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

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

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

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Anxiety 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: 0-597-83738-4 1. Anxiety 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.

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on anxiety 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 ANXIETY DISORDERS ................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Anxiety Disorders......................................................................... 7 E-Journals: PubMed Central ....................................................................................................... 66 The National Library of Medicine: PubMed ................................................................................ 67 CHAPTER 2. NUTRITION AND ANXIETY DISORDERS .................................................................... 111 Overview.................................................................................................................................... 111 Finding Nutrition Studies on Anxiety Disorders...................................................................... 111 Federal Resources on Nutrition ................................................................................................. 113 Additional Web Resources ......................................................................................................... 113 CHAPTER 3. ALTERNATIVE MEDICINE AND ANXIETY DISORDERS .............................................. 115 Overview.................................................................................................................................... 115 National Center for Complementary and Alternative Medicine................................................ 115 Additional Web Resources ......................................................................................................... 122 General References ..................................................................................................................... 124 CHAPTER 4. DISSERTATIONS ON ANXIETY DISORDERS ................................................................ 125 Overview.................................................................................................................................... 125 Dissertations on Anxiety Disorders........................................................................................... 125 Keeping Current ........................................................................................................................ 127 CHAPTER 5. CLINICAL TRIALS AND ANXIETY DISORDERS ........................................................... 129 Overview.................................................................................................................................... 129 Recent Trials on Anxiety Disorders........................................................................................... 129 Keeping Current on Clinical Trials ........................................................................................... 142 CHAPTER 6. PATENTS ON ANXIETY DISORDERS ........................................................................... 145 Overview.................................................................................................................................... 145 Patents on Anxiety Disorders.................................................................................................... 145 Patent Applications on Anxiety Disorders ................................................................................ 161 Keeping Current ........................................................................................................................ 178 CHAPTER 7. BOOKS ON ANXIETY DISORDERS .............................................................................. 179 Overview.................................................................................................................................... 179 Book Summaries: Federal Agencies............................................................................................ 179 Book Summaries: Online Booksellers......................................................................................... 183 The National Library of Medicine Book Index ........................................................................... 190 Chapters on Anxiety Disorders.................................................................................................. 190 Directories.................................................................................................................................. 197 CHAPTER 8. MULTIMEDIA ON ANXIETY DISORDERS .................................................................... 199 Overview.................................................................................................................................... 199 Bibliography: Multimedia on Anxiety Disorders ...................................................................... 199 CHAPTER 9. PERIODICALS AND NEWS ON ANXIETY DISORDERS ................................................. 201 Overview.................................................................................................................................... 201 News Services and Press Releases.............................................................................................. 201 Newsletter Articles .................................................................................................................... 204 Academic Periodicals covering Anxiety Disorders .................................................................... 205 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 207 Overview.................................................................................................................................... 207 U.S. Pharmacopeia..................................................................................................................... 207 Commercial Databases ............................................................................................................... 208 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 213 Overview.................................................................................................................................... 213

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NIH Guidelines.......................................................................................................................... 213 NIH Databases........................................................................................................................... 215 Other Commercial Databases..................................................................................................... 218 The Genome Project and Anxiety Disorders.............................................................................. 218 APPENDIX B. PATIENT RESOURCES ............................................................................................... 223 Overview.................................................................................................................................... 223 Patient Guideline Sources.......................................................................................................... 223 Associations and Anxiety Disorders.......................................................................................... 230 Finding Associations.................................................................................................................. 230 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 233 Overview.................................................................................................................................... 233 Preparation................................................................................................................................. 233 Finding a Local Medical Library................................................................................................ 233 Medical Libraries in the U.S. and Canada ................................................................................. 233 ONLINE GLOSSARIES................................................................................................................ 239 Online Dictionary Directories ................................................................................................... 241 ANXIETY DISORDERS DICTIONARY.................................................................................... 243 INDEX .............................................................................................................................................. 315

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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 anxiety 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 anxiety 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 anxiety 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 anxiety 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 anxiety 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 anxiety 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 ANXIETY DISORDERS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on anxiety 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 anxiety 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 “anxiety 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: •

