will also be probed. Identification of modifiers of treatment response will help inform future studies and clinical decision-making. The career development plan will revolve around the acquisition of skills related to Dr. Weintraub becoming a research geriatric- and neuro-psychiatrist with expertise in Parkinson's disease and proficient in conducting intervention research in this area. The specific skill areas to be developed during the course of the proposed award relate to: (1) intervention research and biostatistics; (2) clinical neuroscience; and (3) the neurology of Parkinson's disease (PD). Methods of career development include: (1) the proposed research study; (2) the mentorship of Drs. Ira Katz and Matthew Stern; (3) consultation with experts in assessment and treatment of geriatric depression and neuropsychiatric disease; (4)
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Affective Disorders
formal coursework in clinical trials research, biostatistics, clinical neuroscience, and neurology; (5) training in the assessment and treatment of Parkinson's disease (6) attendance at scientific meetings; and (7) mentored data analysis and manuscript preparation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DETERMINANTS LOCALIZATION
OF
DENDRITIC
POTASSIUM
CHANNEL
Principal Investigator & Institution: Trimmer, James S.; Professor; Biochemistry and Cell Biology; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 24-JUL-2001; Project End 30-JUN-2003 Summary: Dendritic voltage-gated K+ channels, or Kv channels, are fundamental components of dendritic signalling. Dendritic Kv channels control the characteristics of backpropagating action potentials, and thus influence synaptic efficacy. In addition, these channels can influence the spread of postsynaptic potentials to the soma, influencing the integration of synaptic input and the response of neurons to external stimuli. Lastly dendritic Kv channels can dramatically influence Ca2+ signalling in dendrites, which can have far reaching implications for neuronal plasticity. This proposal is aimed at determining the fundamental mechanisms that determine dendritic function through the regulation of the abundance, distribution and function of dendritic Kv channels. We will focus our studies on the Kv2.1 Kv channel, which underlies a major component of the dendritic delayed rectifier current. This proposal is aimed at determining the dynamic cellular mechanisms that localize Kv2.1 at important sites of Ca2+ signalling in neurons, the phosphorylation sites on Kv2.1 that regulate localization and function, and the role of these Kv2.1-associated neuronal Ca2+ signalling proteins, and other Kv2.1-interacting proteins, in Kv2.1 localization and function. These studies will yield important insights into the reciprocal physiological regulation of Kv2.1 channel activity and Ca2+ signalling in the soma and dendrites of mammalian central neurons. As regulation of dendritic Kv channel activity influences action potential duration, amplitude and frequency, and synaptic efficacy, understanding the mechanisms controlling the composition of Kv channel complexes at the molecular level, anticipated from our proposed studies, will provide insights into the normal and abnormal function of neurons. It will thus contribute to the eventual understanding and treating of a variety of neurological disorders, including diseases associated with altered neuronal excitability such as genetic and acquired epilepsy, cognitive disorders, and affective disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYNAMIC TECHNIQUES FOR TREATMENT EFFECTIVENESS ANALYSES Principal Investigator & Institution: Leon, Andrew C.; Professor of Biostatistics; Psychiatry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-JAN-2004 Summary: (Applicant's abstract): This methodological project proposes a novel statistical strategy. The strategy integrates two components that are fundamental to longitudinal analysis of treatment effectiveness in an observational study. First, treatment status and level of psychopathology are dynamic processes, in that they change over the course of an illness. Second, there are clinical and demographic characteristics, which define, in part, the propensity of an individual to be treated.
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Standard data analytic strategies fail to capture the complex nature of treatment effectiveness over extended follow-up. Rosenbaum and Rubin (1983) have shown that the propensity scoring method can be used for causal inference from observational data. This proposal extends their approach to a dynamic model for analysis of longitudinal treatment effectiveness data. The procedure that is proposed here will adapt a mixedmodel approach to propensity score methodology (Aim 1). It will be used to examine antidepressant treatment effectiveness in subjects who were initially identified with affective disorders and have been followed-up over 15 years as part of the NIMH Collaborative Study of the Psychobiology of Depression. This dynamic data analytic approach provides a framework for incorporating multiple observations per subject, over the repeated episodes and recoveries that typically comprise a chronic illness, into an evaluation of treatment effectiveness (Aim 2). Furthermore, incorporating the propensity for treatment in the analyses reduces the bias that is inherent in an observational study of effectiveness. The methodology that is proposed here will also be applied to archival randomized clinical trial (RCT) data sets. The propensity for study completion and the propensity for missingness will be accounted for in the evaluation of treatment effectiveness in RCTs (Aim 3). Its use could preclude the need for both endpoint and completer analyses. The performance of the proposed methodology will be evaluated and compared to standard procedures in a Simulation Study (Aim 4). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EARLY EXPERIENCE ALTERS ADULT BEHAVIOR AND THE HPA AXIS Principal Investigator & Institution: Plotsky, Paul M.; Professor and Director; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 30-NOV-2002 Summary: (adapted from applicant's abstract): Both basic and epidemiological studies implicate psychosocial stressors and life events in the development of affective disorders. This stress diathesis model is partially based on the findings that a traumatic stressor often precedes the onset of affective episodes. Accumulating evidence strengthens the concept that the experience of early trauma serves as an important vulnerability factor in this sequelae. Dysfunction of one or more neuronal systems has been postulated in the etiology of major affective disorders, including the noradrenergic (NA) system, the serotonergic (5-HT) system, and the hypothalamicpituitary-adrenal (HPA) axis. Clinical and animal studies have identified apparent dysregulation of the HPA axis in major depression and its experimental analogs. Dysregulation includes resistance to glucocorticoid negative feedback, elevated concentrations of corticotropin-releasing factor (CRF) in the CSF and/or in specific neuronal structures, and alterations in either peripheral and/or central glucocorticoid receptor density. In animals studies administration of exogenous CRF not only produces activation of the HPA axis, but is associated with many symptoms of depression. Given this burgeoning evidence for a major role for CRF in the pathogenesis of affective disorders coupled with the observed psychiatric impact of early trauma, the investigators hypothesize that early trauma such as that induced by maternal deprivation or abuse may modify hypothalamic and/or extrahypothalamic CRF neurons and may alter inputs to these CRF neurocircuits in such a way as to produce neurochemical, endocrine, and behavioral hyperresponsivity to stressors in adults. Their recent research utilizing neonatal maternal separation in rats has not only verified the existence of alterations in the function of central CRF systems of glucocorticoid receptor density associated with early traumatic experience, but has also uncovered evidence
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Affective Disorders
supporting the involvement of adrenergic, serotonergic and GABAergic/benzodiazapine (BZ) systems in either mediating and/or maintaining these maladaptive alterations. In the current application, the investigators propose to further characterize these changes, to elucidate the mechanisms underlying these changes and to evaluate the potential of pharmacological interventions to reverse these dysfunctions. Overall, this research will augment understanding of the role of perinatal life expereince in the development of individual differences in stress responsiveness as well as in identification of neural processes that define this vulnerability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EDUCATING PHYSICIANS ABOUT GENETICS AND BRAIN DISORDERS Principal Investigator & Institution: Tanner, T Bradley.; President; Clinical Tools, Inc. 431 W Franklin St, #30 Chapel Hill, Nc 27516 Timing: Fiscal Year 2002; Project Start 20-SEP-2001; Project End 31-MAR-2004 Summary: The expanding field of molecular genetics has quickly outpaced the knowledge of medical providers, due in part to the Human Genome Project. The genetics of brain illnesses are only beginning to be understood, nevertheless, providers treating patients with mental health, substance abuse and neurological disorders need to understand clearly what is and is not known about genetics and brain illnesses. It is likely that genetic aspects of schizophrenia, autism, mental retardation, bipolar disorder, among others, will be further identified in the near future, creating confusion and difficult choices for patients and families. Current and future providers must be prepared to explain and understand genetic susceptibility as it applies to a full range of illnesses. In Phase I, we will develop and evaluate an Internet-based CE program focusing on genetic issues related to alcoholism. We will also use the course the discuss upcoming technologies as well as issues related to discussing genetic risk with a patient. Phase II will produce 7 additional course on a variety of topic related to illnesses of the brain including Mixed Substance Abuse, Alzheimer's Disease, Schizophrenia, Affective Disorders, Attention Deficit, Huntington's Disease, and Mental Retardation. For each course we will highlight: 1) how genetic knowledge may affect patients and be used in clinical practice; 2) communication of genetic knowledge with patients and families: preparing for patients' questions; 3) where relevant, ethical, legal and psychosocial issues related to genetic testing, and 4) understanding emerging technologies and findings in genetics. A multidisciplinary team including representatives from psychiatry, genetics, genetic counseling, and primary care will create the content. We will evaluate the courses' effect on knowledge, clinical skills and self-efficacy using simple randomized studies comparing subjects using the genetics course to subjects using an online CE course on another topic. If successful, the training will expand the capabilities of the existing pool of providers and improve the training of future providers regarding the role of genetics in illnesses of the brain. PROPOSED COMMERCIAL APPLICATIONS: Physicians are required to obtain CME credit to maintain licensure and privileges. Managed care organizations (MCOs), such as large HMOs, may be interested in purchasing access to CE that can be offered to participant professionals. Pharmaceutical companies may also want to support development of courses based on the model described in this application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EMORY CONTE CENTER FOR NEUROSCIENCE OF MENTAL DISORDERS Principal Investigator & Institution: Nemeroff, Charles B.; Reunette W. Harris Professor and Chair; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: This revised application seeks support for the Emory Center for the Neuroscience of Mental Disorders (ECNMD) in the Department of Psychiatry and Behavioral Sciences at the Emory University School of Medicine. The major goal of this five year research plan is to characterize the persistent neurobiological consequences of adverse events early in life and to determine the relationship of such long-lived central nervous system (CNS) alterations to the development of affective disorders, particularly depression, in adulthood. Two animal models of early adverse experience, for which pilot data on persistent neurobiological alterations exist, will comprise the bulk of the proposed work. These two models include a particularly well documented rodent model of maternal separation and a non-human primate variable foraging demand model of early stress. Gender-specific effects of early life stress will also be evaluated in these models. All of the preclinical projects will receive CNS tissue and biological fluids from each of these animal models. Neural circuits that have been implicated in both the neurobiology of stress and anxiety as well as the neurobiology of depression-like syndrome will be scrutinized, including corticotropin-releasing factor (Proj l; PI: Plotsky), serotonin (Proj 2; PLC Owens), dopamine and norepinephrine (Proj 3; PI: Kuhar), and signal transduction systems (Proj 4; PI: Nestler), hippocampal neurogenesis and remodeling (Proj 5; PI: Gould) and acoustic startle plasticity (Proj 6; PI: Davis) will be characterized in these models. In addition two clinical research projects will be included. Project 7, conducted both at Emory University (PI: Nemeroff) and Yale University (PI: Bremner), will examine the neurobiological consequences of child abuse by studying women with a past history of child abuse who are currently suffering from an episode of major depression versus a group of women who are currently depressed without a history of child abuse and a group of women with a history of child abuse without major depression. Finally, Project 8 will seek to determine the neurobiological and behavioral consequences of maternal depression during pregnancy or in the postpartum period on their children (PI: S.Goodman, Stowe). These research projects will be supported by an administrative core led by the Center Director, a rodent animal core (PI: Plotsky, Weiss), a primate animal core (PI: Insel, Winslow), an assay core (PI: Bonsall, Ritchie), and an integrated functional brain imaging core (PI: M. Goodman, Kilts). We postulate a model in which genetic vulnerability coupled with early trauma in a critical plastic period of development results in sensitization of neural systems which when exposed to even mild stressors in adulthood responds in a heightened manner, resulting in the neurobiological alterations that underlie the syndrome of depression. These studies have important implications not only for the neurobiology of depression but the development of novel treatment strategies for both depression and child abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPIDEMIOLOGY OF DISTURBED SLEEP AMONG ADOLESCENTS Principal Investigator & Institution: Roberts, Robert E.; Professor; Behavioral Sciences; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 23-MAY-2002; Project End 30-APR-2007
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Affective Disorders
Summary: (provided by applicant): The proposed research focuses on the epidemiology of disordered sleep among adolescents. There are two primary objectives. The first is descriptive, focusing on prevalence, incidence, natural history and phenomenology. The second is analytic, in which there are two foci. The first analytic focus is to examine the role of risk and protective factors in the etiology of disordered sleep. The second analytic focus is to examine the consequences of disordered sleep on subsequent functioning of adolescents. We also will examine the role of ethnicity as a risk or protective factor among adolescents. We are interested in whether there is a unique risk for sleep disorders associated with ethnic culture above and beyond the risk attributable to other factors, and if so, what it is about ethnic culture that enhances or reduces risk. The proposed study involves a three-wave, prospective design. In addition to disordered sleep, other mental health outcomes of interest are DSM-lV anxiety and affective disorders, disruptive, and substance abuse disorders. Data will be collected from a cohort of 2,250 European, Latino, and African American adolescents aged 15-21 years of age residing in the Houston urban area. These youths were surveyed initially as part of the Teen Health 2000 study when they were 11-17 years of age (n=4200) and again a year later, when they were 12-18 years of age (n=3,150). Data on sleep will be collected using three strategies. First, a Sleep-Wake Diary will elicit information on sleep-wake patterns for the previous 24 hours. Second, a DSM-lV diagnostic module will elicit data permitting diagnosis of DSM-lV sleep disorders. Third, we will collect data using the same sleep module used in the first two-waves. Questions focus on amount of sleep, perceived need for sleep, bedtime and wake times, use of hypnotics, perceived quality of sleep, and a list of 13 symptoms of problematic sleep experienced during the past four weeks and frequency of occurrence. We will estimate point prevalence, incidence, natural history, and comorbidity with psychiatric disorders: affective disorders (such as major depression, dysthymia and mania/hypomania), anxiety disorders (such as generalized anxiety, posttraumatic stress disorder and panic), and behavioral disorders (conduct, oppositional defiant and attention-deficit/hyperactivity disorder), alcohol abuse and other substance abuse. Ethnicity is assessed using a multifactorial strategy, including generational status, language use, salience of ethnicity, ethnic identity, and discrimination. Social placement factors include age, gender, ethnic status, and marital/parental status. Stressors include discrimination, acculturative stress, indicators of stress exposure (acute, chronic, and traumatic life events), poor health, financial strain, poor school performance, and stressful neighborhood context Personal and social resources include factors such as social support, relations with parents, socioeconomic status, coping, self-esteem and mastery. Data will be collected using laptop computers and audio-computer assisted self-interview (ACASI) technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN EFFECTS ON ANXIETY RELATED NEURAL SYSTEMS Principal Investigator & Institution: Altemus, Margaret; Associate Professor; Psychiatry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2005 Summary: (Adapted from the Investigator's Abstract) This Mentored Clinical Scientist Development Award, a program of research and career development, is proposed to establish a foundation for future independent research in behavioral neuroscience, with a focus on reproductive hormones and emotional regulation. The research component of the proposal is a series of studies investigating the hypothesis that estrogen restrains fear associated behaviors. Clinical data indicates that reproductive hormones fluxes
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have profound effects on the course of anxiety disorders and depression, but the neurobiological determinants of these clinical observations are not well understood. The specific aims of the research plan are to: 1) study the effects of estrogen on a battery of behavioral tests of anxiety; 2) examine the effects of estrogen on glucocorticoid and stress induced enhancement of fear behaviors; 3) examine the effects of estrogen on extrahypothalamic CRH and glucocorticoid receptors, a neuroendocrine system known to modulate fear and anxiety and 4) define the anatomic sites of estrogen action on fear behaviors. Fear associated neural circuits involving the amygsala, bed nucleus of the stria terminalis, and medial prefrontal cortex will be studied using local administration of estrogen and estrogen antagonists. The training portion of this proposal consists of basic neuroscience coursework and seminars as well as hands-on instruction in behavioral analysis and functional neuroanatomic techniques. Studies of the effects of estrogen on anxiety related neural systems provides an opportunity for the investigator to expand her area of expertise from clinical neuroendocrinology and clinical psychiatry to behavioral neuroscience where the effects of hormones on brain function can be studied more directly. This field of investigation is likely to improve understanding and treatment of anxiety and affective disorders, both of which are widely prevalent, chronic public health problems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETIOLOGIC CONNECTIONS OF AFFECTIVE AND ANXIETY DISORDERS Principal Investigator & Institution: Mackinnon, Dean F.; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 07-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Affective disorder are common, severe, recurrent, heterogeneous psycniatric diseases with an elusive pathophysiology. Their clinical and etiological complexity may obscure efforts to uncover mechanisms and tc discover therapeutic agents against those mechanisms. One common clinical feature that heightens complexity is comorbid anxiety. Combined anxiety and affective disorder syndromes exacerbate functional morbidity and suffering of patients, but may also present an opportunity to discover shared etiologic factors The candidate for this career development award is an academic psychiatrist at a teaching hospital with a strong historical commitment to medical research. The candidate has already established a reputation as a clinical specialist in affective disorders and has a research background in the genetics of affective disorder; by the end of the award period he plans to have established firmly a clinical and research direction aimed a comorbid anxiety and affective disorders, with fluency in psychophysiological methods. The award will facilitate this process by providing the time and resources to pursue further training in psychophysiology, neuroscience, and genetics. The starting points for the proposed research are 1) epidemiological findings that bipolar and panic disorders commonly occur together (comorbid risk), 2) symptom provocation studies ir panic disorder that reveal latent panic vulnerability in relatives of panic disorder patients (familial risk), and 3 family study results that show both familial and comorbid risk for panic disorder. The research program proposed here will address further questions about the relationship of panic and bipolar disorders by the use of carbon dioxide inhalation to provoke panic symptoms in study subjects ascertained for genetic linkage study of bipolar disorder. Risk of panic response to carbon dioxide in subjects without prior panic disorder will be analyzed as a function of familial and comorbid risk (as compared to the risk in positive and negative control subjects). If there is a specific genetic risk
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Affective Disorders
factor for both bipolar and panic disorder in a subset of families, then familial and comorbid risk will interact to produce higher risk of provoked panic than will either risk factor alone. Results of this work will then be applied to ongoing genetic studies of bipolar disorder, and will inform the candidate's further research into affective and anxiety disorder etiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FACTORS IN AN ADOLESCENT SUICIDE CLUSTER Principal Investigator & Institution: Norberg, Karen E.; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 05-FEB-2000; Project End 31-JAN-2005 Summary: The purpose of this project is to develop the candidate as an independent researcher with skills in clinical psychiatry, epidemiology, and economics, investigating the role of social and economic factors in an epidemic of adolescent suicide. The Research Plan will have three components: (1) a case/control retrospective investigation of an outbreak of adolescent suicide in South Boston in 1997, with a focus on the role of social networks linking victims of suicide and a large number of adolescents in the community who made non-lethal attempts during the outbreak; (2) a record linkage study, making use of a unique database collected by the candidate and by the Boston Emergency Services Team, comparing the roles of neighborhood risk and protective factors as predictors of adolescent self-injury in South Boston and in neighborhoods elsewhere in Boston; and (3) an econometric analysis, using cross-sectional and longitudinal data, placing the South Boston epidemic in a national context. The Training Plan is designed to develop the candidate's practical skills in research methodology and biostatistics, and to deepen her theoretical background in the psychological study of trauma and affective disorders, economic theory, and epidemiology. Her training will involve three components: (1) individual guidance and instruction from a multidisciplinary group of mentors and consultants, representing the disciplines of psychology, epidemiology, and economics; (2) formal coursework in biostatistics, economics, other social sciences, and epidemiology, and (3) the completion of the three research projects, as outlined. The principal mentors for the candidate's career development will be Dr. Terence Keane (psychology) and Prof. Jonathan Gruber (economics); other consultants will include Drs. Eva Deykin and Madelyn Gould (psychiatric epidemiology), and Drs. David Cutler and Richard Frank (health economics). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FAMILY THERAPY FOR ADOLESCENT BULIMIA NERVOSA Principal Investigator & Institution: Le Grange, Daniel; None; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant): Bulimia nervosa (BN) is a disabling eating disorder and affects as many as 2% of young women. It is a major source of psychiatric and medical morbidity that often impairs several areas of functioning. BN is occurring with increasing frequency among adolescents and preadolescents. Applying stringent diagnostic criteria for BN, studies have found 2-5% of adolescent girls surveyed qualify for diagnosis of BN. Research specific to treatment of child and adolescent eating disorders remains limited. No psychological treatment has been systematically evaluated in the treatment of adolescents with BN. The rationale for the proposed study
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derives from the candidate's participation in the conduct of treatment studies for adolescents with anorexia nervosa at the Maudsley Hospital in London. These data indicate that a specific form of family therapy is effective in the treatment of adolescents with anorexia nervosa. Involving the parents and siblings in treatment has beneficial effects on reversing the course of the eating disorder as well as improving family interaction. A preliminary report from the Maudsley group has also shown that this family therapy may be helpful in the treatment of adolescents with BN. Because most young adolescents still live with their families of origin, and are embedded in their families. This raises the important clinical possibility that adolescent BN patients can also be successfully treated with family therapy. We hypothesize that family therapy is an effective and essential way to reduce binging and purging in adolescents with BN, and will lead to long-term amelioration of bulimic symptoms. In the proposed study we aim to adapt and pilot a recently developed family therapy manual for adolescent anorexia nervosa for use in the treatment of adolescent BN patents, and to compare the efficacy of this conceptually and procedurally distinct family therapy treatment with a manualized individual control psychotherapy. To achieve these aims, we propose a fiveyear controlled treatment study to be carried out at The University of Chicago. Ninety newly referred adolescents meeting DSM-IV diagnostic criteria for BN will be randomly allocated to one of two groups: 1) family therapy or 2) individual supportive control treatment. All patients will receive the same medical evaluation and monitoring throughout the study period. Assessment of psychiatric and medical outcome measures will be carried out at the onset of treatment, during treatment, at the end of treatment, and again at six-month follow-up. The primary clinical outcome variables assessed will be binge and purge frequency (Eating Disorder Examination), while secondary outcome variables will include the Schedule for Affective Disorders and Schizophrenia, Rosenberg Self-esteem Scale, and Expressed Emotion. The candidate is a clinical psychologist who seeks to acquire skills in sophisticated statistical techniques for longitudinal data analysis, more in-depth knowledge of child and adolescent development and mentoring to conduct an independent controlled treatment trial in adolescent BN. This award will allow the candidate to train in appropriate research methodology and statistical procedures, and provide instruction, mentorship and experience in conducting a randomized trial of psychosocial treatments. Dr. Le Grange will engage in course work, workshops, controlled treatment trial research, and have ongoing mentorship from experts in the field. Through this award, the candidate will be able to build upon his prior experience as a participant in the conduct of controlled studies, put himself in a competitive position to apply for funding in the future, and establish himself as an independent treatment outcomes researcher. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FIBROMYALGIA: ETIOPATHOGENESIS
CENTRAL
FACTORS
IN
ITS
Principal Investigator & Institution: Bradley, Laurence A.; Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 31-MAY-2005 Summary: There is substantial evidence of abnormal pain sensitivity and functional brain activity in patients with fibromyalgia (FM). It has been suggested that FM may be a stress-related disorder, given the evidence of abnormal function of the neuroendocrine axes and the tendency of stress to exacerbate FM symptoms. However, no investigator to date has examined the effects of stress on pain sensitivity or functional brain activity in FM patients and controls. We propose study to test 10 hypotheses derived from our
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model of abnormal pain perception in FM regarding the effects of stress on pain sensitivity and functional activity in brain structures that process pain. We will assess the effects of noxious thermal stimulation and personally relevant, stressful imagery on pain thresholds and tolerance, magnitude estimates of sensory intensity and unpleasantness, and functional activity of brain structures that process the sensory and affective dimensions of pain. We will perform these evaluation procedures with 120, non- depressed, right-handed women with FM and 60, non-depressed, healthy control women. The patients will be classified in one of two groups according to symptom onset (traumatic vs. insidious). We hypothesize that during noxious thermal stimulation, patients, compared to controls, will (a) produce higher ratings of pain intensity and unpleasantness; and (b) show an abnormal pattern of brain activation characterized by bilateral increases in regional cerebral blood flow (rCBF) in the somatosensory cortices and increases in the ipsilateral anterior cingulate (AC) cortex. We also hypothesize that during exposure to personally relevant, stressful imagery, patients, compared to controls will show (a) smaller increases in salivary cortisol; and (b) greater increases in blood pressure, pulse rate, thermal pain intensity and unpleasantness ratings, and thermal pain-induced change in the contralateral and ipsilateral somatosensory cortices as well as in the ipsilateral AC cortex. This study will allow us to assess the effects of stress on pain perception and functional brain activity in patients with FM independently of the influence of affective disorders. The results will advance our knowledge regarding the effects of stress on abnormal pain sensitivity and the biologic processes that underlie this sensitivity in persons with FM. Thus, the results of the study may eventually lead to improved pharmacologic inteventions that may normalize the central biologic abnormalities that produce painful symptoms in FM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC INVESTIGATION OF MOOD DISORDERS Principal Investigator & Institution: Mcinnes, Lynne A.; Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Major depression (MDD) is a common and potentially devastating illness which likely has many etiologies, environmental as well as genetic. Unfortunately, biochemical and physiological experiments have so far failed to provide unequivocal, objective diagnostic markers for the illness, or to delineate specific pathological processes that are rectified by pharmacological treatments. Genetic approaches may only partially elucidate the neurobiology of depression, but the discovery of even one rare MDD predisposing gene will help guide efforts to understand mood disorders in general. Obstacles to identifying genes for psychiatric disorders include the lack of objective criteria for defining the disease phenotype and extensive etiologic heterogeneity. However, recent technological advances in molecular genetics have facilitated processing of the large samples required to find genes of small effect. As well, it is now generally recognized that genetic heterogeneity can be reduced by defining only the most severe form of a particular phenotype as affected and, possibly, by studying genetically isolated populations. Thus, the candidate intends to identify genes predisposing to mood disorder by applying population genetic mapping methods to study subjects with early onset recurrent MDD collected from an isolated population in the Central Valley of Costa Rica. The candidate is a postdoctoral fellow in psychiatry and has spent the last three years investigating the genetics of bipolar disorder in the laboratory of Nelson Freimer MD at UCSF. Short term career goals are to remain in this laboratory as an adjunct assistant professor, to further develop her knowledge of
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statistical approaches to the genetics of complex traits and to characterize the phenotypes associated with the genes she discovers for mood disorders. The latter endeavor will aid and be aided by 20 percent time clinical work related to affective disorders. The candidate's long-term goal is to establish an independent academic career continuing her genetic investigation of psychiatric disorders. It is hoped this work will ultimately lead to better patient care, the revision of psychiatric nosology in terms of etiology rather than symptoms, and the elimination of some of the stigma that surrounds mental illness that persists, in part, because of our inability to characterize the biology of complex behaviors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC LINKAGE STUDIES IN BIPOLAR DISORDERS Principal Investigator & Institution: Gershon, Elliot S.; Chairman; Psychiatry; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 15-APR-2000; Project End 31-MAR-2004 Summary: This application is submitted under the Program Announcement "Collaborative Studies of Mental Disorders." The broad aims are to expand a unique, existing set of pedigrees and test candidate regions for linkage and association with bipolar disorder. For the Johns Hopkins site this represents a revised competing renewal application while for the University of Chicago site this is a new proposal. Together we propose to double the existing family resource by ascertaining an additional 80 moderate-sized families through bipolar I probands with 2 or more siblings affected with recurrent major affective disorders. All participants will be interviewed by trained psychiatrists who have established excellent inter-rater reliability. Diagnoses will be assigned by 2 non-interviewing psychiatrists who review all clinical data. This sample has already proven to be of considerable value to the field. Among clinical findings that have spawned new research directions are our reports of anticipation, parent-of-origin effects, a high prevalence of BPII among the close relatives of the bipolar I probands, and high rates of comorbid panic disorder in a subset of families. This sample provided the first support for previous evidence of linkage to the peri-centromeric region of chromosome 18, the first evidence of linkage to 18q, and the first molecular evidence for a parent-of-origin effect in bipolar disorder. Findings from prospective studies of the 2nd half of this sample demonstrate strikingly high allele-sharing between bipolar II sib pairs at several loci in 18q2l. Exploratory analyses of co- morbid panic disorder and alcoholism have also suggested methods for predicting heterogeneity between bipolar families. In addition to collecting more families, we propose to genotype the existing and additional family sets at candidate regions implicated by a recent genome-wide scan for linkage that has been completed on 68 pedigrees from this sample. We further propose to use standard and innovative linkage and association methods to extract the maximal genetic information needed to locate genes influencing susceptibility to bipolar disorder. This is the most carefully clinically assessed family set in the field. The studies generated from this family resource have already demonstrated its value and have provided testable hypotheses for further work. The enlargement, continued maintenance, and analysis of this unique family resource is important to the field and will form the basis for many future studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC LINKAGE STUDIES IN BIPOLAR FAMILIES Principal Investigator & Institution: Depaulo, J R.; Associate Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218
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Affective Disorders
Timing: Fiscal Year 2002; Project Start 01-JUL-1988; Project End 31-MAR-2004 Summary: (Adapted from investigator's abstract): This application is submitted as one of two collaborating 4-year proposals under the Program Announcement "Collaborative Studies of Mental Disorders." The broad aims are to expand a unique, existing set of pedigrees and test candidate regions for linkage and association with bipolar disorder. For the Johns Hopkins site, this represents a revised competing renewal application while for the University of Chicago site this is a new proposal. Together, the two sites propose to double the existing family resource by ascertaining an additional 80 moderate-sized families through bipolar I probands with 2 or major siblings affected with recurrent major affective disorders. All participants will be interviewed by trained psychiatrists who have established excellent inter-rater reliability. Diagnoses will be assigned by 2 non-interviewing psychiatrists who review all clinical data. This sample has already proven to be of value to the field of psychiatric genetics. Among clinical findings that have spawned new research directions are the reports of anticipation, parent-of-origin effects, a high prevalence of BPII among the close relatives of bipolar I probands, and high rates of co-morbid panic disorder in a subset of families. The sample provided the first evidence of linkage to 18q, and the first molecular evidence for a parent-of-origin effect in bipolar disorder. Findings from prospective studies of the 2nd half of this sample demonstrate high allele sharing between bipolar II sib pairs at the several loci in 18q21. Exploratory analyses of co-morbid panic disorder and alcoholism have suggested methods for predicting heterogeneity between bipolar families. In addition to collecting more families, the investigators propose to genotype the existing and additional family sets at candidate regions implicated by a recent genome-wide scan for linkage that has been completed on 68 pedigrees from this sample. It is also proposed to use linkage and association methods to extract the maximal genetic information needed to locate genes influencing susceptibility to bipolar disorder. This is a carefully clinically assessed family set. The studies generated from this resource have demonstrated its value and have provided testable hypotheses for further work. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIGH EFFICIENCY SCREENING FOR BIOACTIVE LIPIDS Principal Investigator & Institution: Johnson, Mitchell E.; Chemistry and Biochemistry; Duquesne University 600 Forbes Avenue Pittsburgh, Pa 15282 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 31-JUL-2005 Summary: (provided by applicant): We will develop efficient, extremely sensitive methods to detect and screen for fatty acid amides in biological samples. We will complement the high efficiency screening, which will have limited structural information, with newly developed standardized methods for lipid profiling. The profiles will include, for the first time, fatty acid amides in the profile strategy. Using these methods, we will screen standard neuroblastoma cell lines and neuro-endocrine tissue samples to determine the presence and distribution of basal (unstimulated) levels of primary fatty amides, such as oleamide. Fatty acid amides comprise a relatively unexplored class of compounds with neuromodulatory activity. Oleamide (cis-9octadecenamide), the "parent" molecule of the class, potentiates, quite specifically, specific 5-hydroxytryptamine receptors and gamma-aminobutyric acid receptors and inhibits gap junction communication. This class of compounds may have a very specific role in the etiology of affective disorders. Such disorders as depression, anxiety, and bipolar disorders affect one in six Americans. The availability of tools to study amides is important in developing a better picture of how these lipids modulate neural transmission and other processes. These compounds are relatively difficult to study,
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because they are chemically and spectroscopically almost "invisible." Based on substantial previous work on the chromatography, electrophoresis, and the chemistry of derivatization of these and similar lipid compounds, we have proposed a series of derivatization methods that will allow us to use high efficiency capillary electrophoresis methods coupled with high sensitivity laser-induced fluorescence for detection of amides. The development of comprehensive lipid screening protocols using liquid chromatography will allow us to optimize the isolation of amides from other lipids in such a way as to maintain the overall high efficiency of the screening process. In addition, we will incorporate, for the first time, amides in the scheme of lipid profiling. We hope that this will encourage some progress towards high resolution, comprehensive lipid profiling to complement proteomic studies of complex metabolic pathways involving bioactive lipids Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPROVING INTERVENTIONS FOR DRUG ABUSE-PARTNER VIOLENCE Principal Investigator & Institution: Connelly, Cynthia D.; Children's Hospital Research Center 3020 Children's Way, Mc 5074 San Diego, Ca 92123 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAY-2007 Summary: (Provided by Applicant) The applicant is requesting five years of funding through the Mentored Career Development Award (K01) program to establish an independent program of substance abuse research focused on improving the identification and intervention for substance abuse, intimate partner violence (IPV) and co-occurring affective disorders (AD) in early intervention settings. The applicant?s strong background of academic, research and nurse clinical training in substance abuse, violence, family health, and health services research provides an excellent foundation for this work. The proposed training goals provide additional instruction and mentoring in 1) the complex linkage between ATOD, IPV, and AD and engagement and treatment strategies for early preventive intervention, 2) longitudinal data analysis and modeling techniques, 3) cultural issues and health disparities that complicate early intervention efforts among diverse populations, and 4) training in the ethical conduct of research. This training will prepare the applicant to pursue a research career in prevention science targeting substance abuse among women of childbearing age. In Phase I secondary data analysis will be conducted on longitudinal data provided by two large samples of postpartum women to examine the role of ATOD, IPV and AD on engagement and participation with an early intervention: home visitation. Subgroup analyses based on age, race/ethnicity and combinations of ATOD, IPV and AD will be examined. In Phase II, existing protocols for provider education and training in assessment including instrumentation, interpretation, and triage will be critically examined in two model programs. Phase III will use findings from Phases I and II as well as mentoring from experts in specific content areas to inform the development of strategies and preliminary protocols to strengthen early preventive interventions addressing these specific issues and to pilot test these protocols. Phase III will identify characteristics that impact implementation at the provider, family, and program level and will generate preliminary data to inform research and program development. The data will form the basis for a R01 application to prospectively test the effectiveness of strategies designed to improve provider education and practice related to ATOD, IPV, and AD among women of childbearing age. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HORMONES
INTEGRATING
ENERGY
STORAGE,
HIPPOCAMPUS
AND
Principal Investigator & Institution: Lucas, Jeffrey R.; Associate Professor; Biological Sciences; Purdue University West Lafayette West Lafayette, in 479072040 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2004 Summary: Seasonal Affective Disorder (SAD) is a seasonal pattern of clinical depression that also correlates with changes in appetite, weight regulation, hormone profiles, and social interactions. This suite of correlated traits (except for the depression) is characteristic of many birds that show dramatic seasonal shifts in energy regulation and social structure as an adaptive anticipatory response or an adaptive reactive response to seasonal environmental changes. Thus, birds may be excellent models for understanding basic physiological processes that are associated with seasonal affective disorders in humans. However, while we understand many of the component parts of these seasonal cycles, we know relatively little about the adaptive significance of the joint regulation of these cycles. To this end, we propose an experiment designed to evaluate the correlated changes in spatial memory, neuroanatomy, hormone profiles, energy regulation patterns and activity budgets in adult Carolina chickadees maintained under natural photoperiods. Carolina chickadees will be used in this study because these birds store food in hundreds to thousands of distinct sites; retrieval of this food is partly dependent on spatial memory. Thus seasonal variation in energy storage patterns should be correlated with seasonal variation in hippocampal formation (HF) and spatial memory capacity. The project includes a yearlong study where adult birds are housed under laboratory conditions with natural photoperiods but constant temperature. Caching rates and body mass will be monitored under constant rates of food access for a 32-day period, then the birds will be given a set of spatial memory tests in which they are allowed to search a room for previously stored seeds. These data will provide a direct comparison between energy regulation tactics and spatial memory capacity. Movement patterns and general time budgets will be generated from focal-animal behavioral samples. After the behavioral tests are completed, we will test for correlated changes in size and cytogenesis in the HF. Cytogenesis will be measured using BrdU injections administered during the spatial memory trials; HF size will be measured on each bird at the end of each experiment. Hormone profiles will be measured from fecal samples taken at dawn and dusk throughout the experiment. Seasonal cycles of depression often correlate with seasonal cycles in a variety of physiological traits. Only an integrative approach will tell us how these cycles relate to on another. An understanding of the adaptive significance of the suite of traits that cycle annually in natural systems will give us a unique insight into this important component of these seasonal disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IONIC MECHANISMS RELATED TO SECRETION IN PITUITARY CELLS Principal Investigator & Institution: Oxford, Gerry S.; Professor; Cellular/Molecular Physiology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JUL-1982; Project End 30-JUN-2003 Summary: The functional coupling between membrane electrical events and exocytotic release of hormones from endocrine cells is a key element in the physiology of secretion in endocrine glands. In the case of pituitary hormone secretion several membrane ion
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channels are involved and the molecular mechanisms coupling stimulatory and inhibitory secretogogue receptors to these ion channels are only now being revealed. Many secretogogue receptors belong to the superfamily of seven membrane spanning domain receptors signal via guanine nucleotide binding proteins (G-proteins). Among such receptors are those for dopamine (D2 type), the primary regulator of prolactin secretion, and somatostatin which governs inhibition of growth hormone release. Among the effectors to which these classes of receptor couple are potassium and calcium channels. In recent years, many elements of the signal transduction pathways linking dopamine receptors to these ion channels have been cloned. In particular the potassium channels activated by these receptors are members of a two transmembrane spanning domain superfamily of inwardly rectifying K channels. We hypothesize these G- protein coupled K channels, or GIRKs, to be the critical link between receptor activation and the inhibition of secretion. The principle objectives of the present study are to (1) examine the molecular specificity of the signaling pathway which involves GIRK both in terms of G-proteins and GIRK channels, (2) to critically test the central involvment of GIRK channels in the regulation of secretion, and (3) to examine the mechanisms and functional role of modifications to the pathway such as desensitization. To this end we will combine molecular methods to both potentiate and interfere with Gprotein and channel function with electrophysiological and optical assays of channel and secretory behavior, respectively. All experiments will be performed in single, isolated pituitary cells of the rat or in mouse pituitary tumor cells. This research will lead to a clearer understanding of the events underlying regulated hormone secretion in pituitary cells. In addition, the common identity of dopamine receptor subtypes in both pituitary and brain as well as similarities in G-protein gated K channels in each tissue, suggest that these studies may provide mechanistic insight into the actions of these neurotransmitters in affective disorders and neural regulation of vegetative functions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPRESSION
LONG-TERM
ANTIDEPRESSANT
OUTCOME
IN
BIPOLAR
Principal Investigator & Institution: Ghaemi, S Nassir.; Cambridge Health Alliance 1493 Cambridge St Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 10-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from the Applicant's Abstract):Summary: This is an application for an NIMH Mentored Patient-Oriented Research Career Development Award (K-23) to develop expertise in evaluating, designing and applying research methods for assessing pharmacological treatments for bipolar depression, based on a balanced program of didactic, tutorial, and practical research experiences. The applicant will study the impact of continuing vs. discontinuing antidepressants in a naturalistic, but controlled and randomized, long-term (up to 3 year) clinical study of patients with bipolar disorder who are clinically maintained on mood-stabilizing treatment. The proposal will be completed as part of the national NIMH-sponsored Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) project. Rationale: In contrast to unipolar major depression, bipolar depression is among the least studied depressive illnesses, with very little research on the long-term efficacy or safety of antidepressants used in conjunction with mood-stabilizing agents, or their effect on the course of bipolar disorders, including induction of mania, mixed states, psychosis, or rapid-cycling. Despite these potential risks, the depressive phase of bipolar disorder is sufficiently compelling clinically that antidepressants rather than mood-stabilizing agents are the most commonly used treatments in bipolar disorder, supporting the timelines of the present
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Affective Disorders
proposal. It is unknown if these antidepressant treatments are effective or even safe in these circumstances. Environment: The project is based at the Massachusetts General Hospital project site of the NIMH national STEP-BD study of long-term treatment of bipolar disorder, with the collaboration of two other STEP-BD sites. Included are a program of practical training and supervised research under primary mentorship of Ross J. Bladessarni MD, co-sponsorship by Gary S. Sachs MD, and consultation by bipolar disorder expert Frederick K. Goodwin MD and biostatistician John Hennen PhD. Career development plan: Training is designed to assume that the applicant achieves competence in the critical evaluation and design of long-term pharmacological studies in adults with major affective disorders, as well as in applying these skills to the design, conduct, and analysis of a supervised clinical trial. Training includes completion of MPH coursework at the Harvard School of Public Health and tutorials on the theory and analysis of research designs and statistical methods for longitudinal studies supervised by the biostatistical consultant in collaboration with the mentor, co-sponsor, and consultants. In this process, the applicant will develop competence to lead independent studies of the long-term treatment of bipolar disorder as a principal investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAGNETIC RESONANCE SPECTROSCOPY IN AFFECTIVE ILLNESS Principal Investigator & Institution: Moore, Constance M.; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-JUL-2006 Summary: The specific aim of this application is to afford the applicant, a physicist, the opportunity to become an independent researcher applying magnetic resonance spectroscopy (MRS) in affective disorders. Two components are proposed to accomplish this: formal academic training in psychology and neuroscience; and two research projects. There is an established literature that suggests the pathophysiology of affective illness may lie in irregularities in second messenger and signal transduction pathways; in particular the phosphatidylcholine (PtdCho) and phosphatidylinositol (PtdIno) cycles. Elements of the PthCho and PtdIno cycles are detectable using proton (1 H) and phosphorous (31 P) MRS, in particular choline containing compounds (Cho), myo-Inositol containing compounds (Ino), phosphomonoesters (PME), phosphodiesters (PDE) and the nucleotide triphosphates (NTPs). Over the five year course of the study 35 subjects with Major Depressive Disorder (MD), 35 subjects with Bipolar I Disorder (BD) and 20 comparison subjects (NC) will be recruited. A priori regions of interest are the anterior cingulate gyrus and the caudate nuclei since functional neuroimaging studies have noted mood state dependent alterations in metabolic activity in these regions and preliminary MRS data from these brain regions have demonstrated moodstate, medication, and diagnosis- dependent alterations in Cho, Ino, beta-NTP and PME. In the first two years of funding subjects will be examined using proton echo planar spectroscopic imaging (PEPSI) at 1.5 T. For the final three years of funding subjects will be examined using 1H decoupled 31P MRSI at 4.0 T. The use of PEPSI at 1.5 T and 1H decoupled 31P MRSI at 4.0 T will allow for the acquisition of spectra from smaller regions of interest, such as the anterior cingulate and the caudate, than is possible with older techniques. In addition, PEPSI affords a time advantage which allows for the absolute quantification of the metabolites detected. All subjects will be examined on two occasions six weeks apart and the following hypotheses will be tested: Increased right cingulate cortex Cho will be associated with depression. A decrease in the left cingulate cortex Cho will occur as a result of antidepressant treatment. Decreased right cingulate
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cortex Ino will be associated with depression. Decreased caudate nucleus beta-NTP will be associated with depression. An increase in caudate nucleus PME will occur as a result of lithium treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF NEUROPATHOGENESIS IN BORNA DISEASE Principal Investigator & Institution: Hornig, Mady; Epidemiology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 15-JUL-1998; Project End 30-JUN-2003 Summary: (Applicant's Abstract): Borna disease virus (BDV) is a newly classified RNA virus that infects the CNS of warm blooded animals to cause disturbances of movement and behavior. Natural infection has been confirmed only in horses, sheep, cattle, birds, and cats; however, primates can be infected experimentally. Although the data remain controversial, several investigators have reported evidence of infection in schizophrenia and affective disorders. Most previous work in BDV pathogenesis has focused on infected adult immunocompetent rodents and ungulates where dramatic disturbances in behavior, limbic circuitry, and monoamine neurotransmitter systems are reminiscent of aspects of some neuropsychiatric syndromes (autism, schizophrenia, or bipolar disorder). While these models are intriguing they are associated with CNS inflammation, marked loss of brain mass and gliosis and may be less relevant to neuropsychiatric diseases than those in neonatally infected rats where BDV induces subtle disturbances of behavior, and hippocampal and cerebellar dysgenesis without inflammatory cell infiltration. The broad objectives of this project will be to: (1) determine the mechanisms by which viral infections alter CNS architecture and function without invoking infiltrating inflammatory elements and (2) establish and investigate nonhuman primate models for BDV infection. Whereas models for persistent tolerant infection of neonatal rats have been described, nonhuman primate studies have been pursued only in acutely infected adult rhesus macaques. Studies proposed here will clarify whether primates can be infected in the perinatal period and, if so, whether the clinical, behavioral, and neuropathologic sequelae are consistent with human psychiatric disease. The investigators hypothesize that perinatal infections of Rhesus monkeys will manifest as subtle neurobehavioral and neuropathologic disturbances in a primate counterpart to the neonatal rat model of persistent BDV infection. They further propose that elucidation of the pathogenesis of such neurologic dysfunction through more extensive studies of neonatal BDV infection of rats will provide critical information about mechanisms of viral-CNS interactions that will then permit more focused, informed investigations in humans and nonhuman primates. Specific aims in the neonatal rat model are: i) characterize the nature of the behavioral, cognitive, and motor deficits; ii) examine the neuropathology associated with the neurologic abnormalities; iii) evaluate changes in levels of cytokines as potential mediators of BDVrelated damage; iv) discern whether apoptosis contributes to the neuropathology observed after neonatal infections and v) assess regional changes in neurotransmitter and neuroendocrine systems following neonatal BDV infection. The specific aims of the primate component of this application are to: 1) establish nonhuman primate models for BDV CNS infection using fetal and weanling Rhesus macaques; 2) determine the timecourse of the humoral immune response to BDV in infected fetal (intraventricular infection in utero) and weanling (intracerebral or intranasal infection) Rhesus macaques; 3) assess whether BDV nuclei acids can be detected in peripheral white blood cells (WBC) of infected Rhesus macaques; in the event that WBC are found to contain BDV nucleic acids can be detected in peripheral white blood cells (WBC) or infected Rhesus
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Affective Disorders