Psychological Care of Patients With Insulin-Dependent Diabetes Mellitus Source: New England Journal of Medicine. 334(19): 1249-1253. May 9, 1996. Summary: In this article, the author explores the psychological care of patients with insulin-dependent diabetes mellitus (IDDM). Topics include developing and maintaining the therapeutic relationship; the onset of disease; short-term and long-term complications; adherence to treatment; the prevalence of depression; eating disorders; and anxiety disorders. The author stresses that, as compared with patients with better glycemic control, high-risk patients appear to have a higher prevalence of concomitant psychiatric illnesses, such as depression and eating disorders, are more apt to live in families that have high levels of conflict, and may be disengaged from medical care so that they keep appointments inconsistently. Thus, the goal of promoting the patient's

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well-being while preventing complications requires a treatment approach that incorporates an understanding of the social, psychological, and psychiatric ramifications of IDDM. 3 tables. 65 references. (AA-M). •

Depression and Anxiety in the Person with Diabetes Source: Practical Diabetology. 17(4): 16-18, 20. December 1998. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Summary: This article examines the relationship between depression and anxiety in people who have diabetes. Depression is generally not listed as a complication of diabetes, but it can be one of the most common and dangerous consequences. Some studies have shown that depression may have an adverse effect on diabetic control. The diagnosis of diabetes is a major life stressor, and people who are newly diagnosed with diabetes may go through the typical stages of mourning. These stages are denial, anger, depression, and acceptance. The symptoms of depression may be attributed to diabetes, so a medical professional or mental health clinician is usually needed to distinguish between the two. There have been major advances in the treatment of depression, and there are medicines and psychotherapy techniques that have been shown to help depression. Medications include tricyclic antidepressants and selective serotonin reuptake inhibitors. Cognitive psychotherapy is one of the methods that has demonstrated good results for depression. Anxiety and stress can also cause large fluctuations in blood glucose levels. Specific medications and therapies have been shown to be effective in treating anxiety disorders. 7 references.

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Update on Vestibular Rehabilitation Therapy Source: Otolaryngologic Clinics of North America. 29(2): 359-371. April 1996. Summary: This article provides an update on vestibular rehabilitation therapy. Topics include the physiologic rationale for vestibular rehabilitation, including central nervous system plasticity, acute compensation for vestibular lesions, chronic compensation, decompensation, and the therapeutic implications of vestibular compensation. The authors discuss treatment efficacy and patient selection criteria, including controlled studies of efficacy, positional vertigo, disequilibrium of aging, rehabilitation after vestibular surgery, head injury, malingering, panic disorder and other anxiety disorders, Meniere's disease, diagnostic trial, and inappropriate candidates. Common techniques of vestibular rehabilitation are described, including habituation of pathologic responses, postural control exercises, visual-vestibular interaction, conditioning activities, maintenance of initial results, and the roles of the therapist and physician in patient education and vestibular rehabilitation. Two brief case reports are presented. 3 tables. 25 references.

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Fourteen-Year Follow-Up of Speech/Language-Impaired and Control Children: Psychiatric Outcome Source: Journal of the American Academy of Child and Adolescent Psychiatry. 40(1): 7582. January 2001. Contact: Available from Lippincott Williams and Wilkins. Subscription Department, P.O. Box 350, Hagerstown, MD 21740-0350. (800) 638-3030. Website: www.aacap.org/journal/journal.htm.

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Summary: This article reports on a study undertaken to examine the association between early childhood speech and language disorders and young adult psychiatric disorders. In a longitudinal community study conducted in Ontario, Canada, interviewers administered structured psychiatric interviews to age 19 participants who were originally identified as speech impaired only, language impaired, or non-impaired at age 5. The first stage of the study took place in 1982 when participants were 5 years old, and the latest stage of the study took place between 1995 and 1997 when participants had a mean age of 19 years. This article examines the association between early childhood speech language status and young adult psychiatric outcome. The results showed that children with early language impairment had significantly higher rates of anxiety disorder in young adulthood compared with non-impaired children. The majority of participants with anxiety disorders had a diagnosis of social phobia. Trends were found toward associations between language impairment and overall and antisocial personality disorder rates. Males from the language impaired group had significantly higher rates of antisocial personality disorder compared with males from the control group. Age of onset and comorbidity did not differ by speech language status. The majority of participants with a disorder had more than one disorder. These results support the association between early childhood speech and language functioning and young adult psychiatric disorder over a 14 year period. This association underscores the importance of effective and early interventions. 1 figure. 3 tables. 36 references. •

Changes in Resident and Facility Risk Factors for Psychotropic Drug Use in Nursing Homes Since the Nursing Home Reform Act Source: Journal of Applied Gerontology. 18(1): 77-98. March 1999. Summary: This journal article examines the resident and facility risk factors for the use of psychotropic drugs in nursing homes before and after implementation of the Nursing Home Reform Act (NHRA). The analysis uses Minimum Data Set (MDS) data collected for 2,170 residents in 1990 and 2,088 residents in 1993, and On-line Survey and Certification of Automated Records (OSCAR) data from 1991 and 1994. The MDS is an assessment of nursing home residents, and the OSCAR contains facility and aggregated resident data. The 1993 data indicate that the likelihood of antipsychotic drug use is increased by having greater cognitive impairment, being female, and having a history of psychiatric problems, dementia, depression, and anxiety disorders. The likelihood of antianxiety or hypnotic drug use is increased by depression and anxiety disorders. With regard to facility characteristics, a high Medicaid census increases the likelihood of antipsychotic drug use, whereas a medium Medicaid census increases the likelihood of antianxiety/hypnotic drug use. Both resident and facility risk factors for psychotropic drug use differed for the periods before and after implementation of the NHRA. 5 tables, 36 references.

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Anxiety in the Elderly: Anxiety and Its Treatment in the Elderly Source: International Psychogeriatrics. 11(1): 25-45. March 1999. Summary: This journal article reviews published research and clinical experience on treating phobic disorders, generalized anxiety, obsessive-compulsive disorder, panic disorder, mixed anxiety-depression, and mixed anxiety-dementia in the elderly. The authors discuss factors which may account for the fact that anxiety appears to be rare in established dementia; the relationships between agitation and anxiety and pain and anxiety; and whether treating anxiety could result in improved cognition. They present information on the few controlled studies available on interventions for anxiety in

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dementia, and suggest the possibility of using psychosocial therapies to treat anxiety, although limited data exist to support this option. The authors conclude that the profusion of clinical recommendations on treating anxiety disorders contrasts with the lack of controlled clinical trials. Numerous references. •

Erectile Dysfunction in Diabetes Source: Practical Diabetology. 19(2): 16, 18-23. June 2000. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Summary: This review article discusses the etiology, pathology, diagnosis, and management of erectile dysfunction (ED) in men who have diabetes. The causes of ED generally fall within the categories of organic or psychogenic. Organic causes include the categories of vascular, traumatic or postsurgical, neurologic, endocrinologic, and drug induced. Psychogenic causes include mood and anxiety disorders and relationship difficulties. Among men who have diabetes, risk factors for developing ED include age, poor glycemic control, hypertension, smoking, excessive alcohol intake, the presence of claudication, and neuropathy. The natural history of ED in men who have diabetes usually progresses gradually. Autonomic neuropathy appears to be a major contributor to the development of ED in men who have diabetes. Diagnosis of ED is based on the medical history, physical examination, and several simple diagnostic tests. The management of ED usually involves the use of oral agents such as sildenafil, yohimbine, apomorphine, and phentolamine. In men who are not candidates for oral therapy, intracavernosal injection with alprostadil can be an acceptable alternative. Other agents that have been used in injection therapy include papaverine, phentolamine, and moxisylyte hydrochloride. Mechanical treatments are also available for patients who are not candidates for drug therapy. These treatment options include external vacuum devices and constriction rings. Surgical therapy may also be considered when other forms of therapy have not been successful. The most utilized surgical procedure has been prosthetic penile implantation. Penile revascularization is another surgical option. Several preventive measures can help minimize the risk of developing ED, including improving glycemic control, quitting smoking, reducing excessive alcohol intake, and controlling hypertension. 1 figure. 3 tables. 23 references.