macaques; and in the event that WBC are found to contain BDV nucleic acids, to determine the distribution of BDV nucleic acids with respect to cell type and timecourse after infection; 4) define the hematologic, chemical, and virologic profile of cerebrospinal fluid (CFS) in infected fetal and weanling Rhesus macaques; 5) characterize the nature of any neurobehavioral, socioemotional, or motor deficits, and 6) evaluate neuropathology through in vivo (MRI and PET brain imaging) and postmortem analyses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELATONIN-LIGHT INTERACTION ON CIRCADIAN ACTIVITY Principal Investigator & Institution: Dubocovich, Margarita L.; Professor; Mol Pharm & Biol Chemistry; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-MAY-1996; Project End 30-JUN-2004 Summary: (applicant's abstract): Our long term goal is to understand the molecular, biochemical, signaling and functional properties of melatonin receptor subtypes in the mammalian central nervous system and to determine the role of this hormone in regulating the transmission of visual and circadian information. The overall goal of the present application is to elucidate the cellular and functional mechanism(s) through which activation of G-protein linked melatonin receptor subtypes (mt1 and MT2) and putative nuclear melatonin receptors (ROR-beta) within the circadian timing system (retina, SCN and IGL) affects circadian rhythms, regulates the entrainment of circadian rhythms following alterations in the light/dark cycle and modulates light responses reaching the circadian timing system. The experiments proposed in this application make use of new advances in the field of melatonin receptor research that occurred since the last submission. This includes the cloning of new mammalian melatonin receptor subtypes (mt1(Mel1a), MT2(Mel1b)], the discovery of specific and selective MT2 melatonin receptor antagonists as well as the establishment of mice lines with disruption of the mt1 melatonin receptor gene or the putative nuclear melatonin receptor gene, ROR-beta. The use of these probes and animal models permits to investigate the localization of melatonin receptor subtypes within the mammalian timing system, to establish their functional role in the regulation of circadian responses and interaction with light and to assess the consequence of their activation on signaling and gene regulation. We will address the following specific aims: 1) to determine within the circadian timing system the cellular localization of melatonin receptor subtypes (mt1 and MT2) and colocalization with the nuclear receptor ROR-beta, glutamate receptors (NMDA, AMPA, metabotropic), and per genes (per1, per2, per3); 2) to determine the melatonin receptor type involved in melatonin-mediated phase shifts of circadian rhythms and the signal transduction pathways altering clock activity in vitro; 3) to assess the receptor subtypes and mechanism(s) of light-melatonin interaction leading to advances in the phase of the clock; 4) to assess the mechanism(s) by which melatonin affects the rate of reentrainment following an abrupt phase advance of the dark cycle. The results of these studies will allow the rational design and synthesis of subtypes selective melatonin receptor agonists and antagonists that when administered at specific times will lead to either advances or delays of the clock. These novel therapeutic agents could be used for the treatment of insomnia or circadian disturbances involving abnormal phase advance (Advanced Sleep Phase Syndrome, endogenous depression, east jet flight) or phase delays (Delayed Sleep Phase Syndrome; seasonal affective disorders, west jet flight). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MENTAL MANAGED CARE
HEALTH
SERVICES
RESEARCH
PROGRAM
39
IN
Principal Investigator & Institution: Mclaughlin, Thomas J.; Harvard Pilgrim Health Care, Inc. 93 Worcester St Wellesley, Ma 02481 Timing: Fiscal Year 2002; Project Start 10-APR-1998; Project End 31-MAR-2004 Summary: (Applicant's Abstract): As organized systems of care move towards becoming the predominant form of health delivery system in the U.S., managed care organizations are attempting to measure and improve health outcomes per unit cost ("value"). This agenda, characteristic of today's managed care organization, is due in large part to the demands of the marketplace which expects reorganization of the health care system in order to maximize benefit at the lowest possible cost. Harvard Pilgrim Health Care (HPHC) proposes to develop a research infrastructure building program (RISP) of mental health services and clinical research in the context of managed care which complements and extends an existing and highly developed process of clinical quality management and improvement cycles. The proposed work will accelerate and facilitate a continuously emerging mental health infrastructure within this large health maintenance organization. It is likely that processes of skill-building and formation of multidisciplinary research groups "invented" or developed at HPHC will be applicable to other managed care organizations. Specific aims of the proposed RISP are to develop multidisciplinary groups of mental health researchers that will: (1) study the organization, process and outcomes of care for mental illness in primary care. This group will be represented by core individuals from within the different divisions of HPHC, researchers from academic organizations with a solid track record in mental health research and educational training, and representatives from the public sector who are increasingly important actors in defining and evaluating mental health care for their clients; (2) explore mechanisms to link primary care providers to mental health specialists in order to improve access to and outcomes of care for common and expensive mental illnesses such as depression with or without substance abuse; (3) examine experiments in the re-organization of mental health care delivery within staff and medical groups components of HPHC to improve patient and provider satisfaction and care ("hybrid models"); (4) examine patient factors associated with access and particularly patient-directed interventions aimed at facilitating entry into traditional health and mental health programs, (5) and, finally to study the special needs of publicly-insured members, especially Medicaid populations which are characterized by disproportionately high levels of serious and chronic mental illness such as schizophrenia and major affective disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MONOAMINERGIC NEUROPSYCHIATRY
FUNCTION
IN
GERIATRIC
Principal Investigator & Institution: Smith, Gwenn S.; Associate Professor; Long Island Jewish Medical Center 270-05 76Th Ave New Hyde Park, Ny 11040 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Applicant's abstract): An important therapeutic issue in neuropsychiatric disease, particularly in geriatric patients, is the variability in treatment response and the inability to predict treatment outcome. Decreased monoaminergic responsiveness may be a potential neurobiologic mechanism underlying treatment resistance across several neuropsychiatric disorders. The overarching theme of the candidate's funded research in AD, schizophrenia and geriatric depression is that decreased monoaminergic
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Affective Disorders
responsiveness is related to treatment resistance. To evaluate monoaminergic function in vivo, the candidate has developed methods using Positron Emission Tomography (PET) imaging, radiotracers for neurotransmitter receptors and pharmacologic challenges. This application of PET methodology represents the most direct, noninvasive and quantitative method of measuring neurotransmitter activity in the living human brain. The PET studies performed thus far have consistently demonstrated substantial between subject variability in monoamine responsiveness in normal controls and in patients. Variability of monoamine responsiveness has been observed also in pharmacologic challenge studies using behavioral and neuroendocrine outcome measures. The goals of this Independent Scientist Award are to obtain training in methods complementary to brain imaging techniques that will enable the candidate to better interpret the variability in monoaminergic responsiveness observed in the PET data. The goals of the training experience are to incorporate genetic markers of monoamine receptor and transporter alleles and polysomnographic methods into her existing research program and to obtain training in the neuroanatomy of cholinergic and monoaminergic interactions and neuroimaging in affective disorders. The research plan is conducted within the framework of three funded studies to use PET to investigate 1) serotonin-dopamine interactions in schizophrenia; 2) cholinergic modulation of monoamine function in Alzheimer's Disease; and 3) the effects of sleep deprivation and antidepressant treatment on cerebral glucose metabolism in geriatric depression. These studies are designed to relate alterations in monoamine responsiveness to subsequent therapeutic response. The long term goal of the candidate's research is to understand the neurobiologic substrates of treatment resistance in neurodegenerative disorders and to use the genetic, polysomnographic and imaging data to predict the course of pharmacotherapy. The Independent Scientist Award will enable the candidate to firmly focus her research in the area of geriatric neuropsychiatry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MRS STUDIES OF CORTICAL GABA IN DEPRESSION Principal Investigator & Institution: Sanacora, Gerard; Assistant Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: (adapted from applicant's abstract): I have been fortunate to work in stimulating environments that have afforded me substantial opportunities to engage in research training throughout my graduate (M.D., Ph.D.) and residency training. In July, I will continue my training an additional year with the Daniel X. Freedman Clinical Neuroscience Fellowship at Yale University. However, without support from a K08 award, I would be required to assume substantial clinical responsibilities in order to support my salary when I join the Yale faculty in July, 1999. I have designed this K08 award to enable me to pursue a comprehensive five-year research-training Plan. This plan will provide me with the background and skills necessary to become an independent investigator-using novel magnetic resonance spectroscopy (MRS) techniques. I would like to apply these techniques to the study of GABA and glutamate neurotransmission related to the pathophysiology and treatment of affective disorders. Over the past two years I have developed basic skills in-proton-MRS (1H-MRS). We have produced exciting preliminary data describing reductions in cortical GABA associated with depression, and elevation of cortical GABA levels following electroconvulsive therapy (ECT). I propose to continue these investigations with two aims. 1) To fully characterize both GABAergic and glutamatergic systems in affective disorder disease states. (Years 1-3) and 2) To use pharmacological probes along with
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[13C]-MRS to examine possible pathophysiological mechanisms related to amino acid neurotransmitter regulation in depression. In order to advance the use of MRS applications in the study of affective disorders, I have identified several key areas where I will require additional training including: 1) nuclear magnetic resonance, 2)1 neurochemistry, kinetic modeling, and related neuroimaging technologies, 3) clinical and basic neuropharmacology applicable to affective disorders research; and 4) clinical trials methodologies. I believe my background in the basic sciences will enable me to complete the rigorous training plan outlined in this application. This training along with continued practical application of the technology under the co-mentorship of Drs. Rothman and Krystal should thoroughly prepare me for a career as an independent investigator using MRS technology to study brain neurochemistry. This novel line investigation will open previously inaccessible areas of research, with a broad range of future applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MUSCARINIC RECEPTOR COUPLING TO INOSITIDES IN CNS Principal Investigator & Institution: Fisher, Stephen K.; Professor; Pharmacology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-SEP-1986; Project End 30-NOV-2003 Summary: Alterations in muscarinic receptor neurotransmission in the central nervous system have been observed in Alzheimer's disease, narcolepsy, affective disorders, Parkinsonism and as a consequence of aging. As a result, significant effort has been expended in the design and development of muscarinic ligands that might be of potential therapeutic value. To date, five subtypes of muscarinic cholinergic receptors (mAChRs) have been described, three of which (m1, m3, m5) couple to a phosphoinositide-specific phospholipase C, with the attendant formation of inositol trisphosphate and diacylglycerol. Knowledge of the mechanisms underlying the regulation of mAChRs is important for evaluating the role played by mAChRs in signal transduction and in the rational design of therapeutic agents that could target this signaling pathway. In this proposal, we plan to extend our ongoing studies of the regulation of mAChR signaling to phosphoinositide turnover by examining the molecular mechanism underlying agonist-induced internalization of the receptor in human SH-SY5Y neuroblastoma cells. Specifically, the hypothesis to be tested is that the activity of phosphatidylinositol 4- kinase (PI4K), is an absolute requirement for the occurrence of receptor endocytosis. We will evaluate this hypothesis by the following approaches. By pharmacological means, we will determine the ability of known inhibitors of PI4K to inhibit mAChR endocytosis. By means of biochemical, immunological and cell biological approaches, we will determine the specific isoform(s) of PI4K that are involved in receptor endocytosis and their site of action within the endocytic cycle. To evaluate cause and effect, molecular genetic approaches will be employed to examine the effects of depletion and over-expression of PI4K on the extent of receptor internalization. Although phosphoinositides have been implicated in membrane trafficking events, most emphasis has been placed on the 3'phosphoinositides. The present proposal focuses on the potential role played the quantitatively major 4'-phosphoinositides in this process, evidence for which is beginning to accumulate in both normal and pathological states. This proposal presents strong preliminary evidence linking PI4P synthesis to the internalization of mAChRs. It is likely that the knowledge gained from these studies will be of fundamental
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Affective Disorders
importance to understanding the regulation of cell signaling events in neural cells initiated not only by mAChRs, but also by other G-protein coupled receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MUTATIONAL RHYTHMICITY
ANALYSIS
OF
VERTEBRATE
CIRCADIAN
Principal Investigator & Institution: Cahill, Gregory M.; Associate Professor; Biology and Biochemistry; University of Houston 4800 Calhoun Rd Houston, Tx 77004 Timing: Fiscal Year 2002; Project Start 01-JAN-2000; Project End 31-DEC-2003 Summary: The long term goal of this project is to define basic molecular mechanisms that underlie circadian rhythms of behavior in vertebrates. A wide variety of biochemical and physiological processes are regulated by circadian clocks, resulting in coordinated daily rhythms of gene expression, metabolism, neurochemical and hormonal functions, and behavior. Disruption of the human circadian system due to disease, aging or voluntary disruption of sleep-wake cycles can lead to diminished sensory and motor performance, sleep disorders or affective disorders. An understanding of the biological basis of circadian rhythmicity will be important for undertanding and treatment of these disorders. The specific goal of this project is to identify and characterize vertebrate genes that are involved in circadian rhythmicity through mutational analysis of the zebrafish circadian system. Recent advances in zebrafish genetics and genomics, together with recently-developed methods for efficient measurement of zebrafish circadian rhythms, make this a useful and economical model system for genetic studies of vertebrate circadian clocks. The specific aims of this project are to: 1) Screen for mutations that affect behavioral circadian rhythms in matugenized zebrafish, recover mutant lines, and characterize the phenotypes of these mutations at the system and cellular levels. 2) Map these mutations on the zebrafish genetic linkage map. 3) Clone and map zebrafish homologs of known circadian clock-related genes and determine whether any of these are disrupted by the newly identified mutations. 4) Use candidate and positional cloning techniques to clone mutated clock genes. This project is expected to result in the identification of novel vertebrate circadian clock genes, and in new information about the functional roles and mechanisms of action of previouslyidentified clock-related genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROBEHAVIORAL CHANGES IN PEDIATRIC AFFECTIVE DISORDER Principal Investigator & Institution: Ryan, Neal D.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JUL-1986; Project End 30-JUN-2007 Summary: (provided by applicant): This is a revised re-submission of a competing renewal for a Program Project grant that focuses on pediatric affective disorders (depression and anxiety). These disorders are frequent, chronic, recurrent, and associated with significant morbidity, functional impairment, and mortality. In response to the previous review we have clarified issues raised by the IRG, provided additional information and descriptions regarding several areas of the studies, and have better delineated the inter-relatedness across the projects and cores. The four projects in the revised application will: (I) Study patterns of mood, cognition, behavior, sleep/activity patterns, social activities, media use and daily stressors in home environments in a new sample of PAD and control subjects before and during acute treatment; (2) Study the
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multi-year course of our large longitudinal sample of children and adolescents with PAD and controls as they enter young adulthood; (3) Use event related fMRI to examine reward-expectancy, experience of reward, experience of loss, and decision-making under varying reward contingencies to investigate the neurobehavioral systems involved in reward-anticipation, loss, and behavioral choice in PAD and control children; (4) Study mood, cognition, and behavior in the home in a sample of bipolar adolescents, characterizing day-to-day variability and changes in response to naturalistic treatment. Common themes through the work of these projects include: the neurobehavioral systems involved in positive and negative affect and approach/withdrawal behaviors; serotonergic systems, the importance of studying complex behavior in a natural setting; and the importance of understanding the longitudinal course of these interrelated disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROBIOLOGY OF DISEASE -- TEACHING WORKSHOP Principal Investigator & Institution: Lipton, Stuart A.; Professor and Director; Society for Neuroscience 11 Dupont Cir Nw, Ste 500 Washington, Dc 20036 Timing: Fiscal Year 2002; Project Start 01-AUG-1983; Project End 31-MAY-2006 Summary: The Society for Neuroscience (SFN) is the major professional organization for scientists who study the nervous system. An important goal of this organization is to encourage scientists in training to undertake research related to diseases of the nervous system. The objective of this grant application is to support teaching workshops that introduce young neuroscientists to current concepts about the etiology and pathogenesis of disorders of the nervous system. For each workshop, about 12 faculty are chosen by the Organizing Committee after eliciting proposals from the Society at large. Clinical presentations provide enrollees with an experience of the human dimension of particular diseases. Lectures cover both clinical research and relevant laboratory work. In addition to lectures, enrollees are given a choice of attending two of four small group workshops that emphasize either specific or methodological issues and encourage lively discussion. Since its inception, 20 workshops have been held, usually on the day prior to the start of the Society for Neuroscience meeting. Topics have included: Infections in the nervous system, epilepsy, Huntington's and Alzheimer's diseases, muscular dystrophy, multiple sclerosis, prion diseases, drug addiction, pain and affective disorders, stroke and excitotoxicity, neuromuscular diseases, amyotrophic lateral sclerosis, schizophrenia, migraine, mental retardation and developmental disorders, Tourette's syndrome and obsessive-compulsive disorder, and the neurobiology of brain tumors. Enrollment generally runs between 100 and 200 attendees. Most enrollees are graduate students or postdoctoral fellows. Current plans are to cover the following topics in the near future: Genes, free radicals, mitochondria and apoptosis in Parkinson's disease, AIDS dementia, peripheral neuropathy, pain, language disorders, and affective disorders. Other topics will be chosen depending on their potential interest to young neuroscientists, their impact on society and the quality of recent research related to that disease area. We are especially interested in covering diseases of the nervous system which are important clinically but which are in need of enhanced basic cellular and molecular understanding. Society members are encouraged to suggest topics in the SFN Newsletter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROBIOLOGY OF PERSONALITY AND EMOTION Principal Investigator & Institution: Depue, Richard A.; Professor; Human Development; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853
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Affective Disorders
Timing: Fiscal Year 2002; Project Start 01-MAR-1997; Project End 31-OCT-2003 Summary: Dopamine facilitation of incentive motivation lays the very foundation of normal goal-oriented behavior, and is suspected of being involved directly or indirectly in an array of abnormal behavioral conditions. Incentive-motivated behavior is facilitated by corticolimbic glutamatergic afferents that carry the salient context predictive of reward to DA neurons in the ventral tegmental area (VTA) and to spiny neurons in the nucleus accumbens (NAS). Much animal work demonstrates that individual differences in VTA DA and NAS DA functioning modulate the extent to which salient incentive contexts a) are bound to VTA and NAS neurons, and hence b) facilitate the behavioral expression of incentive motivational processes in the NAS. We demonstrated (Depue & Collins, 1999) that the foundation of the major personality trait of extraversion is positive incentive motivation, and that variation in both of these is associated with individual differences in DA functioning. Therefore, it can be hypothesized that variation in extraverted affect and behavior is associated with variation in the strength to which salient context comes to facilitate incentive motivational processes. The proposed studies specifically test this hypothesis through four experimental studies that assess a) the extent to which context is paired with a methylphenidate-facilitated incentive motivational state, b) dose dependence of these effects, and the extent to which the effects are modified by c) latent inhibition and d) extinction processes. Significance of the work derives from its development of new methodology, performance measures, and pharmacological designs to study contextmotivational associations in humans. Also, these studies are designed to provide information that may enlighten several psychiatric problems that may involve a contribution of DA to, and contextual facilitation of, disordered behavior. Recent research raises the possibility that determination of DA-behavior relations could have benefit in understanding, and perhaps in treating, pathological forms of personality disorders, some forms of affective disorders, and schizophrenic positive symptoms. Furthermore, the proposed studies may have direct implications for understanding and modeling the genetic-experiential interactive liabilities to alcohol and psychostimulant substance abuse that may depend on the sensitivity of DA receptor systems in interaction with environmental context. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELATONIN
NEUROENDOCRINE/IMMUNE
INTERACTIONS:
ROLE
OF
Principal Investigator & Institution: Yellon, Steven M.; Professor; Center for Perinatal Biology; Loma Linda University Loma Linda, Ca 92350 Timing: Fiscal Year 2002; Project Start 20-JAN-2000; Project End 30-NOV-2003 Summary: (applicant's abstract): Physiological adaptations anticipate and coincide with changes in season. Failures to adapt are associated with increased incidence of disease, mortality and mental dysfunctions that include seasonal affective disorders and depression. Day length is the primary environmental cue that regulates a variety of physiological adaptations that anticipate seasonal challenges. Preliminary studies indicate that day length selectively regulates immune functions in the Siberian hamster, a seasonal breeding species in which the mechanism that controls physiological adaptations to day length has been extensively studied. Hamsters in short days (analogous to winter) had increased numbers of leukocytes, T helper cells and eosinophils; natural killer cell cytolytic activity and spontaneous lymphoblastogenesis were also enhanced. In contrast, other indices of immune cell functions were reduced, including T cell-dependent antibody production, as well as phagocytosis and oxidative
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burst activities by granulocytes and monocytes. Since the neuroendocrine system that mediates the influence of day length on seasonal reproductive physiology involves the circadian pineal melatonin rhythm, the major focus of the proposal is to test the hypothesis that the pineal melatonin rhythm mediates photoperiod control of innate and adaptive immune system functions. An integrative approach to this hypothesis is based upon assessment of the magnitude and tempo of immune responses to changes in day length. The possibility that daily rhythms in immune cell functions are driven by changes in specific immunophenotypes will be addressed. To determine whether photoperiod effects on immune functions depend on the melatonin rhythm, hamsters will be pinealectomized and administered timed treatments to replace specific aspects of the melatonin rhythm. Measures were developed for this seasonal animal model to assess multiple immune system indices by highly sensitive and sophisticated flow cytometry methods for phenotyping, cell-mediated cytolysis, antibody isotype switching and phagocytic cell function. Regulation of specific immune system parameters by photoperiod may potentiate disease resistance, promote adaptations to seasonal challenges in the environment, and provide the foundation to address the therapeutic value of such treatments to selectively modulate immune function in other species. Fundamental knowledge of circadian time keeping and neuroimmune interactions may lead to development of novel approaches to maximize immune responsiveness or slow the deterioration of immune system function that is associated with immunodeficiency, autoimmunity, sleep disturbances, aging and seasonality in behavioral disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NIMH COLLABORATIVE DEPRESSION STUDY Principal Investigator & Institution: Coryell, William H.; Professor; Psychiatry; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-JUL-1977; Project End 31-MAY-2004 Summary: (Applicant's Abstract): Results from the NIMH Collaborative Depression Study (CDS) have clearly show that affective illness is a lifetime disorder and the longterm observation will be necessary to adequately characterize it. Follow-up so far shows high rates of recovery, recurrence, changes in inter-episode psychosocial functioning, comorbid alcoholism, minor affective syndromes, mortality and suicide. Recoveries are likely even after lengthy periods of illness, the distribution of episode length is relatively constant and unimpaired psychosocial functioning appears to require a complete absence of symptoms. It is essential that this follow-up continue, especially as the probands enter their sixth and seventh decades of life. This application seeks to extend the prospective annual follow-up of the CDS proband sample to at least 22 years for all subjects. The general aim in doing this is to describe the long-term course of the affective disorders. The specific aims are to collect data that will describe more fully: 1) the cumulative probability of recovery and recurrence, and the changes in polarity, severity, and episode and cycle lengths; 2) the predictors of long-term course and diagnostic change; 3) the eventual level of psychosocial functioning, physical health likelihood of suicide and mental health services utilization; 4) the influence of naturalistically applied treatments as a mediating variable; 5) the course and outcomes of subsyndromal states of affective disorders; and 6) the long-term inter-relationships of the affective disorders and other chronic and recurrent disorders such as alcohol and drug us disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NIMH COLLABORATIVE DEPRESSION STUDY Principal Investigator & Institution: Endicott, Jean J.; Professor of Clinical Psychology; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-FEB-1991; Project End 30-JUN-2004 Summary: Results from the NIMH Collaborative Depression Study (CDS) have clearly shown that affective illness is a lifetime disorder and that long-term observation will be necessary to adequately characterize it. Follow-up so far shows high rates of recovery, recurrence, changes in inter- episode psychosocial functioning, co-morbid alcoholism, minor affective syndromes, mortality and suicide. Recoveries are likely even after lengthy periods of illness, the distribution of episode length is relatively constant and unimpaired psychosocial functioning appears to require a complete absence of symptoms. It is essential that this follow-up continue, especially as the probands enter their sixth an seventh decades of life. This application seeks to extend the prospective annual follow-up of the CDS proband sample to at least 22 years of for all subjects. The general aim in doing this is to describe the long-term course of the affective disorders. The specific aims are to collect data that will describe more fully: 1.) the cumulative probability of recovery and recurrence, and the changes in polarity, severity, and episode and cycle lengths; 2.) the predictors of long-term course and diagnostic change; 3.) the eventual level of psychosocial functioning, physical health, likelihood of suicide and mental health service utilization; 4.) the influence of naturalistically applied treatments as a mediating variable; 5.) the course and outcomes of subsyndromal states of affective disorders; and 6.) the long-term inter-relationships of the affective disorders and other chronic and recurrent disorders such as alcohol and drug use disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHILDREN
ONE-SESSION
TREATMENT
FOR
SPECIFIC
PHOBIAS
IN
Principal Investigator & Institution: Ollendick, Thomas H.; Professor; Psychology; Virginia Polytechnic Inst and St Univ 460 Turner Street, Suite 306 Blacksburg, Va 24060 Timing: Fiscal Year 2002; Project Start 15-MAY-2001; Project End 30-APR-2005 Summary: The overall aim of the proposed investigation is to examine the efficacy of a cognitive-behavioral treatment (One- Session Treatment; Ost, 1989a) in reducing symptoms and sequellae of Specific Phobia in children and adolescents. Findings indicate that clinically significant specific phobias are present in approximately 5 percent of children in community samples and in about 15 percent to 20 percent of children presenting at phobic and anxiety disorders clinics. Furthermore, findings indicate that clinic-referred children who present with specific phobias in specialized clinics are likely to be co-morbid with other anxiety disorders, affective disorders, and disruptive behavior disorders. For many children, the phobia results in considerable academic, social, and personal distress, as well as interference in day-to-day activities. Phobias may persist for a lifetime. One-Session Treatment has been found to be a rapid and effective treatment for adults with phobic disorders. Surprisingly, this treatment has not been evaluated in countries other than Sweden, and its utility in the treatment of childhood phobias has not been examined. A systematic evaluation of its efficacy in Virginia and Sweden is proposed. Specific aims are threefold: 1) to evaluate the efficacy of One- Session Treatment with children in a controlled, randomized trial; 2) to undertake systematic evaluation of its efficacy in Virginia and Sweden; and 3) to explore predictors of treatment outcome, including parental psychopathology, over-involved
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parenting styles, and child co-morbidity. One-hundred-and twenty children in Virginia (60 boys, 60 girls) and 120 children in Sweden (60 boys, 60 girls) between 8 and 14 years of age and meeting DSM-IV criteria for a primary diagnosis of specific phobia will be randomly assigned to One-Session Treatment, Education/Support, or Waitlist Control conditions. Following the waitlist period, children still meeting criteria for a Specific Phobia in the waitlist control and the Education/Support conditions will be provided One-Session Treatment. Depending upon remission and attrition rates, this strategy will permit a relatively robust examination of the efficacy of One-Session Treatment, its systematic evaluation in Sweden and Virginia, and the predictors of treatment outcome. As such, the present investigation will build on strengths in the current literature by using cognitive-behavioral procedures that have some, albeit limited, support in the treatment of phobic children (Ollendick and King, 1998, in press). At the same time, it will address shortcomings in extant studies by examining a treatment not studied heretofore with children (but with considerable support for its use with adults) and by examining the role of parental psychopathology, parental over- protectiveness, and child co-morbidity in moderating treatment outcome. Effectiveness studies in "realworld" clinical settings (Hoagwood, Hibbs, Brent, and Jensen, 1995) await results of this more laboratory-based controlled trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OUTCOMES OF PEDIATRIC AFFECTIVE DISORDERS Principal Investigator & Institution: Birmaher, Boris; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: SUBPROJECT ABSTRACT NOT PROVIDED Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOLOGICAL GAMBLING--COURSES, CONSEQUENCES, AND CAUSES Principal Investigator & Institution: Eisen, Seth A.; Professor of Internal Medicine; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: The broad goals of this proposal are to examine the courses, consequences, and causes of problem and pathological gambling (P&PG) in a sample of 1,200 middleaged male-male monozygotic and dizygotic twin pair members (2,400 individuals) of the Vietnam Era Twin (VET) Registry. The project has four specific aims: (1) characterize the longitudinal course of P&PG by examining the prevalence and predictors of initiation, progression, persistence, and recovery of P&PG from 1992 to 2001; (2) explore the nosology of P&PG by examining the evidence for a continuity model of P&PG, empirically derived P&PG subtypes, and classic P&PG subtypes described in the P&PG literature; (3) assess the consequences associated 'with P&PG and different P&PG subtypes on health-related quality-of-life, emotional well-being, social adjustment, and socioeconomic status; (4) compare alternate etiological models of P&PG by examining the genetic and environmental overlap in the causes of P&PG with other addictive disorders, disorders of behavioral undercontrol, and disorders of negative affectivity. The twin sample, enriched for individuals at increased risk for developing symptoms of P&PG, has been identified from a cohort of 3,359 twin pairs 'who completed an interview that assessed P&PG in 1992. A broad range of relevant demographic and psychiatric data has already been collected by studies performed in 1987, 1990, and 1992.
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In the proposed project, a telephone interview will be conducted by the Institute for Survey Research of Temple University to update and expand information about access to gambling, gambling involvement, recent and lifetime symptoms of DSM-III-R and DSM-IV pathological gambling disorder, alcohol abuse and dependence, affective disorders, post-traumatic stress disorder, and antisocial personality disorder. Data will be analyzed using standard epidemiologic (Aim 1), latent class analysis (Aim 2), cotwincontrol (Aim 3) and biometrical genetic techniques (Aim 4). Our twin design overcomes a major problem for researchers wishing to perform a population-based study of P&PG by providing a method to efficiently identity individuals who are at increased risk for developing P&PG symptoms. This, combined with the extensive information previously collected from VET Registry members, our large sample size, and the unique analytical flexibility provided by data derived from twins, will permit us to successfully address the project's aims. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTION OF GERATRIC DEPRESSION Principal Investigator & Institution: Alexopoulos, George S.; Professor and Vice Chair; Psychiatry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-MAY-1994; Project End 31-JAN-2004 Summary: As an increasing number of elderly are treated for depression, systematic data are crucially necessary to help guide continued clinical care. This study will: 1) determine clinical and neuroradiographic predictors of early relapse and recurrence; 2) test the efficacy and safety of maintenance nortriptyline (NT); and 3) identify those plasma levels of 10- OH-NT (an NT metabolite) associated with low protective power against relapse and recurrence and/or with cardiovascular and cognitive side effects. Thus, the study is expected to help clinicians identify patients in greatest need for longterm drug treatment, assess the risk-benefit ratio of preventive NT therapy, and refine guidelines for the NT prescription. Subjects will be 125 elderly patients who have recovered from an episode of non-delusional major depression after acute treatment with NT (50% of subjects will have mild to moderate dementia and the remainder will not have cognitive impairment). Upon completion of a continuation phase (4 months after recovery) with NT at plasma levels of 80-120 ng/ml, subjects will be randomly assigned to NT or placebo maintenance (after 4 months from recovery) gradually over 10 weeks. The principal methods of data analysis will be generalized regression models for repeated measures and survival analysis. We have previously characterized the heterogeneity of geriatric depression, tested its response to acute pharmacologic treatments, and described its course under naturalistic conditions. This pioneering controlled-treatment study therefore represents a logical next step. While well aware of the methodological problems and confounds posed by studying a "sick and old" population, we bring to this project a committed and experienced research team, the support and structure of a Developing CRC specifically targeted to study the outcomes of geriatric affective disorders, and our established recruitment procedures in a remarkably large psychiatric inpatient/outpatient geriatric service. Accordingly, we are well positioned to meet the challenges inherent in this difficult but important area of research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PRODUCTION AND SCREENING OF MOUSE NEUROLOGICAL MUTATIONS Principal Investigator & Institution: Frankel, Wayne N.; Senior Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2002; Project Start 18-SEP-2000; Project End 31-AUG-2005 Summary: The mouse has emerged as the premiere experimental mammal because of its power for analyzing known genes and for the variety of new heritable phenotypic variants available for study. Mouse genetics has made significant contributions to several complex areas of mammalian biology, but the central nervous system (CNS) is a challenge as its components are physically inter connected throughout life in complex networks and yet retain a great degree of plasticity. Recent progress in gene cloning, expression and gene targeting promise to further our knowledge, but genotype-based approaches alone are insufficient due to the CNS' interrelated and often redundant functions. The next step is to systematically collect a large number of mouse mutants for specific neurological disorders and mechanisms. Large-scale mutagenesis offers a progressive resource towards this end. We will establish a Neuroscience Mutagenesis Facility at The Jackson Laboratory to produce new mouse models for human neurological disease. We will generate new mutations using ENU in both genome-wide and specific genomic region screens, in both normal C57BL/6J mice and sensitized mutants. We will also implement new mutagenesis technologies that rely on treating embryonic stem cells with mutagens other than ENU, to make screens more efficient. Our broad phenotypic scope includes high-throughput screens in major focus areas of motor function, epilepsy, neural obesity, hearing, vision and learning, and we will work with collaborators or enable Visiting Investigators to develop high-throughput screens in areas such as ingestive behaviors, affective disorders, sensorimotor gating, substance abuse and anxiety. We will implement a distribution and sharing plan that provides the scientific community with widespread access to pathogen- free mice, sperm and embryos, and a database for experimental results as well as Internet access to all information generated and protocols used. We aim to place new neurological models per year into hands of the scientific community, and to preserve several hundred additional potential models for those who wish to pursue them. Our goal is to maximize the number of neurological mutants that become important research tools. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PSYCHOLOGICAL RESEARCH ON SCHIZOPHRENIC CONDITIONS Principal Investigator & Institution: Nuechterlein, Keith H.; Professor; Psychology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-JUL-1976; Project End 30-JUN-2004 Summary: This training program is designed to train investigators in the basic skills needed to conduct clinical research with individuals who have schizophrenia or major affective disorders. The program emphasizes four major research domains that are consistent with the research directions of the participating faculty: (1) psychosocial factors in the course and outcome of schizophrenia and major affective disorders and their relevance to treatment response, (2) neurocognitive and psychophysiological deficits in patients with schizophrenia and major affective disorders and in their relatives and the contributions of these deficits to functional impairment, psychiatric symptoms, and rehabilitative response, (3) improved psychological rehabilitative interventions for schizophrenia and major affective disorders, and (4) improved
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psychopharmacological interventions for schizophrenia and major affective disorders. The program has four components: (1) skill training in the systematic assessment of symptoms and functional outcome in these severe mental illnesses, (2) participation in an ongoing weekly core research seminar, (3) development by trainees of an individual research project supervised by program mentors, and (4) academic course work. There are two related training programs, one for predoctoral trainees who are students admitted to the Ph.D. program in psychology at UCLA and a second for postdoctoral trainees. The latter program is available to persons who have received a Ph.D. in psychology or an M.D. followed by a psychiatric residency. Typically, half of the postdoctoral trainees are Ph.D.'s and half are M.D.'s. Trainees are assigned to primary and secondary mentors who supervise their training activities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGIONAL PRIMATE RESEARCH CENTER Principal Investigator & Institution: Dorsa, Daniel; Professor; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 01-MAY-1978; Project End 30-APR-2004 Summary: This 5-year renewal for Grant P51 RR00163 includes requests for support of the Center's AIDS-related research programs and improvement and Modernization projects. The application reflects the significant changes that have occurred at the Center since it was last reviewed in 1994, as well as our plans for expanding the use of nonhuman primates (NHPs) as models for human disease. The aims of this application are to: 1) provide the infrastructure support necessary to conduct advanced research for which NHPs are uniquely suited for solutions of human health problems; 2) enhance the Center's resources (scientific expertise, laboratories, animal services and equipment so as to serve as a regional, national and international resource research through support of our unique programs to develop genetically identical animals, to produce SPF animals free of viruses such as herpes B, and to define animal parentage and genotype; and 4) build new research programs utilizing NHPs in functional genomics, aging, gene therapy and vaccine development. These aims facilitate the research programs housed n the research divisions. Research in the Division of Neuroscience focuses n neuroendocrinology, the effects of aging on brain function, etiology of stress-related pathologies and affective disorders, growth factors and lung development, drug addiction and depression, dietary components is involved in research that includes molecular aspects of CMV latency, blood brain barrier dysfunction in AIDS, studies of SIV neurotropism, effects of altered cell tropism on the pathologic potential of type D retrovirus, the role of T and B cell responses in retrovirus infections, an the role of homocysteine in atherosclerosis. The Division of Reproductive Sciences houses projects including nuclear embryos transfer, causes of premature labor, neuroendocrine regulation of the menstrual cycle and prolactin secretion, the role of sex steroids in ovarian function and vascular occlusion, hormonal control of the reproductive tract, and the cell biology of fertilization. Support services for the intra- and extramural research programs are provided by three services divisions. The Division of Administration oversees all of the operations of the Center. The Division of Animal Resources is responsible for the veterinarian and animal care that supports the health and well being of our animal population. The Division of Information Technology and Engineering oversees all of the communications and bioengineering services of the Center. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGION-SPECIFIC, INDUCIBLE AXONAL TRACT-TRACING IN BRAIN Principal Investigator & Institution: Anderson, David J.; None; California Institute of Technology Mail Code 201-15 Pasadena, Ca 91125 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): The objective of this proposal is to develop improved methods for inducible genetic marking, mapping and manipulation of specific brain regions or neuronal subpopulations in the mammalian brain. In Aim I, methods for isolating brain region-restricted and cell type-specific genes utilizing laser-capture microdissection together with DNA microarray analysis will be developed and optimized. These experiments will focus on identifying markers for limbic system structures, including the amygdala, BNST, hypothalamus and lateral septum. In Aim II, the utility and efficacy of different genetically encoded primary axonal markers will be compared, and genetically encoded, inducible anterograde and retrograde transneuronal tracers will be developed and tested in vivo. Proof-of-principle will first be established in the PNS using a well-defined model system, and then extended to the CNS. Aim III encompasses the development and in vivo testing of two alternative combinatorial, positive coincidence-detection systems for achieving region- or cell subtype-specific control of heterologous gene expression (e.g., neuronal tracers or silencers), without having to identify specific transcriptional enhancer elements for such regions or cells. One method is based on inducible site-specific DNA recombination. The other method is based on a "two-hybrid" system for inducible transcriptional activation. In both cases, expression of the reporter/tracer gene is induced only in cell populations in which the expression of two different "co-driver" genes overlaps. This "Venn diagram" approach allows different pairwise combinations of driver genes to be used to express reporter or tracer genes in only a restricted subset of the regions in which each individual co-driver gene is expressed. These methods will initially be developed, tested and optimized using highly specific genes with known overlapping patterns of expression in specific subsets of pain-sensing primary sensory neurons. In Aim IV, based on the outcome of Aim III, either the recombination-based or two-hybrid system will be selected for extension to the CNS, using an overlapping pair(s) of limbic systemspecific genes identified in Aim I. In addition, the recombination-based system will be extended to permit activity-dependent trans-neuronal tracing of neurons expressing a specific marker gene. The combination of new limbic system-specific molecular markers and genetically encoded tract-tracing and neuronal ablation methods should improve our understanding of the functional neuroanatomy of emotion and affective disorders such as anxiety and depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF 5HT1A RECEPTOR FUNCTION Principal Investigator & Institution: Clarke, William P.; Associate Professor; Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: (from applicant's abstract): The serotonin alpha (5-HTIalpha) receptor system plays a central role in the control of serotonergic neurotransmission and, as such, features prominently in many behaviors and physiological functions. In addition. the regulation of this receptor and its effector mechanisms has been the focus of intense interest because of their importance in the therapeutic action of anxiolytic and
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antidepressant drugs. For example, numerous basic and clinical investigations are being carried out to test the theory that a progressive decrease in the responsiveness (desensitization) of 5-HT1alpha autoreceptors is necessary for the therapeutic effectiveness in depression of selective serotonin reuptake inhibitors (SSRIs). Although we have learned a considerable amount about the cellular signal transduction pathways coupled to the 5-HT1alpha receptor, we know very little about how the function of this important receptor system is regulated. An understanding of cellular factors that regulate 5-HT1alpha receptor signaling may provide insight into the etiology of affective disorders, help us to understand the mechansism of action of drugs such as SSRIs, and possibly aid in the development of new drugs and/or therapeutic strategies. Our goal is to study regulation of the responsiveness of the 5-HT1alpha receptor system by activation of two major cellular signaling cascades (phospholipases C {PLC} and alpha2 {PLalpha2}). Experiments with clonal cell lines are designed to delineate the mechanisms by which the PLC and PLA2 signaling cascades regulate 5-HT1alpha receptor system responsiveness. Through the use of selective inhibitors, antisense strategies, receptor phosphorylation and site-directed mutagenesis studies, we will identify the components of the PLC and Plalpha2 signaling cascades that differentially regulate 5-HT1alpha receptor function and determine if the 5-HTIA receptor itself is the target for their actions. The generation of stable cell lines that express cloned G-proteingated inward rectifier channels (GIRKs) will permit regulation of both responses coupled to the 5-HT1alpha receptor (inhibition of adenylyl cyclase and increase in K+ conductance) to be studied in the same cells. The physiological relevance of effects elicted by activation of phospholipase signaling cascades will be probed with experiments using rat brain slices containing the dorsal raphe nucleus and hippocampus as models for pre-and postsynaptic 5-HT I A receptors, respectively. Components of the phospholipase cascades responsible for changes in functon will be identified using intracellular deliverv of selective inhibitors with whole cell recording techniques. The integration of brain slice preparations and clonal cell systems Will pernift rigorous study of the regulation of 5-HTI A receptor function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF DORSAL AND MEDIAN RAPHE NEURAL ACTIVITY Principal Investigator & Institution: Beck, Sheryl G.; Associate Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: The 5-hydroxytryptamine (5-HT, serotonin) neurotransmitter system maintains many homeostatic functions; it has also been implicated in the etiology and treatment of neurological and affective disorders, such as depression, anxiety, obesity, anorexia, and Alzheimer's disease. One of the PI's primary areas of interest is to understand the cellular mechanisms underlying the etiology and treatment of affective disorders. In the past the PI has focused on characterizing normal hippocampal neural activity and the changes in that normal physiology by chronic treatment with antidepressants or the "stress" hormone corticosterone. The working hypothesis is that the actions of the drugs or mechanism underlying pathological status is due to differential modification of cellular properties or components of the 5-HT neurotransmitter system. In support of this hypothesis chronic treatment with corticosterone or fluoxetine was found to alter hippocampal pyramidal cell neural activity by changing basic cell properties as well as postsynaptic 5-HT receptor mediated responses. As predicted, the nature of the modulatory effects of the chronic
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treatments are not the same in the CA1 and CA3 subfields. Another likely target for differential modifications in the 5-HT neurotransmitters system is at the level of the 5HT cell bodies. The median (MR) and dorsal raphe (DR) are the principal sites where 5HT cell bodies are located. These two nuclei provide the majority of the 5-HT innervation of the forebrain. Even though they share many of the same features, differences between these two nuclei have been identified. The goal of the experiments outlined in this application is to set up a raphe brain slice preparation maintained in vitro to delineate both the common and disparate features of MR and DR cell neural activity. The development of the raphe brain slice will expand the depth of the PIs research focus. The use of the raphe (5-HT cell body) and hippocampal (5-HT fiber projection area) slice preparations in conjunction will provide a mechanism for a more systematic approach to the analysis of the normal physiology and pathophysiological processes of the 5-HT neurotransmitter system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF AMYGDALA SYSTEMS IN ASSOCIATIVE LEARNING Principal Investigator & Institution: Holland, Peter C.; Associate Professor; Psychological & Brain Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-AUG-1995; Project End 31-JUL-2006 Summary: Previous research in this project investigated behavioral and neural bases of two changes in attentional processing in associative learning mediated by the amygdala central nucleus (CN): the potentiation of orienting to conditioned stimuli (CSs) paired with food unconditioned stimuli (USs), and the enhancement of CS associability that occurs when contingencies between the CS and other events are altered. The proposed research extends that work by investigating the relation of these attentional changes to other aspects of attention, and by continuing systems analysis of these functions. The project will use a variety of behavioral procedures, asymmetrical lesion techniques, transient, reversible inactivation procedures, and electrophysiological recording methods, with rat subjects, to address four specific aims. The first aim is to distinguish between CN-systems effects on the acquisition and expression of conditioned orienting and associability changes. The second aim is to examine cortical neural encoding of attentional changes in associative learning that depend on CN and its regulation of the basal forebrain cholinergic system. The third aim is to examine the roles of CN attentional systems in performance of selective attention tasks. The fourth aim is to examine cortical activity during performance of selective attention tasks. This research may provide a basis for new insights into cognitive functions of the amygdala, as well as the integration of cognitive and emotional function. In addition, it may have wide clinical implications, because the neural systems to be studied are involved in a number of pathological conditions, for example, Alzheimer's disease (learning and attention deficits often signal the onset of more complete dementia), schizophrenia (deficits in focusing attention on relevant events and ignoring extraneous events), and various affective disorders (inappropriate assignment of motivational value to life events). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF BDNF IN THE PHOTIC CONTROL OF CIRCADIAN RHYTHMS Principal Investigator & Institution: Earnest, David J.; Associate Professor; Human Anatomy and Medical Neurobiology; Texas A&M University Health Science Ctr College Station, Tx 778433578
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Timing: Fiscal Year 2002; Project Start 10-FEB-2001; Project End 31-JAN-2004 Summary: The broad objective of the proposed research is to gain insight into a new area in mammalian circadian biology: the role of neurotrophins in SCN cicadian function. Recent findings indicate that the neurotrophin, brain- derived neurotrophic factor (BDNF0, enhances neuronal signaling in other brain regions. Our central hypothesis is that BDNF plays a comparable role in the SCN by regulating photic input and its effects on the circadian peacemaker mechanism. To address this hypothesis, the proposed studies will determine: whether retinohypothalamic tract (RHT) fibers innervating the SCN or cells receiving RHT input express TrkB tyrosine kinase receptors, the cognate receptor for BDNF, using imunochistochemical and tract tracing methods and whether alterations in BDNF and TrkB expression or inhibition of BDNF action in the rodent SCN produce predictable changes in the phase-shifting effect of light on the circadian rhythm of wheel-running behavior. Experiments will be conducted to determine whether: 1) localization of TrkB receptor immuno reactivity in the ventral SCN by electron and/or light microscopy is observed on RHT fibers or on cells receiving RHT innervation and is diminished after blinding; 2) infusion of exogenous BDNF into the SCN enables light to induce phase shifts during the subjective day when the cicadian peacemaker is normally insensitive to light; 3) transgenic deficits in BDNF and TrkB expression in heterozygous knock-out mice(bdnf+/- and trkB+/-) abate the phase-shifting effect of light during the subjective night; 4) infusion of the tyrosine kinase inhibitor, K252a, into the phase-shifting effect of light; 5) administration of TrkB-IgG fusion protein, which scavenges endogenous BDNF, similarly blocks lightinduced phase shifts. These studies will purvey critical support of the role of BDNF in regulating the effects of light on the SCN peacemaker. In view of it's potential to advance our knowledge of how circadian rhythms are regulated by light in a timedependent manner, this research has applied relevance for developing strategies in the treatment, diagnosis and understanding of disorders in human mental health and performance that result from internal desynchronization of body process, including affective disorders, dementia and physiological decline during aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF NEURAL PLASTICITY IN PUBERTY Principal Investigator & Institution: Plant, Tony M.; Professor; Cell Biology and Physiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-APR-1980; Project End 30-JUN-2004 Summary: The long term goal of this project is to understand the mechanisms that are responsible for triggering the onset of puberty in our own species. In man and other higher primates, the hypothalamic GnRH pulse generating system, which, in the adult, provides the principal drive to the pituitary-gonadal axis, is functional during infancy. During prepubertal development, however, activity of the neuroendocrine axis governing primate gonadal function is arrested and held in a protracted state of quiescence by non-gonadal restraint of the hypothalamic GnRH pulse generator. Puberty in primates is thus triggered by a reawakening of GnRH pulse generator activity. Such a pubertal control system appears unique to man, apes and monkeys. Although puberty represents a major landmark in human development that is associated with dramatic changes in behavior, cognitive function, outlook, and, in some cases, with the onset of affective disorders, little is known about the fundamental neurobiology underlying the onset of this developmental stage. This problem will be addressed in the present proposal using the agonadal male rhesus monkey, a