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Efficacy of Treatment for Geropsychiatric Patients With Severe Mental Illness Source: Psychopharmacology Bulletin. 2(4): 501-524. 1993. Summary: This review article provides a comprehensive overview of currently available treatments for psychogeriatric disorders, summarizing the efficacy of each of the various treatment approaches based on current research evidence. The review emphasizes papers published in the last decade which generally have used randomized, placebocontrolled, double-blind methodology to establish the efficacy of particular treatments in severe mental disorders in older people: delirium, dementia, depression, mania, psychotic disorders, and anxiety disorders. The author states that today's treatment guidelines for psychogeriatric disorders are more clearly defined now than a decade ago. However, more needs to be learned about treatment response of some of the patients with greatest need, medically fragile or very old patients, and those in nursing homes and residential care facilities. According to the authors, treatment research has largely ignored older patients with subsyndromal depressive syndromes, or with mixed depression/anxiety symptom presentations, and those presenting with minor cognitive impairment not of great enough severity to be considered dementia. The author states

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that these knowledge gaps, and others identified in the review, need attention; and that dissemination to clinical practice of known, effective treatments for psychogeriatric disorders is essential to assure that appropriate and adequate treatment is available to these patients. Appendices provide the Centers for Disease Control (CDC) Panel's Recommendations on Safe and Effective Treatment of Depression in the Elderly, and the CDC Panel's Recommendations on the Most Promising Questions for Future Research, abstracted from the NIH Consensus Development Conference on Diagnosis and Treatment of Depression in Late Life. 4 tables, 96 references.

Federally Funded Research on Anxiety Disorders The U.S. Government supports a variety of research studies relating to anxiety 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 anxiety 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 anxiety disorders. The following is typical of the type of information found when searching the CRISP database for anxiety disorders: •

Project Title: 5-HT TRANSPORTER FUNCTION IN VIVO: STUDIES USING KO MICE Principal Investigator & Institution: Daws, Lynette C.; Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 11-DEC-2001; Project End 30-NOV-2006 Summary: The serotonin (5-HT) transporter (SERT) is responsible for terminating serotonergic neurotransmission by high-affinity uptake of 5-HT from extracellular fluid (ECF) and is therefore critical in determining concentrations of 5-HT in ECF. Drugs that act at the SERT, such as selective serotonin reuptake inhibitors, ameliorate several neuropsychiatric disorders, including depression and certain anxiety disorders. The SERT is also a primary site of action of drugs of abuse such as "Ecstasy" (MDMA). However, there is remarkable variability in the response of individuals to these drugs and the reason for this is not clear. For example, some individuals respond well to antidepressant treatment while others do not. Also, certain people will overdose on MDMA at a dose that will only mildly affect others. Allelic variations in the SERT have now been identified that influence SERT activity and may be associated with a number of psychiatric disorders and/or to an individual's response to drug treatment. The main goal of this proposal is to study the functional and adaptive consequences of geneticallyinduced reductions in the expression of the SERT and 5-HT1B receptor on the clearance

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

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of 5-HT from ECF in vivo. Using in vivo high-speed chronoamperometry we have found that the 5-HT1B autoreceptor can regulate clearance of 5-HT from ECF and also, that alterations in the density of the SERT can change the clearance rate of 5-HT. This proposal will take advantage of two lines of mice with null mutations of the SERT or the 5-HT1B receptor gene (the SERT knockout (KO) and 5-HT1B receptor KO mice), to gain new insight into both the regulation of the SERT and the effect of altered gene expression on drug sensitivity in these animals in vivo. It is predicted that in heterozygotes of both KO strains (which express 50 percent fewer SERTs and 5-HT1B receptors respectively), clearance rates of 5-HT will not differ from wild-type mice under basal conditions, but defects will be revealed in response to pharmacologic challenge. Our general hypothesis is that changes in the kinetics of 5-HT clearance as an adaptive consequence of reduced SERT or 5-HT1B receptor density will alter the sensitivity of these mice to psychotropic drugs. Changes in sensitivity will be indexed by the ability of these drugs to influence the kinetics (KT and Vmax) of 5-HT clearance in the three genotypes of each KO strain. High-speed chronoamperometry will be used to measure 5-HT clearance in vivo. Quantitative autoradiography will be used to assess the effect of genetic mutation of the SERT on 5-HT1B receptor density and vice- versa. Alterations in the uptake of 5-HT by these mice and in the response of these mice to psychotropic drugs will provide information important to our better understanding of the pathobiology of neuropsychiatric disorders and addiction as well as to the selection of drug treatment in individuals with allelic variations of the SERT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A GENETIC ANALYSIS OF THE ROLE OF AMYGDALA IN LEARNED FEAR Principal Investigator & Institution: Kandel, Eric R.; Professor; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): The aim of Project 1A is to develop a molecular genetic approach to extend the analysis of learned fear to the molecular level. This approach involves two phases: (1) discovery of genes important for learned fear, and (2) mechanistic studies of gene candidates and the development of animal models of anxiety. In a large sense, we hope that in accomplishing phases (1) and (2), we will be able to contribute to developing a paradigm for obtaining genetic insight into a complex mental disorder: the spectrum of Anxiety Disorders. In phase 1 of Project 1A we propose to study genes induced in the amygdala during learned fear, a form of fear that engages the neural mechanisms that are driven by danger and threat, and which sets in place long-term and enduring adaptive defensive responses. It is a naturally occurring and highly adaptive function of the brain, and it has proved to be experimentally tractable at the level of behavior, anatomy, information processing, and molecular genetics, and each of these levels is reasonably conserved across species. By using fear conditioning, we know we are activating fundamental and phylogenetically ancient mechanisms that support appropriate emotional responses to danger. Since anxiety disorders all involve inappropriate fear responses, we are hopeful that by identifying the molecular genetic basis of fear conditioning we will uncover means of probing the genetic mutations that underlie anxiety disorders. To maximize our identification of candidate genes, we will drive the defense system with a wide range of fearconditioning methodologies, using both 1st and 2nd order cued conditioning, 1st and 2nd order unpaired cue conditioning (conditioned inhibition of fear), and contextual conditioning. All of these behavioral protocols have been fully developed in our hands.

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In Phase 2 of Project 1A, we will screen for genes that are regulated in the amygdala of wild-type mice exposed to learned fear, and then developing genetically engineered mice that have trans genes regionally restricted to the amygdala and temporally regulated. In addition, we will study, in a like manner, other genes that are known to be important for learned fear. Our mechanistic studies will involve behavioral, electrophysiological, and molecular genetic studies designed to examine the effects of genes identified in the gene discovery phase on behavioral fear conditioning and on amygdala function. In doing so, we will attempt to relate these genes to signal transduction pathway important for LTP on the one hand and to behavioral learning of fears, safety, context and 2nd order learning on the other. We have already succeeded in expressing transgenes in the lateral nucleus of the amygdala, including a Grp-IRES-tTA knock-in cassette. This mouse line shows tTA expression at high levels in the lateral nucleus; this nucleus is known to be an input for both US and CS for Pavlovian fearconditioning. One of the genes so identified is GRP, and its receptor, GRPR. We have examined mice with knockout of GRPR and found a powerful enhancement of fear. We continue to work with single cell cDNA libraries from the lateral amygdala to delineate other promoters that generate restricted patterns of expression. However, we would emphasize that even though we will be able to express genes at high levels in the lateral nucleus, this expression is not likely to be completely restricted and this has so far proved to be unavoidable. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A LONGITUDINAL FOLLOW UP OF CHILDREN AT RISK FOR ANXIETY Principal Investigator & Institution: Rosenbaum, Jerrold F.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-MAY-1993; Project End 31-JAN-2004 Summary: In the proposed study, we seek to address a basic scientific question: Is it possible to predict the development of anxiety disorders among young children whose parents have panic disorder (PD)? This question is straightforward, yet the answer has broad implications. Although it is well established that children of parents with PD are at high risk for anxiety disorders, only some of these children will develop psychopathology. The identification of a predictor would facilitate primary prevention by delineating a group of young children at very high risk for anxiety disorders among those already at risk by having a PD parent. During the prior funding period we have completed a cross-sectional study of over 200 children at risk for PD and comparison offspring of normal control parents. Our sample is unique in that the children have been identified and characterized extensively before they entered the age of risk for childhood anxiety disorders. These youngsters have already been assessed for behavioral inhibition, psychophysiological markers, and early signs of anxiety as well as for markers of psychosocial adversity. A subsample who have grown old enough to be reliably assessed for DSM-IV diagnoses, have already been assessed for psychopathology using structured clinical interviews. Therefore this valuable sample affords us the unique opportunity to track the development of dysfunction and psychopathology in prospectively followed children at risk for psychopathology. To our knowledge, this would represent the largest such sample followed longitudinally. As we describe in the Progress Report, our work suggests that multiple domains of measurement will be useful predictors of psychopathology in high risk children. These domains are: parental disorders, child temperament (as indexed by "behavioral inhibition to the unfamiliar" [BI]), psychophysiologic abnormalities, and psychosocial