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representative higher primate, as an experimental paradigm. The following Specific Aims Will be addressed: Specific Aim 1 - To test the hypothesis that an increase in NPY tone in the mediobasal hypothalamus (MBH) is a critical component of the restraint that is imposed upon pulsatile GnRH release during prepubertal development; Specific Aim 2 - To determine the phenotype of the synaptic input to GnRH perikarya that is lost during the transition from the juvenile to the pubertal state; Specific Aim 3 - To determine whether structural remodeling of the GnRH network at the level of the median eminence, in addition to that at the cell body and dendrites, occurs in association with the onset of the pubertal reaugmentation of pulsatile GnRH release; Specific Aim 4 - To determine whether inhibition of structural remodeling within the GnRH neuronal network at the end of the prepubertal phase of development prevents the onset of puberty. RNAse protection assays and in situ hybridization will be used to track developmental changes in NPY gene expression. Protein levels will be determined by Western blotting. The action of NPY in the MBH will be blocked using NPY receptor antagonists or antibodies administered intracerebroventricularly. Synthesis of NPY will be blocked with antisense oligodeoxynucleotides. Structural remodeling in the hypothalamus will be studied using both the light and electron microscope. Standard pre-embedding and post-embedding immunocytochemical procedures will be applied to quantitate changes in synaptic input and glial ensheathment of GnRH perikarya, dendrites and axonal terminals. Attempts will be made to block plasticity in the GnRH network of the pubertal hypothalamus by injecting or overexpressing endoneuraminidase in this region of the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SECRETED SCN FACTORS AND CIRCADIAN LOCOMOTOR ACTIVITY Principal Investigator & Institution: Weitz, Charles J.; Associate Professor; Neurobiology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): The circadian clock in the suprachiasmatic nucleus (SCN) of the brain drives daily cycles of behavioral activity by rhythmically releasing secreted factors that act on receptors near the 3rd ventricle, through either a paracrine or synaptic mechanism. Current evidence indicates that the SCN has a dual action, with activating factors promoting locomotor activity at one phase and inhibitory factors blocking activity at another. The identity of these factors is unknown. The aim of this proposal is identify SCN factors regulating locomotor activity, both those promoting behavioral activity and those inhibiting it. The strategy for doing so is divided into two parts. The first is aimed at generating, to the extent practical, a comprehensive collection of peptide and protein factors secreted by SCN cells by means of a secretion trap genetic screen in yeast. The second is the systematic evaluation of secreted SCN factors for a role in locomotor activity in hamsters, as predicted by the hypothesis. Known factors and those newly identified in the secretion trap will be tested for an effect on locomotor activity after chronic infusion into the 3rd ventricle. Any found to do so would be studied further to determine if they satisfy additional predictions for physiological involvement in the circadian regulation of locomotor activity. The discovery of these secreted SCN factors would make possible the identification of specific molecular pathways and neuronal circuits underlying circadian locomotor activity, about which virtually nothing is known. Knowledge of factors and receptors in an endogenous system mediating daily activity cycles might prove of great value in the treatment of
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neurological, sleep, or affective disorders in which cycles of rest and activity are disturbed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEX DIFFERENCES IN HYPOTHALAMO-PITUITARY-ADRENAL AXIS Principal Investigator & Institution: Handa, Robert J.; Professor; Anatomy and Neurobiology; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2002; Project Start 15-JAN-2001; Project End 31-DEC-2003 Summary: (applicant's abstract): The focus of this proposal is to determine the mechanisms by which estrogen and testosterone act to influence peptide containing neurons in the paraventricular nucleus of the hypothalamus (PVN) that are involved in regulating endocrine responses to stress. Females exhibit a more robust adrenocorticotropic hormone (ACTH) and corticosterone (CORT) response to stress when compared to males. This sex difference arises as a result of circulating adult hormone levels. Estrogen augments and testosterone suppresses stress related ACTH and CORT secretion. A novel form of estrogen receptor, termed beta (ER-beta), has been found in magnocellular and parvocellular neurons of the PVN, whereas the classically described alpha form is not present. ER-beta-containing neurons are uniquely distributed and may allow transduction of the estrogen signal to neuropeptide genes. In contrast androgen receptors (AR) are not found in neuroendocrine neurons of the PVN, but are found in neurons in the medial preoptic area (MPOA) and bed nucleus of the stria terminalis (BnST) that project to the PVN. This proposal describes studies to test the hypothesis that estrogen acts directly upon corticotropin releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXY) neurons in the PVN, whereas androgen acts indirectly by modulating GABAergic neurons in the MPOA and BnST that project to the PVN. 5 specific aims are proposed: 1) to determine if the local application of estrogen or testosterone to the PVN alters stress responsive hormone secretion, neuropeptide mRNA, protein content and heteronuclear RNA levels in the PVN. 2) To determine if androgen receptor or estrogen receptor act upon nucleotide sequences in the CRH, AVP or OXY gene promoters. 3) To determine if AR positive, GABA positive neurons in the BnST project to the PVN. 4) To determine if estrogen or androgen modulate glucocorticoid receptor mediated negative feedback regulation of neuropeptide genes in the PVN. 5) To determine if ER-beta or AR interact with glucocorticoid receptor to regulate transcription of reporter genes downstream of the CRH, AVP or OXY gene promoters. Since a dysregulation of stress-responsive hormone secretion is a characteristic of affective disorders, and these are more prevalent in females than males, the long-term goals of this project are to define the role played by estrogen and androgen in the pathology of affective disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SIGNAL RECOVERY IN SUSCEPTIBILITY BASED FUNCTIONAL MRI Principal Investigator & Institution: Noll, Douglas C.; Associate Professor; Bioengineering; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): This project will develop, analyze and evaluate methods that enable the efficient use of functional Magnetic Resonance Imaging (MRI)
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using blood oxygenation level dependent (BOLD) contrast in regions of the brain that are proximal to tissue interfaces with air or bone. This project is motivated by the large signal voids and image distortions caused by magnetic susceptibility differences between tissue and air or bone. These artifacts are ubiquitous in fMRI for many inferior brain structures, for example, orbito-frontal cortex, inferior and medial temporal lobes, brain stem structures and the frontal pole. This project is further motivated by a trend in fh4RI towards using higher magnetic field systems, which improves sensitivity in many parts of the brain, but also exacerbates the artifacts. Many current techniques to remove these distortions have a large cost in terms of temporal resolution or sensitivity for detection of activation. As part of the research plan, methods will be developed that reduce the susceptibility-induced artifact but preserve the speed, robustness to motion and physiological noise, and contrast sensitivity of standard single- shot fMRI techniques. Unlike many other approaches, we will address both in-plane and throughplane sources of artifact. The methods under investigation include three-dimensional tailored excitation pulses and asymmetric spin-echo acquisitions for reduction of signal voids, and iterative image reconstruction methods and parallel receiver coil imaging for reduction of imaging distortions. These methods will be evaluated with respect to effectiveness in reducing susceptibility-induced artifact, reliability of activation in visual and motor areas, sensitivity to activation in the amygdala structure near the paranasal sinus, and temporal accuracy. Success in this project will lead to valuable new fMRI methods capable of probing all major brain structures in a manner that is sensitive to functional activation and robust to artifacts. The methods will be fast and sensitive to BOLD contrast, allowing common fMRI techniques, like event-related studies, to be used over the entire brain. In addition, they will dramatically aid in the study of brain regions implicated in a wide variety of neurological, psychiatric, and behavioral disorders, including pain disorders, affective disorders, schizophrenia, and alcohol and drug abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP DEPRIVATION, EEG, & FUNCTIONAL MRI IN DEPRESSION Principal Investigator & Institution: Clark, Camellia P.; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002; Project Start 20-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from applicant's abstract): The objective of this 5-year Mentored Clinical Scientist Development Award for Cametlia Clark, M.D. is to develop the candidate's expertise in functional magnetic resonance imaging (MRI) while building on her previous skills in neuroimaging and sleep research. This goal will be accomplished through a carefully designed training plan involving didactic courses and mentorship by experts (at and outside UCSD) in basic neuroscience, structural MRI, functional MRI (fMRI) physics, sleep and affective disorders research, and statistics as well as intensive instruction in fMRI research in a setting featuring state-of-the-art scanners, innovative pulse sequences (particularly perfusion-weighted), and the first fMRI studies utilizing sleep deprivation (SD) to study cognitive function in normal subjects (published recently in Nature and NeuroReport. This training program will enable Dr. Clark to complete the transition to independent investigator and provide the foundation for a long-term research program utilizing fMRI and polysomnography to investigate brain function in affective disorders. The research plan utilizes one night of partial SD (PSD), an excellent model of antidepressant treatment which is fast-acting, and does not require medications. The applicants hypothesize: I) depressed responders' baseline perfusion signal intensity in the ventral anterior cingulate (BA 25 and ventral 24) / medial
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prefrontal cortical (BA 32) areas will be greater than that of nonresponders and controls; 2) following PSD, perfusion in the ventral anterior cingulate (BA 25 and ventral 24) / medial prefrontal cortical (BA 32 and 10) areas will significantly decrease in responders only. The applicants will also look for between-groups and within-groups differences in other regions where functional abnormalities have been reported in depression, including (but not limited to) dorsal anterior cingulate, dorsolateral prefrontal cortices, medial frontal cortices, amygdala, hippocampus, thalamus, and basal ganglia. Finally, the applicants will look for possible between-groups structural MRJ differences, which could potentially confound fMRI analyses. FMRI perfusion data will be analyzed by the analysis of variance algorithm in AFNI (Analysis of Functional Neural Images) software. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP/AROUSAL IN ADOLESCENCE: PATHWAYS TO ALCOHOL ABUSE Principal Investigator & Institution: Dahl, Ronald E.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 30-APR-2005 Summary: The program of research described in this application uses measures of sleep, arousal, pubertal timing, and family history of alcohol dependence to examine developmental trajectories from childhood affective disorders to adolescent alcohol problems. It is hypothesized that an altered pattern of sleep/arousal regulation in children with anxiety and affective disorders will predict elevated rates of alcohol abuse/dependence during clinical follow-up across late-adolescence and into early adulthood. This work builds upon an existing psychobiologic study where a broad range of biological, clinical, and family history data have been obtained in samples of children with depression, anxiety disorders, controls with high family loading for affective disorders, and low-risk controls. The investigations described in the current proposal will add a new set of measures and analyses to that existing study, in order to address key questions relevant to adolescent development, sleep and arousal regulation, and pathways to alcohol abuse/dependence into early adulthood. These new measures will include multi variate EEG analyses applied to previously collected sleep data. Subjects (n=367) had psychobiologic measures obtained at ages 8-14 years of age and will be followed longitudinally for alcohol use problems developing across adolescence. The study will also examine gender differences and the influence of early pubertal timing on the development of affective and alcohol disorders. The study will obtain new biologic data on an informative sub-sample of subjects (n=90) studied in later pubertal maturation (ages 14-21). The long-term goal of this research is to understand maturational changes in sleep, arousal, and affect regulation across adolescence relevant to the development of alcohol abuse and dependence. Advancing knowledge in these areas may lead to more effective early intervention strategies (prevention or early treatment) for alcohol abuse/dependence in targeted high-risk populations of youth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SOCIAL COMPARISON--DEVELOPMENT AND FUNCTIONAL ANALYSES Principal Investigator & Institution: Ruble, Diane N.; Professor; Psychology; New York University 15 Washington Place New York, Ny 10003 Timing: Fiscal Year 2002; Project Start 10-MAY-1990; Project End 31-MAR-2004
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Summary: This research analyzes changes in individuals' social orientations during periods of transition across the lifespan. It is suggested that changes in knowledge during the course of a transition influence how an individual approaches and responds to relevant social information. Because the focus is on transitions relevant to social, rather than cognitive outcomes, they are referred to here as "socializing transitions." A common conceptualization is applied to three major instigators of socializing transitions: changes in social understanding (about gender and stable, personal traits), social experiences (the first few years of school and hospitalization), and biologically based role changes (becoming a parent for the first time). The changes in social orientations predicted during these transitions are conceptualized in terms of three explanatory constructs: motivation to acquire information; information processing; and the meaning or significance of the information. It is hypothesized that individuals are maximally motivated to acquire certain kinds of information during early stages of a transition but that once conclusions are drawn, changes in motivation and information processing make them difficult to modify. Such changes are important because of the implication that the information available during relatively circumscribed periods of a transition control significant socialization outcomes of that experience. Six sets of studies are proposed, involving both cross-sectional and longitudinal designs, and combining self-reports, observational techniques, and experimental manipulation. The theoretical significance of the research involves an increased understanding of intervening processes contributing to transformations in personal and interpersonal perceptions and behaviors often resulting from a period of transition. These processes are expected to have general applicability to any transition. Moreover, because the research involves natural settings, the findings have practical, mental health applications for these settings. Study Set 5, for example, examines children's adaptation to a brief stay in a hospital. The present focus on developmental change in information-seeking and level of understanding will be useful for developing programs to meet the needs of children at different ages, and thereby minimize the negative psychological consequences of hospitalization. Similar though less direct implications are foreseen with respect to the proposed research on performance-related self esteem in school, and affective disorders after the birth of a first child. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDIES OF GENOMIC IMPRINTING IN BIPOLAR DISORDER Principal Investigator & Institution: Potash, James B.; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from applicant's abstract) This mentored clinician-scientist award (K08) proposal is a five-year plan to enable the candidate to develop into an independent investigator in the genetics of bipolar disorder. As a fully trained psychiatrist with sub-specialty experience in affective disorder, the candidate has an excellent grasp of the phenotype. This proposal provides for extensive development of his skills in molecular genetic methods. There will also be opportunities to learn statistical genetic methods. This will be accomplished through formal course work, extensive mentorship in a collaborative research environment, and implementation of a study that will be the first step toward a larger body of research aimed at investigating the genetics of bipolar disorder. Mentorship will be provided by Dr. J. Raymond DePaulo, Jr., the director of the affective disorders genetics research group at Johns Hopkins, and by Dr. Andrew Feinberg, an expert on genomic imprinting at the Johns Hopkins Center for Medical Genetics. Dr. Terri Beaty, director of genetic epidemiology
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at the Johns Hopkins School of Public Health will provide valuable consultation in statistical genetics methods. The training program will be enhanced by a research plan based on the hypothesis that the parent-of-origin-specific expression of imprinted genes modifies susceptibility to bipolar disorder. This hypothesis derives from clinical evidence for a parent-of-origin effect in transmission of the disorder, from linkage evidence for a parent-of-origin effect on chromosome 18, and from linkage evidence for a parent-of-origin effect in other areas of the genome. The candidate intends to take advantage of two valuable existing bipolar disorder family data sets collected under the direction of Dr. DePaulo as well as a third currently being ascertained. The specific aims are as follows: 1) to identify transcribed single nucleotide polymorphisms in genes from a candidate region for bipolar disorder on chromosome 1 8q; 2) to search for imprinted bipolar disorder susceptibility genes on chromosome 18 by testing for monoallelic expression of mRNA; and 3) to perform parental-allele-specific genetic analysis of other chromosomal regions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SUBSTANCE ABUSE IN FIRST EPISODE MANIA Principal Investigator & Institution: Strakowski, Stephen M.; Associate Professor; Psychiatry; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 15-JUL-1999; Project End 31-MAR-2004 Summary: Up to 60% of people with bipolar disorder abuse drugs and alcohol, and, in contrast to the general population, bipolar patients are far more likely to meet criteria for substance dependence than abuse. Despite numerous studies documenting this frequent co- occurrence, it is unclear why substance dependence rates are so high in bipolar disorder. It is likely that more than one mechanism accounts for these elevated rates of substance dependence, which confounds studies of this problem. Therefore, one approach to clarify why substance dependence is so common in bipolar disorder is to define subgroups of patients with different mechanisms leading to this co-occurrence and then study how these subgroups differ. With this in mind, we propose that three patient groups defined by age at onset, course of illness, and life-events, will account for the excess of substance dependence in bipolar disorder: 1) patients in whom bipolar disorder initiates substance dependence, 2) patients in whom substance dependence initiates bipolar disorder; and 3) patients in whom both bipolar and substance use disorders develop as a result of a common risk factor (stressful life-events). The first major objective of this proposal, then, is to determine whether these patient groups can be identified in a sample of bipolar patients recruited at the time of their first manic episode, and to determine whether different substances of abuse are more commonly associated with each group. The second major objective is to determine whether these groups demonstrate different clinical outcome and familial rates of substance use and affective disorders. This study is novel in that it examines specific a priori-defined subgroups of bipolar patients with co-occurring substance dependence using prospective outcome, family history, and life events methodology to clarify why these two disorders so commonly co-occur. The study is further strengthened by a hypothesis driven design in a first-episode patient sample thereby eliminating the confounds of illness chronicity and prior treatment. The results of this study could have immediate impact on how treatment of this patient population is developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 778433578 Timing: Fiscal Year 2002; 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 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
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Project Title: DISORDERS
THE
GENETIC
EPIDEMIOLOGY
OF
JUVENILE
ANXIETY
Principal Investigator & Institution: Foley, Debra L.; Assistant Professor; Human Genetics; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2004 Summary: (Adapted from the Applicant's Abstract): Childhood psychiatric disorders demonstrate a discernable developmental chronology; certain juvenile anxiety disorders typically onset earlier than behavioral disorders, which typically onset earlier than affective disorders. Childhood anxiety disorders therefore represent one of the earliest expressions of psychopathologic risk. The relevance of early onset anxiety disorders for consequent juvenile and adult mental health is, however, poorly understood. Developmental genetic epidemiology provides a framework for identifying the
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continuities and discontinuities in genetic and environmental risk factor effects on the chronology of comorbidity by exploiting the information contained in the pattern of disorder overlap within and across time, within individuals and between relatives of different ages. We plan to analyze longitudinal data already collected at personal interview with a large population-based sample of juvenile twins and their parents to develop a detailed understanding of the developmental genetic epidemiology of the more common juvenile anxiety disorders (separation anxiety, overanxious disorder, phobias). Analyses of multi-wave data collected from an epidemiologic sample of twinfamilies will permit identification of (1) the genetic, familial environmental and individual-specific environmental influences on transient versus persistent disorder, (2) the continuity or discontinuity of these risk factors with those for contemporaneous and consequent risk for other anxiety, behavioral and affective disorders, and (3) the maternal and paternal psychiatric disorders associated with the familial transmission of risk. Identification of the genetic and environmental risk factors that underlie developmental trajectories and endpoints of early juvenile psychopathology will guide intervention and prevention efforts designed to minimize the progression and chronicity of mental disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF ADOLESCENT SUICIDE ATTEMPTERS IN DALLAS Principal Investigator & Institution: Emslie, Graham J.; Professor, Chair, and Director; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 12-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): This proposal is to establish an NIMH Research Unit for Pediatric Psychopharmacology and Psychosocial Interventions (RUPP-PI) in Dallas, Texas. Our site, UT Southwestern Medical Center at Dallas, is a major center for research in Affective Disorders, with expertise in the field of efficacy research in children and adolescents with psychiatric disorders. Our team of investigators have successfully worked together on pharmacotherapy (Graham Emslie, Russell Scheffer, Namrata Rao) and cognitive behavior therapy (Graham Emslie, Betsy Kennard, Sunita Stewart) trials with adolescents with mood disorders, and have consistently ranked at the top of recruitment on multi-site trials. The exemplary research protocol targets a major public health issue: although adolescents in this country suffer 2 million suicide attempts annually, no controlled intervention studies for this condition have been conducted. The proposed 5-year study will determine the effectiveness of a multi-modal treatment intervention to prevent additional suicide attempts in 480 depressed adolescents attempters, ages 12 to 18. Eligible subjects will be recruited, carefully assessed, and then randomized equally to two treatment conditions. The Experimental Group will receive a 12-week course of antidepressant medication management (MM); weekly cognitive behavioral therapy adapted for adolescent attempters (CBTASA), and enhanced clinical management (ECM). The Control Group will be referred to a community provider for standard clinical care with additional ECM. Both groups will be assessed at baseline, 4, 8, 12, 16, 20 and 24, 36 and 48 weeks by an independent evaluator blind to treatment assignment. The goal of this study is to determine if the number of suicide attempts, severity of depression, severity of suicidal ideation, and Clinical Global ImpressionsImproved scores differ between the 2 groups at outcome. This exemplary protocol stimulated the formation of a collaborative group of 8 RUPP-PI applicants. By creating the protocol, the group forged an ability to work together. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TREATMENT OF FEAR AND PAIN IN IRRITABLE BOWEL SYNDROME Principal Investigator & Institution: Naliboff, Bruce D.; Clinical Professor; Brentwood Biomedical Research Institute Bldg. 114, Room 218 Los Angeles, Ca 90073 Timing: Fiscal Year 2002; Project Start 06-SEP-2002; Project End 31-MAY-2007 Summary: (provided by applicant) Irritable Bowel Syndrome (IBS) is the most common of the functional gastrointestinal disorders with primary symptoms of chronic abdominal pain or discomfort associated with altered bowel habits. IBS is characterized by stress-related symptom exacerbations and a high co-morbidity with affective disorders, in particular, anxiety. The current proposal is based on a disease model of IBS that emphasizes enhanced responsiveness and conditioning of stress and fear circuits in the central nervous system, and associated hypervigilance, stress-induced hyperalgesia, and altered autonomic responses to visceral sensation. Based on this model and the highly successful exposure treatments now used for anxiety disorders, we have designed and successfully piloted a unique cognitive behavioral treatment (CBT) for IBS. Traditional CBT treatments focus on decreasing general stress responses and increasing coping skills for life stress, and have shown only modest efficacy in IBS. We hypothesize that IBS symptoms can be more effectively treated by specifically changing responses to visceral sensations through decreasing interoceptive conditioned responses, and directing attention away from visceral stimuli. If our hypotheses are correct, we expect to see greater symptom improvements as well as normalization of altered physiological responses following this new CBT approach. We propose to address the following specific aims: 1) Do subjective outcomes differ between the two cognitive behavioral interventions with and without interoceptive exposure and directed attention, and an attention control treatment? 2) Are differential treatment responses accompanied by changes in perceptual and autonomic responses to visceral stimuli? And 3) Are differential treatment responses accompanied by normalization of altered regional brain activation in response to visceral stimuli? In separate studies we will compare CBT with interoceptive exposure and directed attention to tradition CBT (and a control condition) on outcome measures of symptom reduction, beliefs, visceral sensitivity (pain, discomfort, and fear responses to balloon distension), and central responses to visceral stimulation using functional magnetic resonance imaging (fMRI). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRYPTOPHAN DEPLETION: A PHENOTYPIC MARKER FOR DEPRESSION Principal Investigator & Institution: Moreno, Francisco A.; Psychiatry; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The research objectives of this study are to improve our understanding of major depression and its pathophysiology, improve our ability to predict future episodes, and identify susceptibility genes predisposing to major mood disorders. We expect to accomplish these by utilizing a candidate gene approach to study the association of several monoamine related genotypic markers and the depressive response to tryptophan (TRP) depletion as a newly defined phenotype. The TRP depletion paradigm is a broadly utilized research methodology that safely and effectively has contributed to our improved understanding of the physiological effects of serotonin neurotransmission in a variety of research models and subject populations. Specifically, the neurotransmitter depletion paradigms have been proposed as
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phenotypes for major affective disorders based on their ability to induce brief and reversible depressive responses in subjects considered at risk for depression - such as remitted depressives, and subjects with multigenerational family history of affective disorders - but not in healthy controls. We propose to study a new phenotypic definition because "depression" is a highly heterogeneous condition. This, along with the lack of objective biological measurements of the disease, has limited progress in the field. The present study will conduct TRP depletion testing in 100 subjects with history of major depression but who are currently in remission and medication-free for at least three months. TRP depletion involves two 3-day sessions (active depletion and control) in a double blind, controlled, crossover design. Day one involves the ingestion of a TRPfree 15 amino acid drink or a TRP-supplemented 16 amino acid drink. Clinician and selfrated behavioral measurements of depression, anxiety, and somatic symptoms, as well as blood samples for measurement of plasma TRP and large neutral amino acids will be obtained prior to, during, and after testing. Subjects will be monitored prospectively for major depressive recurrences during the follow-up year. TRP depletion testing will take place at two sites: The University of Arizona, and University Hospitals of Cleveland / Case Western Reserve University Departments of Psychiatry. Polymerase Chain Reaction based Genotyping will be performed in order to study several candidate gene polymorphisms relevant to monoamine function. Genotyping will take place at the University of Arizona. A thoughtfully implemented procedure for protection of human subjects is in place to safeguard participant's safety. Compelling pilot data are presented to support the study feasibility and validity of the proposed hypotheses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UTMB CENTER FOR POPULATION HEALTH AND HEALTH DISPARITIES Principal Investigator & Institution: Goodwin, James S.; Professor and Director; Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The proposed project will explore the relationship between neighborhood context and measures of health among Hispanics. In preliminary analyses, the investigators have found that an increasing percentage of Hispanics residing in a census tract is related to low overall mortality, cancer mortality, and cancer incidence among Hispanics, after controlling for numerous community and individual characteristics and risk factors, including immigrant status and acculturation. At the same time, increasing census tract percent Hispanics is associated with decreased survival after a diagnosis of cancer. The investigators now propose to explore the reasons for these strong neighborhood effects on health by examining several data sets linked to census data: Surveillance, Epidemiology, and End Results (SEER) data on cancer incidence and survival, vital registration data on cancer mortality, and the National Health Interview Survey-National Death Index file on cancer prevalence and mortality and all cause mortality. Finally, the researchers will investigate the relationship of Hispanic census tract density and other contextual measures with individual characteristics, health behaviors, social support, affective disorders and physiologic measures using a census-linked NHANES file. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 “affective disorders” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for affective disorders in the PubMed Central database: •
A genome-wide search for chromosomal loci linked to mental health wellness in relatives at high risk for bipolar affective disorder among the Old Order Amish. by Ginns EI, St. Jean P, Philibert RA, Galdzicka M, Damschroder-Williams P, Thiel B, Long RT, Ingraham LJ, Dalwaldi H, Murray MA, Ehlert M, Paul S, Remortel BG, Patel AP, Anderson MC, Shaio C, Lau E, Dymarskaia I, Martin BM, Stubblefield B, Falls KM, Carulli JP, Keith TP, Fann CS, Lacy LG, Allen CR, Hostetter AM, Elston RC, Schork NJ, Egeland JA, Paul SM.; 1998 Dec 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28077
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A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo. by MacKenzie A, Quinn J.; 1999 Dec 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24806
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Early response to light therapy partially predicts long-term antidepressant effects in patients with seasonal affective disorder. by Sher L, Matthews JR, Turner EH, Postolache TT, Katz KS, Rosenthal NE.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=167188
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.
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. 6 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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To generate your own bibliography of studies dealing with affective disorders, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “affective disorders” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for affective disorders (hyperlinks lead to article summaries): •
A differential diagnostic approach to the pharmacological treatment of cognitive, behavioral, and affective disorders after traumatic brain injury. Author(s): Glenn MB. Source: The Journal of Head Trauma Rehabilitation. 2002 August; 17(4): 273-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105997&dopt=Abstract
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Abnormalities of cAMP signaling in affective disorders: implication for pathophysiology and treatment. Author(s): Perez J, Tardito D, Mori S, Racagni G, Smeraldi E, Zanardi R. Source: Bipolar Disorders. 2000 March; 2(1): 27-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254016&dopt=Abstract
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Advances in the pharmacological treatment of bipolar affective disorders. Author(s): McCabe S. Source: Perspectives in Psychiatric Care. 2003 July-September; 39(3): 95-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14606229&dopt=Abstract
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Affective disorders among Jews: a historical review and meta-analysis. Author(s): Kohn R, Levav I, Zolondek S, Richter M. Source: History of Psychiatry. 1999 June; 10(38 Pt 2): 245-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11623879&dopt=Abstract
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Affective disorders and Alzheimer disease: a missing-link hypothesis. Author(s): Rasgon N, Jarvik GP, Jarvik L. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2001 Fall; 9(4): 444-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11739073&dopt=Abstract
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Affective disorders associated with autoimmune thyroiditis. Author(s): Degner D, Meller J, Bleich S, Schlautmann V, Ruther E. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2001 Fall; 13(4): 532-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748327&dopt=Abstract
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Affective disorders in advanced cancer. Author(s): Potash M, Breitbart W. Source: Hematology/Oncology Clinics of North America. 2002 June; 16(3): 671-700. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170575&dopt=Abstract
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Affective disorders in children and adolescents: addressing unmet need in primary care settings. Author(s): Wells KB, Kataoka SH, Asarnow JR. Source: Biological Psychiatry. 2001 June 15; 49(12): 1111-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430853&dopt=Abstract
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Affective disorders in cultural context. Author(s): Kirmayer LJ, Groleau D. Source: The Psychiatric Clinics of North America. 2001 September; 24(3): 465-78, Vii. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11593857&dopt=Abstract
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Affective disorders in hospitalized children and adolescents with mental retardation: a retrospective study. Author(s): Johnson CR, Handen BL, Lubetsky MJ, Sacco KA. Source: Research in Developmental Disabilities. 1995 May-June; 16(3): 221-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7652203&dopt=Abstract
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Affective disorders in neurological diseases: a case register-based study. Author(s): Nilsson FM, Kessing LV, Sorensen TM, Andersen PK, Bolwig TG. Source: Acta Psychiatrica Scandinavica. 2003 July; 108(1): 41-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807376&dopt=Abstract
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Affective disorders in the aftermath of miscarriage: a comprehensive review. Author(s): Klier CM, Geller PA, Ritsher JB. Source: Archives of Women's Mental Health. 2002 November; 5(4): 129-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510205&dopt=Abstract
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Affective disorders, personality and personality disorders. Author(s): Sass H, Junemann K. Source: Acta Psychiatrica Scandinavica. Supplementum. 2003; (418): 34-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956812&dopt=Abstract
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Affective disorders. Author(s): Beach S. Source: J Marital Fam Ther. 2003 April; 29(2): 247-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728781&dopt=Abstract
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An evaluation of two screening methods to identify cases with schizophrenia and affective disorders in a community survey in rural Ethiopia. Author(s): Shibre T, Kebede D, Alem A, Negash A, Kibreab S, Fekadu A, Fekadu D, Jacobsson L, Kullgren G. Source: The International Journal of Social Psychiatry. 2002 September; 48(3): 200-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413248&dopt=Abstract
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Anorexia nervosa and affective disorders: a controlled family history study. Author(s): Rivinus TM, Biederman J, Herzog DB, Kemper K, Harper GP, Harmatz JS, Houseworth S. Source: The American Journal of Psychiatry. 1984 November; 141(11): 1414-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6496785&dopt=Abstract
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Anteroposterior gradients in cerebral glucose use in schizophrenia and affective disorders. Author(s): Buchsbaum MS, DeLisi LE, Holcomb HH, Cappelletti J, King AC, Johnson J, Hazlett E, Dowling-Zimmerman S, Post RM, Morihisa J, et al. Source: Archives of General Psychiatry. 1984 December; 41(12): 1159-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6334502&dopt=Abstract
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Association of 5-HT(2A) receptor gene polymorphism with major affective disorders: the case of a subgroup of bipolar disorder with low suicide risk. Author(s): Bonnier B, Gorwood P, Hamon M, Sarfati Y, Boni C, Hardy-Bayle MC. Source: Biological Psychiatry. 2002 May 1; 51(9): 762-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983190&dopt=Abstract
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Assortative mating in the affective disorders: a systematic review and meta-analysis. Author(s): Mathews CA, Reus VI. Source: Comprehensive Psychiatry. 2001 July-August; 42(4): 257-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11458299&dopt=Abstract
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Autism, affective disorders, and social phobia. Author(s): Smalley SL, McCracken J, Tanguay P. Source: American Journal of Medical Genetics. 1995 February 27; 60(1): 19-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7485230&dopt=Abstract
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Baclofen administration for the treatment of affective disorders in alcoholic patients. Author(s): Krupitsky EM, Burakov AM, Ivanov VB, Krandashova GF, Lapin IP, Grinenko AJa, Borodkin YuS. Source: Drug and Alcohol Dependence. 1993 September; 33(2): 157-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8261880&dopt=Abstract
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Barbiturate anticonvulsants in refractory affective disorders. Author(s): Hayes SG. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1993 March; 5(1): 35-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8348197&dopt=Abstract
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Barriers to reducing burden of affective disorders. Author(s): Bruce ML, Wells KB, Miranda J, Lewis L, Gonzalez JL; NIMH Affective Disorders Workgroup. Source: Mental Health Services Research. 2002 December; 4(4): 187-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558003&dopt=Abstract
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Behavioural habits and affective disorders in old people. Author(s): Jimenez Jimenez C, Alcala Perez T, Serrano Prieto F, Martinez Navia-Osorio P. Source: Journal of Advanced Nursing. 1989 May; 14(5): 356-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2738231&dopt=Abstract
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Biochemistry of the affective disorders. Author(s): Hullin RP. Source: J Int Med Res. 1977; 5(1 Suppl): 140-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=863084&dopt=Abstract
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Biological alterations in the primary affective disorders and other tricyclic-responsive disorders. Author(s): Siever LJ, Uhde TW, Insel TR, Kaye WH, Jimerson DC, Lake CR, Kafka M, Targum S, Murphy DL. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1985; 9(1): 1524. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2986198&dopt=Abstract
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Biological markers in obsessive-compulsive and affective disorders. Author(s): Insel TR, Mueller EA 3rd, Gillin JC, Siever LJ, Murphy DL. Source: Journal of Psychiatric Research. 1984; 18(4): 407-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6512711&dopt=Abstract
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Biological markers of affective disorders and posttraumatic stress disorder: a pilot study with desipramine. Author(s): Kauffman CD, Reist C, Djenderedjian A, Nelson JN, Haier RJ. Source: The Journal of Clinical Psychiatry. 1987 September; 48(9): 366-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3114242&dopt=Abstract
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Bipolar affective disorders linked to DNA markers on chromosome 11. Author(s): Egeland JA, Gerhard DS, Pauls DL, Sussex JN, Kidd KK, Allen CR, Hostetter AM, Housman DE. Source: Nature. 1987 February 26-March 4; 325(6107): 783-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2881209&dopt=Abstract
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Bipolarity: the iceberg of affective disorders? Author(s): Egeland JA. Source: Comprehensive Psychiatry. 1983 July-August; 24(4): 337-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6884010&dopt=Abstract
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Blood cells as biological trait markers in affective disorders. Author(s): Muscettola G, Di Lauro A, Giannini CP. Source: Journal of Psychiatric Research. 1984; 18(4): 447-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6392528&dopt=Abstract
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Blood groups and affective disorders. Author(s): Takazawa N, Kimura T, Nanko S. Source: Jpn J Psychiatry Neurol. 1988 December; 42(4): 753-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3249472&dopt=Abstract
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Blood rubidium level in patients with major affective disorders. Author(s): Malek-Ahmadi P, Adams MK. Source: General Pharmacology. 1987; 18(3): 215-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3552862&dopt=Abstract
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Borna disease virus infection and affective disorders in man. Author(s): Bode L, Ferszt R, Czech G. Source: Arch Virol Suppl. 1993; 7: 159-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8219801&dopt=Abstract
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Borna disease virus. A possible etiologic factor in human affective disorders? Author(s): Amsterdam JD, Winokur A, Dyson W, Herzog S, Gonzalez F, Rott R, Koprowski H. Source: Archives of General Psychiatry. 1985 November; 42(11): 1093-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3931604&dopt=Abstract
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Brain glucose metabolism in anorexia nervosa and affective disorders: influence of weight loss or depressive symptomatology. Author(s): Delvenne V, Goldman S, De Maertelaer V, Wikler D, Damhaut P, Lotstra F. Source: Psychiatry Research. 1997 May 16; 74(2): 83-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9204511&dopt=Abstract
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Brain imaging of affective disorders and schizophrenia. Author(s): Kishimoto H, Yamada K, Iseki E, Kosaka K, Okoshi T. Source: Psychiatry and Clinical Neurosciences. 1998 December; 52 Suppl: S212-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9895149&dopt=Abstract
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Brain lithium concentrations measured with lithium-7 magnetic resonance spectroscopy in patients with affective disorders: relationship to erythrocyte and serum concentrations. Author(s): Kato T, Shioiri T, Inubushi T, Takahashi S. Source: Biological Psychiatry. 1993 February 1; 33(3): 147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8448262&dopt=Abstract
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Brain-derived neurotrophic factor (BDNF) in stress and affective disorders. Author(s): Licinio J, Wong ML. Source: Molecular Psychiatry. 2002; 7(6): 519. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140770&dopt=Abstract
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Childhood parental loss and alcohol dependence among Japanese men: a case-control study. Group for Longitudinal Affective Disorders Study (GLADS). Author(s): Furukawa T, Harai H, Hirai T, Fujihara S, Kitamura T, Takahashi K. Source: Acta Psychiatrica Scandinavica. 1998 June; 97(6): 403-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9669510&dopt=Abstract
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Children of parents with bipolar disorder. A population at high risk for major affective disorders. Author(s): Hodgins S, Faucher B, Zarac A, Ellenbogen M. Source: Child Adolesc Psychiatr Clin N Am. 2002 July; 11(3): 533-53, Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222082&dopt=Abstract
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Chronobiological approach for treatment-resistant rapid cycling affective disorders. Author(s): Kusumi I, Ohmori T, Kohsaka M, Ito M, Honma H, Koyama T. Source: Biological Psychiatry. 1995 April 15; 37(8): 553-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7619980&dopt=Abstract
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Classification of patients with affective disorders using platelet monoamine oxidase activity, serum melatonin and post-dexamethasone cortisol. Author(s): Wahlund B, Saaf J, Wetterberg L. Source: Acta Psychiatrica Scandinavica. 1995 May; 91(5): 313-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7639087&dopt=Abstract
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Clinical and chronobiological effects of light therapy on nonseasonal affective disorders. Author(s): Yamada N, Martin-Iverson MT, Daimon K, Tsujimoto T, Takahashi S. Source: Biological Psychiatry. 1995 June 15; 37(12): 866-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7548461&dopt=Abstract
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Clinical characteristics of patients with major affective disorders and comorbid migraine. Author(s): Fasmer OB, Oedegaard KJ. Source: World J Biol Psychiatry. 2001 July; 2(3): 149-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587198&dopt=Abstract
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Clinical course of affective disorders: were Emil Kraepelin and Jules Angst wrong? Author(s): Grof P, Alda M, Ahrens B. Source: Psychopathology. 1995; 28 Suppl 1: 73-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8903893&dopt=Abstract
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Clinical predictors of response to lamotrigine and gabapentin monotherapy in refractory affective disorders. Author(s): Obrocea GV, Dunn RM, Frye MA, Ketter TA, Luckenbaugh DA, Leverich GS, Speer AM, Osuch EA, Jajodia K, Post RM. Source: Biological Psychiatry. 2002 February 1; 51(3): 253-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839368&dopt=Abstract
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Cognitive and affective disorders associated to HIV infection in the HAART era: findings from the NeuroICONA study. Cognitive impairment and depression in HIV/AIDS. The NeuroICONA study. Author(s): Starace F, Bartoli L, Aloisi MS, Antinori A, Narciso P, Ippolito G, Ravasio L, Moioli MC, Vangi D, Gennero L, Coronado OV, Giacometti A, Nappa S, Perulli ML, Montesarchio V, La Gala A, Ricci F, Cristiano L, De Marco M, Izzo C, Pezzotti P, D'Arminio Monforte A. Source: Acta Psychiatrica Scandinavica. 2002 July; 106(1): 20-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100344&dopt=Abstract
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Cognitive deficits in schizophrenia and affective disorders: evidence for a final common pathway disorder. Author(s): Zihl J, Gron G, Brunnauer A. Source: Acta Psychiatrica Scandinavica. 1998 May; 97(5): 351-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9611085&dopt=Abstract
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Comorbid affective disorders and personality traits in alcohol abuse inpatients at an Air Force Medical Center. Author(s): Bourgeois JA, Nelson JL, Slack MB, Ingram M. Source: Military Medicine. 1999 February; 164(2): 103-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10050565&dopt=Abstract
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Comorbidity of mental retardation and affective disorders. Author(s): Girimaji SC. Source: J Indian Med Assoc. 2000 May; 98(5): 245, 248-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11002623&dopt=Abstract
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Comparison of early- and late-onset rapid cycling affective disorders: clinical course and response to pharmacotherapy. Author(s): Fujiwara Y, Honda T, Tanaka Y, Aoki S, Kuroda S. Source: Journal of Clinical Psychopharmacology. 1998 August; 18(4): 282-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9690693&dopt=Abstract
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Conduct disorder, antisocial personality disorder and substance use disorders in schizophrenia and major affective disorders. 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
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Consensus on minimal criteria of clinical and neuropathological diagnosis of schizophrenia and affective disorders for post mortem research. Report from the European Dementia and Schizophrenia Network (BIOMED I). Author(s): Riederer P, Gsell W, Calza L, Franzek E, Jungkunz G, Jellinger K, Reynolds GP, Crow T, Cruz-Sanchez FF, Beckmann H. Source: Journal of Neural Transmission. General Section. 1995; 102(3): 255-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8788074&dopt=Abstract
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Consequences of deterministic and random dynamics for the course of affective disorders. Author(s): Huber MT, Braun HA, Krieg JC. Source: Biological Psychiatry. 1999 July 15; 46(2): 256-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10418701&dopt=Abstract
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Correlation between serum and urinary calcium levels and psychopathology in patients with affective disorders. Short communication. Author(s): Stern JE, Guinjoan SM, Cardinali DP. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 1996; 103(4): 509-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9617792&dopt=Abstract
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Criminal activities and substance use of patients with major affective disorders and schizophrenia: a 2-year follow-up. Author(s): Hodgins S, Lapalme M, Toupin J. Source: Journal of Affective Disorders. 1999 October; 55(2-3): 187-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10628888&dopt=Abstract
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Cytokines in affective disorders and schizophrenia: new clinical and genetic findings. Author(s): Prolo P, Licinio J. Source: Molecular Psychiatry. 1999 March; 4(2): 109-11. Erratum In: Mol Psychiatry 1999 July; 4(4): 396. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10208441&dopt=Abstract
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Decreasing requirement for lithium carbonate therapy in bipolar affective disorders (hypomanic type) following the onset of chronic renal insufficiency. Author(s): Pandita-Gunawardena R, Donaldson D. Source: J R Soc Health. 1998 February; 118(1): 35-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9724937&dopt=Abstract
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Deficits in sustained attention in schizophrenia and affective disorders: stable versus state-dependent markers. Author(s): Liu SK, Chiu CH, Chang CJ, Hwang TJ, Hwu HG, Chen WJ. Source: The American Journal of Psychiatry. 2002 June; 159(6): 975-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042186&dopt=Abstract
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Depression and cancer risk: a register-based study of patients hospitalized with affective disorders, Denmark, 1969-1993. Author(s): Dalton SO, Mellemkjaer L, Olsen JH, Mortensen PB, Johansen C. Source: American Journal of Epidemiology. 2002 June 15; 155(12): 1088-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048222&dopt=Abstract
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Description of the National Institute of Mental Health family study of affective disorders. Author(s): Gershon ES, Goldin LR, Guroff JJ, Hamovit JR. Source: Genetic Epidemiology. 1989; 6(1): 183-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2731706&dopt=Abstract
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Designing long-term clinical trials in affective disorders. Author(s): Grof P. Source: Journal of Affective Disorders. 1994 April; 30(4): 243-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8014324&dopt=Abstract
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Detection of Borna disease virus-reactive antibodies from patients with affective disorders by western immunoblot technique. Author(s): Fu ZF, Amsterdam JD, Kao M, Shankar V, Koprowski H, Dietzschold B. Source: Journal of Affective Disorders. 1993 January; 27(1): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8432962&dopt=Abstract
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Detection of linkage to affective disorders in the catalogued Amish pedigrees: a reply to Pauls et al. Author(s): Gershon ES, Goldin LR, Badner JA, Berrettini WH. Source: American Journal of Human Genetics. 1996 June; 58(6): 1381-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8651318&dopt=Abstract
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Development of an integrated model of personality, personality disorders and severe axis I disorders, with special reference to major affective disorders. Author(s): von Zerssen D. Source: Journal of Affective Disorders. 2002 April; 68(2-3): 143-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12063143&dopt=Abstract
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Developmental precursors and biological markers for schizophrenia and affective disorders: specificity and public health implications. Author(s): Jones PB, Tarrant CJ. Source: European Archives of Psychiatry and Clinical Neuroscience. 2000; 250(6): 286-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11153963&dopt=Abstract
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Diagnosis of affective disorders and schizophrenia in the U.S.: a 1984 survey of psychiatrists and graduating residents. Author(s): Jampala VC, Sierles FS, Taylor MA. Source: The Journal of Clinical Psychiatry. 1989 June; 50(6): 212-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2722760&dopt=Abstract
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Differential limbic--cortical correlates of sadness and anxiety in healthy subjects: implications for affective disorders. Author(s): Liotti M, Mayberg HS, Brannan SK, McGinnis S, Jerabek P, Fox PT. Source: Biological Psychiatry. 2000 July 1; 48(1): 30-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10913505&dopt=Abstract
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Differential rates of urinary noradrenalin excretion in affective disorders: utility of a short time sampling procedure. Author(s): Lista AL. Source: Psychiatry Research. 1989 December; 30(3): 253-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2616691&dopt=Abstract
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Discriminating psychotic and affective disorders using the WAIS-R. Author(s): Piedmont RL, Sokolove RL, Fleming MZ. Source: Journal of Personality Assessment. 1989 Winter; 53(4): 739-48. Erratum In: J Pers Assess 1990 Fall; 55(1-2): 391. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2607403&dopt=Abstract
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Divalproex sodium in the treatment of refractory affective disorders. Author(s): Schaff MR, Fawcett J, Zajecka JM. Source: The Journal of Clinical Psychiatry. 1993 October; 54(10): 380-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8262880&dopt=Abstract
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Do antidepressant and antianxiety drugs increase chronicity in affective disorders? Author(s): Fava GA. Source: Psychotherapy and Psychosomatics. 1994; 61(3-4): 125-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7915039&dopt=Abstract
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Do minor affective disorders need medication? Author(s): Morgan HG. Source: British Medical Journal (Clinical Research Ed.). 1984 September 29; 289(6448): 783. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6434079&dopt=Abstract
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Do the epilepsies, pain syndromes, and affective disorders share common kindlinglike mechanisms? Author(s): Post RM. Source: Epilepsy Research. 2002 June; 50(1-2): 203-19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151130&dopt=Abstract
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Dreaming away depression: the role of REM sleep and dreaming in affective disorders. Author(s): Beauchemin KM, Hays P. Source: Journal of Affective Disorders. 1996 November 25; 41(2): 125-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8961040&dopt=Abstract
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Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders. Report of the NIMH Collaborative Study Group comparing lithium carbonate, imipramine, and a lithium carbonate-imipramine combination. Author(s): Prien RF, Kupfer DJ, Mansky PA, Small JG, Tuason VB, Voss CB, Johnson WE. Source: Archives of General Psychiatry. 1984 November; 41(11): 1096-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6437366&dopt=Abstract
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Drug treatment of older people with affective disorders in the community: lessons from an attempted clinical trial. Author(s): Stevens T, Katona C, Manela M, Watkin V, Livingston G. Source: International Journal of Geriatric Psychiatry. 1999 June; 14(6): 467-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10398357&dopt=Abstract
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Effect of prophylactic treatment on suicide risk in patients with major affective disorders. Data from a randomized prospective trial. Author(s): Thies-Flechtner K, Muller-Oerlinghausen B, Seibert W, Walther A, Greil W. Source: Pharmacopsychiatry. 1996 May; 29(3): 103-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8738314&dopt=Abstract
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Effects of carbamazepine and lithium on affective disorders. Author(s): Okuma T. Source: Neuropsychobiology. 1993; 27(3): 138-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8232828&dopt=Abstract
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Effects of noise on different disease states of recurrent affective disorders. Author(s): Huber MT, Braun HA, Krieg JC. Source: Biological Psychiatry. 2000 April 1; 47(7): 634-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10745056&dopt=Abstract
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Effects of phototherapy on circadian rhythms of body temperature in affective disorders. Author(s): Daimon K, Yamada N, Tsujimoto T, Shioiri T, Hanada K, Takahashi S. Source: Jpn J Psychiatry Neurol. 1992 March; 46(1): 240. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1635326&dopt=Abstract
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Effects of sleep deprivation on the limbic system and the frontal lobes in affective disorders: a study with Tc-99m-HMPAO SPECT. Author(s): Ebert D, Feistel H, Barocka A. Source: Psychiatry Research. 1991 December; 40(4): 247-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1811242&dopt=Abstract
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Efficacy and safety of risperidone in the treatment of schizoaffective disorder: initial results from a large, multicenter surveillance study. Group for the Study of Risperidone in Affective Disorders (GSRAD). Author(s): Vieta E, Herraiz M, Fernandez A, Gasto C, Benabarre A, Colom F, MartinezAran A, Reinares M. Source: The Journal of Clinical Psychiatry. 2001 August; 62(8): 623-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11561935&dopt=Abstract
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Efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of affective disorders. Author(s): Schlaepfer TE, Kosel M, Nemeroff CB. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 February; 28(2): 201-5. Epub 2002 August 01. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589372&dopt=Abstract
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Electrodermal activity in euthymic patients with affective disorders: one-year retest stability and the effects of stimulus intensity and significance. Author(s): Iacono WG, Lykken DT, Haroian KP, Peloquin LJ, Valentine RH, Tuason VB. Source: Journal of Abnormal Psychology. 1984 August; 93(3): 304-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6470315&dopt=Abstract
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Elemental concentrations in nigerians with affective disorders using proton-induced X-ray emission. Author(s): Durosinmi MA, Ojo JO, Oluwole AF, Ononye AF, Akanle OA, Spyrou NM. Source: Biological Trace Element Research. 1994 Fall; 43-45: 357-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7710849&dopt=Abstract
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Elevated levels of N-acetyl-beta-glucosaminidase in affective disorders and chemical dependence. Author(s): Garvey M, Noyes R Jr, Cook B, Barrickman L, Noel M, Ghosheh R. Source: Journal of Affective Disorders. 1990 August; 19(4): 279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2146305&dopt=Abstract
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Emotions and the brain: linking affective disorders to brain regions. Author(s): May TS. Source: Lancet. Neurology. 2002 June; 1(2): 80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849507&dopt=Abstract
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Enhanced calcium response to serotonin in platelets from patients with affective disorders. Author(s): Yamawaki S, Kagaya A, Okamoto Y, Shimizu M, Nishida A, Uchitomi Y. Source: Journal of Psychiatry & Neuroscience : Jpn. 1996 November; 21(5): 321-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8973051&dopt=Abstract
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Epidemiology of affective disorders: a review. Author(s): Bland RC. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1997 May; 42(4): 367-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9161761&dopt=Abstract
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Epidemiology of geriatric affective disorders. Author(s): Koenig HG, Blazer DG. Source: Clinics in Geriatric Medicine. 1992 May; 8(2): 235-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1600475&dopt=Abstract
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Erythrocyte membrane sodium-potassium adenosine triphosphatase activity in affective disorders. Author(s): Reddy PL, Khanna S, Subhash MN, Channabasavanna SM, Rao BS. Source: Journal of Neural Transmission. General Section. 1992; 89(3): 209-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1327002&dopt=Abstract
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Ethnicity and diagnosis in patients with affective disorders. Author(s): Strakowski SM, Keck PE Jr, Arnold LM, Collins J, Wilson RM, Fleck DE, Corey KB, Amicone J, Adebimpe VR. Source: The Journal of Clinical Psychiatry. 2003 July; 64(7): 747-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934973&dopt=Abstract
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European Collaborative Project on Affective Disorders: interactions between genetic and psychosocial vulnerability factors. Author(s): Souery D, Lipp O, Serretti A, Mahieu B, Rivelli SK, Cavallini C, Ackenheil M, Adolfsson R, Aschauer H, Blackwood D, Dam H, Delcoigne B, Demartelaer V, Dikeos D, Fuchshuber S, Heiden M, Jablensky A, Jakovljevic M, Kessing L, Lerer B, Macedo A, Mellerup T, Milanova V, Muir W, Mendlewicz J, et al. Source: Psychiatric Genetics. 1998 Winter; 8(4): 197-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9861637&dopt=Abstract
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Evidence supporting the independent inheritance of primary affective disorders and primary alcoholism in the families of bipolar patients. Author(s): Duffy A, Grof P, Grof E, Zvolsky P, Alda M. Source: Journal of Affective Disorders. 1998 September; 50(2-3): 91-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9858068&dopt=Abstract
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Excess cardiovascular and suicide mortality of affective disorders may be reduced by lithium prophylaxis. Author(s): Ahrens B, Muller-Oerlinghausen B, Schou M, Wolf T, Alda M, Grof E, Grof P, Lenz G, Simhandl C, Thau K, et al. Source: Journal of Affective Disorders. 1995 February 21; 33(2): 67-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7759663&dopt=Abstract
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Extent and determinants of burden among families of patients with affective disorders. Author(s): Chakrabarti S, Kulhara P, Verma SK. Source: Acta Psychiatrica Scandinavica. 1992 September; 86(3): 247-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1414422&dopt=Abstract
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Facial discrimination and emotional recognition in schizophrenia and affective disorders. Author(s): Feinberg TE, Rifkin A, Schaffer C, Walker E. Source: Archives of General Psychiatry. 1986 March; 43(3): 276-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3954548&dopt=Abstract
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Factors affecting the distribution of age at onset in patients with affective disorders. Author(s): Smeraldi E, Gasperini M, Macciardi F, Bussoleni C, Morabito A. Source: Journal of Psychiatric Research. 1982-83; 17(3): 309-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7187692&dopt=Abstract
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Factors associated with relapse during maintenance treatment of affective disorders. Author(s): Leverich GS, Post RM, Rosoff AS. Source: International Clinical Psychopharmacology. 1990 April; 5(2): 135-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2380544&dopt=Abstract
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Familial patterns and possible modes of inheritance of primary affective disorders. Author(s): Smeraldi E, Negri F, Heimbuch RC, Kidd KK. Source: Journal of Affective Disorders. 1981 June; 3(2): 173-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6454711&dopt=Abstract
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Familial transmission of major affective disorders. Is there evidence supporting the distinction between unipolar and bipolar disorders? Author(s): Tsuang MT, Faraone SV, Fleming JA. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1985 March; 146: 268-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3986436&dopt=Abstract
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Family and genetic studies of affective disorders. Author(s): Blehar MC, Weissman MM, Gershon ES, Hirschfeld RM. Source: Archives of General Psychiatry. 1988 March; 45(3): 289-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3277580&dopt=Abstract
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Family and genetic studies on the relationship of schizophrenia to affective disorders. Author(s): Maier W, Rietschel M, Lichtermann D, Wildenauer DB. Source: European Archives of Psychiatry and Clinical Neuroscience. 1999; 249 Suppl 4: 57-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10654110&dopt=Abstract
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Family history of affective disorders and the significance for prophylactic effect of lithium treatment. Author(s): Nylander PO, Engstrom C, Nordqvist-Karlsson B, Astrom M. Source: Biological Psychiatry. 1999 April 15; 45(8): 1079-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10386198&dopt=Abstract
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Fatigue syndromes: a comparison of chronic “postviral” fatigue with neuromuscular and affective disorders. Author(s): Wessely S, Powell R. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1989 August; 52(8): 940-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2571680&dopt=Abstract
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Features of families with major affective disorders. Author(s): Stierlin H, Weber G, Schmidt G, Simon FB. Source: Family Process. 1986 September; 25(3): 325-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3758309&dopt=Abstract
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Fenfluramine stimulation of serum cortisol in patients with major affective disorders and healthy controls: further evidence for a central serotonergic action of lithium in man. Author(s): Muhlbauer HD, Muller-Oerlinghausen B. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 1985; 61(1-2): 81-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2984331&dopt=Abstract
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Food and mood: relationship between food, serotonin and affective disorders. Author(s): Wallin MS, Rissanen AM. Source: Acta Psychiatrica Scandinavica. Supplementum. 1994; 377: 36-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8053364&dopt=Abstract
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Frequency of comorbid personality disorders in bipolar and unipolar affective disorders. Author(s): Brieger P, Ehrt U, Marneros A. Source: Comprehensive Psychiatry. 2003 January-February; 44(1): 28-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524633&dopt=Abstract
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Functional aspects of the norepinephrine receptor coupled adenylate cyclase system in the limbic forebrain and its modification by drugs which precipitate or alleviate depression: molecular approaches to an understanding of affective disorders. Author(s): Sulser F. Source: Pharmakopsychiatr Neuropsychopharmakol. 1978 January; 11(1): 43-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=204950&dopt=Abstract
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Functional brain asymmetry and affective disorders. Author(s): Sackeim HA, Decina P, Malitz S. Source: Adolesc Psychiatry. 1982; 10: 320-35. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7171104&dopt=Abstract
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Functional cerebral asymmetry in affective disorders: new facts contributed by transcranial magnetic stimulation. Author(s): Garcia-Toro M, Montes JM, Talavera JA. Source: Journal of Affective Disorders. 2001 October; 66(2-3): 103-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11578662&dopt=Abstract
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Funeral mania in recurrent bipolar affective disorders: reports of three cases. Author(s): Ranga K, Krishnan R, Swartz MS, Larson MJ, Santoliquido G. Source: The Journal of Clinical Psychiatry. 1984 July; 45(7): 310-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6735990&dopt=Abstract
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Further association study on dopamine D2 receptor variant S311C in schizophrenia and affective disorders. Author(s): Arinami T, Itokawa M, Aoki J, Shibuya H, Ookubo Y, Iwawaki A, Ota K, Shimizu H, Hamaguchi H, Toru M. Source: American Journal of Medical Genetics. 1996 April 9; 67(2): 133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8723039&dopt=Abstract
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Further evidence for an association between affective disorders and anxiety disorders: review and case reports. Author(s): Cohen LS, Biederman J. Source: The Journal of Clinical Psychiatry. 1988 August; 49(8): 313-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3045101&dopt=Abstract
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Further study on N1-methylnicotinamide urinary output in patients with affective disorders. Author(s): Galasso R, Allaria E, Bellodi L, Sacchetti E. Source: Agressologie. 1977; 18(5): 273-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=146439&dopt=Abstract
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GABA and affective disorders. Author(s): Lloyd KG, Morselli PL, Bartholini G. Source: Med Biol. 1987; 65(2-3): 159-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2821330&dopt=Abstract
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Gender differences in outpatient research subjects with affective disorders: a comparison of descriptive variables. Author(s): Rapaport MH, Thompson PM, Kelsoe JR Jr, Golshan S, Judd LL, Gillin JC. Source: The Journal of Clinical Psychiatry. 1995 February; 56(2): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7852255&dopt=Abstract
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Gender inequalities in health: social position, affective disorders and minor physical morbidity. Author(s): Popay J, Bartley M, Owen C. Source: Social Science & Medicine (1982). 1993 January; 36(1): 21-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8424181&dopt=Abstract
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Gender, marital status and treated affective disorders in South Verona: a case register study. Author(s): Bebbington P, Tansella M. Source: Journal of Affective Disorders. 1989 July-August; 17(1): 83-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2525579&dopt=Abstract
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Genetic analysis of the affective disorders: summary of GAW5. Author(s): Rice J, Risch N. Source: Genetic Epidemiology. 1989; 6(1): 161-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2659428&dopt=Abstract
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Genetic and immunological factors in affective disorders and schizophrenia. Author(s): Mendlewicz J, Sevy S. Source: Prog Brain Res. 1986; 65: 1-15. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3538158&dopt=Abstract
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Genetic and pharmacological models of cholinergic supersensitivity and affective disorders. Author(s): Overstreet DH, Russell RW, Crocker AD, Gillin JC, Janowsky DS. Source: Experientia. 1988 June 15; 44(6): 465-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3288493&dopt=Abstract
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Genetic approach to the study of heterogeneity of affective disorders. Author(s): Gasperini M, Orsini A, Bussoleni C, Macciardi F, Smeraldi E. Source: Journal of Affective Disorders. 1987 March-April; 12(2): 105-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2955001&dopt=Abstract
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Genetic epidemiologic studies of affective disorders in childhood and adolescence. Author(s): Merikangas KR. Source: European Archives of Psychiatry and Clinical Neuroscience. 1993; 243(3-4): 12130. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8117755&dopt=Abstract
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Genetic factors in moderately severe and mild affective disorders. Author(s): Torgersen S. Source: Archives of General Psychiatry. 1986 March; 43(3): 222-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3954541&dopt=Abstract
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Genetic implications for major affective disorders. Author(s): Simmons-Alling S. Source: Archives of Psychiatric Nursing. 1990 February; 4(1): 67-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2317101&dopt=Abstract
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Genetic modification of corticosteroid receptor signalling: novel insights into pathophysiology and treatment strategies of human affective disorders. Author(s): Muller M, Holsboer F, Keck ME. Source: Neuropeptides. 2002 April-June; 36(2-3): 117-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359503&dopt=Abstract
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Genetic studies and biologic strategies in the affective disorders. Author(s): Gershon ES, Targum SD, Kessler LR, Mazure CM, Bunney WE Jr. Source: Prog Med Genet. 1977; 2: 101-64. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=897198&dopt=Abstract
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Genetic studies of affective disorders: should we be starting with childhood onset probands? Author(s): Todd RD, Neuman R, Geller B, Fox LW, Hickok J. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1993 November; 32(6): 1164-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8282660&dopt=Abstract
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Genetic transmission of major affective disorders: quantitative models and linkage analyses. Author(s): Faraone SV, Kremen WS, Tsuang MT. Source: Psychological Bulletin. 1990 July; 108(1): 109-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2200070&dopt=Abstract
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Genetics and pathophysiology of affective disorders: relationship to fibromyalgia. Author(s): Ackenheil M. Source: Zeitschrift Fur Rheumatologie. 1998; 57 Suppl 2: 5-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10025073&dopt=Abstract
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Genetics of affective disorders. Author(s): Johansson C, Jansson M, Linner L, Yuan QP, Pedersen NL, Blackwood D, Barden N, Kelsoe J, Schalling M. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2001 December; 11(6): 385-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704415&dopt=Abstract
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Genetics of affective disorders. Author(s): Gandini E. Source: Journal of Psychiatric Research. 1992 October; 26(4): 271-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1491353&dopt=Abstract
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Genetics of schizophrenia and affective disorders. Author(s): Maier W, Zobel A, Rietschel M. Source: Pharmacopsychiatry. 2003 November; 36 Suppl 3: S195-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14677079&dopt=Abstract
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Genome-wide search for linkage of bipolar affective disorders in a very large pedigree derived from a homogeneous population in quebec points to a locus of major effect on chromosome 12q23-q24. Author(s): Morissette J, Villeneuve A, Bordeleau L, Rochette D, Laberge C, Gagne B, Laprise C, Bouchard G, Plante M, Gobeil L, Shink E, Weissenbach J, Barden N. Source: American Journal of Medical Genetics. 1999 October 15; 88(5): 567-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10490718&dopt=Abstract
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Hallucinations and delusions in 1,715 patients with unipolar and bipolar affective disorders. Author(s): Black DW, Nasrallah A. Source: Psychopathology. 1989; 22(1): 28-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2657835&dopt=Abstract
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Hemispheric asymmetries of function in patients with major affective disorders. Author(s): Miller EN, Fujioka TA, Chapman LJ, Chapman JP. Source: Journal of Psychiatric Research. 1995 May-June; 29(3): 173-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7473294&dopt=Abstract
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High rate of affective disorders in probands with attention deficit disorder and in their relatives: a controlled family study. Author(s): Biederman J, Munir K, Knee D, Armentano M, Autor S, Waternaux C, Tsuang M. Source: The American Journal of Psychiatry. 1987 March; 144(3): 330-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3826433&dopt=Abstract
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High-affinity 3H-imipramine binding in platelets of children and adolescents with major affective disorders. Author(s): Rehavi M, Weizman R, Carel C, Apter A, Tyano S. Source: Psychiatry Research. 1984 September; 13(1): 31-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6595683&dopt=Abstract
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Histocompatibility antigens in affective disorders. Author(s): Stember RH, Fieve RR. Source: Clinical Immunology and Immunopathology. 1977 January; 7(1): 10-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=852150&dopt=Abstract
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Historical development and present status of the schedule for affective disorders and schizophrenia for school-age children (K-SADS). Author(s): Ambrosini PJ. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2000 January; 39(1): 49-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10638067&dopt=Abstract
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Historical overview of the relationship between anxiety disorders and affective disorders. Author(s): Himmelhoch J, Levine J, Gershon S. Source: Depression and Anxiety. 2001; 14(2): 53-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668658&dopt=Abstract
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HLA haplotype A26-B38 in affective disorders: lack of association. Author(s): Biederman J, Keller M, Lavori P, Harmatz J, Knee D, Dubey D, Yunis E. Source: Biological Psychiatry. 1987 February; 22(2): 221-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3814672&dopt=Abstract
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HLA may be involved in resistance and susceptibility to affective disorders. Author(s): Payami H, Dubay C, Valenzuela RC. Source: Genetic Epidemiology. 1989; 6(1): 293-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2731718&dopt=Abstract
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HLA-DR2-frequencies in affective disorders. Author(s): Korner J, Propping P, Fritze J. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1990 June; 156: 907-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2207531&dopt=Abstract
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Hormonal response pattern in the combined DEX-CRH test is stable over time in subjects at high familial risk for affective disorders. Author(s): Modell S, Lauer CJ, Schreiber W, Huber J, Krieg JC, Holsboer F. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1998 April; 18(4): 253-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9509493&dopt=Abstract
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Hospital-treated and general-population morbidity from affective disorders. Comparison of prevalence and inception rates. Author(s): Sashidharan SP, Surtees PG, Kreitman NB, Ingham JG, Miller PM. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1988 April; 152: 499-505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3167401&dopt=Abstract
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How different from pacemaker patients are recipients of implantable cardioverterdefibrillators with respect to psychosocial adaptation, affective disorders, and quality of life? Author(s): Duru F, Buchi S, Klaghofer R, Mattmann H, Sensky T, Buddeberg C, Candinas R. Source: Heart (British Cardiac Society). 2001 April; 85(4): 375-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11250956&dopt=Abstract
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Human corticotropin releasing hormone: clinical studies in patients with affective disorders, alcoholism, panic disorder and in normal controls. Author(s): von Bardeleben U, Holsboer F. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1988; 12 Suppl: S165-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2854897&dopt=Abstract
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Human fibroblasts as a relevant model to study signal transduction in affective disorders. Author(s): Manier DH, Shelton RC, Ellis TC, Peterson CS, Eiring A, Sulser F. Source: Journal of Affective Disorders. 2000 December; 61(1-2): 51-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11099740&dopt=Abstract
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Hyperactivity of CRH neuronal circuits as a target for therapeutic interventions in affective disorders. Author(s): Keck ME, Holsboer F. Source: Peptides. 2001 May; 22(5): 835-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11337098&dopt=Abstract
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Hypericum in the treatment of seasonal affective disorders. Author(s): Martinez B, Kasper S, Ruhrmann S, Moller HJ. Source: Journal of Geriatric Psychiatry and Neurology. 1994 October; 7 Suppl 1: S29-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7857504&dopt=Abstract
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Hyperthyroxinemia in major affective disorders. Author(s): Styra R, Joffe R, Singer W. Source: Acta Psychiatrica Scandinavica. 1991 January; 83(1): 61-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2011957&dopt=Abstract
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Hypocholesterolemia and affective disorders. Author(s): Glueck CJ, Tieger M, Kunkel R, Hamer T, Tracy T, Speirs J. Source: The American Journal of the Medical Sciences. 1994 October; 308(4): 218-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7942980&dopt=Abstract
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Hypothalamic functions, sleep and circadian rhythms in affective disorders. Author(s): Mendlewicz J, Linkowski P. Source: Adv Biochem Psychopharmacol. 1987; 43: 221-36. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3035888&dopt=Abstract
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Identification of minor affective disorders and implications for psychopharmacotherapy. Author(s): Winter P, Philipp M, Buller R, Delmo CD, Schwarze H, Benkert O. Source: Journal of Affective Disorders. 1991 July; 22(3): 125-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1918656&dopt=Abstract
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Identifying chronic affective disorders in outpatients: validation of the General Behavior Inventory. Author(s): Klein DN, Dickstein S, Taylor EB, Harding K. Source: Journal of Consulting and Clinical Psychology. 1989 February; 57(1): 106-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2925959&dopt=Abstract
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Impairments of attention and effort among patients with major affective disorders. Author(s): Cohen R, Lohr I, Paul R, Boland R. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2001 Summer; 13(3): 385-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11514646&dopt=Abstract
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Improving the recognition of concerns and affective disorders in cancer patients. Author(s): Maguire P. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002; 13 Suppl 4: 177-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401687&dopt=Abstract
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Inadequate availability of pharmacological treatment for affective disorders in New Zealand. Author(s): Porter RJ, Mulder RT. Source: N Z Med J. 2002 February 22; 115(1148): 78-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913939&dopt=Abstract
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Increased incidence of affective disorders, anxiety disorders, and non-natural mortality in women after breast cancer diagnosis: a nation-wide cohort study in Denmark. Author(s): Hjerl K, Andersen EW, Keiding N, Mortensen PB, Jorgensen T. Source: Acta Psychiatrica Scandinavica. 2002 April; 105(4): 258-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11942929&dopt=Abstract
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Increased platelet intracellular calcium concentration in patients with bipolar affective disorders. Author(s): Dubovsky SL, Christiano J, Daniell LC, Franks RD, Murphy J, Adler L, Baker N, Harris RA. Source: Archives of General Psychiatry. 1989 July; 46(7): 632-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2735813&dopt=Abstract
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Increased prevalence of type 2 diabetes mellitus among psychiatric inpatients with bipolar I affective and schizoaffective disorders independent of psychotropic drug use. Author(s): Regenold WT, Thapar RK, Marano C, Gavirneni S, Kondapavuluru PV. Source: Journal of Affective Disorders. 2002 June; 70(1): 19-26. Erratum In: J Affect Disord. 2003 February; 73(3): 301-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12113916&dopt=Abstract
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Increased risk of affective disorders in males after second trimester prenatal exposure to the Dutch hunger winter of 1944-45. Author(s): Brown AS, Susser ES, Lin SP, Neugebauer R, Gorman JM. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1995 May; 166(5): 601-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7620744&dopt=Abstract
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Increased risk of developing dementia in patients with major affective disorders compared to patients with other medical illnesses. Author(s): Kessing LV, Nilsson FM. Source: Journal of Affective Disorders. 2003 February; 73(3): 261-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547295&dopt=Abstract
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Individual and familial risk factors for bipolar affective disorders in Denmark. Author(s): Mortensen PB, Pedersen CB, Melbye M, Mors O, Ewald H. Source: Archives of General Psychiatry. 2003 December; 60(12): 1209-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14662553&dopt=Abstract
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Linkage of bipolar affective disorders to markers on chromosome 11p is excluded in a second lateral extension of Amish pedigree 110. Author(s): Pauls DL, Gerhard DS, Lacy LG, Hostetter AM, Allen CR, Bland SD, LaBuda MC, Egeland JA. Source: Genomics. 1991 November; 11(3): 730-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1774072&dopt=Abstract
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Measuring mood and complex behavior in natural environments: use of ecological momentary assessment in pediatric affective disorders. Author(s): Axelson DA, Bertocci MA, Lewin DS, Trubnick LS, Birmaher B, Williamson DE, Ryan ND, Dahl RE. Source: Journal of Child and Adolescent Psychopharmacology. 2003 Fall; 13(3): 253-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642013&dopt=Abstract
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Neuroendocrine, polysomnographic and psychometric observations in healthy subjects at high familial risk for affective disorders: the current state of the 'Munich vulnerability study'. Author(s): Krieg JC, Lauer CJ, Schreiber W, Modell S, Holsboer F. Source: Journal of Affective Disorders. 2001 January; 62(1-2): 33-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11172871&dopt=Abstract
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Neurometric subgroups in attentional and affective disorders and their association with pharmacotherapeutic outcome. Author(s): Suffin SC, Emory WH. Source: Clin Electroencephalogr. 1995 April; 26(2): 76-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7781194&dopt=Abstract
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Neuropsychological differences between first-admission schizophrenia and psychotic affective disorders. Author(s): Mojtabai R, Bromet EJ, Harvey PD, Carlson GA, Craig TJ, Fennig S. Source: The American Journal of Psychiatry. 2000 September; 157(9): 1453-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10964862&dopt=Abstract
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Neuropsychological function in subjects with psychotic and affective disorders. Relationship to diagnostic category and duration of illness. Author(s): Verdoux H, Liraud F. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2000 June; 15(4): 236-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10951607&dopt=Abstract
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No association of an insertion/deletion polymorphism in the angiotensin I converting enzyme gene with bipolar or unipolar affective disorders. Author(s): Furlong RA, Keramatipour M, Ho LW, Rubinsztein JS, Michael A, Walsh C, Paykel ES, Rubinsztein DC. Source: American Journal of Medical Genetics. 2000 December 4; 96(6): 733-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11121171&dopt=Abstract
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Parental attitudes towards early intervention in children at high risk for affective disorders. Author(s): Post RM, Leverich GS, Fergus E, Miller R, Luckenbaugh D. Source: Journal of Affective Disorders. 2002 July; 70(2): 117-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117623&dopt=Abstract
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Quantitative analysis of leukocyte mitochondrial DNA deletion in affective disorders. Author(s): Kato T, Winokur G, McMahon FJ, DePaulo JR, Crowe RR. Source: Biological Psychiatry. 1997 September 1; 42(5): 311-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9276070&dopt=Abstract
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Quantitative assessment of smooth pursuit gain and catch-up saccades in schizophrenia and affective disorders. Author(s): Abel LA, Friedman L, Jesberger J, Malki A, Meltzer HY. Source: Biological Psychiatry. 1991 June 1; 29(11): 1063-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1873370&dopt=Abstract
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Quantitative proton magnetic resonance spectroscopy of the basal ganglia in patients with affective disorders. Author(s): Hamakawa H, Kato T, Murashita J, Kato N. Source: European Archives of Psychiatry and Clinical Neuroscience. 1998; 248(1): 53-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9561353&dopt=Abstract
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Rational polypharmacy in the bipolar affective disorders. Author(s): Post RM, Ketter TA, Pazzaglia PJ, Denicoff K, George MS, Callahan A, Leverich G, Frye M. Source: Epilepsy Res Suppl. 1996; 11: 153-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9294735&dopt=Abstract
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Reducing the risk for suicide in schizophrenia and affective disorders. Author(s): Meltzer HY, Baldessarini RJ. Source: The Journal of Clinical Psychiatry. 2003 September; 64(9): 1122-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14628990&dopt=Abstract
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Regional cerebral blood flow in patients with affective disorders. Author(s): Delvenne V, Delecluse F, Hubain PP, Schoutens A, De Maertelaer V, Mendlewicz J. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1990 September; 157: 359-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2245265&dopt=Abstract
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Relationship between affective disorders and Axis II diagnoses in geropsychiatric patients. Author(s): Molinari V, Marmion J. Source: Journal of Geriatric Psychiatry and Neurology. 1995 January; 8(1): 61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7710650&dopt=Abstract
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Relationship between prophylactic effect of lithium therapy and family history of affective disorders. Author(s): Engstrom C, Astrom M, Nordqvist-Karlsson B, Adolfsson R, Nylander PO. Source: Biological Psychiatry. 1997 September 15; 42(6): 425-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9285078&dopt=Abstract
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Reliability of the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) mania and rapid cycling sections. Author(s): Geller B, Zimerman B, Williams M, Bolhofner K, Craney JL, DelBello MP, Soutullo C. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 April; 40(4): 450-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11314571&dopt=Abstract
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Research in affective disorders comes of age. Author(s): Kupfer DJ. Source: The American Journal of Psychiatry. 1999 February; 156(2): 165-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9989549&dopt=Abstract
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Research on reducing burden of affective disorders for special populations: introduction and general recommendation. Author(s): Miranda J, Gonzalez JJ; NIMH Affective Disorders Workgroup. Source: Mental Health Services Research. 2002 December; 4(4): 223-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558007&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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Risk factors for substance use disorders among inpatients with major affective disorders in Taiwan Chinese. Author(s): Bai YM, Lin CC, Hu PG, Yeh HS. Source: General Hospital Psychiatry. 1998 November; 20(6): 377-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9854651&dopt=Abstract
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Schizotypal symptoms and signs in the Roscommon Family Study. Their factor structure and familial relationship with psychotic and affective disorders. Author(s): Kendler KS, McGuire M, Gruenberg AM, Walsh D. Source: Archives of General Psychiatry. 1995 April; 52(4): 296-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7702446&dopt=Abstract
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Season of birth: comparison of patients with schizophrenia, affective disorders and alcoholism. Author(s): Modestin J, Ammann R, Wurmle O. Source: Acta Psychiatrica Scandinavica. 1995 February; 91(2): 140-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7778473&dopt=Abstract
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Seasonality in affective disorders in Switzerland. Author(s): Wirz-Justice A, Graw P, Krauchi K, Wacker HR. Source: Acta Psychiatrica Scandinavica. Supplementum. 2003; (418): 92-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956822&dopt=Abstract
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Self-esteem, social adjustment and suicidality in affective disorders. Author(s): Daskalopoulou EG, Dikeos DG, Papadimitriou GN, Souery D, Blairy S, Massat I, Mendlewicz J, Stefanis CN. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2002 September; 17(5): 265-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381496&dopt=Abstract
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Sensory evoked potentials in patients with affective disorders accompanying suicidal behavior. Author(s): Wang H, Chen X, Bai P, Yin L. Source: Chinese Medical Journal. 2002 November; 115(11): 1675-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609086&dopt=Abstract
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Severe tardive dyskinesia in affective disorders: treatment with vitamin E and C. Author(s): Michael N, Sourgens H, Arolt V, Erfurth A. Source: Neuropsychobiology. 2002; 46 Suppl 1: 28-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571430&dopt=Abstract
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Smooth pursuit performance in patients with affective disorders or schizophrenia and normal controls: analysis with specific oculomotor measures, RMS error and qualitative ratings. Author(s): Friedman L, Jesberger JA, Siever LJ, Thompson P, Mohs R, Meltzer HY. Source: Psychological Medicine. 1995 March; 25(2): 387-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7675926&dopt=Abstract
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Social influences on bipolar affective disorders. Author(s): Ramana R, Bebbington P. Source: Social Psychiatry and Psychiatric Epidemiology. 1995 July; 30(4): 152-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7491510&dopt=Abstract
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Substance P and Substance P receptor antagonists in the pathogenesis and treatment of affective disorders. Author(s): Herpfer I, Lieb K. Source: World J Biol Psychiatry. 2003 April; 4(2): 56-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692775&dopt=Abstract
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Suicide, suicidality and suicide prevention in affective disorders. Author(s): Moller HJ. Source: Acta Psychiatrica Scandinavica. Supplementum. 2003; (418): 73-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956819&dopt=Abstract
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The circadian system and the therapeutics of the affective disorders. Author(s): Healy D, Waterhouse JM. Source: Pharmacology & Therapeutics. 1995 February; 65(2): 241-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7792317&dopt=Abstract
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The clinical nature and formal diagnosis of premenstrual, postpartum, and perimenopausal affective disorders. Author(s): Rapkin AJ, Mikacich JA, Moatakef-Imani B, Rasgon N. Source: Current Psychiatry Reports. 2002 December; 4(6): 419-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441021&dopt=Abstract
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The dichotomy of schizophrenia and affective disorders in extended pedigrees. Author(s): Maier W, Lichtermann D, Franke P, Heun R, Falkai P, Rietschel M. Source: Schizophrenia Research. 2002 October 1; 57(2-3): 259-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223257&dopt=Abstract
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The economic burden of affective disorders. Author(s): Rice DP, Miller LS. Source: The British Journal of Psychiatry. Supplement. 1995 April; (27): 34-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7794592&dopt=Abstract
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The metyrapone test in affective disorders and schizophrenia II. Changes upon treatment. Author(s): Perini GI, Fava GA, Morphy MA, Carson SW, Molnar G, Jusko WJ. Source: Journal of Affective Disorders. 1984 December; 7(3-4): 265-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6151957&dopt=Abstract
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The Munich Vulnerability Study on Affective Disorders: risk factors for unipolarity versus bipolarity. Author(s): Modell S, Huber J, Holsboer F, Lauer CJ. Source: Journal of Affective Disorders. 2003 April; 74(2): 173-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706519&dopt=Abstract
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The Munich Vulnerability Study on Affective Disorders: stability of polysomnographic findings over time. Author(s): Modell S, Ising M, Holsboer F, Lauer CJ. Source: Biological Psychiatry. 2002 September 1; 52(5): 430-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12242059&dopt=Abstract
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The relationship between anxiety and substance use disorders among individuals with severe affective disorders. Author(s): Goodwin RD, Stayner DA, Chinman MJ, Wu P, Tebes JK, Davidson L. Source: Comprehensive Psychiatry. 2002 July-August; 43(4): 245-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107861&dopt=Abstract
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The serotonin transporter intronic VNTR enhancer correlated with a predisposition to affective disorders has distinct regulatory elements within the domain based on the primary DNA sequence of the repeat unit. Author(s): Lovejoy EA, Scott AC, Fiskerstrand CE, Bubb VJ, Quinn JP. Source: The European Journal of Neuroscience. 2003 January; 17(2): 417-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542679&dopt=Abstract
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Thyroid function and affective disorders. Author(s): Green AI. Source: Hosp Community Psychiatry. 1984 December; 35(12): 1188-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6439621&dopt=Abstract
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Underuse of evidence-based pharmacotherapies for affective disorders. Author(s): Dwight-Johnson M, Lagomasino IT, Simpson GM. Source: Psychiatric Services (Washington, D.C.). 2003 August; 54(8): 1076-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883130&dopt=Abstract
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Update on neuroreceptor mechanisms and their implication for the pharmacotherapy of affective disorders. Author(s): Sulser F. Source: The Journal of Clinical Psychiatry. 1986 October; 47 Suppl: 13-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3020011&dopt=Abstract
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Urinary 3-methoxy-4-hydroxyphenylglycol and major affective disorders. A replication and new findings. Author(s): Muscettola G, Potter WZ, Pickar D, Goodwin FK. Source: Archives of General Psychiatry. 1984 April; 41(4): 337-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6703853&dopt=Abstract
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Urinary adenosine 3',5'-monophosphate excretion in affective disorders. Author(s): Paul MI, Ditzion BR, Pauk GL, Janowsky DS. Source: The American Journal of Psychiatry. 1970 April; 126(10): 1493-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4314024&dopt=Abstract
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Urinary MHPG, stress response, personality factors and somatosensory evoked potentials in normal subjects and patients with major affective disorders. Author(s): Buchsbaum MS, Muscettola G, Goodwin FK. Source: Neuropsychobiology. 1981; 7(4): 212-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7196513&dopt=Abstract
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Use of biologic markers in a general hospital affective disorders program. Author(s): Lieber AL, Newbury N. Source: The Journal of Clinical Psychiatry. 1985 June; 46(6): 217-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3922959&dopt=Abstract
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Use of selective serotonin reuptake inhibitors and other serotonergic drugs in the biological dissection of affective disorders. Author(s): Nutt DJ, Wilson SJ, Coupland NJ. Source: International Clinical Psychopharmacology. 1995 January; 9 Suppl 4: 53-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7622825&dopt=Abstract
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Use of statistical techniques in classification of affective disorders. Author(s): Gurney C, Roth M, Garside RF. Source: Proc R Soc Med. 1970 March; 63(3): 232-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5445556&dopt=Abstract
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Use of the Research Diagnostic Criteria and the Schedule for Affective Disorders and Schizophrenia to study affective disorders. Author(s): Endicott J, Spitzer RL. Source: The American Journal of Psychiatry. 1979 January; 136(1): 52-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=758828&dopt=Abstract
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Using Peplau's model in affective disorders. Author(s): Bristow F, Callaghan P. Source: Nurs Times. 1991 May 1-7; 87(18): 40-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2023841&dopt=Abstract
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Validity of the Millon Clinical Multiaxial Inventory in the assessment of affective disorders. Author(s): Choca J, Bresolin L, Okonek A, Ostrow D. Source: Journal of Personality Assessment. 1988 Spring; 52(1): 96-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3361415&dopt=Abstract
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Valproate treatment of comorbid panic disorder and affective disorders in two alcoholic patients. Author(s): Brady KT, Sonne S, Lydiard RB. Source: Journal of Clinical Psychopharmacology. 1994 February; 14(1): 81-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8151011&dopt=Abstract
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Verapamil in affective disorders: a controlled, double-blind study. Author(s): Hoschl C, Kozeny J. Source: Biological Psychiatry. 1989 January 15; 25(2): 128-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2649156&dopt=Abstract
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Verbal memory deficits associated with major affective disorders: a comparison of unipolar and bipolar patients. Author(s): Wolfe J, Granholm E, Butters N, Saunders E, Janowsky D. Source: Journal of Affective Disorders. 1987 July-August; 13(1): 83-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2959704&dopt=Abstract
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Visual perceptual dysfunction in patients with schizophrenic and affective disorders versus control subjects. Author(s): Flach F, Kaplan M, Bengelsdorf H, Orlowski B, Friedenthal S, Weisbard J, Carmody D. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 1992 Fall; 4(4): 4227. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1422169&dopt=Abstract
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Vitamin B12 and folate levels and lithium administration in patients with affective disorders. Author(s): Cervantes P, Ghadirian AM, Vida S. Source: Biological Psychiatry. 1999 January 15; 45(2): 214-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9951569&dopt=Abstract
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Vocal indicators of affective disorders. Author(s): Scherer KR, Zei B. Source: Psychotherapy and Psychosomatics. 1988; 49(3-4): 179-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3070621&dopt=Abstract
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Voluntary control of saccadic eye movements in patients with schizophrenic and affective disorders. Author(s): Fukushima J, Morita N, Fukushima K, Chiba T, Tanaka S, Yamashita I. Source: Journal of Psychiatric Research. 1990; 24(1): 9-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2366215&dopt=Abstract
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Vulnerability of Jews to affective disorders. Author(s): Levav I, Kohn R, Golding JM, Weissman MM. Source: The American Journal of Psychiatry. 1997 July; 154(7): 941-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9210744&dopt=Abstract
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Vulnerability to delusions over time in schizophrenia and affective disorders. Author(s): Harrow M, MacDonald AW 3rd, Sands JR, Silverstein ML. Source: Schizophrenia Bulletin. 1995; 21(1): 95-109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7770745&dopt=Abstract
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Water distribution in affective disorders. Author(s): Anderson WM, Dawson J. Source: Journal of Psychosomatic Research. 1967 November; 11(3): 291-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6076922&dopt=Abstract
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Well-being therapy. A novel psychotherapeutic approach for residual symptoms of affective disorders. Author(s): Fava GA, Rafanelli C, Cazzaro M, Conti S, Grandi S. Source: Psychological Medicine. 1998 March; 28(2): 475-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9572104&dopt=Abstract
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What do we know about affective disorders? Author(s): Favazza A. Source: The American Journal of Psychiatry. 1986 October; 143(10): 1328. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3766813&dopt=Abstract
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Why not treat melancholia with melatonin and tryptophan and treat seasonal affective disorders with bright light? Author(s): Maurizi CP. Source: Medical Hypotheses. 1988 December; 27(4): 271-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3226357&dopt=Abstract
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X-linkage in affective and schizoaffective disorders: genetic and diagnostic implications. Author(s): Baron M, Risch N. Source: Neuropsychobiology. 1982; 8(6): 304-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6984491&dopt=Abstract
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CHAPTER 2. NUTRITION AND AFFECTIVE DISORDERS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and affective disorders.
Finding Nutrition Studies on Affective Disorders 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 “affective disorders” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 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 affective disorders: •
Shedding dietary light on seasonal affective disorder. Source: Tufts-University-diet-and-nutrition-letter (USA). (March 1994). volume 12(1) page 1-2.
Additional consumer oriented references include:
The following information is typical of that found when using the “Full IBIDS Database” to search for “affective disorders” (or a synonym): •
5-HT uptake in platelets of lithium-treated patients with affective disorders and of healthy controls. Author(s): Department of Psychiatry, Free University of Berlin, Germany. Source: Thies Flechtner, K Weigel, I Muller Oerlinghausen, B Pharmacopsychiatry. 1994 July; 27 Suppl 14-6 0176-3679
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Affective disorders in cultural context. Author(s): Division of Social and Transcultural Psychiatry, McGill University, Montreal, Quebec, Canada.
[email protected] Source: Kirmayer, L J Groleau, D Psychiatr-Clin-North-Am. 2001 September; 24(3): 46578, vii 0193-953X
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An intronic polymorphic domain often associated with susceptibility to affective disorders has allele dependent differential enhancer activity in embryonic stem cells. Author(s): Department of Veterinary Pathology, University of Edinburgh, UK. Source: Fiskerstrand, C E Lovejoy, E A Quinn, J P FEBS-Lett. 1999 September 17; 458(2): 171-4 0014-5793
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Bone mineral density in pre-and post-menopausal women with affective disorder treated with long-term L-thyroxine augmentation. Author(s): Department of Psychiatry, Bipolar Disorders Unit, University of Pennsylvania Medical Center, 3600 Market Street, Room 800, Philadelphia, PA 19104, USA.
[email protected] Source: Gyulai, L Bauer, M Garcia Espana, F Hierholzer, J Baumgartner, A Berghofer, A Whybrow, P C J-Affect-Disord. 2001 October; 66(2-3): 185-91 0165-0327
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Carbamazepine as adjunct or alternative to lithium in the prophylaxis of recurrent affective disorders. Author(s): Department of Clinical Research, Troponwerke, Koln, Germany. Source: Fritze, J Beneke, M Lanczik, M Schneider, B Walden, J Pharmacopsychiatry. 1994 September; 27(5): 181-5 0176-3679
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Clinical predictors of response to lamotrigine and gabapentin monotherapy in refractory affective disorders. Author(s): National Institute of Mental Health, Biological Psychiatry Branch, Bethesda, Maryland 20892, USA. Source: Obrocea, Gabriela V Dunn, Robert M Frye, Mark A Ketter, Terence A Luckenbaugh, David A Leverich, Gabriele S Speer, Andrew M Osuch, Elizabeth A Jajodia, Kamal Post, Robert M Biol-Psychiatry. 2002 February 1; 51(3): 253-60 0006-3223
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Compliance with long-term lithium treatment in major affective disorders. Author(s): Clinique Psychiatrique, Centre Hospitalier Regional, Strasbourg, France.
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Source: Danion, J M Neunreuther, C Krieger Finance, F Imbs, J L Singer, L Pharmacopsychiatry. 1987 September; 20(5): 230-1 0176-3679 •
Diurnal and seasonal variations of melatonin and serotonin in women with seasonal affective disorder. Author(s): Institute of Physiology, Russian Academy of Medical Science, Novosibirsk. Source: Danilenko, K V Putilov, A A Russkikh, G S Duffy, L K Ebbesson, S O ArcticMed-Res. 1994 July; 53(3): 137-45 0782-226X
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Eating style in seasonal affective disorder: who will gain weight in winter? Author(s): Psychiatric University Clinic, Basel, Switzerland. Source: Krauchi, K Reich, S Wirz Justice, A Compr-Psychiatry. 1997 Mar-April; 38(2): 807 0010-440X
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Effect of lithium treatment on the GH-clonidine test in affective disorders. Author(s): Ospedale Psichiatrico Pini, Milano, Italy. Source: Brambilla, F Catalano, M Lucca, A Smeraldi, E Eur-J-Clin-Pharmacol. 1988; 35(6): 601-5 0031-6970
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Effect of prophylactic treatment on suicide risk in patients with major affective disorders. Data from a randomized prospective trial. Author(s): Department of Psychiatry, Freie Universitat Berlin, Germany. Source: Thies Flechtner, K Muller Oerlinghausen, B Seibert, W Walther, A Greil, W Pharmacopsychiatry. 1996 May; 29(3): 103-7 0176-3679
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Effects of chronic treatment with trihexyphenidyl and carbamazepine alone or in combination with haloperidol on substance P content in rat brain: a possible implication of substance P in affective disorders. Author(s): Division of Mental Disorder Research, National Center of Neurology and Psychiatry, Tokyo, Japan. Source: Mitsushio, H Takashima, M Mataga, N Toru, M J-Pharmacol-Exp-Ther. 1988 June; 245(3): 982-9 0022-3565
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Epi-inositol and inositol depletion: two new treatment approaches in affective disorder. Author(s): Beer-Sheba Mental Health Center, PO Box 4600, Beer-Sheba, Israel. Source: Bersudsky, Y Einat, H Stahl, Z Belmaker, R H Curr-Psychiatry-Repage 1999 December; 1(2): 141-7 1523-3812
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Erythrocyte membrane sodium-potassium adenosine triphosphatase activity in affective disorders. Author(s): Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India. Source: Reddy, P L Khanna, S Subhash, M N Channabasavanna, S M Rao, B S J-NeuralTransm-Gen-Sect. 1992; 89(3): 209-18 0300-9564
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Factors associated with relapse during maintenance treatment of affective disorders. Author(s): Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892. Source: Leverich, G S Post, R M Rosoff, A S Int-Clin-Psychopharmacol. 1990 April; 5(2): 135-56 0268-1315
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Gender differences in glycosylated hemoglobin levels in seasonal affective disorder patients and controls. Author(s): Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, MD 20892-1390, USA.
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Source: Neuhaus, I M Schwartz, P J Turner, E H Feldman Naim, S Matthews, J R Lam, G Rosenthal, N E Compr-Psychiatry. 1999 May-June; 40(3): 234-7 0010-440X •
Hypericum in the treatment of seasonal affective disorders. Author(s): Psychiatrische Universitatsklinik Bonn, Germany. Source: Martinez, B Kasper, S Ruhrmann, S Moller, H J J-Geriatr-Psychiatry-Neurol. 1994 October; 7 Suppl 1S29-33 0891-9887
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Intracellular calcium signalling in peripheral cells of patients with bipolar affective disorder. Author(s): Department of Psychiatry, University of Colorado School of Medicine, Denver 80262. Source: Dubovsky, S L Thomas, M Hijazi, A Murphy, J Eur-Arch-Psychiatry-ClinNeurosci. 1994; 243(5): 229-34 0940-1334
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Length of lithium treatment needed to eliminate the high mortality of affective disorders. Author(s): Department of Psychiatry, Free University of Berlin, Germany. Source: Ahrens, B Muller Oerlinghausen, B Grof, P Br-J-Psychiatry-Suppl. 1993 September; (21): 27-9 0960-5371
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Lithium in the prophylaxis of affective disorders: a twenty years experience. Author(s): Dept. Psychiatry, Hradec Kralove, CSSR. Source: Hanus, H Zapletalek, M Kindernayova, H Tuma, I Act-Nerv-Super-(Praha). 1989 April; 31(1): 27 0001-7604
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Long-term therapy of affective disorders: monotherapy or polypharmacy? Author(s): Psychiatric Hospital Weinsberg, FRG. Source: Konig, W Rissom, R Kalfoglu, G Stein, A Reimer, F Pharmacopsychiatry. 1988 November; 21(6): 272-3 0176-3679
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Magnetic resonance spectroscopy in affective disorders. Author(s): Department of Psychiatry, Shiga University of Medical Science, Japan.