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adversity. The proposed work seeks to validate these measures as predictors of subsequent psychopathology and dysfunction by following up the sample five years after their baseline evaluation. The main aims of this project were determined by our past 12 years of work studying BI and anxiety disorders among young children. Our three main aims are: l) to characterize the psychopathologic and functional outcomes of children at risk for panic disorder; 2) to determine predictors of adverse outcomes among children at risk for anxiety disorders; and 3) to characterize the developmental sequence of anxiety disorders in these children. Moreover, under separate funding, we are collecting DNA samples from this cohort of families. Thus, by assuring that DNA samples will be available in the future, we leave open the possibility that our sample will be useful for prospectively predicting psychiatric disorders and disability from putative anxiety genes. Given that we are also assessing adverse features of the environment, we will also be able to determine if gene-environment interactions play a role in the genesis of anxiety disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADOLESCENT PSYCHOPATHOLOGY AND ALCOHOL USE DISORDERS Principal Investigator & Institution: Clark, Duncan B.; Associate Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: This Independent Scientist Award (K02) is proposed for the applicant to acquire necessary skills to apply the developmental psychopathology conceptual framework and innovative statistical techniques for categorical longitudinal data to creating a model for the relationships among alcohol use disorders (AUD) and other mental disorders in adolescence. Based on empirical findings to date, the specific hypotheses focus on antisocial disorders (i.e., conduct disorder, oppositional defiant disorder) and negative affect disorders (i.e., mood and anxiety disorders) as possible predictors, consequences, or moderators of the structure, course and consequences of adolescent AUD. The applicant, trained as a child clinical psychologist and adult psychiatrist, is the Scientific Director of the NIAAA-funded Pittsburgh Adolescent Alcohol Research Center (PAARC). The career development plan focuses on the acquisition of a thorough foundation in statistical modeling techniques and related methodological issues, including the implications of sampling strategies, missing data imputation, model selection, and controversies concerning causal inference from observational data. The applicant will learn statistical methods based on regression for modeling time-dependent relationships among continuous and categorical variables. The focus on methods for categorical variables is relevant to longitudinal research involving symptom and diagnostic categories. Relevant statistical techniques include methods for observed variables, including proportional hazards and random regression modeling and methods for latent variables, including latent class analysis, latent transition analysis, and growth mixture modeling with latent trajectory classes. Bayesian approaches to model selection and causal inference will also be considered. These methods will be specifically applied to examining the relationships among AUD, antisocial disorders, and negative affect disorders using longitudinal data from PAARC (n=1000 adolescents). Methods for evaluating the extent and the influence of sampling bias will assessed through comparison of the model generated using PAARC data with models generated with other data sets, including studies using high-risk and community sampling approaches. The integration of the concepts of developmental psychopathology with innovative longitudinal statistical modeling methods will