[email protected] Source: Kato, T Inubushi, T Kato, N J-Neuropsychiatry-Clin-Neurosci. 1998 Spring; 10(2): 133-47 0895-0172
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Melatonin in psychiatric disorders - subtyping affective disorder. Author(s): Institute of Clinical Neuroscience, Department of Psychiatry, Karolinska Institute, Stockholm, Sweden.
[email protected] Source: Wahlund, B Biol-Signals-Recept. 1999 Jan-April; 8(1-2): 120-5 1422-4933
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Modulation of 5-HT2 receptor-mediated intracellular calcium movement in platelets and its function in affective disorders. Author(s): Division of Mental Disorder Research, National Institute of Neuroscience, NCNP, Kodaira. Source: Kagaya, A Mikuni, M Takahashi, K Jpn-J-Psychiatry-Neurol. 1991 March; 45(1): 117-8 0912-2036
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Mortality in 497 patients with affective disorders attending a lithium clinic or after having left it. Author(s): Department of Internal Medicine, Soder Hospital, Stockholm, Sweden. Source: Kallner, G Lindelius, R Petterson, U Stockman, O Tham, A Pharmacopsychiatry. 2000 January; 33(1): 8-13 0176-3679
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Neurochemical effects of dieting: relevance to changes in eating and affective disorders. Source: Cowen, P.J. Anderson, I.M. Fairburn, C.G. Bristol-Myers-Squibb-Mead-JohnsonNutr-Symp. San Diego, Calif. : Academic Press. 1992. volume 10 page 269-284.
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Neuroendocrine factors in affective disorders. Source: Tirrell, C DeForest, D Arch-Psychiatr-Nurs. 1987 August; 1(4): 225-9 0883-9417
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Novel uses of thyroid hormones in patients with affective disorders. Author(s): Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill 27599-7160, USA. Source: Prange, A J Thyroid. 1996 October; 6(5): 537-43 1050-7256
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On the pathogenesis of abnormal involuntary movements in lithium-treated patients with major affective disorder. Author(s): Department of Psychiatry and Neurochemistry, St. Lars Hospital, University of Lund, Sweden. Source: Axelsson, R Nilsson, A Eur-Arch-Psychiatry-Clin-Neurosci. 1991; 241(1): 1-7 0940-1334
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Pharmacogenetics in affective disorders. Author(s): Department of Psychiatry, Instituto Scientifico H San Raffaele, Vita-Salute University, Fondazione Centro San Raffaele del Monte Tabor, Via Stamira D'Ancona 20, 20127, Milan, Italy.
[email protected] Source: Serretti, Alessandro Lilli, Roberta Smeraldi, Enrico Eur-J-Pharmacol. 2002 March 8; 438(3): 117-28 0014-2999
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Quality of interepisodic periods in patients with affective disorders under long-term lithium treatment. Author(s): Department of Psychiatry, Free University of Berlin (West), Germany. Source: Volk, J Muller Oerlinghausen, B Pharmacopsychiatry. 1988 November; 21(6): 426-7 0176-3679
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Rapid cycling in severely multidisabled children: a form of bipolar affective disorder? Author(s): Department of Pediatrics, University of British Columbia, Vancouver, Canada. Source: January, J E Abroms, I F Freeman, R D Brown, G M Espezel, H Connolly, M B Pediatr-Neurol. 1994 February; 10(1): 34-9 0887-8994
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Rational polypharmacy in the bipolar affective disorders. Author(s): Biological Psychiatry Branch, NIMH, Bethesda, MD 20892-1272, USA. Source: Post, R M Ketter, T A Pazzaglia, P J Denicoff, K George, M S Callahan, A Leverich, G Frye, M Epilepsy-Res-Suppl. 1996; 11153-80 0922-9833
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Schizophrenia and bipolar affective disorders: likenesses and differences. Author(s): New York State Psychiatric Institute, N.Y. 10032. Source: Klein, D F Hillside-J-Clin-Psychiatry. 1989; 11(1): 3-15 0193-5216
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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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Supraphysiological doses of L-thyroxine in the maintenance treatment of prophylaxis-resistant affective disorders. Author(s): Department of Psychiatry and Psychotherapy, Charite, Humboldt University of Berlin, Berlin, Germany.
[email protected] Source: Bauer, M Berghofer, A Bschor, T Baumgartner, A Kiesslinger, U Hellweg, R Adli, M Baethge, C Muller Oerlinghausen, B Neuropsychopharmacology. 2002 October; 27(4): 620-8 0893-133X
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The long term prophylaxis of affective disorders. Author(s): Centro Lucio Bini, Rome, Italy. Source: Koukopoulos, A Reginaldi, D Minnai, G Serra, G Pani, L Johnson, F N AdvBiochem-Psychopharmacol. 1995; 49127-47 0065-2229
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The perimenopause and affective disorders. Author(s): Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda, Maryland 20892-1276, USA. Source: Schmidt, P J Roca, C A Bloch, M Rubinow, D R Semin-Reprod-Endocrinol. 1997 February; 15(1): 91-100 0734-8630
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The role of lithium in the affective disorders. Author(s): Department of Psychological Medicine, University of Sydney, Concord Hospital, New South Wales, Australia. Source: Johnson, G Aust-N-Z-J-Psychiatry. 1996 December; 30(6): 715-9 0004-8674
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The value of TSH in affective disorders. Source: Clower, C G Indiana-Med. 1989 August; 82(8): 608-10 0746-8288
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Therapy of affective disorders. Author(s): College of Pharmacy, University of Iowa, Iowa City. Source: Alexander, B Cook, B Prim-Care. 1990 September; 17(3): 565-88 0095-4543
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Thyroid function in affective disorders and alcoholism. Author(s): Vanderbilt University Medical Center, Nashville, Tennessee. Source: Loosen, P T Neurol-Clin. 1988 February; 6(1): 55-82 0733-8619
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Traditional Chinese medicine typing of affective disorders and treatment. Author(s): Shanghai Mental Health Center, China. Source: Zhang, L D Zhang, Y L Xu, S H Zhou, G Jin, S B Am-J-Chin-Med. 1994; 22(3-4): 321-7 0192-415X
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Treatment of affective disorder and obesity with topiramate. Author(s): College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.
[email protected] Source: Teter, C J Early, J J Gibbs, C M Ann-Pharmacother. 2000 November; 34(11): 12625 1060-0280
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Tryptophan depletion in lithium-stabilized patients with affective disorder. Author(s): Department of Clinical Neuroscience, St Goran's Hospital, Karolinska Institute, Stockholm, Sweden.
[email protected] Source: Johnson, L El Khoury, A Aberg Wistedt, A Stain Malmgren, R Mathe, A A Int-JNeuropsychopharmacol. 2001 December; 4(4): 329-36 1461-1457
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Use of selective serotonin reuptake inhibitors and other serotonergic drugs in the biological dissection of affective disorders. Author(s): Psychopharmacology Unit, School of Medical Sciences, Bristol, UK. Source: Nutt, D J Wilson, S J Coupland, N J Int-Clin-Psychopharmacol. 1995 January; 9 Suppl 453-9 0268-1315
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Why not treat melancholia with melatonin and tryptophan and treat seasonal affective disorders with bright light? Source: Maurizi, C P Med-Hypotheses. 1988 December; 27(4): 271-6 0306-9877
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
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The following is a specific Web list relating to affective disorders; 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 Vitamin D Source: Healthnotes, Inc.; www.healthnotes.com
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Minerals Fluoxetine Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND AFFECTIVE DISORDERS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to affective disorders. 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 affective disorders 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 “affective disorders” (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 affective disorders: •
“Diet pills” and major depression in the Canadian population. Author(s): Patten SB. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 June; 46(5): 438-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11441784&dopt=Abstract
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Affective disorders in cultural context. Author(s): Kirmayer LJ, Groleau D. Source: The Psychiatric Clinics of North America. 2001 September; 24(3): 465-78, Vii. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11593857&dopt=Abstract
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Efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of affective disorders. Author(s): Schlaepfer TE, Kosel M, Nemeroff CB. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 February; 28(2): 201-5. Epub 2002 August 01. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589372&dopt=Abstract
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Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy. Author(s): Nahas Z, Kozel FA, Li X, Anderson B, George MS. Source: Bipolar Disorders. 2003 February; 5(1): 40-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656937&dopt=Abstract
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Light therapy for seasonal affective disorder in primary care: randomised controlled trial. Author(s): Wileman SM, Eagles JM, Andrew JE, Howie FL, Cameron IM, McCormack K, Naji SA. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2001 April; 178: 311-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11282809&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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Psycho-affective disorder in intensive care units: a review. Author(s): Hewitt J. Source: Journal of Clinical Nursing. 2002 September; 11(5): 575-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12201884&dopt=Abstract
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Putative common pathways in therapeutic brain stimulation for affective disorders. Author(s): Bolwig TG. Source: Cns Spectr. 2003 July; 8(7): 490-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894030&dopt=Abstract
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Spiritual beliefs in bipolar affective disorder: their relevance for illness management. Author(s): Mitchell L, Romans S. Source: Journal of Affective Disorders. 2003 August; 75(3): 247-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880937&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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Update on seasonal affective disorder (SAD). Author(s): Mazarelo F, Donaldson D. Source: J R Soc Health. 1999 June; 119(2): 77-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11042997&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 affective disorders; 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 Bipolar Disorder Source: Healthnotes, Inc.; www.healthnotes.com
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Depression Source: Healthnotes, Inc.; www.healthnotes.com Depression Source: Integrative Medicine Communications; www.drkoop.com Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Seasonal Affective Disorder Source: Healthnotes, Inc.; www.healthnotes.com Seasonal Affective Disorder (SAD) Source: Integrative Medicine Communications; www.drkoop.com •
Alternative Therapy Color Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,683,00.html Light Therapy Source: Healthnotes, Inc.; www.healthnotes.com Light Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,713,00.html
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Herbs and Supplements 5-Hydroxytryptophan Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hypericum Perforatum Source: Integrative Medicine Communications; www.drkoop.com Klamathweed Source: Integrative Medicine Communications; www.drkoop.com Lithium Source: Healthnotes, Inc.; www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com
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Melatonin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,804,00.html Phenylalanine Source: Healthnotes, Inc.; www.healthnotes.com Phenylalanine Source: Prima Communications, Inc.www.personalhealthzone.com Pregnenolone Source: Healthnotes, Inc.; www.healthnotes.com Selective Serotonin Reuptake Inhibitors (SSRIS) Source: Integrative Medicine Communications; www.drkoop.com St. John’s Wort Alternative names: Hypericum perforatum Source: Healthnotes, Inc.; www.healthnotes.com St. John's Wort Alternative names: Hypericum perforatum, Klamathweed Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Source: Prima Communications, Inc.www.personalhealthzone.com St. John's Wort Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,824,00.html
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 AFFECTIVE DISORDERS Overview In this chapter, we will give you a bibliography on recent dissertations relating to affective disorders. 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 “affective disorders” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on affective disorders, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Affective Disorders 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 affective disorders. 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: •
Central-Peripheral Aspects of Serotonin Metabolism : a Model for the Evaluation of Peripherally-Measured Monoamine Metabolites Following Peripheral Decarboxylase Inhibition As Indices of Brain Monoamine Function in Affective Disorders by Warsh, Jerry Jerome; PhD from University of Toronto (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK28012
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Cognitive Patterns in Symptomatic Depression between Unipolar and Bipolar Depressives (Mood Disorder, Clinical, Abnormal Psychology, Affective Disorders) by Brown, Paul Wendell, PhD from The University of Mississippi, 1984, 75 pages http://wwwlib.umi.com/dissertations/fullcit/8502608
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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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Gender and Illness among Lauan Fijians: Somatic and Affective Disorder by Herr, Barbara, PhD from University of California, Los Angeles, 1983, 334 pages http://wwwlib.umi.com/dissertations/fullcit/8408813
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Self-rated Depression in Adolescents (High School, Affective Disorders) by Sullivan, William Oscar, PhD from University of South Carolina, 1985, 174 pages http://wwwlib.umi.com/dissertations/fullcit/8528216
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Sensory Modulation and Affective Disorders in Children and Adolescents with Asperger Syndrome by Pfeiffer, Elizabeth A., PhD from Nova Southeastern University, 2003, 141 pages http://wwwlib.umi.com/dissertations/fullcit/3099904
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The Effects of Depression on Academic and Social-Behavioral Performances of Latency-Aged Children (Underachievers, Elementary, Affective Disorders, Maria Kovacs, Warren Weinberg) by Whalen, Susan Joan, EDD from Clark University, 1985, 358 pages http://wwwlib.umi.com/dissertations/fullcit/8608773
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The Impact of Parental Alcoholism on Ego Development and Affective Disorders in Offspring (Alcoholism, Adult Children of Alcoholics) by Guerra, Linda L., PhD from Temple University, 1991, 149 pages http://wwwlib.umi.com/dissertations/fullcit/9207860
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The Relationship between Social Workers' Knowledge of Affective Disorders and the Timely Referral of Depressed Patients for Psychiatric Evaluation by Hollander, Susan L., PhD from Barry University School of Social Work, 1987, 188 pages http://wwwlib.umi.com/dissertations/fullcit/8807202
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The Relative Efficacy of Cluster Analysis of WISC-R/WRAT Scores in the Differential Diagnosis of Neuropsychological and Affective Disorders in Children and Adolescents by Barile, Frank Andrew, PhD from University of Pittsburgh, 1981, 108 pages http://wwwlib.umi.com/dissertations/fullcit/8202222
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 AFFECTIVE DISORDERS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning affective disorders.
Recent Trials on Affective Disorders The following is a list of recent trials dedicated to affective disorders.8 Further information on a trial is available at the Web site indicated. •
Clinical Trial of Propranolol for Seasonal Affective Disorder Condition(s): Seasonal Affective Disorder; Healthy 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 what dose of a new timedrelease tablet of the drug propranolol will reduce secretion of the hormone melatonin in healthy volunteers. This study will also determine whether suppressing melatonin will improve depressive symptoms in people with seasonal affective disorder (SAD). SAD (sometimes referred to as winter depression) is a condition in which people experience depression as a result of seasonal variations in light. Human brains have a circadian pacemaker that regulates many body functions. As the seasons change and light duration varies, the circadian pacemaker regulates seasonal behavior by transmitting a signal of day length to the pineal gland, which secretes the hormone melatonin. Melatonin secretion increases in the winter as the duration of light decreases. Evidence suggests that the melatonin signal of seasonal change is present in people with SAD but not in healthy volunteers; thus there is a possibility that seasonal changes which influence the duration of melatonin secretion control the course of illness in individuals with SAD. This study will determine whether propranolol can shorten the duration of melatonin secretion and mimic the effect of summer days to improve symptoms of depression in people with SAD. Healthy volunteers will be admitted to the hospital for about 2 days. The volunteers will receive either propranolol or placebo (an inactive pill)
8
These are listed at www.ClinicalTrials.gov.
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before going to bed and upon awakening. Blood samples will be collected at various times throughout the study. Participants with SAD will be interviewed periodically on an outpatient basis to determine the onset of depression in the fall or winter. Two weeks after depressive symptoms arise, participants will begin treatment with either propranolol or placebo. At the beginning of the treatment, participants will be hospitalized for about 2 days and will have blood collected at various times. During the hospital stay, participants will continue treatment with either propranolol or placebo in the morning and at night; all participants will receive propranolol at some point during the study. Participants will be interviewed weekly for 4 weeks. Premenopausal women with or without SAD will keep a record of their menstrual cycles and will use a urine test kit to identify the time of ovulation during the month before and after admission to the hospital. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016666 •
Cognitive Behavioral Therapy for the Treatment of Seasonal Affective Disorder (SAD) Condition(s): Seasonal Affective Disorder; Depression 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 assess the effectiveness of cognitive behavioral therapy (CBT) in treating seasonal affective disorder (SAD), commonly called the "winter blues." Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00076245
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Rapid Treatment for Psychotic Depression Condition(s): Affective Disorders, Psychotic 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 role of hormones in psychotic depression. This study will also determine the effectiveness of an investigational medication called mifepristone for treating patients with psychotic depression. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048269
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Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Condition(s): Mood Disorders; Affective Disorders, Psychotic; Bipolar Disorder; Cyclothymic Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: STEP-BD is the largest treatment study ever conducted for bipolar disorder. It is a long-term outpatient study (5 years) that aims to find out which treatments, or combinations of treatments, are most effective for treating episodes of depression and mania and for preventing recurrent episodes. In addition, the study will evaluate treatment effectiveness in terms of quality of life, adherence to treatment, ability to work, social functioning, and treatment cost-effectiveness. While many treatments are used currently for bipolar disorder, including medications and psychotherapies, doctors are uncertain which of these treatments or combination of treatments actually work best. Findings from STEP-BD will help improve the treatment standards used by doctors in everyday clinical practice. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012558
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 “affective disorders” (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 AFFECTIVE DISORDERS 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 “affective disorders” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on affective disorders, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Affective Disorders By performing a patent search focusing on affective disorders, 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. 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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The following is an example of the type of information that you can expect to obtain from a patent search on affective disorders: •
Amelioration of neurological disorders by the administration of (2R),(3S), and/or (2S),3(S) stereoisomers of valnoctamide Inventor(s): Bialer; Meir (Jerusalem, IL), Roeder; Michael (Gomaringen, DE), Schurig; Volker (Tubingen, DE), Spiegelstein; Ofer (Mevasseret Zion, IL), Yagen; Boris (Jerusalem, IL) Assignee(s): Yissum Research Development Company of the Hebrew University of Jerusalem (jerusalem, Il) Patent Number: 6,417,399 Date filed: July 13, 1999 Abstract: The present invention generally relates to the individual stereoisomers of the drug valnoctamide (a mixture of four stereoisomer kinds, VCD-valmethamide or 2ethyl-3-methyl pentanamide) useful in treatment of neurological and psychotic disorders such as different kinds of epilepsy and affective disorders, and useful as tranquilizers and to treat pain, and to pharmaceutical compositions containing, as an active ingredient, these stereoisomers. The present invention further relates to a method for stereoselective separation and quantification of the four stereoisomers from a racemic mixture of VCD or plasma of patients treated with the racemic drug. The present invention further relates to a unique method for the synthesis of the individual stereoisomers. Excerpt(s): The present invention further relates to a unique method for the synthesis of the individual stereoisomers. Epilepsy is an ancient disease which affects about 1% of the global population. Despite the progress in antiepileptic therapy, about 25% of the epileptic patients continue to suffer from uncontrolled seizures and medication toxicity. At present, there are four major epileptic drugs in use: phenobarbital, phenytoin, carbamazepine and valproic acid. Valproic acid (VPA) is one of the major antiepileptic drugs. It has two major side effects, teratogenicity and hepatotoxicity, which have been associated with valproate therapy. Valnoctamide (VCD-valmethamide or 2-ethyl-3methyl pentanamide) is an isomer of valpromide (VPD) and is sold as an over- thecounter drug in several European countries. It has been available clinically for many decades and is still used as a mild tranquilizer and occasionally as an antiepileptic drug (Chambon JP, Perio A, Neurosci. Lett [Suppl]5: S327-S327, 1980). Valpromide (VPD) is used as an anticonvulsant and antipsychotic agent, and in humans it is a prodrug of valproic acid (VPA). VPD may also be useful in treatment of neurological disorders and psychotic or affective disorders such as convulsions and epilepsy, and useful as tranquilizers and to treat pain. Recently, interest in VCD was revived by the observation that this compound possesses marked anticonvulsant activity in animal models. Both VCD and VPD are three times more potent as anticonvulsants than VPA. In addition, VPD, unlike VPA, has not been found to be teratogenic in animals possibly because it contains a carboxamide moiety instead of a carboxylic acid. However, in humans VPD acts as a prodrug to VPA and therefore its superiority over VPA in animal models does not have clinical implications. Unlike VPD, VCD acts as a drug on its own in both animals and humans and undergoes only slow and very little transformation to its corresponding (less active) valnoctic acid (VCA). Based on its anticonvulsant potency, metabolic stability and lack of teratogenicity, VCD was viewed as having potential to become a new antiepileptic drug. It was recently found, however, that VCD is an inhibitor of the enzyme epoxide hydrolase. This inhibition was regarded as a drawback
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to the development of racemic VCD as a new antiepileptic drug. In the present invention, for the first time, characterization of the pharmacokinetics (PK) of the four stereoisomers of VCD in humans was performed This characterization clearly demonstrates that VCD pharmacokinetics is stereoselective, with one isomer exhibiting a much higher clearance and a shorter half-life compared with the other stereoisomers. Stereoselective pharmacokinetics has been demonstrated previously with different drugs, such as verapamil and mephenytoin, but this is the first time that PK stereoselectivity has been shown for an amide of an aliphatic short-chain fatty acid. Web site: http://www.delphion.com/details?pn=US06417399__ •
Aminoalkyloximes for treating depression and affective disorders Inventor(s): Freed; Brian S. (Phillipsburg, NJ), Hamer; R. Richard L. (Lebanon, NJ), Shutske; Gregory M. (Pittstown, NJ), Tomer, IV; John D. (Perkasie, PA) Assignee(s): Hoechst Marion Roussel, Inc. (cinncinnati, Oh) Patent Number: 5,686,447 Date filed: June 1, 1995 Abstract: Novel aminoalkyloximes, precursors and processes for the preparation thereof, and methods of treating depression and obsessive compulsive disorders are described. Excerpt(s): As used throughout the specification and appended claims, the term "alkyl" refers to a straight or branched chain hydrocarbon radical containing no unsaturation and having 1 to 8 carbon atoms. Examples of alkyl groups are methyl, ethyl, 1-propyl, 2propyl, 1-butyl, 1-hexyl, 3-hexyl, 4-heptyl, 2-octyl and the like. The term "alkoxy" refers to a monovalent substituent which consists of an alkyl group linked through an ether oxygen having its free valence bond from the ether oxygen. Examples of alkoxy groups are methoxy, ethoxy, propoxy, 1-butoxy, 1-pentoxy, 3-hexoxy, 4-heptoxy, 2-octoxy and the like. The term "alkanol" refers to a compound formed by a combination of an alkyl group and hydroxy radical. Examples of alkanols are methanol, ethanol, 1- and 2propanol, 2,2-dimethylethanol, hexanol, octanol and the like. The term "halogen" refers to a member of the family fluorine, chlorine, bromine, or iodine. The term "lower" as applied to any of the aforementioned groups refers to a group having a carbon skeleton containing up to and including 6 carbon atoms. The compounds of the present invention which lack an element of symmetry exist as optical antipodes and as the racemic forms thereof. The optical antipodes may be prepared from the corresponding racemic forms by standard optical resolution techniques, involving, for example, the separation of diastereomeric salts of those instant compounds characterized by the presence of a basic amino group and an optically active acid, or by synthesis from optically active precursors. In the Z-isomer, the aminoalkyloxy group of the oxime function and the phenyl moiety, the group of greater priority, are cis to each other and in the E-isomer, the aminoalkyloxy group of the oxime function and the phenyl moiety, are trans to each other. The wiggly (.about.) line in the formulas of the aminoalkyloximes of formula 1 indicate that the compound may be the E- or Z-isomer. See B. Unterhalt, Methodicum Chimicum 6, 403 (1975), for a discussion of the E-Z nomenclature. Web site: http://www.delphion.com/details?pn=US05686447__
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Composition and methods employing it for the treatment of 5-HT-mediated disorders Inventor(s): Evenden; John (Wellesley, MA), Thorberg; Seth-Olov (Strangnas, SE) Assignee(s): Astra Aktiebolag (sodertalje, Se) Patent Number: 6,172,105 Date filed: July 9, 1999 Abstract: The invention relates to a composition comprising a first component (a) which is (R)-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxa mide hydrogen (2R,3R)-tartrate monohydrate and a second component (b) which is a 5-HT reuptake inhibitor, excluding citalopram and paroxetine. The invention is further directed to the preparation of the composition, pharmaceutical formulations containing said composition, and a method of treatment of affective disorders such as mood disorders and anxiety disorders with said composition, as well as a kit containing said composition. Excerpt(s): The present invention relates to a composition which comprises a first component (a) which is (R)-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1benzopyran-5-carboxa mide hydrogen (2R,3R)-tartrate monohydrate (NAD 299) and a second component (b) which is a 5-HT reuptake inhibitor, excluding citalopram and paroxetine. The present invention also relates to a process for the preparation of the inventive composition, pharmaceutical formulations containing said composition and to the use of said composition either by concomitant administration or by separate administration as an improvement of the treatment of affective disorders such as depression, anxiety, obsessive compulsive disorder (OCD), etc. Today, it is generally considered that antidepressants take 2-4 weeks to reach full clinical effect. In contrast, the side effects occur immediately. Thus, slow onset of action of antidepressants leads to a vulnerable period for patients in which they experience the side effects, but not the therapeutic effects of drugs. There is often a heavy burden on the treating physician to persuade the patient to continue with the treatment during this period. Furthermore, in suicidal patients, as the onset of action is gradual, initiative may be regained without the experiencing of full reversal of symptoms, leaving a window of risk for suicide and a frequent requirement for hospitalization. An antidepressant with fast onset of action would not only be beneficial due to the faster symptom reduction, but would also be more acceptable to patients and physicians and reduce the need for, and duration of, hospitalization. The same long period to reach full clinical effect has been shown in the treatment of other affective disorders such as anxiety and OCD. In WO 96/33710 is disclosed the combination of the compound (R)-5-carbamoyl-8-fluoro-3-N,Ndicyclobutylamino-3,4-dihydro-2H-1-benzopyr an, which has high affinity to 5-HT receptors and antagonizes 5-HT.sub.1A -mediated responses, with a serotonin reuptake inhibitor. Web site: http://www.delphion.com/details?pn=US06172105__
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Methods for diagnosing and assessing a predisposition to bipolar affective disorder Inventor(s): Adams; Linda Jacqueline (Mortdale, AU), Mitchell; Philip Bowden (Epping, AU), Schofield; Peter Robert (Marsfield, AU) Assignee(s): Garvan Institute of Medical Research (darlinghurst, Au) Patent Number: 6,274,352 Date filed: February 19, 1999
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Abstract: A method of assessing an individual's predisposition to bipolar affective disorder comprises determining the presence of one or more bipolar affective disorderlinked markers on chromosome 4 or analyzing allelic variation in relation to a bipolar affective disorder susceptibility gene on chromosome 4. Excerpt(s): This invention relates to methods for diagnosing and assessing a predisposition to bipolar affective disorder (BAD). In a first aspect, the present invention provides a method of assessing an individual's predisposition to bipolar affective disorder (BAD), comprising a step of determining the presence of a BADlinked marker(s) on chromosome 4. Preferably, the method comprises determining the presence of a BAD-linked marker(s) at the chromosomal locus 4q35. Web site: http://www.delphion.com/details?pn=US06274352__ •
Methods of neuroendocrine regulation of affective disorders Inventor(s): De Castro Paixao; Julio Licinio (Bethesda, MD), Flier; Jeffrey S. (West Newton, MA), Gold; Philip W. (Washington, DC), Wong; Ma-Li (Bethesda, MD) Assignee(s): Beth Israel Deaconess Medical Center (boston, Ma) Patent Number: 5,866,547 Date filed: January 20, 1998 Abstract: Methods of treating an affective disorder in an individual are disclosed. Affective disorders include major depression, melancholic and atypical subtypes, and dysthymia. Excerpt(s): Affective and mood disorders are included in a group of mental disorders characterized by neuroendocrine dysregulation and are characterized by a disturbance in the regulation of mood, behavior, and affect. Affective and mood disorders can have serious impact on an individual's functional ability, interpersonal relationships and behavior. Major depression and dysthymia are examples such disorders. Major depression is a syndromal, episodic and recurrent illness with both psychological and biological components. A diagnosis of bipolar disorder is given to those patients with recurring depression and mania. Those patients with recurrent depression alone have a unipolar pattern. Within the spectrum of depressive illness, there are two distinct subtypes: melancholic depression and atypical depression (Gold et al., N. Engl. J. Med., 319:348-353 (1988); and Gold et al., N. Engl. J. Med., 319:413-420 (1988)). Melancholic depression is equally common among those with a pattern of unipolar and bipolar depression. Melancholic depression is characterized by hyposomnia (early morning awakening), anorexia and diurnal variation in mood, and is associated with a state of hyperarousal in which patients are painfully preoccupied with personal inadequacy, loss, feelings of worthlessness, guilt and suicidal ideation (Licinio et al., Bailliere's Clin. Endocrin. Met., 5(1):51-58 (1991)). Web site: http://www.delphion.com/details?pn=US05866547__
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Methods of treating affective disorders using derivatives of (-)-venlafaxine Inventor(s): Bhongle; Nandkumar N. (Shrewsbury, MA), Jerussi; Thomas P. (Framingham, MA), Senanayake; Chrisantha H. (Shrewsbury, MA) Assignee(s): Sepracor, Inc. (marlborough, Ma) Patent Number: 6,441,048 Date filed: December 14, 2001 Abstract: Methods of preparing, and compositions comprising, derivatives of (-)venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders. Excerpt(s): The invention relates to optically pure derivatives of (-)-venlafaxine, methods of their synthesis, compositions comprising them, and methods of their use. A number of nontricyclic antidepressants have recently been developed that diminish the cardiovascular and anticholinergic liability characteristic of tricyclic antidepressants. Some of these compounds are used as anti-obesity agents and have shown promise in the treatment of cerebral function disorders such as Parkinson's disease and senile dementia. See, es., WO 94/00047 and WO 94/00114. The nontricyclic compound venlafaxine, chemically named (.+-.)-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexanol, is an antidepressant which has been studied extensively and which is described in, for example, U.S. Pat. No. 4,761,501 and Pento, J. T. Drugs of the Future 13(9):839-840 (1988). Its hydrochloride salt is currently commercially available in the United States under the trade name Effexor.RTM. Effexor.RTM., which is a racemic mixture of the (+) and (-) enantiomers of venlafaxine, is indicated for the treatment of depression. Kuamerus, K. J. et al. J. Clin. Pharmacol. 32:716-724 (1992). All of these metabolites are racemic. In vitro studies suggest that O-desmethylvenlafaxine is a more potent inhibitor of norepinephrine and dopamine uptake than the parent compound racemic venlafaxine. Muth, E. A. et al. Drug Develop. Res. 23:191-199 (1991). Odesmethylvenlafaxine has also been reported to have a half-life (t1/2) of about 10 hours, which is approximately 2.5 times as long as that of venlafaxine. Klamerus, K. J. et al. J. Clin. Pharmacol. 32:716-724 (1992). Studies directed at understanding the activity of Odesmethylvenlafaxine as compared to its parent have been hampered, however, by the metabolic difference between laboratory animals and man in their exposure to venlafaxine. Howell, S. R. et al. Xenobiotica 24(4):315-327 (1994). Web site: http://www.delphion.com/details?pn=US06441048__
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N-aminoalkyl-2-anthraquinonecarboxamides: specific ligands
new
dopamine
receptor
subtype
Inventor(s): Chen; Xi (New Haven, CT), Wasley; Jan William Francis (Guilford, CT) Assignee(s): Neurogen Corporation (branford, Ct) Patent Number: 5,922,879 Date filed: December 22, 1997 Abstract: Disclosed are compounds of the formula: or the pharmaceutically acceptable acid addition salts thereof wherein:R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6,
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and R.sub.7 are the same or different and represent hydrogen, halogen, alkyl, alkoxy, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy; --O.sub.2 CR', --NHCOR', -COR', --SO.sub.m R', where R' is C.sub.1 -C.sub.6 alkyl and wherein m is 0, 1 or 2; orR.sub.1 R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.7 independently represent --CONR'R", or --NR'R" where R' and R" independently represent hydrogen or C.sub.1 -C.sub.6 alkyl;R.sub.8 is hydrogen or lower alkyl;X represents an optionally substituted alkylene group; andY represents a mono-, di- or trisubsituted cyclic amino group,which compounds are useful in the treatment of affective disorders such as schizophrenia, depression, Alzheimer's disease, movement disorders such as Parkinsonism and dystonia, and other disorders which respond to dopaminergic blockade such as substance abuse and obsessive compulsive disorders. Further, compounds of this invention may be useful in treating the extrapyramidal side effects associated with the use of conventional neuroleptic agents. Excerpt(s): This invention relates to anthraquinonecarboxamide derivatives which selectively bind to brain dopamine receptor subtypes. More specifically, it relates to NAminoalkylanthraquinonecarboxamides and to pharmaceutical compositions comprising such compounds. It further relates to the use of such compounds in the treatment or prevention of various neuropsychological disorders such as schizophrenia and other central nervous system diseases. The therapeutic effect of conventional antipsychotics, known as neuroleptics, is generally believed to be exerted through blockade of dopamine receptors. However, neuroleptics are frequently responsible for undesirable extrapyramidal side effects (EPS) and tardive dyskinesias, which are attributed to blockade of D.sub.2 receptors in the striatal region of the brain. The dopamine D.sub.3 receptor subtype has recently been identified (Sokoloff et al., Nature, 347, 146 (1990)). Its unique localization in limbic brain areas and its differential recognition of various antipsychotics indicates that the D.sub.3 receptor plays a significant role in the etiology of schizophrenia Selective D.sub.3 antagonists are thought to be effective antipsychotics free from the neurological side effects displayed by conventional neuroleptics. U.S. Pat. No. 5,395,835 discloses N-aminoalkyl-2napthalamides said to have affinity at dopamine D.sub.3 receptors. Web site: http://www.delphion.com/details?pn=US05922879__ •
Portable light unit for treatment of seasonal affective disorders Inventor(s): Hyman; Henry H. (P.O. Box 216, Owings Mills, MD 21117) Assignee(s): Hyman; Henry H. (pikesville, Md) Patent Number: 6,488,698 Date filed: August 16, 2000 Abstract: A portable light unit for treatment of seasonal affective disorders. The portable device is carried in a small case having four bulbs capable of emitting full spectrum light at 10,000 lux intensity for each therapy session. Therefore, the device can be carried by the patient or the physician to the patient. Excerpt(s): The present invention relates generally to an illumination device. More specifically, the invention is a portable briefcased illumination device for treatmemt of seasonal affective disorders. The relative art of interest describes various illumination devices, but none discloses the present invention. There is a need for a portable illumination device adapted to treat seasonal affective syndromes and disorders. The related art will be discussed in the order of perceived relevance to the present invention.
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Web site: http://www.delphion.com/details?pn=US06488698__ •
Topiramate sodium trihydrate Inventor(s): Almarsson; Orn (Shrewsbury, MA), Peterson; Matthew L. (Framingham, MA), Remenar; Jules (Framingham, MA) Assignee(s): Transform Pharmaceuticals, Inc. (lexington, Ma) Patent Number: 6,559,293 Date filed: September 3, 2002 Abstract: The invention encompasses novel salts of topiramate, and pharmaceutically acceptable polymorphs, solvates, hydrates, dehydrates, co-crystals, anhydrous, or amorphous forms thereof, as well as pharmaceutical compositions and pharmaceutical unit dosage forms containing the same. In particular, the invention encompasses pharmaceutically acceptable salts of topiramate, including without limitation topiramate sodium, topiramate lithium, topiramate potassium, or polymorphs, solvates, hydrates, dehydrates, co-crystals, anhydrous, and amorphous forms thereof. The invention further encompasses novel co-crystals or complexes of topiramate, as well as pharmaceutical compositions comprising them. The invention also encompasses methods of treating or preventing a variety of diseases and conditions including, but not limited to, seizures, epileptic conditions, tremors, cerebral function disorders, obesity, neuropathic pain, affective disorders, tobacco cessation, migraines, and cluster headache. Excerpt(s): This invention relates to compounds, pharmaceutical compositions, and methods for the treatment or prevention of seizures, epilepsy, tremors, affective disorders, obesity, neuropathic pain, and migraines. Topiramate is a white crystalline powder with a solubility in water of 9.8 mg/mL, and it is freely soluble in acetone, chloroform, dimethylsulfoxide, and ethanol. See, Physician's Desk Reference, 56.sup.th ed., pp. 2590-2595 (2002). Topiramate is sold in the United States under the trade name TOPAMAX.RTM. (Ortho-McNeil Pharmaceutical, Inc., Raritan, N.J., U.S.A.). TOPAMAX.RTM. has been approved for use as an antiepileptic agent as an adjuvant therapy for patients with partial onset seizures, or primary generalized tonic-clonic seizures. See generally, Physician's Desk Reference, 56.sup.th ed., 2590-2595 (2002); see also, U.S. Pat. No. 4,513,006. Adverse effects associated with the administration of topiramate include, but are not limited to, somnolence, dizziness, ataxia, speech disorders and related speech problems, psychomotor slowing, abnormal vision, difficulty with memory, paresthesia, diplopia, renal calculi (kidney stones), hepatic failure, pancreatitis, renal tubular acidosis, acute myopia and secondary angle closure glaucoma. Physician's Desk Reference, 56.sup.th ed., pp. 2590-2595 (2002). Web site: http://www.delphion.com/details?pn=US06559293__
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Use of fluorinated triazoles in treating affective and attention disorders Inventor(s): Schmutz; Markus (Schoenenbuch, CH) Assignee(s): Novartis AG (basel, Ch) Patent Number: 6,156,775 Date filed: March 1, 1999
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Abstract: The present invention relates to the use of fluorinated triazoles in treating affective disorders. Excerpt(s): The present invention relates to a new pharmaceutical use of fluorinated triazoles. The compounds of formula I as well as their production process are known e.g. from European Patent No. 199 262. This patent also discloses the use of the compounds of formula I for the treatment of convulsions of different origin, e.g. of epilepsy. In accordance with the present invention, it has now surprisingly been found that the compounds of formula I are useful in the treatment of affective disorders including bipolar mood disorders. Web site: http://www.delphion.com/details?pn=US06156775__
Patent Applications on Affective Disorders 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 affective disorders: •
APPARATUS AND METHOD FOR DIFFERENTIATING BETWEEN SENSORY ATTENTIONAL DISORDER AND AFFECTIVE DISORDERS
LOW
Inventor(s): Bars, Donald R.; (Boise, ID), Heyrend, F. LaMarr; (Boise, ID) Correspondence: Dykas, Shaver & Nipper, Llp; P O Box 877; Boise; ID; 83701-0877; US Patent Application Number: 20020133088 Date filed: March 13, 2001 Abstract: An apparatus and method of testing an individual to identify whether the individual is experiencing: (a) solely an attention disorder (ADD) based upon a low sensory arousal system; (b) another disorder (attentive-type); or (c) a combination of low sensory system attention disorder (ADD) and other attentive disorders. Excerpt(s): This invention generally relates to an apparatus and method for identifying people with attentional disorders based upon a low sensory arousal system by obtaining and processing electroencephalographic information and applying that data to an algorithm to differentiate between low sensory attentional disorders and other, affective type, disorders. In the field of child and adolescent psychiatry, AttentionDeficit/Hyperactivity Disorder, originally known as minimal brain dysfunction, has been theorized to be of a neurobiological nature. The predominant view is that cognitive and behavioral deficits exhibited with this disorder are the consequences of brain dysfunction although the exact etiology and biological substrata such as lowered levels of reticular activating system excitation which results in low cortical arousal, cortical immaturity or delayed maturation and/or attention-inhibition deficits is not known with any degree of certainty. There are a number of attentional disorders based upon a low sensory arousal system. Perhaps the best known, and most common of these is Attention-Deficit/Hyperactivity Disorder, for which a definition is found in the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. It states: "[t]he essential feature of Attention-Deficit/Hyperactivity Disorder is a persistent pattern of inattention and/or hyperactivity-impulsivity that is more 10
This has been a common practice outside the United States prior to December 2000.
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frequent and severe than is typically observed in individuals at a comparable level of development. There must be clear evidence of interference with developmentally appropriate social, academic, or occupational functioning. The disturbance does not occur exclusively during the course of a Pervasive Developmental Disorder, Schizophrenia, or other Psychotic Disorder and is not better accounted for by another mental disorder (e.g. a Mood Disorder, Anxiety Disorder, Dissociative Disorder, or Personality Disorder. " Attention-Deficit/Hyperactivity Disorder is also found in those suffering from other Attentive Disorders such as obsessive compulsive disorders, bipolar disorders, rumination disorders, manic and hypo-manic disorders, and depression. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Aryloxy-and arylthiosubstituted pyrimidines and triazines and derivatives thereof Inventor(s): Chorvat, Robert John; (West Chester, PA), Rajagopalan, Parthasarathi; (Wilmington, DE) Correspondence: Bristol-myers Squibb Squibb Pharma Company; Patent Department; P.O. Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20020040026 Date filed: October 2, 2001 Abstract: The present invention provides novel compounds, and pharmaceutical compositions thereof, and methods of using same in the treatment of affective disorders, anxiety, depression, post-traumatic stress disorders, eating disorders, supranuclear palsey, irritable bowl syndrome, immune supression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa, drug and alcohol withdrawal symptoms, drug addiction, inflammatory disorders, or fertility problems. The novel compounds provided by this invention are those of formula: 1wherein R.sup.1, R.sup.3, R.sup.5, Q, Z, Y, V, X and X' are as defined herein. Excerpt(s): The present invention relates to novel compounds, pharmaceutical compositions containing said compounds and to methods of using same in the treatment of affective disorders, anxiety, depression, post-traumatic stress disorders, eating disorders, supranuclear palsey, irritable bowl syndrome, immune supression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa, drug and alcohol withdrawal symptoms, drug addiction, inflammatory disorders, or fertility problems. Corticotropin releasing factor (herein referred to as CRF), a 41 amino acid peptide, is the primary physiological regulator of proopiomelanocortin(POMC)-derived peptide secretion from the anterior pituitary gland [J. Rivier et al., Proc. Nat. Acad. Sci. (USA) 80:4851 (1983); W. Vale et al., Science 213:1394 (1981)]. In addition to its endocrine role at the pituitary gland, immunohistochemical localization of CRF has demonstrated that the hormone has a broad extrahypothalamic distribution in the central nervous system and produces a wide spectrum of autonomic, electrophysiological and behavioral effects consistent with a neurotransmitter or neuromodulator role in brain [W. Vale et al., Rec. Prog. Horm. Res. 39:245 (1983); G. F. Koob, Persp. Behav. Med. 2:39 (1985); E. B. De Souza et al., J. Neurosci. 5:3189 (1985)]. There is also evidence demonstrating that CRF may also play a significant role in integrating the response of the immune system to physiological, psychological, and immunological stressors [J. E. Blalock, Physiological Reviews 69:1 (1989); J. E. Morley, Life Sci. 41:527 (1987)]. Clinical data has demonstrated that CRF may have implications in psychiatric disorders and neurological diseases including depression, anxiety-related disorders and feeding disorders. A role for CRF
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has also been postulated in the etiology and pathophysiology of Alzheimer's disease, Parkinson's disease, Huntington's disease, progressive supranuclear palsy and amyotrophic lateral sclerosis as they relate to the dysfunction of CRF neurons in the central nervous system [for review see E. B. De Souza, Hosp. Practice 23:59 (1988)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Bupropion metabolites and methods of their synthesis and use Inventor(s): Fang, Qun K.; (Wellesley, MA), Jerussi, Thomas P.; (Farmingham, MA), McCullough, John R.; (Hudson, MA), Senanayake, Chrisantha H.; (Shrewsbury, MA) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20020052340 Date filed: November 16, 2001 Abstract: Methods and compositions are disclosed which utilize metabolites of bupropion for treating disorders ameliorated by inhibition of neuronal monoamine reuptake. Such disorders include, but are not limited to, erectile dysfunction, affective disorders, cerebral function disorders, cigarette smoking, and incontinence. The invention further discloses methods of making optically pure bupropion metabolites. Excerpt(s): This invention relates to synthesis of, methods of using, and compositions comprising bupropion metabolites and isomers thereof. Bupropion, a racemic mixture of (+)- and (-)-1-(3-chlorophenyl)-2-[- (1,1-dimethylethyl)amino]-1-propanone, is an antidepressant of the aminoketone class, and is described in U.S. Pat. Nos. 3,819,706 and 3,885,046. The hydrochloride salt of bupropion is sold under the trade names WELLBUTRIN.RTM. and WELLBUTRIN SR.RTM. for the treatment of depression. Bupropion is also sold under the trade name ZYBAN.RTM. as a drug useful to achieve smoking cessation. Additional benefits of bupropion maleate are reported in European Patent Application No. 118036. Although its mechanism of action is poorly understood, bupropion is reportedly a weak but selective inhibitor of dopamine. Its potency as an inhibitor of norepinephrine reuptake is reportedly only half of that for dopamine, and it shows little affinity for the serotonergic transport system. Ascher, J. A., et al., J. Clin. Psychiatry, 56:395-401 (1995). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Combination of a serotonin reuptake inhibitor and irindalone Inventor(s): Bogeso, Klaus Peter; (Horsholm, DK), Cremers, Thomas Ivo Franciscus Hubert; (Groningen, NL) Correspondence: Darby & Darby P.C.; 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20020103249 Date filed: December 6, 2000 Abstract: The present invention relates to the use of a combination of irindalone and a serotonin reuptake inhibitor (SRIs), or any other compound, which causes an elevation in the level of extracellular serotonin, for the treatment of depression and other affective disorders.
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Excerpt(s): The present invention relates to the use of a combination of irindalone and a serotonin reuptake inhibitor (SRI), or any other compound, which causes an elevation in the level of extracellular serotonin, for the treatment of depression and other affective disorders. Selective serotonin reuptake inhibitors (hereinafter referred to as SSRIs) haste become first choice therapeutics in the treatment of depression, certain forms of anxiety and social phobias, because they are effective, well tolerated and have a favourable safety profile compared to the classic tricyclic antidepressants. However, clinical studies on depression and anxiety disorders indicate that non-response to SSRIs is substantial, up to 30%. Another, often neglected, factor in antidepressant treatment is compliance, which has a rather profound effect on the patient's motivation to continue pharmacotherapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Imidazolyl derivatives as corticotropin releasing factor inhibitors Inventor(s): Dasgupta, Bireshwar; (Middletown, CT), Dubowchik, Gene M.; (Middlefield, CT), Han, Xiaojun; (Cheshire, CT), Michne, Jodi A.; (Middletown, CT), Vrudhula, Vivekananda M.; (Killingworth, CT), Zuev, Dmitry; (Wallingford, CT) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20020183375 Date filed: January 11, 2002 Abstract: The present invention relates to novel heterocyclic antagonists of Formula (I) and pharmaceutical compositions comprising said antagonists of the corticotropin releasing factor receptor ("CRF receptor") 1useful for the treatment of depression, anxiety, affective disorders, feeding disorders, post-traumatic stress disorder, headache, drug addiction, inflammatory disorders, drug or alcohol withdrawal symptoms and other conditions the treatment of which can be effected by the antagonism of the CRF-1 receptor. Excerpt(s): This non-provisional application claims priority from provisional application U.S. Ser. No. 60/264,570 filed Jan. 26, 2001. The present invention relates to antagonists and pharmaceutical compositions comprising said antagonists of the corticotropin releasing factor receptor ("CRF receptor") useful for the treatment of depression, anxiety, affective disorders, feeding disorders, post-traumatic stress disorder, headache, drug addiction, inflammatory disorders, drug or alcohol withdrawal symptoms and other conditions the treatment of which can be effected by the antagonism of the CRF-1 receptor. It has been shown that the neuropeptide, corticotropin releasing factor ("CRF"), acting through its binding to the CRF-1 receptor, is a primary mediator of stress- and anxiety-related physiological responses in humans and other mammals by stimulating ACTH secretion from the anterior pituitary gland. See A. J. Dunn, et al., Brain Res. Rev., 15: 71-100 (1990). Antagonists of the CRF-1 receptor, both peptides (J. Gulyas, et al., Proc. Natl. Acad. Sci. U.S.A., 92: 10575-10579 (1995) and small molecules (J. R. McCarthy, et al., Curr. Pharm. Design, 5: 289-315 (1999), have demonstrated the ability to ameliorate the effects of stressful stimuli in several animal models. In addition, marked elevations of CRF in cerebrospinal fluid have been detected in a large portion of individuals diagnosed with major depression and anxiety disorders, and the levels correlate with severity of the disease. See F. Holsboer, J. Psychiatric Res., 33: 181-214 (1999). Following antidepressant treatment, the increased CRF levels observed in depressed patients were reduced. See C. M. Banki, et al., Eur. Neuropsychopharmacol.,
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2: 107-113 (1992); see also Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated. Zobel A W, Nickel T, Kunzel H E, Ackl N, Sonntag A. Ising M, Holsboer F J Psychiatr Res 2000, 34, 171-181. CRF has also been shown to be a key mediator of several immune system functions through its effect on glucocorticoid plasma levels. See E. L. Webster, et al., Ann. N.Y. Acad. Sci., 840: 21-32 (1998). Recent reviews of the activity of CRF-1 antagonists include P. J. Gilligan, et al., J. Med. Chem., 43: 1641-1660 (2000) and J. R. McCarthy, et al., Ann. Rep. Med. Chem., 34: 11-20 (1999). There appears a need to discover novel small molecule CRF antagonists in order to treat a wide variety of human disorders including depression, anxiety, bipolar disorder, and other stress-related illnesses. See WO 98/35967, WO 99/01454, WO 99/10350, wo 99/67247, 00/01675, WO 00/01697, WO 00/39127, WO 00/59907, WO 00/59908, EP 778277, EP 812831. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
In vitro screening for ligands of the estrogen receptor Inventor(s): Langer, Gernot; (Berlin, DE), Mitev, Youriy; (Jena, DE), Patchev, Vladimir; (Jena, DE), Wolf, Siegmund; (Jena, DE) Correspondence: Striker, Striker & Stenby; 103 East Neck Road; Huntington; NY; 11743; US Patent Application Number: 20030087303 Date filed: November 20, 2001 Abstract: A method of an in vitro screening for a ligand using two assay systems i.e. in a first cellular or tissue assay system, selecting the ligand with transcriptional ERmediated activity measured by an ER-driven reporter gene, whereby in the first assay system the ligand activates the potency with an EC.sub.50(ER) (half-maximally effective ligand concentration) lower than to 10 nmol/l, and, in a second enzymatic assay system, selecting the physical-chemical interaction (recruitment) of SRC-1, wherein the ligand activates the ER and induces interaction with the co-present SRC-1 with an EC.sub.50(ER+SRC) higher than to 100 nmol/l.The ligands found by the inventive screening can be used for the treatment and prevention of neuro-degeneration in the cerebral cortex and are thus useful for treatment and prevention of age-related cognitive disorders, affective disorders, Alzheimer's diseases and cerebral ischemia/stroke. Excerpt(s): The invention relates to an in vitro method for detecting ligands and in vitro screening for ligands of the estrogen receptor having neurotropic and minimal systemic estrogen-like properties. The invention further relates to an in vitro use of a steroid receptor coactivator-1 (SRC-1) for detecting ligands of the estrogen receptor having defined properties. The international application WO 99/42108 of PATCHEV et al. describes steroids as medication for selectively supplementing estrogen deficiency in the central nervous system without influencing other organs or systems. Such compounds (ligands) have selective neurotropic properties; they do not affect other estrogensensitive organs. The selective neurotropic effect on the nervous system was tested in animal models. The desired profile of drugs for the treatment of symptoms of estrogen deficiency in the central nervous system requires that these drugs act on estrogendependent target genes in the brain while having only minor effects or no effect in estrogen-sensitive organs of the reproductive system (e.g., endometrium, breast, pituitary). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Materials and methods for the treatment of depression Inventor(s): Druzgala, Pascal; (Santa Rosa, CA) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20010056119 Date filed: April 24, 2001 Abstract: The subject invention provides compounds which are easily metabolized by the metabolic drug detoxification systems. Particularly, fluvoxamine analogs which have been designed to include esters within the structure of the compounds are taught. Also provided are methods of treating depression and affective disorders, such as obsessive compulsive disorder. Pharmaceutical compositions of the fluvoxamine analogs are also taught. Excerpt(s): This application claims priority from provisional patent application U.S. Ser. No. 60/199,343, filed Apr. 24, 2000. Major depression represents one of the most common mental illness, affecting between 5-10% of the population. The disease is characterized by extreme changes in mood which may also be associated with psychoses. It has generally been found that most antidepressant agents exert significant effects on the regulation of monoamine neurotransmitters, including serotonin. A number of types of antidepressants have been developed in recent years. Many of these compounds regulate serotonin (5-hydroxytryptamine; 5-HT). Trazodone controls the actions of 5-HT while fluoxetine is a potent and selective inhibitor of 5-HT reuptake. 3Chloroimipramine which inhibits both 5-HT and norepinephrine reuptake has been extensively used as an antidepressant in Europe and Canada. Other compounds which are of current interest or have been examined as antidepressants include fluvoxamine, citalopram, zimeldine, sertraline, bupropion and nomifensine. Fluvoxamine facilitates serotoninergic neurotransmission via potent and selective inhibition of serotonin reuptake into presynaptic neurons. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of using and compositions comprising (-) sibutramine optionally in combination with other pharmacologically active compounds Inventor(s): Jerussi, Thomas P.; (Framingham, MA), Young, James W.; (Palo Alto, CA) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20020006963 Date filed: January 29, 2001 Abstract: This invention encompasses methods for the treatment and prevention of disorders that include, but are not limited to, eating disorders; weight gain; obesity; irritable bowel syndrome; obsessive-compulsive disorders; platelet adhesion; apnea; affective disorders such as attention deficit disorders, depression, and anxiety; male and female sexual function disorders; restless leg syndrome; osteoarthritis; substance abuse including nicotine and cocaine addiction; narcolepsy; pain such as neuropathic pain, diabetic neuropathy, and chronic pain; migraines; cerebral function disorders; chronic disorders such as premenstrual syndrome; and incontinence.The invention further encompasses pharmaceutical compositions and dosage forms which comprise
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optically pure (-) sibutramine, optionally in combination with a phosphodiesterase inhibitor or a lipase inhibitor. Excerpt(s): This is a continuation-in-part of U.S. patent application 09/721,669, filed Nov. 27, 2000, which is a continuation of U.S. patent application 08/461,608, both of which are incorporated herein by reference in their entireties. This invention is directed to methods and compositions for the treatment or prevention of conditions using optically pure (-) sibutramine, optionally in combination with other pharmacologically active compounds. Sibutranmine, chemically named [N-1-[1-(4chlorophenyl)cyclobutyl]-- 3-methylbutyl]-N,N-dimethylamine, is a neuronal monoamine reuptake inhibitor which was originally disclosed in U.S. Pat. Nos. 4,746,680 and 4,806,570. Sibutramine inhibits the reuptake of norepinephrine and, to a lesser extent, serotonin and dopamine. See, e.g., Buckett et al., Prog. Neuro-psychopharm. & Biol. Psychiat., 12:575-584, 1988; King et al., J. Clin. Pharm., 26:607-611 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of treating affective disorders using derivatives of (-)- venlafaxine Inventor(s): Bhongle, Nandkumar N.; (Shrewsbury, MA), Jerussi, Thomas P.; (Framingham, MA), Senanayake, Chrisantha H.; (Shrewsbury, MA) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20020086904 Date filed: December 14, 2001 Abstract: Methods of preparing, and compositions comprising, derivatives of (-)venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders. Excerpt(s): The invention relates to optically pure derivatives of (-)-venlafaxine, methods of their synthesis, compositions comprising them, and methods of their use. A number of nontricyclic antidepressants have recently been developed that diminish the cardiovascular and anticholinergic liability characteristic of tricyclic antidepressants. Some of these compounds are used as anti-obesity agents and have shown promise in the treatment of cerebral function disorders such as Parkinson's disease and senile dementia. See, e.g., WO 94/00047 and WO 94/00114. The nontricyclic compound venlafaxine, chemically named (.+-.)-1-[2-(dimethylamino)-1-(4-m- ethoxyphenyl)ethyl]cyclohexanol, is an antidepressant which has been studied extensively and which is described in, for example, U.S. Pat. No. 4,761,501 and Pento, J. T. Drugs of the Future 13(9):839-840 (1988). Its hydrochloride salt is currently commercially available in the United States under the trade name Effexor.RTM. Effexor.RTM., which is a racemic mixture of the (+) and (-) enantiomers of venlafaxine, is indicated for the treatment of depression. Klamerus, K. J. et al. J. Clin. Pharmacol. 32:716-724 (1992). All of these metabolites are racemic. In vitro studies suggest that O-desmethylvenlafaxine is a more potent inhibitor of norepinephrine and dopamine uptake than the parent compound racemic venlafaxine. Muth, E. A. et al. Drug Develop. Res. 23:191-199 (1991). Odesmethylvenlafaxine has also been reported to have a half-life (t{fraction (1/2)}) of about 10 hours, which is approximately 2.5 times as long as that of venlafaxine.
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Klamerus, K. J. et al. J. Clin. Pharmacol. 32:716-724 (1992). Studies directed at understanding the activity of O-desmethylvenlafaxine as compared to its parent have been hampered, however, by the metabolic difference between laboratory animals and man in their exposure to venlafaxine. Howell, S. R. et al. Xenobiotica 24(4):315-327 (1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of using and compositions comprising sibutramine metabolites optionally in combination with other pharmacologically active compounds Inventor(s): Fang, Qun K.; (Wellesley, MA), Jerussi, Thomas P.; (Framingham, MA), Senanayake, Chrisantha H.; (Shrewsbury, MA) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20020010198 Date filed: January 29, 2001 Abstract: Methods are disclosed for the treatment and prevention of disorders and conditions such as, but are not limited to: eating disorders; weight gain; obesity; irritable bowel syndrome; obsessive-compulsive disorders; platelet adhesion; apnea; affective disorders such as attention deficit disorders, depression, and anxiety; male and female sexual function disorders; restless leg syndrome; osteoarthritis; substance abuse including nicotine and cocaine addiction; narcolepsy; pain such as neuropathic pain, diabetic neuropathy, and chronic pain; migraines; cerebral function disorders; chronic disorders such as premenstrual syndrome; and incontinence.Pharmaceutical compositions and dosage forms are also disclosed which comprise a racemic or optically pure sibutramine metabolite and an optional additional pharmacologically active compound. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/662,135, filed Sep. 14, 2000, which is a continuation-in-part of U.S. application Ser. No. 09/372,158, filed Aug. 11, 1999, both of which are incorporated herein by reference in their entireties. The invention relates to methods of using and compositions comprising dopamine reuptake inhibitors such as racemic and optically pure metabolites of sibutramine, optionally in combination with other pharmacologically active compounds. Sibutramine, chemically named [N-1-[1-(4-chlorophenyl)cyclobutyl]3- -methylbutyl]-N,N-dimethylamine, is a neuronal monoamine reuptake inhibitor which was originally disclosed in U.S. Pat. Nos. 4,746,680 and 4,806,570. Sibutramine inhibits the reuptake of norepinephrine and, to a lesser extent, serotonin and dopamine. See, e.g., Buckett et al., Prog. Neuro-psychopharm. & Biol. Psychiat., 12:575-584, 1988; King et al., J. Clin. Pharm., 26:607-611 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel heteroaryl derivatives, their preparation and use Inventor(s): Andersen, Kim; (Virum, DK), Krog-Jensen, Christian; (Copenhagen, DK), Mikkelsen, Gitte; (Ballerup, DK), Mikkelsen, Ivan; (Koge, DK), Moltzen, Ejner Knud; (Gentofte, DK), Rottlander, Mario; (Valby, DK), Ruhland, Thomas; (Valby, DK) Correspondence: Darby & Darby P.C.; 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20030050306 Date filed: June 25, 2002 Abstract: A heteroaryl derivative having the formula (I) 1any of its enantiomers or any mixture thereof, wherein X is --O--, --S--, or CR.sup.4R.sup.5--; and Y is -CR.sup.6R.sup.7; --CR.sup.6R.sup.7--CR.s- up.8R.sup.9--, or --CR.sup.6--CR.sup.7; or X and Y together form a group --CR.sup.4.dbd.R.sup.5--, or --CR.sup.4.dbd.CR.sup.5-CR.sup.6R.sup.7--; Z is --O--, or --S--; W is N, C, or CH; n is 2, 3, 4, 5, 6, 7, 8, 9 or 10; m is 2 or 3; A is O or S wherein the doted lines mean an optional bond. The compounds of the invention are considered useful for the treatment of affective disorders such as general anxiety disorder, panic disorder, obsessive compulsive disorder, depression, social phobia and eating disorders, and neurological disorders such as psychosis. Excerpt(s): This application is a Continuation of International Application No. PCT/DK00/00741, filed Dec. 29, 2000. The disclosure of the prior application is hereby incorporated by reference. The present invention relates to novel heteroaryl derivatives potently binding to the 5-HT.sub.1A receptor, pharmaceutical compositions containing these compounds and the use thereof for the treatment of certain psychiatric and neurological disorders. The compounds of the invention are also potent dopamine D.sub.4 receptor ligands and are considered to be particularly useful for the treatment of depression and psychosis. Furthermore, many compounds of the invention have potent serotonin reuptake inhibition activity and/or effect at dopamine D.sub.3 receptors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel human neurotransmitter transporter Inventor(s): Feder, John N.; (Belle Mead, NJ), Lee, Liana M.; (North Brunswick, NJ), Ramanathan, Chandra S.; (Wallingford, CT), Sharma, Rahul; (Gurnee, IL), Westphal, Ryan; (Chesire, CT) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20030219774 Date filed: December 13, 2002 Abstract: The invention provides a novel human orphan neurotransmitter transporter belonging to the family of Na.sup.+/Cl.sup.- dependent transporters. Inventive HNTTBMY1 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Further provided are methods for utilizing these polypeptides and polynucleotides in therapy and diagnostic assays for such. The transporter of the present invention is expressed highly in the amygdala brain subregion, which is known to be associated with affective disorders. The inventive transporter shares high homology with the rat orphan neurotransmitter transporter termed NTT4.
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Excerpt(s): This application claims benefit to provisional application U.S. Serial No. 60/340,436 filed Dec. 14, 2001. The entire teachings of the referenced application are incorporated herein by reference. The present invention relates to neurotransmitter transporters. In particular, the invention relates to the Na.sup.+/Cl.sup.- dependent neurotransmitter transporter gene family. Chemical synapses are the primary mechanisms of information transfer in the central nervous system (CNS). Neurotransmitters are the messengers that mediate this information transfer. The release of the neurotransmitter from the presynaptic terminal into the synaptic gap followed by binding to the post-synaptic receptors, and the subsequent termination of the effects constitute the main steps in the synaptic transmission [Goodman and Gilman, The Pharmacological Basis of Therapeutics, Eds.--Goodman L. S. et al., 9.sup.th Ed. McGraw Hill, ST, (1996)]. In both the central and peripheral nervous system, reliable neurotransmission depends on rapid termination of transmitter action following postsynaptic activation. In certain instances, this is achieved by metabolism of the neurotransmitter, as in the case of acetycholine and neuropeptides. However, in many cases, including catecholamines, serotonin, and some amino acids (e.g. GABA, glycine and glutamate), the neurotransmitter is efficiently removed into the presynaptic terminal or surrounding glial cells by neurotransmitter transporters (NTT's), which are membrane-bound polypeptides located in the plasma membrane. Inside the neuron, another family of transporters, vesicular transporters, help store the neurotransmitter in the vesical stores for further release [Neurotransmitter Transporters: Structure, Function and Regulation, Maarten and Reith, Humana Press, N.J., (1997); Methods in Enzymology, Neurotransmitter Transporters, Ed. Amara S. G., Volume 296. Academic Press, N.Y., (1998)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel N-aminoalkyldibenzothiopencarboxamide receptor subtype specific ligands Inventor(s): Chen, Xi; (East Haven, CT), Yuan, Jun; (Clinton, CT) Correspondence: Steven J. Sarussi; Mcdonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20010044461 Date filed: March 19, 2001 Abstract: Disclosed are compounds of the formula: 1or the pharmaceutically acceptable acid addition salts thereof, wherein:R.sub.1, R.sub.2, R.sub.3, R.sub.4 are the same or different and represent hydrogen, C.sub.1-C.sub.6 alkyl, halogen, hydroxy, amino, cyano, nitro, trifluoromethyl, trifluoromethoxy, C.sub.1-C.sub.6 alkoxy, --O.sub.2CR', -NHCOR', --COR', --SO.sub.mR', where R' is C.sub.1-C.sub.6 alkyl and wherein m is 0, 1 or 2; orR.sub.1, R.sub.2, R.sub.3, R.sub.4 independently represent --CONR'R", or --NR'R" where R' and R" independently represent hydrogen or C.sub.1-C.sub.6 alkyl;R.sub.5 is hydrogen or C.sub.1-C.sub.6 alkyl; andR represents an aminoalkyl group,which compounds are useful in the treatment of affective disorders such as schizophrenia, depression, Alzheimer's disease, movement disorders such as Parkinsonism and dystonia, and other disorders which respond to dopaminergic blockade such as substance abuse and obsessive compulsive disorders. Further, compounds of this invention may be useful in treating the extrapyramidal side effects associated with the use of conventional neuroleptic agents. Excerpt(s): This invention relates to dibenzothiophenecarboxamide derivatives which selectively bind to brain dopamine receptor subtypes. More specifically, it relates to N-
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aminoalkyldibenzothiophenecarboxamides and to pharmaceutical compositions comprising such compounds. It further relates to the use of such compounds in the treatment or prevention of various neuropsychochological disorders such as schizophrenia and other central nervous system diseases. The therapeutic effect of conventional antipsychotics, known as neuroleptics, is generally believed to be exerted through blockade of dopamine receptors. However, neuroleptics are frequently responsible for undesirable extrapyramidal side effects (EPS) and tardive dyskinesias, which are attributed to blockade of D.sub.2 receptors in the striatal region of the brain. The dopamine D.sub.3 receptor subtype has recently been identified (Sokoloff et al., Nature, 347: 146 (1990). Its unique localization in limbic brain areas and its differential recognition of various antipsychotics suggest that the D.sub.3 receptor may play a major role in the etiology of schizophrenia. Selective D.sub.3 antagonists may be effective antipsychotics free from the neurological side effects displayed by conventional neuroleptics. Compounds of the present invention demonstrate high affinity and selectivity in binding to the D.sub.3 receptor subtype. They may be of potential use in treatment of schizophrenia, psychotic depression and mania. Other dopamine-mediated diseases such as Parkinsonism and tardive dyskinesias may also be treated directly or indirectly by modulation of D.sub.3 receptors. U.S. Pat. No. 5,395,835 discloses Naminoalkyl-2-napthalamides which have affinity at dopamine D.sub.3 receptors. The compounds the present invention differ significantly from this prior art in that they possess a dibenzothiophenecarboxamide substructure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical compositions for the treatment of depression or symptoms suggesting depression Inventor(s): Kovacs, Peter; (Debrecen, HU), Racz, Anna; (Budapest, HU), Varga, Csilla; (Nyiregyhaza, HU) Correspondence: The Firm OF Karl F Ross; 5676 Riverdale Avenue; PO Box 900; Riverdale (bronx); NY; 10471-0900; US Patent Application Number: 20040010021 Date filed: January 13, 2003 Abstract: The invention relates to the human therapeutic application of famotidine or its therapeutically acceptable salts for the treatment of depression or symptoms suggesting depression, including somatic depression, unipolar depression, functional diseases of psychic origin, atypical depression, dysthymia, bipolar affective disorders, seasonal depression and persistent mood disorder. The invention also relates to such application of a pharmaceutical composition and its manufacturing. Excerpt(s): The present invention relates to the administration of pharmaceutical preparations containing the active ingredient famotidine, in the treatment of depression or symptoms suggesting depression. Moreover, the invention also relates to cases with acid related diseases. It is also a widely known fact that the group of patients suffering in gastrointestinal diseases is much more prone to hazards relating to depression, in other words they often develop different forms of depression or symptoms suggesting depression (for example functional dyspepsia). These may counteract on the underlying disease, often impeding or preventing recovery. Therefore it could be desirable, if pharmaceutical preparations developed for gastrointestinal diseases also had a positive effect on complaints relating to depression, but at least they should not worsen the clinical case. Unfortunately, the applied preparations show a rather heterogeneous
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picture. Several publications--e.g. Hassan and Saieed (Eur. J. Pharm. Sci., 6, Suppl. 1, S88, 1998)--have dealt with the psychiatric effects of H.sub.2-receptor antagonistsie with a high sales record. The firstly developed member of the group, cimetidine, was found to have a marked depressant effect (see e.g. Mangla J. C., Clin. Res. 33., No. 2, Pt. 1, 323 A, 1985 or Rush P. J., Am. J. Med. Sci. 286, No.3, 31-34, 1983). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Piperidine, tetrahydropyridine and piperazine derivatives, their preparation and use Inventor(s): Bjornholm, Berith; (Vaerlose, DK), Krog-Jensen, Christian; (Kobenhavn O, DK), Moltzen, Ejner Knud; (Gentofte, DK) Correspondence: Darby & Darby P.C.; 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20020035113 Date filed: July 9, 2001 Abstract: A piperidine, tetrahydropyridine or piperazine derivative having formula (I), 1any of its enantiomers or any mixture thereof, or an acid addition salt thereof, wherein B is C.sub.1-10-alkylene, C.sub.1-10-alkenylene or C.sub.1-10-alkynylene; X is --O--, --S--, or CR.sup.4R.sup.5--; and Y is --CR.sup.6R.sup.7, --CR.sup.6R.sup.7--CR.sup.8R.sup.9, or CR.sup.6.dbd.CR.sup.7--; or X and Y together form a group --CR.sup.4.dbd.CR.sup.5, or --CR.sup.4--CR.sup.5--CR.sup.6R.sup.7--; Z is --O--, or --S--; W is N, C, or CH, and the dotted line is an optional bond; A is a bicyclic ring selected from (Ia) or (Ib) wherein E.sup.1, E.sup.2 and E.sup.3 are selected from O, S, N, NR.sup.11, C, CR.sup.12 and CHR.sup.13, and the dotted line indicates an optional bond, provided that E.sup.2 and E.sup.1 and/or E.sup.3 may not simultaneously be O, or S. The compounds of the invention are considered useful for the treatment of affective disorders, such as depression, psychosis, anxiety disorders including general anxiety disorder, panic disorder, obsessive compulsive disorder, and eating disorders. Excerpt(s): The present invention relates to novel piperidine, tetrahydropyridine and piperazine derivatives which are potent serotonin reuptake inhibitors, pharmaceutical compositions containing these compounds and the use thereof for the treatment of disorders or diseases responsive to the inhibition of serotonin re-uptake. The compounds of the invention also possess antagonistic activity at 5-HT.sub.1A receptors and are considered to be particularly useful for the treatment of depression. Selective serotonin (or 5-HT) reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, sertraline, fluvoxamine and citalopram represent a major step forward in the treatment of depression because they have fewer and less severe side effects compared to first generation antidepressant (tricyclics and non-selective MAO inhibitors). The side effects associated with first generation antidepressants are such that they cause some patients to withdraw from treatment. SSRIs and all other antidepressants currently available suffer from a serious drawback in that several weeks of treatment are necessary to produce the therapeutic effect. The late onset of action is a significant problem, particularly in the treatment of patients with severe depression and suicide potential. Further, one in three patients are not responsive to SSRIs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Propylisopropyl acetic acid and propylisopropyl acetamide stereoisomers, a method for their synthesis and pharmaceutical compositions containing them Inventor(s): Bialer, Meir; (Jerusalem, IL), Spigelstein, Ofer; (Mevasseret Zion, IL), Yagen, Boris; (Jerusalem, IL) Correspondence: Thomas R. Stiebel, JR.; Mayer, Brown, Rowe & Maw; P.O. Box 2828; Chicago; IL; 60690-2828; US Patent Application Number: 20030212131 Date filed: April 22, 2003 Abstract: The present invention relates to racemic propylisopropyl acetic acid and propylisopropyl acetamide and their isomers in their racemic and stereospecific forms, for use in treatment of neurological and psychotic disorders, and affective disorders and to treat pain, headaches and migraines. The isomers are of the compound formula I 1R.sub.1 is a methyl or ethyl group;R.sub.2 is H, methyl or an ethyl group;R.sub.3 is ethyl or a propyl group; andR.sub.4 is a hydroxyl or amide group,and the total number of carbon atoms in said compound is 8, provided that when R1 is a methyl group and R4 is an amide group, R2 and R3 are not ethyl, further provided that when R1 is an ethyl and R4 a hydroxyl group, only stereoisomers of the compound are referred to.The present invention further relates to a method for the stereoselective synthesis of the 2R stereoisomer of PID and PIA. The present invention also relates to pharmaceutical compositions containing as an active ingredient a racemic mixture or stereoisomers of the compounds of the general formula (I), which are useful for the treatment of neurological and psychotic disorders, and affective disorders and to treat pain, headaches and migraines. Excerpt(s): The present invention generally relates to propylisopropyl acetic acid (PIA) and propylisopropyl acetamide (PID) in their racemic and stereospecific forms, to some of their isomers and to stereoisomers thereof, for use in treatment of neurological and psychotic disorders, and affective disorders and to treat pain, including headaches and migraine pains. The present invention further relates to a method for the synthesis of PIA and PID stereoisomers. The present invention further relates to pharmaceutical compositions containing, as an active ingredient, said racemic or stereoisomer forms. Headaches, especially in the form of migraine pain are a wide spread malady. Valproic acid (VPA), also used in antiepileptic therapy, is a drug which was approved for the treatment of migraine and has been utilized in the treatment of epilepsy for the last 25 years with a few side effects. Two major side effects being teratogenicity and hepatotoxicity, have been associated with valproate therapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Substituted arylpyrazines Inventor(s): DeLombaert, Stephane; (Madison, CT), Doller, Dario; (Wallingford, CT), Ge, Ping; (Durham, CT), Hodgetts, Kevin J.; (Killingworth, CT), Horvath, Raymond F.; (Guilford, CT), Yoon, Taeyoung; (Guilford, CT), Zhang, Cunyu; (Morrisville, NC) Correspondence: Dike, Bronstein, Roberts And Cushman,; Intellectual Property Practice Group; Edwards & Angell, LLP.; P.O. Box 9169; Boston; MA; 02209; US Patent Application Number: 20030018035 Date filed: February 16, 2001
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Abstract: Arylpyrazine compounds are provided, including arylpyrazines that can bind with high affinity and high selectivity to CRF.sub.1 receptors, including human CRF.sub.1 receptors. The invention thus includes methods for treatment of disorders and diseases associated with CRF.sub.1 receptors, including CNS-related disorders and diseases, particularly affective disorders and diseases, and acute and chronic neurological disorders and diseases. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/182,934 filed Feb. 16, 2000 and of U.S. Provisional Application Serial No. 60/206,455 filed May 22, 2000, the teachings of which are incorporated herein by reference. The present invention relates to novel arylpyrazine compounds that have useful pharmacological properties in that they bind to cellular receptors, including CRF receptors. Certain of these compounds can bind to and modulate the activity of such receptors. Importantly, the compounds of the invention include compounds that bind with high selectivity and/or high affinity to CRF1 receptors (Corticotropin Releasing Factor type 1 Receptors). This invention also relates to pharmaceutical compositions comprising such compounds and to the use of such compounds as pharmaceutical agents, e.g., in treatment of psychiatric disorders and neurological diseases, including major depression, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders, as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress. Additionally this invention relates to the use such compounds as probes for the localization of cellular receptors in tissue sections. Corticotropin releasing factor (CRF), a 41 amino acid peptide, is the primary physiological regulator of proopiomelanocortin (POMC) derived peptide secretion from the anterior pituitary gland. In addition to its endocrine role at the pituitary gland, immunohistochemical localization of CRF has demonstrated that the hormone has a broad extrahypothalamic distribution in the central nervous system and produces a wide spectrum of autonomic, electrophysiological and behavioral effects consistent with a neurotransmitter or neuromodulator role in brain. There is also evidence that CRF plays a significant role in integrating the response of the immune system to physiological, psychological, and immunological stressors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substituted bicyclic derivatives for treating central nervous system disorders Inventor(s): Butler, Todd William; (Salem, CT), Fliri, Anton Franz Joseph; (Norwich, CT) Correspondence: Paul H. Ginsburg; Pfizer INC.; 235 East 42nd Street, 20th Floor; New York; NY; 10017-5755; US Patent Application Number: 20020019401 Date filed: September 27, 2001 Abstract: The present invention relates to compounds of the formula 1and the pharmaceutically acceptable salts and solvates thereof wherein X.sup.1, X.sup.2, X.sup.3, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined herein. The invention also relates to pharmaceutical compositions containing the above compounds and to methods of treating shizophrenic and shizo-affective disorders, and related disorders which may be treated by administering compounds having dopaminergic activity such as the above compounds of formula 1.
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Excerpt(s): This Application claims the benefit of U.S. Provisional Application No. 60/083,421, filed Apr. 29, 1998. The present invention relates to novel substituted bicyclic derivatives that are dopamine receptor subtype ligands having a preference for the D4-dopamine receptor. These compounds exhibit central dopaminergic activity, as defined below, and are useful in the treatment and prevention of disorders of the dopamine system, including schizophrenic and schizo-affective disorders, akinesia, dementia, Parkinson's disease, nausea, bipolar disorders, emesis, tardive dyskinesia, extrapyramidal side effects from neuroleptic agents, neuroleptic malignant syndrome, hyperprolactemia and amenorrhoea. It is known that dopamine receptors are important for many functions in mammals. For example, altered functions of these receptors are thought to participate in the genesis of psychosis, drug addiction, compulsive disorders, bipolar disorders, vision, emesis, sleep, feeding, learning, memory, sexual behavior, regulation of immunological responses and blood pressure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Susceptability and resistance genes for bipolar affective disorder Inventor(s): Egeland, Janice A.; (Hershey, PA), Ginns, Edward I.; (Bethesda, MD), Paul, Steven M.; (Carmel, IN) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20020192655 Date filed: June 13, 2001 Abstract: Chromosomal regions comprising loci associated with susceptibility and resistance to bipolar affective disorder have been identified. Methods and compositions are provided for determining the contribution of these chromosomal regions to bipolar affective disorder in an affected family, for determining in an affected family a genotype associated with increased or decreased susceptibility or resistance to bipolar illness, and for assessing an increased or decreased risk of developing bipolar illness for a tested individual from an affected family. Excerpt(s): This application claims priority to U.S. Provisional Application Ser. No. 60/062,924, filed Oct. 20, 1997. This application is related to Ser. No. 08/827,568, filed Mar. 28, 1997, and 60/014,334, filed Mar. 29, 1996. These disclosures are incorporated herein by reference for all purposes. This invention relates to the field of diagnosis and treatment of bipolar affective disorders. The most characteristic features of bipolar affective disorder (manic-depressive illness) are episodes of mania (bipolar I, BPI) or hypomania (bipolar II, BPII) that are interspersed with periods of depression. If untreated, manic-depressive illness is associated with an approximately 20% risk of suicide. Even with treatment, this disorder constitutes a major public health problem, afflicting approximately one percent of the population. Goodwin et al., ManicDepressive Illness (Oxford University Press, New York, 1990). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Topiramate salts and compositions comprising them Inventor(s): Almarsson, Orn; (Shrewsbury, MA), Peterson, Matthew L.; (Framingham, MA), Remenar, Julius; (Framingham, MA) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030166581 Date filed: November 18, 2002 Abstract: The invention encompasses novel salts of topiramate, and pharmaceutically acceptable polymorphs, solvates, hydrates, dehydrates, co-crystals, anhydrous, or amorphous forms thereof, as well as pharmaceutical compositions and pharmaceutical unit dosage forms containing the same. In particular, the invention encompasses pharmaceutically acceptable salts of topiramate, including without limitation topiramate sodium, topiramate lithium, topiramate potassium, or polymorphs, solvates, hydrates, dehydrates, co-crystals, anhydrous, and amorphous forms thereof. The invention further encompasses novel co-crystals or complexes of topiramate, as well as pharmaceutical compositions comprising them. The invention also encompasses methods of treating or preventing a variety of diseases and conditions including, but not limited to, seizures, epileptic conditions, tremors, cerebral function disorders, obesity, neuropathic pain, affective disorders, tobacco cessation, migraines, and cluster headache. Excerpt(s): This application is related to U.S. provisional patent application Nos. 60/356,764, filed Feb. 15, 2002, 60/380,288, filed May 15, 2002, and ______ filed Aug. 30, 2002, all of which are incorporated herein by reference in their entireties. This invention relates to compounds, pharmaceutical compositions, and methods for the treatment or prevention of seizures, epilepsy, tremors, affective disorders, obesity, neuropathic pain, and migraines. Topiramate is a white crystalline powder with a solubility in water of 9.8 mg/mL, and it is freely soluble in acetone, chloroform, dimethylsulfoxide, and ethanol. See, Physician's Desk Reference, 56.sup.th ed., pp. 2590-2595 (2002). 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 affective disorders, 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 “affective disorders” (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 affective disorders. You can also use this procedure to view pending patent applications concerning affective disorders. 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 AFFECTIVE DISORDERS Overview This chapter provides bibliographic book references relating to affective disorders. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on affective disorders 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 “affective disorders” (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 affective disorders: •
Dementias: Crossroads Between Neurology and Psychiatry Source: St. Louis, MO: Warren H. Green, Inc. 1992. 187 p. Contact: Available from Warren H. Green, Inc. 8356 Olive Boulevard, St. Louis, MO 63132. (314) 991-1335 or (800) 537-0655. PRICE: $27.50 plus $2.00 for shipping and handling. ISBN: 875273505. Summary: This book discusses neurobiological research in brain disorders such as dementia. The book focuses on research in cell biology and biochemistry, with a particular emphasis on acetylcholine and the amino acid neurotransmitters. These excitatory neurotransmitters have been implicated in the etiology of affective disorders, limbic epilepsy, and the degenerative disorders of the brain. The book is particularly concerned with the neurotransmitter function of glutamate, its possible role in neuropsychiatric disorders, and the use of kainic acid as a tool in neurobiological
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research. One chapter includes a discussion of neurotoxic amino acids in Alzheimer's disease. Another chapter is devoted to the role of the cholinergic system in Alzheimer's disease, the effects of cholinergic and anticholinergic drugs on learning and memory, and treatment with the acetylcholinesterase inhibitors physostigmine and THA. 367 references.
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 “affective disorders” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “affective disorders” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “affective disorders” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Affective and Schizoaffective Disorders; ISBN: 3540520716; http://www.amazon.com/exec/obidos/ASIN/3540520716/icongroupinterna
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Affective and Schizoaffective Disorders: Similarities and Differences by A. Marneros, M.T. Tsuang (Editor); ISBN: 0387520716; http://www.amazon.com/exec/obidos/ASIN/0387520716/icongroupinterna
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Affective Disorders by John M. Davis (Editor), James W. Maas (Editor); ISBN: 0880482141; http://www.amazon.com/exec/obidos/ASIN/0880482141/icongroupinterna
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Affective Disorders by Joseph, Becker; ISBN: 0382250966; http://www.amazon.com/exec/obidos/ASIN/0382250966/icongroupinterna
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Affective Disorders (Directions in Psychiatry Monograph Series, No 3) by Frederic Flach (Editor); ISBN: 0393700550; http://www.amazon.com/exec/obidos/ASIN/0393700550/icongroupinterna
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Affective Disorders and the Family: Assessment and Treatment by John F. Clarkin (Editor), et al; ISBN: 0898621011; http://www.amazon.com/exec/obidos/ASIN/0898621011/icongroupinterna
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Affective Disorders in Childhood and Adolescence: An Update by Dennis P. Cantwell (Editor), Gabrielle Carlson (Editor); ISBN: 0852006306; http://www.amazon.com/exec/obidos/ASIN/0852006306/icongroupinterna
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Affective Disorders in the Elderly (Medicine in Old Age) by Elaine Murphy (Editor); ISBN: 0443032599; http://www.amazon.com/exec/obidos/ASIN/0443032599/icongroupinterna
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Affective Disorders Reassessed--1983 (Proceedings Fifteenth Annual Taylor Manor Hospital Psychiatric Symposium, eLlicott City, MD , April 8-9, 198) by Taylor Manor Hospital Psychiatric Symposium; ISBN: 999331966X; http://www.amazon.com/exec/obidos/ASIN/999331966X/icongroupinterna
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Affective Disorders, Psychopathology and Treatment by E. R. Val (Editor); ISBN: 0815189524; http://www.amazon.com/exec/obidos/ASIN/0815189524/icongroupinterna
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Affective Disorders: Perspectives on Basic Research and Clinical Practice by Tetsuhiko Kariya, Michio Nakagawara (Editor); ISBN: 0876306741; http://www.amazon.com/exec/obidos/ASIN/0876306741/icongroupinterna
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Affective Disorders: Psychoanalytic Contributions to Their Study by Phyllis Greenacre (Editor); ISBN: 0823601005; http://www.amazon.com/exec/obidos/ASIN/0823601005/icongroupinterna
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Affective Disorders: The Assessment Development and Treatment Strategies of Manic Depressive Structure by Sandra G. Landsman; ISBN: 0935571000; http://www.amazon.com/exec/obidos/ASIN/0935571000/icongroupinterna
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Alcoholism and affective disorders : clinical, genetic, and biochemical studies; ISBN: 0893350737; http://www.amazon.com/exec/obidos/ASIN/0893350737/icongroupinterna
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Alcoholism and Affective Disorders: Clinical, Genetic, and Biochemical Studies With Emphasis on Alcohol-Lithium Interaction by Donald W. Goodwin, Erickson E. Carlton; ISBN: 0893350893; http://www.amazon.com/exec/obidos/ASIN/0893350893/icongroupinterna
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Anticonvulsants in Affective Disorders by H. M. Emrich (Editor), et al; ISBN: 0444805729; http://www.amazon.com/exec/obidos/ASIN/0444805729/icongroupinterna
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Biogenic amines and affective disorders : proceedings of a symposium held in London, 18-21 January 1979; ISBN: 8716086384; http://www.amazon.com/exec/obidos/ASIN/8716086384/icongroupinterna
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Biological Aspects of Affective Disorders (Neuroscience Perspective Series) by Roger Horton (Editor), Cornelius Katona (Editor); ISBN: 0123565103; http://www.amazon.com/exec/obidos/ASIN/0123565103/icongroupinterna
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Bipolar Affective Disorder : Etiology and Treatment by Jorg Walden, Heinz Grunze; ISBN: 0865779996; http://www.amazon.com/exec/obidos/ASIN/0865779996/icongroupinterna
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Brain Imaging in Affective Disorders by Jair C. Soares (Editor); ISBN: 0824708849; http://www.amazon.com/exec/obidos/ASIN/0824708849/icongroupinterna
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Brain Imaging in Affective Disorders (Progress in Psychiatry Series, No 34) by Peter Hauser (Editor); ISBN: 088048456X; http://www.amazon.com/exec/obidos/ASIN/088048456X/icongroupinterna
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Canadian Consensus Guidelines for the Treatment of Seasonal Affective Disorder by Raymond W. Lam, Anthony J. Levitt; ISBN: 0968587402; http://www.amazon.com/exec/obidos/ASIN/0968587402/icongroupinterna
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Clinical Guidelines for the Treatment of Seasonal Affective Disorder by Raymond Lam, Anthony Levitt; ISBN: 0968587410; http://www.amazon.com/exec/obidos/ASIN/0968587410/icongroupinterna
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Comorbidity in Affective Disorders by Mauricio Tohen (Editor); ISBN: 0824702123; http://www.amazon.com/exec/obidos/ASIN/0824702123/icongroupinterna
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Critical Issues in the Treatment of Affective Disorders (International Academy for Biomedical and Drug Research, Vol 9) by Giorgio Racagni, et al; ISBN: 380556032X; http://www.amazon.com/exec/obidos/ASIN/380556032X/icongroupinterna
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Depression Sourcebook: Basic Consumer Health Information About Unipolar Depression, Bipolar Disorder, Postpartum Depression, Seasonal Affective Disorder, and Other Types of (Health Reference Series) by Karen Bellenir (Editor), Rhonda Rhea; ISBN: 0780806115; http://www.amazon.com/exec/obidos/ASIN/0780806115/icongroupinterna
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Don't Be Sad: Fight the Winter Blues-Your Guide to Conquering Seasonal Affective Disorder by Celeste A. Peters; ISBN: 1896015018; http://www.amazon.com/exec/obidos/ASIN/1896015018/icongroupinterna
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Gender Differences in the Epidemiology of Affective Disorders and Schizophrenia by Marco Piccinelli, Francesca Gomez Homen; ISBN: 0119517884; http://www.amazon.com/exec/obidos/ASIN/0119517884/icongroupinterna
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Genetic Analysis of Complex Traits: Affective Disorders by John Rice (Editor), et al; ISBN: 0471509930; http://www.amazon.com/exec/obidos/ASIN/0471509930/icongroupinterna
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Genetic Studies in Affective Disorders: Overview of Basic Methods, Current Directions, and Critical Research Issues (Publication Series of the Depar) by Demitri F. Papolos (Editor), et al; ISBN: 0471000752; http://www.amazon.com/exec/obidos/ASIN/0471000752/icongroupinterna
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Handbook of Affective Disorders, Second Edition by Eugene S. Paykel (Editor); ISBN: 0898626749; http://www.amazon.com/exec/obidos/ASIN/0898626749/icongroupinterna
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Handbook of Psychopharmacology (Section III: Human Psychopharmacology) Vol. 14: Affective Disorders: Drug Actions in Animals and Man by Leslie L. Iversen, et al; ISBN: 0306389347; http://www.amazon.com/exec/obidos/ASIN/0306389347/icongroupinterna
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If You Think You Have Seasonal Affective Disorder (A Dell Mental Health Guide) by Clifford Taylor (Author); ISBN: 0440225426; http://www.amazon.com/exec/obidos/ASIN/0440225426/icongroupinterna
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Interpersonal Factors in the Origin and Course of Affective Disorders by Christoph Mundt, Hugh L. Freeman; ISBN: 0902241907; http://www.amazon.com/exec/obidos/ASIN/0902241907/icongroupinterna
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Lectures in Psychiatry: The Functional Psychoses: The Schizophrenias and Major Affective Disorders by Ken Reed; ISBN: 0875273394; http://www.amazon.com/exec/obidos/ASIN/0875273394/icongroupinterna
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Marriage and fertility of women suffering from schizophrenia or affective disorders by Barbara Christine Stevens; ISBN: 0197121411; http://www.amazon.com/exec/obidos/ASIN/0197121411/icongroupinterna
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Modern Perspectives in the Psychiatry of the Affective Disorders (Modern Perspectives in Psychiatry, No 13) by John G. Howells (Editor); ISBN: 0876305311; http://www.amazon.com/exec/obidos/ASIN/0876305311/icongroupinterna
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Neuropharmacology of cyclic nucleotides : role of cyclic AMP in affective disorders, epilepsy, and modified behavioral states; ISBN: 0806715219; http://www.amazon.com/exec/obidos/ASIN/0806715219/icongroupinterna
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Neuropsychopharmacology and the affective disorders by Joseph J. Schildkraut; ISBN: 0700001859; http://www.amazon.com/exec/obidos/ASIN/0700001859/icongroupinterna
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New Directions in Affective Disorders by Bernard Lerer, Samuel Gershon (Editor); ISBN: 0387967699; http://www.amazon.com/exec/obidos/ASIN/0387967699/icongroupinterna
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New Directions in Affective Disorders; ISBN: 3540967699; http://www.amazon.com/exec/obidos/ASIN/3540967699/icongroupinterna
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Origin Prevention and Treatment of Affective Disorders by Mogens Schou, Erik Stromgren; ISBN: 0126289506; http://www.amazon.com/exec/obidos/ASIN/0126289506/icongroupinterna
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Pharmacotherapy of Affective Disorders: Theory and Practice by W.G. Dewhurst (Editor); ISBN: 0814717772; http://www.amazon.com/exec/obidos/ASIN/0814717772/icongroupinterna
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Positive Options for Seasonal Affective Disorder (SAD): Self-Help and Treatment by Fiona Marshall, Peter Cheevers; ISBN: 089793413X; http://www.amazon.com/exec/obidos/ASIN/089793413X/icongroupinterna
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Psychobiology of Affective Disorders by Pfizer Symposium on Depression, J. Mendels (Editor); ISBN: 380551400X; http://www.amazon.com/exec/obidos/ASIN/380551400X/icongroupinterna
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Psychopharmacology Affective Disorders by Paykel; ISBN: 0192611402; http://www.amazon.com/exec/obidos/ASIN/0192611402/icongroupinterna
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Rating scales for affective disorders : their validity and consistency by Per Bech; ISBN: 8716091051; http://www.amazon.com/exec/obidos/ASIN/8716091051/icongroupinterna
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Recent Advances in the Research of Affective Disorders in Japan by Teruo Okuma (Editor), et al; ISBN: 0444507485; http://www.amazon.com/exec/obidos/ASIN/0444507485/icongroupinterna
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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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Seasonal Affective Disorder by Chris Thompson, Trevor Silverstone; ISBN: 1869868714; http://www.amazon.com/exec/obidos/ASIN/1869868714/icongroupinterna
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Seasonal affective disorder : January 1986 through December 1991 : 402 citations (SuDoc HE 20.3615/2:91-18) by Lori Klein; ISBN: B000109BGS; http://www.amazon.com/exec/obidos/ASIN/B000109BGS/icongroupinterna
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Seasonal Affective Disorder and Beyond: Light Treatment for Sad and Non-Sad Conditions by Raymond W. Lam (Editor); ISBN: 0880488670; http://www.amazon.com/exec/obidos/ASIN/0880488670/icongroupinterna
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Seasonal Affective Disorder: Practice and Research by Timo Partonen (Editor), Andres Magnusson (Editor); ISBN: 0192632256; http://www.amazon.com/exec/obidos/ASIN/0192632256/icongroupinterna
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Seasonal Affective Disorder: Who Gets It, What Causes It, How to Cure It by Angela Smyth, Chris Thompson (Contributor); ISBN: 0722525699; http://www.amazon.com/exec/obidos/ASIN/0722525699/icongroupinterna
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Seasonal Affective Disorders and Phototherapy by Norman Edward Rosenthal (Editor), Mary C. Blehar (Editor); ISBN: 0898627419; http://www.amazon.com/exec/obidos/ASIN/0898627419/icongroupinterna
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Serotonin in Affective Disorders (Advances in Biological Psychiatry, Vol 14) by J. Mendlewicz (Editor), et al; ISBN: 3805538987; http://www.amazon.com/exec/obidos/ASIN/3805538987/icongroupinterna
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Signal Transduction in Affective Disorders by H. Ozawa (Editor), et al; ISBN: 4431702105; http://www.amazon.com/exec/obidos/ASIN/4431702105/icongroupinterna
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Symptomatic Affective Disorders: A Study of Depression and Mania Associated With Physical Disease and Medication by Francis Anton Whitlock; ISBN: 012747580X; http://www.amazon.com/exec/obidos/ASIN/012747580X/icongroupinterna
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Tardive Dyskinesia and Affective Disorders by George Gardos (Editor); ISBN: 0880480602; http://www.amazon.com/exec/obidos/ASIN/0880480602/icongroupinterna
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The Cheese Effect and New Reversible MAO-A Inhibitors: Proceedings of the Round Table of the International Conference on New Directions in Affective Disorders, Jerusalem, April 5-9, 1987; ISBN: 3211820310; http://www.amazon.com/exec/obidos/ASIN/3211820310/icongroupinterna
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The Influence of Effort on Impairments of Attention Associated With Major Affective Disorders by Ilan Lohr; ISBN: 1581120834; http://www.amazon.com/exec/obidos/ASIN/1581120834/icongroupinterna
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Treatment of Affective Disorders in the Elderly (Progress in Psychiatry Series) by Charles A. Shamoian (Editor); ISBN: 0880480866; http://www.amazon.com/exec/obidos/ASIN/0880480866/icongroupinterna
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Understanding Seasonal Affective Disorder by Jennifer Eastwood; ISBN: 1874690405; http://www.amazon.com/exec/obidos/ASIN/1874690405/icongroupinterna
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Vascular Disease and Affective Disorders by Edmond, Am, Mbbs, Dpm, Franzcp Chiu (Editor), et al; ISBN: 1841841528; http://www.amazon.com/exec/obidos/ASIN/1841841528/icongroupinterna
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Winter Blues: Seasonal Affective Disorder: What It Is and How to Overcome It, Revised and Upda by Norman Edward Rosenthal (Author); ISBN: 1572303956; http://www.amazon.com/exec/obidos/ASIN/1572303956/icongroupinterna
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Winter Blues: Seasonal Affective Disorders: What It Is and How to Conquer It by Norman Rosenthal, Chris Thompson; ISBN: 0006376584; http://www.amazon.com/exec/obidos/ASIN/0006376584/icongroupinterna
Chapters on Affective Disorders In order to find chapters that specifically relate to affective disorders, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and affective disorders 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 “affective
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disorders” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on affective disorders: •
Genetic Aspects of Aging Source: in Rossman, I., ed. Clinical Geriatrics, 3rd ed. Philadelphia, PA: J.B. Lippincott Company. 1986. p. 68-91. Contact: Available from J.B. Lippincott Company. East Washington Square, Philadelphia, PA 19105. (215) 238-4200. PRICE: $69.50. ISBN: 0397506724. Summary: Despite the great strides in deciphering the genetic code and elucidating a variety of genetic mechanisms, the genetic aspects of aging, remain virtually unexplored. This book chapter summarizes and discusses information available in three specific areas: genetic analysis and life span (giving consideration to pedigrees of longevous twin families, population samples, twin and twin-family samples); genetics and common disorders of the aged (cardiovascular diseases (hypertension; coronary artery disease); neoplastic diseases; mental diseases (presenile dementias; dementia of the Alzheimer type (presenile onset; senile onset); multi-infarct dementia; affective disorders; paranoid disorders); and mental functioning in normal aging. The authors conclude that, despite the paucity of studies dealing directly with genetic factors in aging, such factors have been shown whenever an adequate search for etiologic components has been undertaken. 184 references.
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Psychiatric Disorders Source: in Rossman, I., ed. Clinical Geriatrics, 3rd ed. Philadelphia, PA: J.B. Lippincott Company. 1986. p. 593-605. Contact: This publication may be available from your local medical library. Call for information. ISBN: 0397506724. Summary: This chapter discusses four of the more common psychiatric disorders in late life: (1) primary degenerative dementia (loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning); (2) affective disorders (depression); (3) hypochondriasis (unrealistic interpretation of physical signs or sensations as abnormal, leading to fear or belief of having a serious disease); and (4) paranoid disorders (suspicion of anything new or unusual). For each of these disorders, information is presented regarding the epidemiology, etiology, diagnosis, and treatment. Each disorder is used to illustrate how myth and fact must be separated if effective care is to be provided for older adults. 28 references.
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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)
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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. •
Behavioral Pain Management Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 587-591. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email:
[email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on behavioral pain management is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). In addition to symptoms of diarrhea, rectal bleeding, and weight loss, abdominal pain is described by more than 75 percent of patients with inflammatory bowel disease. Although psychological characteristics have not been shown to cause inflammatory bowel disease, patients having this disorder have been found to be more hypochondriacal, depressed, anxious, obsessive-compulsive, and nonassertive than normal control populations in many studies, even though there are some exceptions. In addition, patients with IBD have been reported by some investigators as being similar to patients diagnosed with psychosomatic disorders such as spastic colitis on measures of anxiety, neurotic tendencies, or affective disorders. These findings have led to the conclusion that the interaction between emotional stress and psychological characteristics can affect the onset or exacerbation of symptoms associated with IBD. As a consequence, behaviorally based treatments useful in the management of chronic pain arising from other disorders can be applied in the treatment of pain associated with IBD. The author offers guidelines for recognizing patients with a chronic pain syndrome, summarizes the important facets of the physician-patient relationship, and outlines specific behavioral pain management for IBD, including stress management, somatic anxiety, biofeedback, relaxation training, behavior therapy, and family therapy; the use of narcotic analgesic (pain killing) medications is also mentioned. The chapter concludes with a case report that illustrates the successful treatment of chronic pain in a patient with IBD. 13 references.
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Essentials of Geriatric Psychiatry for Dental Practitioners Source: in Holm-Pedersen, P.; Loe, H., eds. Textbook of Geriatric Dentistry. 2nd ed. Copenhagen, Denmark: Munksgaard. 1996. p. 234-247. Contact: Available from Munksgaard. 35 Norre Sogade, P.O. Box 2148, DK-1016, Copenhagen K, Denmark. Telephone +45 33 12 70 30; Fax +45 33 12 93 87; E-mail:
[email protected]; http://www.munksgaard.dk/publishers/. PRICE: DKK 520,000; contact directly for current price in US dollars. ISBN: 8716105338.
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Summary: This chapter on geriatric psychiatry for dental practitioners is from a comprehensive text on the processes of aging and their relevance to the delivery of dental health care. Topics include the prevalence of mental disorders among elderly people and the effects on oral health and dental care of major syndromes, including situational disorders, affective disorders, drug-induced dry mouth (xerostomia), the cardiovascular effects of medications, central nervous system effects of medications, anxiety disorders, disorders of cognitive function (dementia, delirium, and toxic confusional states), paranoid states, and chronic mental disorder persisting into late life. The authors outline the key features of each disorder, the oral problems they engender, and the modification of dental practice each requires. The authors conclude that despite recent professional interest in the unmet dental needs of older people, important barriers remain to comprehensive oral care for elderly psychiatric patients. 49 references. (AA-M). •
Head Injury and Taste Source: in Doty, R.L., ed. Handbook of Olfaction and Gustation. New York, NY: Marcel Dekker, Inc. 1995. p. 775-783. 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: This chapter, from a medical text on olfaction and gustation, reviews gustatory dysfunction following head injury, focusing on diagnostic, management, and rehabilitation issues for patients with impaired gustatory function. Topics covered include the historical perspective of this problem; mechanisms of injury, including injury to the tongue, peripheral nerve damage, and cortical contusion; the clinical assessment, including patient history, assessment of related cranial nerve function, head and neck examination, radiographic evaluation, and gustatory function testing; and rehabilitation and special considerations, notably functional issues, counseling issues, disability evaluation, and medicolegal matters. The authors conclude that although there are no specific treatments for posttraumatic ageusia, careful follow-up may reveal spontaneous recovery. The clinician should assure that proper consideration has been given to nontraumatic etiologies of gustatory function, including drug side effects, affective disorders such as depression, and other preexisting conditions. 2 tables. 39 references. (AA-M).
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Psychiatry of the Elderly Source: in Gelder, M., Gath, D. and Mayou, R. Oxford Textbook of Psychiatry. Oxford, England: Oxford University Press. 1989. p. 596-623. Contact: Available from Oxford University Press. 200 Madison Avenue, New York, NY 10016. (800) 451-7556. PRICE: $95.00 (hard cover), $45.00 (paperback). ISBN: 0192616307 (hard cover), 0192616293 (paperback). Summary: While the psychiatric disorders of the elderly have some special features, they do not differ markedly from the psychiatric disorders of younger adults. The needs of elderly psychiatric patients set them apart from others. Hence, the practice of psychogeriatrics requires special psychiatric skills. The chapter begins with a brief account of normal aging, followed by a discussion of the general principles of psychogeriatric care, and then an account is given of different psychiatric syndromes in the elderly. Topics include normal aging, the aging brain, the psychology of aging, physical health, and social circumstances; general considerations such as epidemiology;
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services for the elderly such as primary care, hospital care psychogeriatric assessment units, day and out-patient care, residential care, and domiciliary services; general principles of assessment including history taking, examination, physical investigations, and psychological assessment; treatment such as prescribed medicines, electroconvulsive therapy, psychological treatment, social treatment, and support for relatives; delirium and its clinical features; dementia in the elderly; the prevalence, clinical features, pathology, biochemistry, subtypes, and etiology of Alzheimer's disease; multi-infarct dementia; assessment and treatment of dementia in the elderly; and affective disorders including depression, mania, schizoaffective disorder and its treatment.
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CHAPTER 8. PERIODICALS AND NEWS ON AFFECTIVE DISORDERS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover affective disorders.
News Services and Press Releases One of the simplest ways of tracking press releases on affective disorders 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 “affective disorders” (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 affective disorders. 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 “affective disorders” (or synonyms). The following was recently listed in this archive for affective disorders: •
Migraine more common in bipolar II than in other affective disorders Source: Reuters Medical News Date: January 21, 2002
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Learning disability linked with increased risk of affective disorder Source: Reuters Medical News Date: January 08, 2002
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Neural circuits may mediate pathogenesis of seasonal affective disorder Source: Reuters Medical News Date: December 14, 2001
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Early morning light exposure benefits seasonal affective disorder patients Source: Reuters Medical News Date: January 24, 2001
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High prevalence of affective disorders seen in HIV-infected adolescents Source: Reuters Medical News Date: March 20, 2000
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Prenatal famine link to major affective disorder supported Source: Reuters Medical News Date: February 07, 2000
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Light therapy in the morning best for seasonal affective disorder Source: Reuters Medical News Date: October 19, 1998
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Brain catecholaminergic systems involved in efficacy of light therapy for seasonal affective disorder Source: Reuters Medical News Date: June 23, 1998
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Central Serotonergic Function Altered In Women With Seasonal Affective Disorder Source: Reuters Medical News Date: March 23, 1998
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Seasonal Affective Disorder Hits Children Source: Reuters Health eLine Date: January 23, 1998
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Pediatric Seasonal Affective Disorder Underdiagnosed Source: Reuters Medical News Date: January 23, 1998
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Prenatal Influenza Exposure Linked To Affective Disorder Source: Reuters Medical News Date: December 09, 1997
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Affective Disorders Treatment Effective Against Aggression In Demented Elderly Source: Reuters Medical News Date: October 17, 1997
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Prenatal Exposure To Influenza Linked To Major Affective Disorder Source: Reuters Medical News Date: April 30, 1997
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Light Therapy For Seasonal Affective Disorder Mediated By Serotonin Source: Reuters Medical News Date: January 09, 1997
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Evidence For Inherited Susceptibility To Affective Disorders Mounting Source: Reuters Medical News Date: March 20, 1996
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Family History Of Affective, Nonaffective Disorders Risk Factor For ADHD In Children Source: Reuters Medical News Date: March 11, 1996
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Genetics Plays A Role In Seasonal Affective Disorder Source: Reuters Medical News Date: February 05, 1996
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Fluoxetine Effective Therapy For Seasonal Affective Disorder Source: Reuters Medical News Date: December 19, 1995
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Seasonal Recurrent Depression A Distinct Subtype Of Seasonal Affective Disorder Source: Reuters Medical News Date: June 05, 1995 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 “affective disorders” (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 “affective disorders” (or synonyms). If you know the name of a company that is relevant to
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affective disorders, 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/. 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 “affective disorders” (or synonyms).
Academic Periodicals covering Affective Disorders Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to affective disorders. In addition to these sources, you can search for articles covering affective disorders 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. 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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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 Institute11: •
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/
11
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.12 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:13 •
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
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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
12
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). 13 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
•
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 Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “affective disorders” (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 61975 330 1097 166 56 63624
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “affective disorders” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
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 Biologists19 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.20 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.21 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 Affective Disorders In the following section, we will discuss databases and references which relate to the Genome Project and affective disorders. 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).22 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. 19 Adapted 20
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. 21 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. 22 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 “affective disorders” (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 affective disorders: •
Major Affective Disorder 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?125480
•
Major Affective Disorder 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?309200 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: •
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,
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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
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
•
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
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
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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 “affective disorders” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 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. The Genome Database24 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 “affective disorders” (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).
23
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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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 affective disorders can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased 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 affective disorders. 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 affective disorders. 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 “affective disorders”:
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Other guides Bipolar Disorder http://www.nlm.nih.gov/medlineplus/bipolardisorder.html Mental Health http://www.nlm.nih.gov/medlineplus/mentalhealth.html Seasonal Affective Disorder http://www.nlm.nih.gov/medlineplus/seasonalaffectivedisorder.html
Within the health topic page dedicated to affective disorders, the following was listed: •
General/Overviews Seasonal Affective Disorder Source: American Academy of Family Physicians http://familydoctor.org/267.xml Seasonal Affective Disorder Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00195 Seasonal Depression Source: Cleveland Clinic Foundation http://www.clevelandclinic.org/health/healthinfo/docs/2300/2361.asp?index=9293
•
Diagnosis/Symptoms Symptoms: Learning to Recognize Clinical Depression Source: National Mental Health Association http://www.nmha.org/ccd/support/symptoms.cfm
•
Treatment Understanding Seasonal Affective Disorder and Light Therapy Source: Cleveland Clinic Foundation http://www.clevelandclinic.org/health/healthinfo/docs/1400/1484.asp?index=6412
•
Specific Conditions/Aspects Holiday Depression & Stress Source: National Mental Health Association http://www.nmha.org/infoctr/factsheets/103.cfm
•
Organizations National Alliance for the Mentally Ill http://www.nami.org/ National Institute of Mental Health http://www.nimh.nih.gov/
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National Mental Health Association http://www.nmha.org/ •
Research Seasonal Affective Disorder Has Biological Roots Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZWJ38G5VC& sub_cat=625
•
Teenagers Seasonal Affective Disorder Source: Dept. of Health and Human Services http://www.girlpower.gov/girlarea/general/SAD.htm
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. 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 affective disorders. 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
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMD®Health: http://my.webmd.com/health_topics
Associations and Affective Disorders The following is a list of associations that provide information on and resources relating to affective disorders: •
Depression and Related Affective Disorders Association Telephone: (410) 955-4647 Fax: (410) 614-3241 Email:
[email protected] Web Site: www.drada.org Background: The Depression and Related Affective Disorders Association (DRADA) is a nonprofit organization uniting the efforts of persons with affective disorders, family members, and mental health professionals. The mission of the organization is to provide information, assistance, and support to those with depression and manic depression by assisting self-help groups. In addition, the Association lends support to research programs. Educational materials produced by the Depression and Related Affective Disorders Association include a variety of pamphlets, books, and videos. Relevant area(s) of interest: Affective Disorders
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to affective disorders. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with affective disorders. 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 affective disorders. 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/.
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Simply type in “affective disorders” (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. 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 “affective disorders”. 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 “affective disorders” (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 “affective disorders” (or a synonym) into the search box, and click “Submit Query.”
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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.25
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
25
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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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)26: •
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
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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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/
26
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
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
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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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
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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
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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
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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
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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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
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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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
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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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
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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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/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
191
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
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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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
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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).
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
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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
193
AFFECTIVE DISORDERS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 2-Propanol: An isomer of 1-propanol. It is a colorless liquid having disinfectant properties. It is used in the manufacture of acetone and its derivatives and as a solvent. Topically, it is used as an antiseptic. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [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] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Abducens: A striated, extrinsic muscle of the eyeball that originates from the annulus of Zinn. [NIH] Abducens Nerve: The 6th cranial nerve. The abducens nerve originates in the abducens nucleus of the pons and sends motor fibers to the lateral rectus muscles of the eye. Damage to the nerve or its nucleus disrupts horizontal eye movement control. [NIH] Abducens Nerve Diseases: Diseases of the sixth cranial (abducens) nerve or its nucleus in the pons. The nerve may be injured along its course in the pons, intracranially as it travels along the base of the brain, in the cavernous sinus, or at the level of superior orbital fissure or orbit. Dysfunction of the nerve causes lateral rectus muscle weakness, resulting in horizontal diplopia that is maximal when the affected eye is abducted and esotropia. Common conditions associated with nerve injury include intracranial hypertension; craniocerebral trauma; ischemia; and infratentorial neoplasms. [NIH] Ablation: The removal of an organ by surgery. [NIH] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acculturation: Process of cultural change in which one group or members of a group assimilates various cultural patterns from another. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [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] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH]
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Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Activity Cycles: Bouts of physical irritability or movement alternating with periods of quiescence. It includes biochemical activity and hormonal activity which may be cellular. These cycles are shorter than 24 hours and include sleep-wakefulness cycles and the periodic activation of the digestive system. [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] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [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] Adolescent Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders in individuals 13-18 years. [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] Adrenergic Agents: Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters. [NIH]
Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Affective Symptoms: Mood or emotional responses dissonant with or inappropriate to the behavior and/or stimulus. [NIH]
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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] 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] Ageusia: Complete or severe loss of the subjective sense of taste, frequently accompanied by olfaction disorders. [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] 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] Akinesia: 1. Absence or poverty of movements. 2. The temporary paralysis of a muscle by the injection of procaine. [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] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [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] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH]
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Amenorrhea: Absence of menstruation. [NIH] Amino Acid Neurotransmitters: Amino acids released by neurons as intercellular messengers. Among the amino acid neurotransmitters are glutamate (glutamic acid) and GABA which are, respectively, the most common excitatory and inhibitory neurotransmitters in the central nervous system. [NIH] 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] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [NIH] 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] 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]
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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [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 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] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In
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addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [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] 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]
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] Anterograde: Moving or extending forward; called also antegrade. [EU] Antiallergic: Counteracting allergy or allergic conditions. [EU] 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]
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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] 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] 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-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Anti-Obesity Agents: Agents that increase energy expenditure and weight loss by neural and chemical regulation. Beta-adrenergic agents and serotoninergic drugs have been experimentally used in patients with non-insulin dependent diabetes mellitus (NIDDM) to treat obesity. [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] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antispasmodic: An agent that relieves spasm. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH]
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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] Apnea: A transient absence of spontaneous respiration. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [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] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [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] Articular: Of or pertaining to a joint. [EU] 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] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [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] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. 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
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to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [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] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [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] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [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
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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; 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] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [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] Bewilderment: Impairment or loss of will power. [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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [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 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] Biosynthesis: The building up of a chemical compound in the physiologic processes of a
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living organism. [EU] 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] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [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 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] 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] 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]
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Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [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] Buspirone: An anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam. [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 channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins. [NIH]
Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [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] 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] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [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
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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] 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] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] 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] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [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] 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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH]
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Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [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 Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [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] Central Nervous System Diseases: Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] 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 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 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] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and
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vagina. [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] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chloroform: A commonly used laboratory solvent. It was previously used as an anesthetic, but was banned from use in the U.S. due to its suspected carcinogenecity. [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] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [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] 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] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [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]
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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] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Clonic: Pertaining to or of the nature of clonus. [EU] 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] Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with welldefined distribution patterns in relation to time or place or both. [NIH]
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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] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] 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 behavior therapy: A system of psychotherapy based on the premise that distorted or dysfunctional thinking, which influences a person's mood or behavior, is common to all psychosocial problems. The focus of therapy is to identify the distorted thinking and to replace it with more rational, adaptive thoughts and beliefs. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [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] Colloidal: Of the nature of a colloid. [EU] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [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
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used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [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] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [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] Concomitant: Accompanying; accessory; joined with another. [EU] Concretion: Minute, hard, yellow masses found in the palpebral conjunctivae of elderly people or following chronic conjunctivitis, composed of the products of cellular degeneration retained in the depressions and tubular recesses in the conjunctiva. [NIH] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH]
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Congestion: Excessive or abnormal accumulation of blood in a part. [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] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] 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 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] Contusion: A bruise; an injury of a part without a break in the skin. [EU] 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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] 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
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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] 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] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Corticotropin-Releasing Hormone: A neuropeptide released by the hypothalamus that stimulates the release of corticotropin by the anterior pituitary gland. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Nerves: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other healthrelated variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [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] Curative: Tending to overcome disease and promote recovery. [EU] 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]
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Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] 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] 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] Cytotoxic: Cell-killing. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [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] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH]
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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] 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] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [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] 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] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholingeric activity, through its affinity to muscarinic receptors. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH]
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Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [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 Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [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] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]
Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [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] Dilatation: The act of dilating. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diplopia: A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disability Evaluation: Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for Social Security and workmen's compensation benefits. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU]
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Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [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] 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] Diurnal: Occurring during the day. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] 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] 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] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [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 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
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effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Dysgenesis: Defective development. [EU] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyspepsia: Impaired digestion, especially after eating. [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] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [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] 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] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] 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] 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.,
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radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] 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] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [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] Enkephalin: A natural opiate painkiller, in the hypothalamus. [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] 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
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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] 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] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [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] Estrogen Antagonists: Compounds which inhibit or antagonize the action or biosynthesis of estrogen. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [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] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by
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stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] 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] Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Health: The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members. [NIH]
Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [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
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effect is the inhibition of gastric secretion. [NIH] Fasciculation: A small local contraction of muscles, visible through the skin, representing a spontaneous discharge of a number of fibres innervated by a single motor nerve filament. [EU]
Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [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] 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] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH]
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Fluorescence Polarization: Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [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] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [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] Forearm: The part between the elbow and the wrist. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Functional Disorders: Disorders such as irritable bowel syndrome. These conditions result from poor nerve and muscle function. Symptoms such as gas, pain, constipation, and diarrhea come back again and again, but there are no signs of disease or damage. Emotional stress can trigger symptoms. Also called motility disorders. [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]
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] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] 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
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through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] 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 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] 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] 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 Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [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] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU]
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Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Geriatric Psychiatry: A subspecialty of psychiatry concerned with the mental health of the aged. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. [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] Glutamate: Excitatory neurotransmitter of the brain. [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]
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] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [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] 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] Haematemesis: The vomiting of blood. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH]
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Haloperidol: Butyrophenone derivative. [NIH] Handicap: A handicap occurs as a result of disability, but disability does not always constitute a handicap. A handicap may be said to exist when a disability causes a substantial and continuing reduction in a person's capacity to function socially and vocationally. [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] 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] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [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 influencing life style are socioeconomic, educational, and cultural. [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] 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] Hemoglobinuria: The presence of free hemoglobin in the urine. [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] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH]
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Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 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 virus: A member of the herpes family of viruses. [NIH] 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]
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] Histology: The study of tissues and cells under a microscope. [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] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [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] 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]
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Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hypersecretion: Excessive secretion. [EU] 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] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypochondriasis: (DSM III-R) a mental disorder characterized by a preoccupation with bodily functions and the interpretation of normal sensations (such as heart beats, sweating, peristaltic action, and bowel movements) or minor abnormalities (such as a runny nose, minor aches and pains, or slightly swollen lymph nodes) as indications of highly disturbing problems needing medical attention. Negative results of diagnostic evaluations and reassurance by physicians only increase the patient's anxious concern about his health, and the patient continues to seek medical attention. Called also hypochondriacal neurosis. [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] Hypomania: An abnormality of mood resembling mania (persistent elevated or expansive mood, hyperactivity, inflated self-esteem, etc.) but of lesser intensity. [EU] Hypophyseal: Hypophysial. [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] 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] Imaging procedures: Methods of producing pictures of areas inside the body. [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]
Immaturity: The state or quality of being unripe or not fully developed. [EU] 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
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disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Impotence: The inability to perform sexual intercourse. [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 walking, talking, and self-feeding. [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.
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[EU]
Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] 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] Insomnia: Difficulty in going to sleep or getting enough sleep. [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] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [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
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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] 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] Interpersonal Relations: The reciprocal interaction of two or more persons. [NIH] 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] 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] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [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] Ipsilateral: Having to do with the same side of the body. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Jealousy: An irrational reaction compounded of grief, loss of self-esteem, enmity against the rival and self criticism. [NIH] Jet lag: Symptoms produced in human beings by fast travel through large meridian difference. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH]
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Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. [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] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [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] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] 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 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] 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] Lesion: An area of abnormal tissue change. [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] 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]
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Ligands: A RNA simulation method developed by the MIT. [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] 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] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [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]
Lithium Carbonate: A lithium salt, classified as a mood-stabilizing agent. Lithium ion alters the metabolism of biogenic monoamines in the central nervous system, and affects multiple neurotransmission systems. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [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] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [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).
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[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] 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] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] 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] 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] 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]
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] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Marital Status: A demographic parameter indicating a person's status with respect to marriage, divorce, widowhood, singleness, etc. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Maternal Deprivation: Prolonged separation of the offspring from the mother. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Eminence: Raised area on the infundibular hypothalamus at the floor of the third ventricle of the brain which contains the primary capillary network of the hypophyseal portal system. [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]
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Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] 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 Glycoproteins: Glycoproteins found on the membrane or surface of cells. [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] Memory Disorders: Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with dementia; craniocerebraltrauma; encephalitis; alcoholism (see also alcohol amnestic disorder); schizophrenia; and other conditions. [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 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 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] Mephenytoin: An anticonvulsant effective in tonic-clonic epilepsy. It may cause blood dyscrasias. [NIH]
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Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [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] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [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 animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [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] Mifepristone: A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary Cushing syndrome. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in
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renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] 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] 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] 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 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] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [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]
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Morphological: Relating to the configuration or the structure of live organs. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [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] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [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 (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [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 Hypertonia: Abnormal increase in skeletal or smooth muscle tone. Skeletal muscle hypertonicity may be associated with pyramidal tract lesions or basal ganglia diseases. [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] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutism: Inability or refusal to speak. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] 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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be
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progressive. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [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] 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] Nearsightedness: The common term for myopia. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [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] 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] 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 Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Nervous System Diseases: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH]
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Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]
Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [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] Neuroglia: The non-neuronal cells of the nervous system. They are divided into macroglia (astrocytes, oligodendroglia, and schwann cells) and microglia. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain and blood-retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. [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] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Diseases: A general term encompassing lower motor neuron disease; peripheral nervous system diseases; and certain muscular diseases. Manifestations include muscle weakness; fasciculation; muscle atrophy; spasm; myokymia; muscle hypertonia, myalgias, and musclehypotonia. [NIH]
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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] Neuronal Plasticity: The capacity of the nervous system to change its reactivity as the result of successive activations. [NIH] 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] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [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] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [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] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neurotrophins: A nerve growth factor. [NIH] 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] 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
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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] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [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] 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] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [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] Oculomotor Nerve: The 3d cranial nerve. The oculomotor nerve sends motor fibers to the levator muscles of the eyelid and to the superior rectus, inferior rectus, and inferior oblique muscles of the eye. It also sends parasympathetic efferents (via the ciliary ganglion) to the muscles controlling pupillary constriction and accommodation. The motor fibers originate in the oculomotor nuclei of the midbrain. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] 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] Olfaction Disorders: Loss of or impaired ability to smell. This may be caused by olfactory nerve diseases; paranasal sinus diseases; viral respiratory tract infections; craniocerebral
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trauma; smoking; and other conditions. [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] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [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] Orderly: A male hospital attendant. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [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] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of
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interrelated reactions. [EU] Pain Threshold: Amount of stimulation required before the sensation of pain is experienced. [NIH]
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] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] 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] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranoid Disorders: Chronic mental disorders in which there has been an insidious development of a permanent and unshakeable delusional system (persecutory delusions or delusions of jealousy), accompanied by preservation of clear and orderly thinking. Emotional responses and behavior are consistent with the delusional state. [NIH] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [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] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH] 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] Particle: A tiny mass of material. [EU]
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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] Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used. [NIH] Pathogen: Any disease-producing microorganism. [EU] 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] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [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] 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] Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [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
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and ending 7 to 28 days after birth. [EU] Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [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] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Perivascular: Situated around a vessel. [EU] Personality Disorders: A major deviation from normal patterns of behavior. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] 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] Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [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
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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] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipase C: An enzyme found in the alpha-toxin of Clostridium welchii and other strains of clostridia and bacilli. It hydrolyzes glycerophosphatidates with the formation of 1,2-diacylglycerol and a phosphorylated nitrogenous base such as choline. EC 3.1.4.3. [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] Phosphorous: Having to do with or containing the element phosphorus. [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] Phosphorylated: Attached to a phosphate group. [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] Photoperiod: The time period of daily exposure that an organism receives from daylight or artificial light. It is believed that photoperiodic responses may affect the control of energy balance and thermoregulation. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Physician-Patient Relations: The interactions between physician and patient. [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] Physostigmine: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is
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used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pineal Body: A small conical midline body attached to the posterior part of the third ventricle and lying between the superior colliculi, below the splenium of the corpus callosum. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placebo Effect: An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion. [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] 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] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [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] 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] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [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] 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]
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Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Portal System: A system of vessels in which blood, after passing through one capillary bed, is conveyed through a second set of capillaries before it returns to the systemic circulation. It pertains especially to the hepatic portal system. [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] Postnatal: Occurring after birth, with reference to the newborn. [EU] 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] 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] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [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 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] 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,
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auditory, and somatic origin. [NIH] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoptic Area: Region of hypothalamus between the anterior commissure and optic chiasm. [NIH]
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] 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] 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] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not 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] Program Development: The process of formulating, improving, and expanding educational, managerial, or service-oriented work plans (excluding computer program development). [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
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lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Prone: Having the front portion of the body downwards. [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] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [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] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [NIH]
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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 upon the rectum. [NIH] 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 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] 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] 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] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
Psychology: The science dealing with the study of mental processes and behavior in man and animals. [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] 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] Psychosomatic: Pertaining to the mind-body relationship; having bodily symptoms of psychic, emotional, or mental origin; called also psychophysiologic. [EU]
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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] 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] 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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [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] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of 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]
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] 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] 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] Radioactive: Giving off radiation. [NIH]
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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] 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] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] 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] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [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] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [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]
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Reentry: Reexcitation caused by continuous propagation of the same impulse for one or more cycles. [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 error (myopia, hyperopia, or astigmatism). [NIH] Refractive Errors: Deviations from the average or standard indices of refraction of the eye through its dioptric or refractive apparatus. [NIH] Refractive Power: The ability of an object, such as the eye, to bend light as light passes through it. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [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] 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] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renal tubular acidosis: A rare disorder in which structures in the kidney that filter the blood are impaired, producing using that is more acid than normal. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [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] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [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 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] Response rate: The percentage of patients whose cancer shrinks or disappears after
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treatment. [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] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [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] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rhythmicity: Regular periodicity. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] 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] Rod: A reception for vision, located in the retina. [NIH] Rubidium: An element that is an alkali metal. It has an atomic symbol Rb, atomic number 37, and atomic weight 85.47. It is used as a chemical reagent and in the manufacture of photoelectric cells. [NIH] Saccades: An abrupt voluntary shift in ocular fixation from one point to another, as occurs in reading. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH]
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Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [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] Seasonal Affective Disorder: A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (phototherapy), during the season of recurrence. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [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] 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] Self-Help Groups: Organizations which provide an environment encouraging social interactions through group activities or individual relationships especially for the purpose of rehabilitating or supporting patients, individuals with common health problems, or the elderly. They include therapeutic social clubs. [NIH]
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Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [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] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] 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] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [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. [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] Sexual Partners: Married or single individuals who share sexual relations. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral
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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]
Sibutramine: A drug used for the management of obesity that helps reduce food intake and is indicated for weight loss and maintenance of weight loss when used in conjunction with a reduced-calorie diet. It works to suppress the appetite primarily by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin. Side effects include dry mouth, headache, constipation, insomnia, and a slight increase in average blood pressure. In some patients it causes a higher blood pressure increase. [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 Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [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 Sciences: Disciplines concerned with the interrelationships of individuals in a social environment including social organizations and institutions. Includes Sociology and Anthropology. [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
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provided by churches, groups, etc. [NIH] Socialization: The training or molding of an individual through various relationships, educational agencies, and social controls, which enables him to become a member of a particular society. [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] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [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] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Somnolence: Sleepiness; also unnatural drowsiness. [EU] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] 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 the extents of these reactions. [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
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bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Speech Disorders: Acquired or developmental conditions marked by an impaired ability to comprehend or generate spoken forms of language. [NIH] Sperm: The fecundating fluid of the male. [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 Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [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] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [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] 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 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] Strabismus: Deviation of the eye which the patient cannot overcome. The visual axes assume a position relative to each other different from that required by the physiological conditions. The various forms of strabismus are spoken of as tropias, their direction being indicated by the appropriate prefix, as cyclo tropia, esotropia, exotropia, hypertropia, and hypotropia. Called also cast, heterotropia, manifest deviation, and squint. [EU] 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] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Striatum: A higher brain's domain thus called because of its stripes. [NIH]
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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] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [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] Subiculum: A region of the hippocampus that projects to other areas of the brain. [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]
Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suprachiasmatic Nucleus: An ovoid densely packed collection of small cells of the anterior hypothalamus lying close to the midline in a shallow impression of the optic chiasm. [NIH] Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [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] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin
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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] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systems Analysis: The analysis of an activity, procedure, method, technique, or business to determine what must be accomplished and how the necessary operations may best be accomplished. [NIH] 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] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Teratogenicity: The power to cause abnormal development. [NIH] Terminalis: A groove on the lateral surface of the right atrium. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH]
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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] Thermoregulation: Heat regulation. [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] 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] 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] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness.
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[NIH]
Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [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] 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] Tonicity: The normal state of muscular tension. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] 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] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] 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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] 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] 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] 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] 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
264
Affective Disorders
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 Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trihexyphenidyl: A centrally acting muscarinic antagonist used in the treatment of parkinsonism and drug-induced extrapyramidal movement disorders and as an antispasmodic. [NIH] Trochlear Nerve: The 4th cranial nerve. The trochlear nerve carries the motor innervation of the superior oblique muscles of the eye. [NIH] Trochlear Nerve Diseases: Diseases of the fourth cranial (trochlear) nerve or its nucleus in the midbrain. The nerve crosses as it exits the midbrain dorsally and may be injured along its course through the intracranial space, cavernous sinus, superior orbital fissure, or orbit. Clinical manifestations include weakness of the superior oblique muscle which causes vertical diplopia that is maximal when the affected eye is adducted and directed inferiorly. Head tilt may be seen as a compensatory mechanism for diplopia and rotation of the visual axis. Common etiologies include craniocerebral trauma and infratentorial neoplasms. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] 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] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [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
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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] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconditioned: An inborn reflex common to all members of a species. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Ureters: Tubes that carry urine from the kidneys to the bladder. [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] 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] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Uterine Contraction: Contraction of the uterine muscle. [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] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [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] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH]
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Affective Disorders
Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Venous: Of or pertaining to the veins. [EU] 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] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] 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 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] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [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] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called
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retinoids. [NIH] 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] Volition: Voluntary activity without external compulsion. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [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] Welchii: A genus of anerobic spore-forming bacteria of the family Bacillaceae. [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] 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] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] 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]
269
INDEX 2 2-Propanol, 133, 193 A Abdomen, 193, 202, 229, 231, 242, 259, 266 Abdominal, 5, 63, 162, 193, 222, 229, 242, 248, 265 Abdominal Pain, 5, 63, 162, 193, 222, 229, 265 Abducens, 193, 214 Abducens Nerve, 193, 214 Abducens Nerve Diseases, 193, 214 Ablation, 17, 51, 193 Accommodation, 193, 236, 240 Acculturation, 64, 193 Acetone, 138, 154, 193, 230 Acetylcholine, 155, 193, 206 Acetylcholinesterase, 156, 193 Acidosis, 193 Acoustic, 25, 193 Actin, 193, 238 Action Potentials, 22, 194 Activity Cycles, 55, 194 Adaptation, 59, 87, 194, 228, 246 Adenine, 194 Adenosine, 79, 106, 113, 194, 245 Adenylate Cyclase, 82, 194 Adjustment, 47, 103, 193, 194 Adjuvant, 138, 194, 222 Adjuvant Therapy, 138, 194 Adolescence, 58, 84, 156, 194 Adolescent Psychiatry, 85, 86, 98, 102, 139, 194 Adrenal Cortex, 194, 211, 248 Adrenal Medulla, 194, 204, 218, 239 Adrenergic, 24, 194, 196, 198, 215, 218, 249, 260, 264 Adrenergic Agents, 194, 198 Adverse Effect, 194, 207, 257 Aerobic, 194, 235 Affective Symptoms, 4, 194 Afferent, 195, 211, 247, 256 Affinity, 10, 86, 134, 137, 141, 143, 149, 152, 195, 199, 207, 213, 238, 258 Age of Onset, 195, 264 Ageusia, 163, 195 Agonist, 41, 195, 203, 215, 230, 239 Agoraphobia, 195, 226, 242, 245 Akathisia, 195, 198
Akinesia, 153, 195 Algorithms, 195, 202 Alkaline, 193, 195, 203 Alkaloid, 195, 208, 235, 239 Alleles, 40, 195 Allergen, 195, 213, 256 Alpha-1, 195, 196 Alternative medicine, 167, 195 Ameliorated, 141, 195 Amenorrhea, 196, 197 Amino Acid Neurotransmitters, 155, 196 Amino Acid Sequence, 196, 197, 222 Amino Acids, 64, 148, 156, 196, 201, 208, 222, 239, 243, 247, 250, 265 Amitriptyline, 90, 196 Amnestic, 196, 221, 233 Amphetamine, 17, 196, 214 Amygdala, 12, 13, 51, 53, 57, 58, 147, 196, 201, 231, 256, 262 Anaesthesia, 196, 227 Anal, 23, 26, 196, 218, 220 Analgesic, 162, 196, 235, 241 Analogous, 44, 196, 263 Analysis of Variance, 58, 196 Anaphylatoxins, 196, 209 Anatomical, 13, 16, 21, 196, 200, 227, 238, 255 Androgens, 194, 196, 211 Anemia, 177, 197, 221 Angina, 197, 249 Angina Pectoris, 197, 249 Animal model, 13, 25, 38, 45, 97, 132, 142, 143, 197 Anions, 197, 229, 256 Anisotropy, 197, 221 Anomalies, 197, 261 Anorexia, 17, 29, 52, 68, 70, 135, 140, 197, 222, 265 Anorexia Nervosa, 17, 29, 70, 140, 197 Antagonism, 142, 197, 207 Anterograde, 51, 197 Antiallergic, 197, 211 Antibacterial, 197, 259 Antibiotic, 197, 243, 259 Antibodies, 15, 55, 75, 197, 224, 227, 232, 246 Antibody, 44, 195, 197, 198, 209, 212, 221, 224, 225, 227, 232, 251, 252, 256, 258
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Affective Disorders
Anticholinergic, 136, 145, 156, 196, 197, 246 Anticoagulant, 198, 250 Anticonvulsant, 132, 198, 203, 233, 265 Antiemetic, 198 Antiepileptic, 132, 138, 151, 198 Antigen, 195, 197, 198, 209, 221, 225, 226, 227, 232, 252, 256 Antigen-Antibody Complex, 198, 209 Anti-infective, 198, 229 Anti-inflammatory, 198, 211, 214, 223 Anti-Inflammatory Agents, 198, 211 Antineoplastic, 198, 211 Anti-Obesity Agents, 136, 145, 198 Antipsychotic, 20, 132, 198, 207, 238, 254 Antiseptic, 193, 198 Antispasmodic, 198, 241, 264 Anus, 196, 198, 202, 252 Anxiety Disorders, 26, 27, 46, 58, 61, 63, 82, 86, 89, 134, 142, 150, 163, 199, 242 Anxiolytic, 13, 51, 199, 203 Aorta, 199, 266 Apathy, 199, 238 Apnea, 144, 146, 199 Apoptosis, 37, 43, 199 Applicability, 59, 199 Arachidonic Acid, 199, 249 Arrhythmia, 199, 266 Arterial, 199, 210, 226, 250, 261 Arteries, 199, 202, 210, 234, 236, 251 Arterioles, 199, 202, 203 Articular, 199, 241 Artifacts, 57, 199 Assay, 25, 143, 199, 252 Astrocytes, 199, 223, 235, 238 Asymptomatic, 199, 242 Ataxia, 138, 176, 177, 199, 262 Atrial, 200, 210, 264 Atrioventricular, 200, 210 Atrium, 200, 210, 261, 264, 266 Atrophy, 176, 177, 200, 238 Atypical, 20, 135, 149, 200, 207, 240, 254 Auditory, 19, 200, 219, 224, 248 Autodigestion, 200, 242 Autoimmune disease, 17, 200, 236 Autoimmunity, 45, 200 Autonomic, 6, 12, 16, 63, 140, 152, 193, 198, 200, 211, 237, 239, 244 Autonomic Nervous System, 200, 237, 244 Autoreceptors, 52, 200 Axonal, 9, 51, 55, 200 Axons, 200, 213, 241, 244, 248, 254
B Bacteria, 197, 198, 200, 213, 220, 234, 259, 263, 265, 267 Bacterial Physiology, 194, 200 Bactericidal, 200, 218 Bacteriophage, 200, 263 Basal Ganglia, 58, 101, 198, 199, 200, 206, 221, 231, 236, 240 Basal Ganglia Diseases, 199, 200, 206, 236 Base, 193, 194, 201, 212, 213, 222, 230, 245, 261, 265 Base Sequence, 201, 222 Basophils, 201, 223, 230 Behavior Therapy, 18, 162, 201 Benign, 201, 221, 224, 237 Benzodiazepines, 201, 203 Bewilderment, 201, 209 Bilateral, 14, 30, 201 Bile, 201, 221, 225, 231, 259 Biliary, 201, 203, 242 Biliary Tract, 201, 203, 242 Biochemical, 5, 21, 30, 38, 41, 42, 157, 194, 195, 201, 220, 222, 241, 256 Bioengineering, 50, 56, 172, 201 Biogenic Monoamines, 201, 231 Biological Markers, 6, 75, 201 Biological therapy, 201, 223 Biosynthesis, 199, 201, 218 Biotechnology, 65, 167, 173, 175, 176, 177, 178, 202 Biotransformation, 202 Bladder, 202, 206, 227, 236, 238, 250, 253, 265 Bloating, 5, 202, 229 Blood Coagulation, 202, 203, 262 Blood Glucose, 202, 224 Blood Platelets, 202, 256 Blood pressure, 30, 153, 202, 204, 206, 226, 235, 251, 257, 258 Blood vessel, 202, 203, 204, 205, 210, 229, 243, 257, 258, 260, 261, 262, 265 Blood-Brain Barrier, 202, 245, 261 Body Fluids, 202, 216, 258 Bone Marrow, 202, 227, 232, 235 Bowel, 5, 63, 162, 196, 202, 214, 226, 228, 229, 259, 265 Bowel Movement, 202, 214, 226, 259 Brain Stem, 57, 202, 205, 214, 238 Branch, 112, 113, 115, 116, 189, 202, 216, 239, 243, 251, 258, 260, 262 Breakdown, 202, 214, 221, 241 Breeding, 44, 203
Index
Bromine, 133, 203 Bupropion, 141, 144, 203 Buspirone, 13, 203 C Calcium, 21, 35, 74, 79, 89, 91, 114, 203, 209, 257, 266 Calcium channel blocker, 203, 266 Calcium Channels, 35, 203 Calcium Signaling, 91, 203 Calculi, 138, 203 Cannabidiol, 203 Cannabinoids, 11, 203 Cannabinol, 203 Capillary, 33, 203, 232, 247, 266 Capsules, 203, 215, 222 Carbamazepine, 7, 77, 112, 113, 132, 203 Carbohydrate, 203, 211, 255 Carbon Dioxide, 27, 204, 220, 253 Carcinogenic, 204, 228, 259 Carcinogens, 204, 241 Cardiac, 87, 204, 210, 218, 219, 236, 241, 259 Cardioselective, 204, 249 Cardiovascular, 48, 80, 136, 145, 152, 161, 163, 196, 203, 204, 256 Cardiovascular disease, 161, 204 Carotene, 204, 254 Carrier Proteins, 204, 252 Case report, 82, 162, 204, 207 Case series, 204, 207 Catecholamine, 204, 215, 244 Cations, 204, 229 Caudal, 11, 204, 214, 226, 240, 247 Caudate Nucleus, 37, 201, 204, 237, 240 Causal, 15, 23, 204, 218, 229 Cell Count, 61, 204 Cell Cycle, 204, 266 Cell Death, 199, 205, 237 Cell Differentiation, 205, 257 Cell Division, 176, 200, 204, 205, 223, 233, 235, 246, 249, 255 Cell membrane, 203, 204, 205, 213, 221, 243, 245, 247, 258, 267 Cell proliferation, 205, 257 Cell Respiration, 205, 235, 253 Cell Size, 205, 220 Cell Survival, 205, 223 Central Nervous System Diseases, 137, 149, 205 Central Nervous System Infections, 205, 224 Cerebellar, 37, 199, 205, 252
271
Cerebellum, 205, 211, 247, 252 Cerebral hemispheres, 200, 202, 205, 261 Cerebral Palsy, 205, 258 Cerebrospinal, 38, 142, 205 Cerebrospinal fluid, 38, 142, 205 Cerebrovascular, 201, 204, 205, 262 Cerebrum, 205, 211, 246, 261, 264 Cervix, 205, 253 Character, 197, 206, 212 Chemoreceptor, 198, 206 Chemotactic Factors, 206, 209 Chemotherapy, 194, 206 Chlorine, 133, 206 Chloroform, 138, 154, 206 Cholesterol, 201, 206, 211, 259 Choline, 36, 193, 206, 245 Cholinergic, 40, 41, 53, 84, 91, 156, 196, 198, 206, 239, 256 Cholinesterase Inhibitors, 206, 215 Chorea, 198, 206 Choroid, 206, 254 Chromatin, 199, 206, 217, 239 Chromosomal, 60, 65, 135, 153, 206, 222, 254 Chromosome, 31, 60, 70, 85, 93, 102, 135, 206, 231, 255 Chronic renal, 74, 207, 246, 265 Cimetidine, 150, 207 Circadian, 9, 38, 42, 45, 54, 55, 77, 88, 104, 127, 207 Circadian Rhythm, 38, 42, 54, 77, 88, 207 CIS, 32, 133, 207, 254 Citalopram, 134, 144, 150, 207 Clamp, 11, 207, 243 Clinical study, 35, 207 Clinical trial, 8, 22, 36, 41, 75, 77, 127, 129, 173, 207, 250, 252 Clone, 42, 207 Clonic, 138, 207, 233 Cloning, 38, 42, 49, 202, 207 Clozapine, 115, 207 Cluster Analysis, 100, 126, 207 Coca, 208 Cocaine, 17, 144, 146, 208 Codon, 208, 222 Coenzyme, 208, 221 Cofactor, 208, 250, 262 Cognition, 7, 17, 42, 208, 238 Cognitive behavior therapy, 62, 208 Cognitive restructuring, 208, 259 Cohort Studies, 208, 218 Colitis, 162, 208, 229
272
Affective Disorders
Collagen, 208, 220, 222 Colloidal, 208, 216, 256 Combinatorial, 10, 51, 208 Communication Disorders, 4, 130, 172, 208 Comorbidity, 4, 14, 26, 62, 73, 98, 100, 157, 208 Complement, 9, 32, 196, 209, 222, 256 Complementary and alternative medicine, 119, 123, 209 Complementary medicine, 119, 209 Complete remission, 209, 253 Computational Biology, 173, 175, 209 Concomitant, 134, 209 Concretion, 203, 209 Cones, 209, 254 Confusion, 24, 209, 215, 226, 238, 265 Congestion, 198, 210 Conjunctiva, 209, 210, 245, 264 Connective Tissue, 202, 208, 210, 220, 221, 222, 231, 244 Consciousness, 196, 210, 212, 213, 215 Constipation, 5, 198, 210, 221, 229, 257 Constriction, 210, 229, 240 Consultation, 21, 36, 60, 210 Contamination, 15, 210 Contraindications, ii, 210 Contralateral, 30, 210, 241, 252 Contrast Sensitivity, 57, 210 Contusion, 163, 210 Convulsions, 132, 139, 198, 210, 216, 226 Coordination, 205, 210, 236 Cor, 10, 16, 23, 25, 56, 88, 140, 142, 152, 210, 211 Coronary, 161, 197, 204, 210, 211, 234, 236 Coronary heart disease, 204, 210 Coronary Thrombosis, 211, 234, 236 Cortex, 19, 30, 36, 57, 61, 143, 199, 211, 217, 218, 219, 220, 237, 247, 251, 252 Cortical, 7, 19, 21, 40, 53, 58, 61, 76, 139, 163, 211, 219, 247, 255, 262 Cortices, 30, 58, 211, 224 Corticosteroid, 84, 211 Corticotropin-Releasing Hormone, 16, 143, 211 Cortisol, 30, 72, 81, 211 Cortisone, 211, 214 Cranial, 163, 193, 205, 211, 224, 237, 238, 240, 241, 244, 264 Cranial Nerves, 211, 237 Craniocerebral Trauma, 193, 201, 211, 224, 241, 262, 264
Crossing-over, 211, 252 Cross-Sectional Studies, 211, 218 Cues, 9, 211 Curative, 211, 239, 262 Cutaneous, 211, 242 Cyclic, 137, 158, 194, 211, 245, 249, 255 Cysteine, 20, 212 Cystine, 212 Cytochrome, 207, 212 Cytokines, 37, 74, 212 Cytoplasm, 199, 201, 203, 205, 212, 217, 223, 235, 238, 239, 261 Cytotoxic, 212, 257 D Databases, Bibliographic, 173, 212 Deamination, 212, 235 Decidua, 212, 234 Degenerative, 155, 161, 212, 223, 236, 241 Deletion, 97, 101, 199, 212 Delirium, 7, 162, 163, 164, 198, 212 Delusions, 86, 108, 212, 242, 250 Dendrites, 22, 55, 213, 239 Dendritic, 22, 213, 233, 254 Density, 23, 64, 112, 213, 220, 241 Dental Care, 163, 213 Dental Caries, 213, 221 Dentate Gyrus, 213, 225 Depersonalization, 213, 242, 255 Depolarization, 213, 257 Depressive Disorder, 14, 36, 213, 231 Derealization, 213, 242 Desensitization, 35, 52, 213 Desipramine, 69, 213 Detoxification, 144, 213 Deuterium, 213, 225 Dexamethasone, 72, 214 Dextroamphetamine, 196, 214, 234 Diabetes Mellitus, 198, 214, 224, 228 Diagnostic procedure, 131, 162, 167, 214 Diarrhea, 5, 162, 214, 221, 229 Diastolic, 214, 226 Diathesis, 23, 214 Diencephalon, 205, 214, 218, 226, 238, 247, 261, 262 Dietary Fats, 214, 231 Diffusion, 214, 228 Digestion, 201, 202, 214, 216, 229, 231, 259, 265 Digestive system, 130, 194, 214 Dilatation, 214, 248 Dimethyl, 145, 146, 214 Diplopia, 138, 193, 214, 264
Index
Direct, iii, 34, 40, 44, 59, 214, 215, 253, 260 Disability Evaluation, 163, 214 Discrimination, 26, 80, 214 Disinfectant, 193, 214, 218 Disorientation, 209, 212, 215 Dissection, 106, 116, 215 Dissociation, 195, 215 Distal, 12, 200, 215, 244, 248, 250 Diurnal, 113, 135, 215 Dizziness, 138, 215, 242 Domesticated, 15, 215 Donepezil, 7, 215 Dorsal, 52, 53, 58, 215, 218, 247, 256, 259 Dorsum, 215, 221 Dosage Forms, 138, 144, 146, 154, 215 Drive, ii, vi, 4, 5, 54, 111, 215 Drug Interactions, 215 Drug Tolerance, 215, 263 Duct, 216, 255 Dysgenesis, 37, 216 Dyskinesia, 103, 153, 160, 198, 207, 216 Dyspepsia, 149, 216 Dysphoric, 213, 216 Dysplasia, 177, 216 Dyspnea, 216, 242 Dystonia, 137, 148, 198, 216 Dystrophy, 43, 176, 216 E Eating Disorders, 10, 28, 140, 144, 146, 147, 150, 216 Effector, 15, 16, 51, 193, 209, 216, 239, 245 Effector cell, 216, 239 Efficacy, 4, 7, 10, 17, 22, 24, 29, 35, 46, 48, 51, 62, 63, 78, 120, 126, 166, 203, 216, 264 Elective, 216 Electroconvulsive Therapy, 40, 164, 216 Electrolyte, 211, 212, 216, 234, 247, 258, 265 Electron microscope, 55, 216 Electrons, 201, 216, 229, 232, 251 Electrophoresis, 33, 216 Electrophysiological, 9, 35, 53, 140, 152, 216 Elementary Particles, 216, 232, 250 Embryo, 65, 205, 217, 227 Emesis, 153, 217 Empirical, 21, 92, 217 Encephalitis, 217, 233 Endocrine Glands, 34, 217 Endocrine System, 217, 238 Endocytosis, 41, 217 Endometrium, 143, 212, 217, 233, 234
273
Endotoxins, 209, 217 End-stage renal, 207, 217, 246 Energy balance, 217, 245 Enhancer, 51, 65, 105, 112, 217 Enkephalin, 13, 217 Entorhinal Cortex, 97, 217, 225 Environmental Exposure, 201, 217, 241 Environmental Health, 172, 174, 217 Enzymatic, 143, 201, 203, 204, 209, 213, 217, 225, 254 Enzyme, 97, 132, 193, 194, 201, 208, 216, 217, 231, 235, 243, 245, 250, 257, 262, 263, 267 Eosinophils, 44, 217, 223, 230 Epidemic, 28, 217, 259 Epidemiologic Studies, 84, 201, 217 Epidemiological, 8, 23, 27, 91, 100, 218 Epinephrine, 194, 215, 218, 239, 265 Epithalamus, 214, 218, 231 Erectile, 141, 218, 243 Erection, 218 ERV, 174, 218, 219 Erythrocytes, 197, 202, 218, 256 Esophageal, 5, 218 Esophagus, 214, 218, 259 Essential Tremor, 176, 218 Estrogen, 26, 56, 143, 218, 248 Estrogen Antagonists, 27, 218 Estrogen receptor, 56, 143, 218 Ethanol, 133, 138, 154, 207, 218 Ether, 133, 218 Eukaryotic Cells, 218, 227, 241, 265 Evacuation, 210, 218 Evoke, 218, 259 Evoked Potentials, 103, 106, 218 Excitability, 22, 219, 237 Excitation, 57, 139, 206, 219, 220 Excitatory, 11, 155, 196, 219, 223, 230 Excitatory Amino Acid Agonists, 219, 230 Excitotoxicity, 43, 219 Excrete, 219, 253 Exhaustion, 197, 219 Exogenous, 16, 23, 54, 202, 219, 222, 264 Expiratory, 218, 219 Expiratory Reserve Volume, 218, 219 Extracellular, 17, 141, 142, 199, 210, 217, 219, 220, 238, 258 Extracellular Matrix, 210, 219, 220 Extracellular Space, 17, 219 Extrapyramidal, 137, 148, 149, 153, 195, 198, 215, 219, 264 Eye Movements, 108, 219
274
Affective Disorders
F Fallopian Tubes, 219, 253 Family Health, 33, 219 Family Planning, 173, 219 Family Therapy, 29, 162, 219 Famotidine, 149, 219 Fasciculation, 220, 238 Fat, 199, 202, 204, 210, 211, 220, 230, 231, 236, 258 Fatigue, 5, 81, 220 Fatty acids, 220, 249 Feces, 210, 220, 259 Fetus, 220, 248, 265 Fibroblasts, 88, 220 Fibrosis, 177, 220, 255 Fissure, 193, 213, 220, 247, 264 Fixation, 220, 254, 256 Flatus, 220, 222 Flow Cytometry, 45, 220 Fluorescence, 33, 98, 220, 221 Fluorescence Polarization, 98, 221 Fluorescent Dyes, 220, 221 Fluorine, 133, 221 Fluoxetine, 52, 118, 144, 150, 167, 221 Fluvoxamine, 144, 150, 221 Folate, 107, 221 Folic Acid, 221 Forearm, 202, 221 Frontal Lobe, 14, 78, 221, 247 Functional Disorders, 6, 221 Functional magnetic resonance imaging, 9, 12, 57, 63, 221 G Gallbladder, 193, 201, 214, 221 Ganglia, 193, 200, 221, 237, 244 Ganglion, 221, 240, 254 Gap Junctions, 221, 260, 261 Gas, 5, 204, 206, 214, 218, 220, 221, 225, 229, 236, 239, 240, 260, 265 Gastric, 200, 207, 215, 220, 222, 225, 243 Gastric Acid, 207, 222 Gastrin, 207, 222, 225 Gastroenteritis, 203, 222 Gastrointestinal, 5, 6, 63, 140, 149, 206, 218, 222, 256, 258, 260 Gastrointestinal tract, 5, 206, 218, 222, 256, 258 Gelatin, 222, 223 Gene Expression, 16, 20, 42, 51, 55, 177, 222 Gene Targeting, 49, 222 Generator, 54, 222
Genetic Code, 161, 222, 240 Genetic Counseling, 24, 222 Genetic Engineering, 202, 207, 222 Genetic Markers, 40, 222 Genetic Techniques, 48, 222 Genetic testing, 24, 222 Genetics, 24, 27, 30, 32, 42, 49, 59, 61, 68, 75, 79, 82, 85, 91, 93, 96, 97, 99, 102, 161, 167, 222 Genital, 222, 265 Genitourinary, 5, 222, 265 Genomics, 42, 50, 93, 223 Genotype, 31, 32, 49, 50, 153, 223, 244 Geriatric, 3, 6, 7, 8, 21, 39, 48, 66, 77, 79, 88, 101, 161, 162, 163, 223 Geriatric Psychiatry, 6, 66, 77, 88, 101, 162, 163, 223 Germ Cells, 223, 233, 258 Gestation, 223, 243 Gland, 140, 152, 194, 211, 223, 231, 242, 246, 250, 255, 259, 262 Gliosis, 37, 223 Glucocorticoid, 11, 15, 23, 27, 56, 143, 214, 223, 234 Glucose, 40, 68, 70, 176, 202, 214, 223, 224, 226, 228, 255 Glutamate, 11, 12, 38, 40, 148, 155, 196, 219, 223, 234, 244 Glutamic Acid, 196, 221, 223 Glycine, 148, 223 Gonad, 223 Gonadal, 54, 223, 259 Governing Board, 223, 247 Granulocytes, 45, 223, 257, 267 Growth factors, 50, 223 Gyrus Cinguli, 223, 231 H Haematemesis, 217, 223 Half-Life, 133, 136, 145, 223 Haloperidol, 113, 224 Handicap, 214, 224 Haptens, 195, 224, 252 Headache, 138, 142, 154, 224, 226, 248, 257 Headache Disorders, 224 Health Behavior, 64, 224 Health Services, 33, 224 Health Status, 219, 224 Hearing Disorders, 208, 224 Heart attack, 204, 224 Hemoglobin, 113, 197, 218, 224 Hemoglobinuria, 176, 224 Hemorrhage, 211, 224, 260
Index
Hemostasis, 224, 256 Hepatic, 138, 212, 224, 235, 247 Hepatotoxicity, 132, 151, 224 Hereditary, 224, 236, 254 Heredity, 222, 225 Herpes, 13, 50, 225 Herpes virus, 13, 225 Herpes Zoster, 225 Heterogeneity, 30, 31, 32, 48, 84, 195, 225 Hippocampus, 52, 58, 213, 225, 231, 238, 256, 260 Histamine, 196, 198, 207, 219, 225 Histology, 225, 238 Homogeneous, 14, 85, 225, 244 Homologous, 195, 211, 222, 225, 255, 256, 260, 261 Hormonal, 5, 42, 50, 87, 194, 200, 211, 225, 244 Hormone therapy, 194, 225 Host, 200, 225, 227, 254, 266 Human Development, 43, 54, 172, 225 Humoral, 37, 225 Humour, 225 Hybrid, 39, 51, 207, 225 Hybridization, 9, 225 Hydrogen, 134, 137, 148, 193, 201, 203, 213, 225, 235, 240, 250 Hydrolysis, 193, 202, 226, 245, 247, 250 Hyperalgesia, 63, 226 Hypersecretion, 15, 226 Hypersensitivity, 152, 195, 213, 226, 256 Hypertension, 17, 161, 193, 204, 224, 226, 249, 265 Hyperthyroidism, 226, 249 Hypertrophy, 210, 226, 264 Hypochondriasis, 161, 226 Hypoglycaemia, 212, 226 Hypomania, 26, 153, 226 Hypophyseal, 226, 232 Hypotension, 198, 210, 226 Hypothalamic, 9, 10, 15, 16, 23, 54, 88, 90, 226 Hypoxia, 212, 226, 262 I Id, 117, 121, 180, 181, 188, 190, 226 Idiopathic, 7, 226 Imaging procedures, 226, 263 Imipramine, 77, 86, 90, 226 Immaturity, 139, 226 Immune function, 44, 226 Immune response, 37, 45, 194, 198, 200, 211, 224, 226, 227, 256, 260, 266
275
Immune system, 16, 45, 140, 143, 152, 200, 201, 216, 226, 227, 232, 236, 265, 267 Immunization, 227, 256 Immunodeficiency, 45, 176, 227 Immunogenic, 227, 252 Immunohistochemistry, 13, 227 Immunology, 86, 194, 195, 221, 227 Immunosuppressive, 223, 227 Immunotherapy, 201, 213, 227 Impairment, 4, 7, 42, 48, 49, 72, 199, 201, 212, 216, 227, 233, 250 Impotence, 218, 227 In situ, 9, 16, 55, 227 In Situ Hybridization, 55, 227 In vitro, 9, 10, 15, 20, 38, 53, 136, 143, 145, 227, 256 In vivo, 15, 17, 20, 38, 40, 51, 227 Incision, 227, 229 Incontinence, 136, 141, 144, 145, 146, 227 Indicative, 156, 227, 243, 265 Induction, 35, 196, 198, 227, 248 Infancy, 54, 227 Infarction, 227 Infection, 15, 37, 70, 72, 201, 206, 212, 217, 222, 226, 227, 231, 232, 239, 243, 260, 267 Infiltration, 37, 228, 248 Inflammation, 37, 198, 208, 217, 220, 222, 225, 228, 242, 262, 265 Inflammatory bowel disease, 162, 228 Infusion, 54, 55, 228 Ingestion, 64, 228, 234, 246 Inhalation, 27, 228, 246 Initiation, 47, 228 Innervation, 9, 53, 54, 228, 264 Inositol, 36, 41, 113, 228, 234, 255 Inotropic, 215, 228 Inpatients, 73, 90, 102, 228 Insight, 21, 34, 35, 52, 54, 92, 228 Insomnia, 38, 228, 248, 257 Institutionalization, 6, 228 Insulator, 228, 236 Insulin, 198, 228, 230, 264 Intensive Care, 120, 228 Intensive Care Units, 120, 228 Interleukin-1, 16, 228 Interleukin-2, 229 Intermediate Filaments, 229, 238 Interpersonal Relations, 135, 229 Intervention Studies, 62, 229 Intestinal, 204, 229, 232 Intestine, 202, 229, 230 Intoxication, 212, 229, 267
276
Affective Disorders
Intracellular, 52, 89, 91, 114, 203, 222, 227, 229, 234, 247, 249, 252, 255, 257 Intravenous, 228, 229 Intrinsic, 195, 229 Invasive, 40, 229, 232 Involuntary, 115, 201, 206, 218, 229, 236, 253, 258 Iodine, 133, 229 Ion Channels, 35, 199, 229, 238, 239, 261 Ions, 20, 201, 203, 215, 216, 225, 229, 235, 247, 258 Ipsilateral, 30, 229, 252 Irritable Bowel Syndrome, 4, 5, 6, 63, 144, 146, 221, 229 Ischemia, 143, 193, 197, 200, 229 J Jealousy, 229, 242 Jet lag, 9, 229 Joint, 34, 199, 229, 241, 260 K Kainic Acid, 155, 230 Kb, 172, 230 Ketone Bodies, 193, 230 Kidney Disease, 130, 172, 177, 230 Kidney stone, 138, 230, 253 Kinetic, 41, 230 L Labile, 209, 230 Lactation, 230, 241, 248 Lag, 230 Language Disorders, 4, 43, 208, 230 Large Intestine, 214, 229, 230, 252, 257 Latency, 50, 126, 230 Latent, 27, 44, 48, 230, 247 Lens, 230, 253, 267 Lesion, 11, 53, 223, 230, 231, 261 Lethal, 28, 200, 230 Leukemia, 176, 230 Leukocytes, 44, 201, 202, 206, 212, 217, 223, 230, 235, 239 Library Services, 188, 230 Ligament, 230, 250 Ligands, 41, 136, 143, 147, 148, 153, 231 Limbic, 37, 51, 61, 76, 78, 82, 137, 149, 155, 196, 223, 231, 247 Limbic System, 51, 78, 196, 223, 231, 247 Linkage, 15, 27, 28, 31, 32, 33, 42, 60, 75, 85, 93, 109, 222, 231 Lipase, 145, 231 Lipid, 11, 32, 206, 228, 231, 236 Lithium Carbonate, 74, 77, 231
Liver, 193, 199, 201, 214, 220, 221, 224, 231, 235 Lobe, 14, 231 Localization, 22, 38, 54, 137, 140, 149, 152, 227, 231 Localized, 213, 220, 227, 231, 235, 246 Locomotion, 17, 231, 246 Locomotor, 55, 231 Longitudinal Studies, 36, 211, 231 Luteal Phase, 231, 234 Lutein Cells, 231, 249 Lymph, 225, 226, 231, 232 Lymph node, 226, 231, 232 Lymphatic, 227, 231, 232 Lymphocyte, 198, 232 Lymphoid, 197, 232 Lymphoma, 176, 232 Lytic, 15, 232 M Macrophage, 228, 232 Magnetic Resonance Imaging, 56, 232 Magnetic Resonance Spectroscopy, 36, 40, 71, 101, 232 Malabsorption, 176, 232 Malignant, 153, 176, 198, 232, 237 Malnutrition, 200, 232, 236 Mania, 26, 35, 82, 102, 129, 135, 149, 153, 160, 164, 226, 232 Manic, 60, 136, 140, 145, 153, 157, 182, 198, 202, 231, 232, 250 Manic-depressive psychosis, 232, 250 Manifest, 37, 200, 232, 259 Marital Status, 83, 232 Mastication, 232, 264 Maternal Deprivation, 23, 232 Medial, 11, 14, 27, 56, 57, 223, 232, 241, 256 Median Eminence, 55, 232 Mediate, 20, 21, 148, 166, 215, 232 Mediator, 16, 142, 229, 232, 256 Medical Records, 233, 254 MEDLINE, 173, 175, 177, 233 Medullary, 16, 233, 251 Meiosis, 233, 261 Melanin, 233, 245, 265 Melanocytes, 233 Melanoma, 176, 233 Membrane Glycoproteins, 233 Memory, 3, 4, 14, 17, 19, 34, 95, 107, 138, 153, 156, 197, 212, 213, 233 Memory Disorders, 20, 233 Meninges, 205, 211, 233 Menopause, 233, 243, 249
Index
Menstrual Cycle, 50, 128, 231, 233, 248 Menstruation, 196, 212, 231, 233, 248 Mental Disorders, 19, 25, 31, 32, 62, 130, 135, 139, 163, 194, 233, 242, 250 Mental Health Services, iv, 8, 19, 39, 45, 69, 98, 102, 174, 233 Mental Processes, 215, 233, 250 Mental Retardation, 4, 24, 43, 67, 73, 90, 162, 178, 208, 233 Mentors, 28, 50, 233 Mephenytoin, 133, 233 Mercury, 220, 234 Mesolimbic, 198, 234, 266 Meta-Analysis, 7, 66, 68, 234 Metabolite, 48, 146, 202, 214, 234, 240, 248 Metabotropic, 38, 234 Methanol, 133, 234 Methionine, 214, 234 Methylphenidate, 17, 44, 234 MI, 106, 134, 191, 234 Microbe, 234, 263 Microbiology, 194, 200, 234 Microorganism, 208, 234, 243, 267 Microscopy, 54, 234 Microtubule-Associated Proteins, 234, 238 Microtubules, 229, 234, 238 Mifepristone, 128, 234 Mineralocorticoids, 194, 211, 234 Miscarriage, 67, 235 Mitochondria, 43, 235, 241 Mitosis, 199, 235 Mobilization, 203, 235 Modeling, 33, 41, 44, 235 Modification, 8, 52, 82, 84, 163, 222, 235, 251 Molecular Structure, 235, 264 Molecule, 10, 32, 143, 198, 201, 208, 209, 215, 216, 219, 226, 235, 240, 252, 257, 263, 265 Monitor, 17, 235, 240 Monoamine, 7, 37, 40, 63, 72, 125, 141, 144, 145, 146, 196, 214, 235, 264 Monoamine Oxidase, 7, 72, 196, 214, 235, 264 Monocytes, 45, 228, 230, 235 Mononuclear, 15, 235 Monophosphate, 106, 235 Monotherapy, 72, 112, 114, 235 Mood Disorders, 30, 62, 63, 129, 134, 135, 139, 235 Morphine, 11, 235, 237, 241 Morphological, 9, 217, 233, 236
277
Motility, 221, 236, 256 Motion Sickness, 236, 237 Motor Activity, 210, 236 Motor nerve, 220, 236, 240, 244 Movement Disorders, 137, 148, 198, 236, 262, 264 Mucosa, 236, 249 Mucus, 236, 265 Multiple sclerosis, 43, 236 Muscle Fibers, 236 Muscle Hypertonia, 236, 238 Muscular Atrophy, 176, 236 Muscular Dystrophies, 216, 236 Mutagen, 236 Mutagenesis, 49, 52, 236 Mutism, 4, 236 Myelin, 236, 238 Myocardial infarction, 211, 234, 236, 249 Myocardium, 197, 234, 236 Myopia, 138, 236, 237, 253 Myotonic Dystrophy, 176, 236 N Narcolepsy, 41, 144, 146, 214, 234, 237 Narcosis, 237 Narcotic, 162, 235, 237 Nausea, 153, 198, 215, 222, 237, 242, 248, 265 NCI, 1, 129, 171, 207, 237 Nearsightedness, 236, 237 Necrosis, 199, 227, 234, 236, 237 Need, 3, 5, 21, 23, 24, 26, 43, 48, 67, 76, 134, 137, 143, 155, 160, 183, 194, 207, 237, 263, 264 Neocortex, 237, 238 Neonatal, 23, 37, 237 Neoplasia, 176, 237 Neoplasm, 237 Neoplastic, 161, 232, 237 Neostriatum, 204, 237 Nephropathy, 230, 237 Nerve Growth Factor, 237, 239 Nervous System Diseases, 237 Networks, 19, 28, 49, 237 Neuralgia, 99, 238 Neuroanatomy, 34, 40, 51, 231, 238 Neuroblastoma, 32, 41, 238 Neuroendocrine, 6, 10, 16, 27, 29, 37, 40, 45, 50, 54, 56, 96, 115, 135, 238 Neuroendocrinology, 27, 50, 238 Neurofibrillary Tangles, 7, 238 Neurofilaments, 238 Neurogenic, 17, 238
278
Affective Disorders
Neuroglia, 223, 238 Neuroleptic, 7, 137, 148, 153, 195, 198, 207, 238 Neurologic, 21, 37, 238 Neurology, 5, 6, 21, 78, 81, 88, 101, 113, 155, 238 Neuromuscular, 43, 81, 193, 237, 238, 239, 265 Neuromuscular Diseases, 43, 238 Neuromuscular Junction, 193, 237, 239 Neuronal, 16, 19, 22, 23, 51, 54, 55, 88, 141, 145, 146, 203, 207, 237, 238, 239, 244 Neuronal Plasticity, 22, 239 Neuropathy, 144, 146, 239, 244 Neuropeptide, 16, 56, 142, 211, 239 Neuropharmacology, 41, 158, 239 Neurosis, 226, 239, 245 Neurotic, 162, 239 Neurotoxic, 156, 239 Neurotoxicity, 230, 239 Neurotoxin, 16, 239 Neurotransmitters, 35, 53, 97, 144, 148, 155, 196, 235, 239, 248, 257 Neurotrophins, 54, 239 Neutrophils, 223, 230, 239 Niacin, 239, 264 Nicotine, 144, 146, 239 Nitrogen, 195, 197, 220, 239, 264 Nonverbal Communication, 208, 239, 251 Norepinephrine, 25, 82, 136, 141, 144, 145, 146, 194, 196, 213, 215, 239, 257 Nortriptyline, 48, 240 Nuclear, 38, 41, 50, 61, 200, 216, 218, 221, 231, 237, 240, 254, 262 Nuclei, 36, 37, 53, 61, 196, 216, 218, 222, 232, 235, 240, 241, 246, 250, 256, 262 Nucleic acid, 15, 37, 201, 222, 225, 227, 239, 240, 248 Nucleic Acid Hybridization, 225, 240 Nucleus Accumbens, 9, 11, 44, 240, 266 O Observational study, 22, 240 Occipital Lobe, 214, 240, 266 Ocular, 5, 240, 254 Oculomotor, 103, 214, 240 Oculomotor Nerve, 214, 240 Ointments, 215, 240 Olfaction, 163, 195, 240 Olfaction Disorders, 195, 240 Oncogene, 176, 241 Opacity, 213, 241 Opium, 235, 241
Opsin, 241, 254 Optic Chiasm, 226, 241, 248, 260 Optic Nerve, 9, 241, 254 Oral Health, 163, 241 Orderly, 241, 242 Organelles, 20, 212, 233, 235, 241, 243, 246 Orthostatic, 198, 241 Osteoarthritis, 144, 146, 241 Outpatient, 48, 83, 128, 129, 161, 241 Ovaries, 219, 241, 253, 256 Ovulation, 128, 231, 241 Ovum, 212, 223, 241, 248, 249, 267 Oxygenation, 57, 241 Oxytocin, 56, 241 P Pacemaker, 87, 127, 241 Pain Threshold, 30, 242 Palliative, 242, 262 Palsy, 141, 152, 242 Pancreas, 193, 214, 228, 231, 242, 258 Pancreatic, 176, 242 Pancreatic cancer, 176, 242 Pancreatitis, 138, 242 Panic, 26, 27, 31, 32, 88, 93, 107, 147, 150, 221, 226, 242 Panic Disorder, 27, 31, 32, 88, 93, 107, 147, 150, 221, 226, 242 Paralysis, 195, 242, 258 Paranoid Disorders, 161, 242 Paresthesia, 138, 242 Parietal, 19, 242 Parietal Lobe, 242 Parkinsonism, 41, 137, 148, 149, 198, 242, 264 Paroxetine, 134, 150, 242 Paroxysmal, 176, 197, 224, 242 Partial remission, 242, 253 Particle, 242, 263 Parturition, 243, 248 Patch, 9, 11, 243 Patch-Clamp Techniques, 9, 243 Pathogen, 49, 243 Pathogenesis, 5, 15, 20, 23, 37, 43, 104, 115, 166, 243 Pathologic, 7, 50, 193, 199, 210, 226, 243 Pathologic Processes, 199, 243 Pathologies, 11, 16, 17, 50, 243 Pathophysiology, 5, 27, 36, 40, 63, 66, 84, 85, 91, 141, 243 Pedigree, 85, 93, 243 Pelvic, 243, 250 Penicillin, 197, 243
Index
Penis, 243, 253 Pepsin, 207, 243 Pepsin A, 207, 243 Peptide, 13, 16, 55, 56, 140, 152, 243, 247, 250 Perception, 30, 120, 213, 224, 243, 255 Perfusion, 57, 226, 243 Perimenopausal, 104, 243 Perinatal, 24, 37, 44, 243 Periodicity, 244, 254 Peripheral blood, 15, 244 Peripheral Nerves, 237, 244, 259 Peripheral Nervous System, 148, 237, 238, 242, 244, 248, 258, 260 Peripheral Nervous System Diseases, 238, 244 Peripheral Neuropathy, 43, 244 Perivascular, 16, 244 Personality Disorders, 44, 67, 75, 82, 244 Phagocytosis, 44, 244 Pharmaceutical Preparations, 149, 218, 222, 244 Pharmaceutical Solutions, 215, 244 Pharmacodynamic, 219, 244 Pharmacokinetic, 244 Pharmacologic, 30, 40, 48, 223, 244, 263 Pharmacotherapy, 40, 62, 73, 105, 142, 159, 244 Phenobarbital, 132, 244 Phenotype, 5, 17, 30, 55, 59, 63, 201, 244 Phenyl, 133, 245 Phenylalanine, 123, 243, 245, 265 Phobia, 46, 68, 147, 245 Phobic Disorders, 46, 245 Phosphodiesterase, 145, 245 Phospholipase C, 52, 245 Phospholipases, 52, 245, 257 Phospholipids, 220, 228, 245 Phosphorous, 36, 245 Phosphorus, 203, 245 Phosphorylated, 208, 245 Phosphorylation, 22, 52, 245 Photoperiod, 45, 245 Phototherapy, 77, 160, 245, 255 Physician-Patient Relations, 162, 245 Physiologic, 14, 17, 64, 195, 201, 223, 233, 245, 249, 252 Physiology, 13, 34, 45, 52, 54, 113, 201, 216, 245 Physostigmine, 156, 245 Pigment, 233, 246 Pilot study, 18, 69, 120, 246
279
Pineal Body, 218, 246 Pineal gland, 127, 246 Pituitary Gland, 140, 142, 152, 211, 246 Placebo Effect, 5, 246 Plants, 195, 203, 204, 206, 208, 223, 240, 246, 255, 263, 264, 266 Plasma, 17, 48, 64, 115, 132, 143, 148, 197, 205, 222, 224, 235, 246, 256 Plasma cells, 197, 246 Plasticity, 25, 49, 55, 246 Plastids, 241, 246 Platelet Activation, 246, 257 Platelets, 79, 86, 112, 114, 246, 262 Pleomorphic, 240, 246 Poisoning, 212, 222, 229, 234, 237, 246 Polycystic, 177, 246 Polymorphic, 65, 112, 213, 246 Polymorphism, 68, 97, 99, 246 Polypeptide, 196, 208, 225, 243, 247, 248, 258, 267 Pons, 193, 202, 247 Portal System, 232, 247 Posterior, 196, 199, 205, 206, 215, 218, 240, 241, 242, 246, 247 Postnatal, 247, 259 Postsynaptic, 11, 22, 52, 247, 257, 260, 261 Post-synaptic, 148, 247 Post-traumatic, 48, 140, 142, 152, 224, 236, 247 Post-traumatic stress disorder, 48, 140, 142, 152, 247 Potassium, 35, 79, 113, 138, 154, 235, 247 Potassium Channels, 35, 247 Potentiate, 35, 45, 247 Potentiating, 196, 247 Potentiation, 53, 206, 247, 257 Practicability, 247, 264 Practice Guidelines, 174, 247 Preclinical, 25, 247 Precursor, 199, 206, 215, 216, 217, 239, 245, 247, 248, 264, 265 Predisposition, 105, 134, 135, 247, 261 Prefrontal Cortex, 12, 27, 247 Premenstrual, 104, 144, 146, 248 Premenstrual Syndrome, 144, 146, 248 Prenatal, 90, 166, 217, 248 Preoptic Area, 56, 248 Presynaptic, 9, 11, 144, 148, 200, 248, 260, 261 Presynaptic Terminals, 200, 248, 261 Prevalence, 6, 15, 26, 31, 32, 47, 64, 87, 90, 93, 100, 163, 164, 166, 248
280
Affective Disorders
Prion, 43, 205, 248 Probe, 9, 14, 248 Procaine, 195, 248 Prodrug, 132, 248 Progesterone, 234, 248, 259 Prognostic factor, 248, 260 Program Development, 33, 248 Progression, 47, 62, 197, 248 Progressive, 49, 52, 141, 205, 207, 213, 215, 223, 236, 237, 241, 246, 248, 253 Projection, 53, 240, 241, 247, 248, 252, 266 Prolactin, 35, 50, 248 Prone, 149, 249 Prophase, 249, 261 Prophylaxis, 80, 112, 114, 116, 249 Propranolol, 127, 249 Prospective Studies, 31, 32, 249 Prospective study, 93, 249 Prostaglandin, 16, 249 Prostaglandins A, 249 Prostaglandins F, 234, 249 Prostate, 176, 250, 253 Protein C, 35, 42, 56, 196, 200, 208, 250 Protein S, 15, 21, 177, 202, 222, 250 Proteolytic, 195, 209, 250 Protocol, 62, 250 Protons, 225, 232, 250, 251 Proximal, 12, 57, 215, 248, 250, 256 Psychic, 149, 239, 250, 255 Psychogenic, 15, 250 Psychology, 9, 11, 12, 28, 36, 46, 49, 50, 58, 78, 89, 91, 95, 125, 163, 215, 250 Psychomotor, 138, 203, 212, 238, 250 Psychopathology, 5, 12, 20, 22, 46, 62, 72, 74, 86, 99, 100, 157, 250 Psychophysiology, 27, 250 Psychosis, 35, 147, 150, 153, 198, 250, 251 Psychosomatic, 92, 108, 162, 250 Psychotherapy, 5, 29, 76, 108, 116, 208, 219, 251, 252 Psychotomimetic, 196, 214, 251 Psychotropic, 90, 251 Puberty, 54, 251 Public Health, 9, 27, 36, 60, 62, 75, 93, 153, 174, 251 Public Policy, 173, 251 Public Sector, 39, 251 Publishing, 65, 251 Pulmonary, 202, 206, 210, 251, 266 Pulmonary Artery, 202, 251, 266 Pulmonary Edema, 206, 251 Pulmonary hypertension, 210, 251
Pulse, 30, 54, 57, 235, 251 Pyramidal Tracts, 219, 251 Q Quality of Life, 6, 18, 21, 87, 129, 251 R Race, 33, 132, 133, 136, 141, 145, 146, 151, 251 Radiation, 194, 197, 215, 217, 220, 251, 252, 267 Radiation therapy, 194, 215, 251 Radioactive, 223, 225, 240, 251, 252 Radioimmunoassay, 13, 252 Radioisotope, 252, 263 Radiopharmaceutical, 222, 252 Randomized, 15, 18, 23, 24, 29, 35, 46, 62, 77, 113, 216, 252 Randomized clinical trial, 23, 252 Rape, 247, 252 Reagent, 206, 252, 254 Reality Testing, 250, 252 Reassurance, 226, 252 Receptors, Serotonin, 252, 256 Recombinant, 147, 252, 265 Recombination, 51, 222, 252 Rectal, 162, 252 Rectum, 198, 202, 214, 220, 222, 227, 228, 230, 250, 252 Recur, 244, 252, 255 Recurrence, 18, 19, 45, 46, 48, 202, 207, 232, 244, 252, 255 Red Nucleus, 200, 252, 266 Reentry, 19, 253 Refer, 1, 209, 215, 220, 225, 231, 238, 250, 253, 256, 266 Reflex, 219, 253, 265 Refraction, 197, 236, 253, 258 Refractive Errors, 214, 253 Refractive Power, 236, 253 Refractory, 69, 72, 76, 112, 253 Regimen, 216, 244, 246, 253 Rehabilitative, 49, 253 Relapse, 48, 80, 91, 113, 253 Reliability, 6, 31, 32, 57, 102, 253 Remission, 47, 64, 202, 232, 252, 253 Renal failure, 212, 253 Renal pelvis, 230, 253 Renal tubular, 138, 253 Renal tubular acidosis, 138, 253 Reproductive system, 143, 253 Research Design, 36, 253 Resolving, 21, 253 Respiration, 199, 204, 206, 235, 253
Index
Response rate, 21, 253 Reticular, 61, 139, 254 Retina, 9, 38, 206, 209, 230, 236, 238, 241, 254, 267 Retinal, 9, 241, 254, 266 Retinal Ganglion Cells, 9, 241, 254 Retinoblastoma, 176, 254 Retinol, 254 Retrograde, 11, 51, 254 Retrospective, 28, 67, 254 Retrospective study, 67, 254 Retrovirus, 50, 254 Rhythmicity, 42, 254 Ribose, 194, 254 Risk factor, 15, 28, 60, 62, 64, 90, 102, 105, 218, 249, 254 Risperidone, 78, 254 Rod, 207, 254 Rubidium, 70, 254 S Saccades, 101, 254 Saliva, 254, 255 Salivary, 30, 214, 242, 254, 255, 267 Salivary glands, 214, 254, 255 Saponins, 255, 259 Schizoid, 255, 267 Schizotypal Personality Disorder, 213, 255, 267 Sclerosis, 43, 141, 176, 236, 255 Screening, 13, 21, 32, 68, 143, 207, 255 Second Messenger Systems, 239, 255 Secretory, 20, 35, 255, 260, 261 Sedative, 196, 226, 255 Segregation, 5, 252, 255 Seizures, 91, 132, 138, 154, 203, 212, 242, 255 Self-Help Groups, 182, 255 Sella, 215, 246, 256 Semen, 250, 256 Senile, 136, 145, 161, 256 Sensibility, 196, 226, 256 Sensitization, 25, 97, 256 Septal, 231, 256 Septal Nuclei, 231, 256 Septum, 51, 256 Septum Pellucidum, 256 Serology, 15, 256 Sertraline, 144, 150, 256 Serum, 15, 71, 72, 74, 81, 196, 209, 235, 252, 256 Serum Albumin, 252, 256 Sex Characteristics, 194, 196, 251, 256, 261
281
Sex Determination, 177, 256 Sexual Partners, 93, 256 Shock, 256, 264 Sibutramine, 144, 145, 146, 257 Signal Transduction, 25, 35, 36, 38, 41, 52, 88, 97, 160, 228, 257 Signs and Symptoms, 253, 257, 265 Skeletal, 197, 206, 207, 236, 257, 258 Skeleton, 133, 193, 229, 249, 257 Skull, 211, 257, 261 Sleep Deprivation, 40, 57, 78, 257 Small intestine, 225, 229, 257 Smooth muscle, 196, 225, 235, 236, 249, 257, 258, 260 Social Environment, 251, 257 Social Sciences, 28, 257 Social Support, 26, 64, 257, 259 Socialization, 59, 258 Sodium, 76, 79, 113, 138, 154, 235, 258, 265 Sodium Channels, 258, 265 Soft tissue, 202, 257, 258 Solvent, 193, 206, 218, 234, 244, 258 Soma, 22, 258 Somatic, 64, 126, 149, 162, 194, 211, 225, 231, 233, 235, 244, 248, 258 Somatostatin, 35, 258 Somnolence, 138, 258 Spasm, 198, 238, 258 Spastic, 162, 229, 258 Spasticity, 258 Spatial disorientation, 215, 258 Specialist, 27, 182, 258 Species, 44, 54, 215, 218, 222, 225, 233, 235, 251, 258, 260, 264, 265, 266, 267 Specificity, 35, 75, 195, 203, 258 Spectrum, 5, 17, 135, 137, 140, 152, 258 Speech Disorders, 138, 259 Sperm, 49, 196, 206, 259 Spinal cord, 199, 202, 205, 206, 221, 233, 237, 239, 244, 251, 253, 259 Spinal Nerves, 244, 259 Sporadic, 254, 259 Steel, 207, 259 Stem Cells, 49, 112, 259 Steroid, 16, 143, 211, 255, 259 Stimulant, 196, 214, 225, 234, 259, 261 Stimulus, 78, 194, 215, 216, 219, 228, 229, 230, 245, 253, 259, 262 Stomach, 193, 200, 214, 218, 222, 225, 237, 243, 257, 259 Stool, 227, 229, 230, 259 Strabismus, 214, 259
282
Affective Disorders
Stress management, 162, 259 Stria, 27, 56, 256, 259 Striatum, 9, 237, 240, 259 Stroke, 43, 130, 143, 172, 204, 260 Stupor, 237, 260 Subacute, 227, 260 Subarachnoid, 224, 260 Subclinical, 227, 255, 260 Subiculum, 225, 260 Subspecies, 258, 260 Substance P, 104, 234, 255, 260 Suction, 243, 260 Suppression, 11, 211, 260 Suprachiasmatic Nucleus, 9, 55, 260 Survival Analysis, 48, 260 Sympathomimetic, 196, 214, 215, 218, 240, 260, 264 Symphysis, 250, 260 Symptomatic, 20, 125, 160, 162, 242, 260 Symptomatology, 6, 70, 100, 260 Synapses, 148, 206, 239, 260, 261 Synapsis, 260, 261 Synaptic, 22, 55, 148, 239, 257, 260, 261 Synaptic Transmission, 148, 239, 261 Synaptic Vesicles, 260, 261 Synergistic, 248, 261 Systemic, 16, 143, 199, 202, 212, 218, 227, 238, 247, 251, 261, 264 Systems Analysis, 53, 261 Systolic, 226, 261 T Tacrine, 7, 261 Tardive, 103, 137, 149, 153, 160, 198, 207, 261 Telangiectasia, 177, 261 Telencephalon, 200, 261 Temperament, 12, 261 Temporal, 6, 14, 17, 19, 57, 196, 224, 225, 261 Temporal Lobe, 57, 196, 261 Teratogenic, 132, 261 Teratogenicity, 132, 151, 261 Terminalis, 27, 56, 256, 261, 262 Testosterone, 56, 261 Tetrahydrocannabinol, 203, 262 Thalamic, 61, 199, 218, 262 Thalamic Diseases, 199, 262 Thalamic Nuclei, 61, 218, 262 Thalamus, 58, 61, 214, 218, 231, 247, 262 Therapeutics, 104, 142, 148, 235, 262 Thermal, 30, 197, 215, 262 Thermoregulation, 245, 262
Third Ventricle, 218, 226, 232, 246, 262 Threshold, 219, 226, 262 Thrombin, 250, 262 Thrombocytes, 246, 262 Thrombomodulin, 250, 262 Thrombosis, 250, 260, 262 Thyroid, 105, 115, 116, 226, 229, 262, 265 Thyroid Gland, 226, 262 Thyroid Hormones, 115, 262, 265 Thyroiditis, 66, 262 Thyroxine, 112, 116, 245, 262 Time Management, 259, 262 Tin, 242, 244, 263 Tissue, 25, 32, 35, 57, 143, 152, 198, 199, 200, 201, 202, 203, 204, 206, 210, 212, 215, 217, 218, 220, 226, 227, 228, 230, 231, 232, 233, 236, 237, 239, 242, 243, 244, 246, 253, 254, 257, 258, 259, 263, 264 Tolerance, 30, 263 Tomography, 5, 12, 40, 232, 263 Tonic, 138, 233, 263 Tonicity, 216, 263 Tooth Preparation, 194, 263 Topical, 218, 263 Toxic, iv, 163, 217, 234, 239, 263 Toxicity, 10, 132, 215, 234, 246, 263 Toxicokinetics, 263 Toxicology, 174, 263 Toxins, 198, 203, 217, 227, 263 Trace element, 221, 263 Tracer, 51, 263 Trachea, 262, 263 Traction, 207, 263 Transcriptase, 254, 263 Transduction, 56, 203, 257, 263 Transfection, 202, 263 Translocation, 102, 263 Transmitter, 148, 193, 199, 200, 215, 229, 232, 238, 240, 260, 261, 263, 264 Transplantation, 207, 227, 264 Trauma, 18, 23, 25, 28, 66, 212, 237, 242, 264 Treatment Outcome, 29, 39, 46, 264 Triage, 33, 264 Tricuspid Atresia, 210, 264 Tricyclic, 7, 69, 136, 142, 145, 196, 207, 213, 226, 264 Trigeminal, 99, 264 Trigger zone, 198, 264 Trihexyphenidyl, 113, 264 Trochlear Nerve, 214, 264 Trochlear Nerve Diseases, 214, 264
Index
Tropism, 50, 264 Tryptophan, 63, 108, 116, 117, 208, 256, 264 Tubercle, 240, 264 Tuberous Sclerosis, 177, 264 Type 2 diabetes, 90, 264 Tyramine, 235, 264 Tyrosine, 54, 94, 215, 265 U Ubiquitin, 238, 265 Ulcerative colitis, 162, 228, 265 Unconditioned, 53, 265 Unconscious, 226, 265 Uraemia, 242, 265 Ureters, 230, 265 Urethra, 243, 250, 265 Urinary, 74, 76, 83, 106, 203, 206, 222, 227, 265 Urine, 128, 202, 224, 227, 230, 253, 265 Urogenital, 222, 265 Uterine Contraction, 241, 265 Uterus, 205, 212, 217, 219, 233, 241, 248, 253, 265 V Vaccine, 50, 194, 250, 265 Vacuoles, 217, 241, 265 Vagina, 206, 233, 253, 265 Valproic Acid, 115, 132, 265 Vascular, 50, 160, 206, 224, 227, 262, 265 Vasculitis, 242, 265 Vasodilator, 215, 225, 265 VE, 11, 265 Vector, 263, 265 Vegetative, 35, 266 Vein, 229, 240, 266 Venlafaxine, 136, 145, 266 Venous, 250, 264, 266 Ventral, 9, 44, 54, 57, 226, 240, 247, 259, 266 Ventral Tegmental Area, 44, 266
283
Ventricle, 55, 196, 200, 204, 210, 225, 240, 251, 261, 262, 264, 266 Ventricular, 210, 264, 266 Venules, 202, 203, 266 Verapamil, 107, 133, 266 Vesicular, 148, 225, 266 Vestibular, 5, 266 Vestibule, 266 Veterinary Medicine, 173, 266 Viral, 37, 217, 240, 254, 263, 266 Virulence, 263, 266 Virus, 13, 15, 37, 70, 75, 200, 205, 217, 222, 263, 266 Viscera, 258, 266 Visceral, 6, 63, 200, 211, 231, 266 Visual Acuity, 210, 266 Visual Cortex, 214, 266 Vitamin A, 228, 254, 266 Vitreous Body, 254, 267 Vitro, 9, 143, 267 Vivo, 51, 267 Volition, 229, 267 Voltage-gated, 22, 267 W Wakefulness, 194, 212, 267 War, 247, 267 Weight Gain, 136, 144, 145, 146, 255, 267 Welchii, 245, 267 White blood cell, 37, 197, 230, 232, 236, 246, 267 Windpipe, 262, 267 Withdrawal, 43, 140, 142, 212, 267 Womb, 253, 265, 267 X Xenograft, 197, 267 Xerostomia, 163, 267 X-ray, 78, 220, 236, 240, 251, 267 Y Yeasts, 245, 267 Z Zymogen, 250, 267
284
Affective Disorders