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contribute to the applicant's long-term career goal to advance research on adolescent AUD by clarifying the importance of psychopathology in determining the structure, course and consequences of adolescent alcohol abuse and dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANIMAL MODELS OF FEAR AND ANXIETY Principal Investigator & Institution: Davis, Michael; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 11-AUG-2003; Project End 30-JUN-2008 Summary: Five compounds (the CRH1 receptor antagonist SB723620, the NK1 antagonist G597599, the SSRI/5HT2A agonist Vilazodone, the antidepressant 8hydroxy-bupropion, and the type 4 phosphodiesterase inhbitor SB207499), provided by GlaxoSmithKline as part of The Emory-GSK-NIMH Collaborative Mood Disorders Initiative, will be evaluated for anti-fear and anxiolytic activity using fear-potentiated, light-enhanced, and CRH-enhanced startle paradigms (increased startle in the presence of cues that predict shock, during sustained illumination, or following i.c.v. corticotropin-releasing hormone infusions, respectively). Whereas light- and CRHenhanced startle (which are more akin to anxiety than to fear) are mediated by circuitry that includes the bed nucleus of the stria terminalis (BNST) but not the central nucleus of the amygdala (CeA), fear-potentiated startle is mediated by circuitry that includes the CeA but not the BNST. A central goal of the proposed studies will be to identify differing pharmacological vulnerabilities associated with BNST (anxiety) versus CeA (fear) dependent behaviors. In humans, anxiety disorders are more prevalent in women than in men and, in rats, light-enhanced startle is more robust in females than in males. Interestingly, the BNST is sexually dimorphic in both species. Thus, a second goal will be to compare the influence of gender on BNST- versus CeA-dependent responses, and to evaluate gender influences on drug responses in each model. These same compounds will be evaluated in other laboratories (separate applications) using different behavioral models and non-behavioral assays. It is hoped that this integrated effort will foster new approaches for the rapid evaluation of novel compounds with potential clinical utility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BEHAVIOR IN MOUSE TRYPTOPHAN HYDROXYLASE MUTANTS Principal Investigator & Institution: Patel, Paresh; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): The candidate is a child and adolescent psychiatrist with experience in molecular biology and neuroscience. He holds a tenure track junior faculty appointment with 80 percent research time at the University of Michigan Medical Center. This career development award will serve to expand his skills to include the development of genetic animal models and their behavioral phenotyping. The skill base interdigitates with a commitment by the University of Michigan Mental Health Research Institute (MHRI) to apply novel molecular approaches to identify new candidate genes for major depression and undertake their anatomic, structural, and functional characterizations. It is expected that by the end of this grant, the candidate will have gained sufficient experience and generated several informative animal models for independent research and collaboration. The University of Michigan Medical Center is a thriving research community with ample resources for carrying out the proposed studies. A highly successful core facility is available for transgenic manipulation.

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Faculty in the MHRI bear expertise in the areas of genetic engineering, biochemistry, rodent anatomy, and animal behavior. The candidate is being supervised by a senior research scientist in the MHRI with consultative support from leaders in the field of mouse transgenics and behavior phenotyping. This project applies emerging molecular technology to expand understanding on the role of serotonin biosynthesis and neurotransmitter levels on nervous system development and behavior. The design employs neuron specific and tetracycline-inducible genetic elements to engineer transgenic mice permitting regulation of tryptophan hydroxylase (TPH) activity. TPH is the rate-limiting enzyme in serotonin biosynthesis, and is thereby critical to serotonin turnover. The recombinant animals will permit probing the effects of temporal and tissue-selective up- or down-regulation of brain serotonin on measures of anxiety, attention, learning, memory, aggression, appetite, drug preference, and other behaviors. The proposed research is central to the serotonin hypothesis of mood and anxiety disorders, and offers a model for studying the developmental effects of serotonin turnover on brain maturation. The candidate's long-term career plan is academic research integrating human clinical, genetic and animal model information for major mood disorders Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN FUNCTION IN SUBSTANCE-DEPENDENT ABUSED WOMEN (PILOT) Principal Investigator & Institution: Ernst, Frederick A.; Professor; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: Substance dependence has had an enormous deleterious impact on the health and well-being of Americans. Understanding the process by which persons become vulnerable to substance abuse will be necessary to more effectively prevent and treat this pervasive problem in American society. It is well-known that childhood sexual abuse (CSA) is strongly related to various manifestations of psychopathology including dissociative disorders, anxiety disorders, personality disorders, and substance abuse. However, the empirical study of this relationship is difficult because of the private, very personal, and traumatic nature of the childhood experiences associated with CSA. Current methods of screening for CSA in treatment programs for chemical dependence depend largely on the Addictions Severity Index (ASI) and are believed to be inadequate. Part of this proposed pilot investigation seeks to test the validity of the ASI for the identification of CSA by comprehensive interview methods and through the use psychometric and neuropsychological measures that are likely to indirectly detect adult manifestations of CSA experiences. An additional aim of the proposed investigation is to study prefrontal cortical functioning in eighty women, 40 blacks and 40 whites, from the treatment programs of the Meharry Alcohol and Drug Abuse Program. Forty women with reported histories of CSA will be compared to 40 women who report no history of CSA. It is hypothesized that substance-dependent women with histories of CSA will reveal more severely impaired prefrontal function than women reporting no history of CSA when matched on potential confounding variables including race, SES, age, substance abused, and length and severity of substance dependence. The Emotional Stroop Task, a modified version of the original Stroop, the Trails A and B, a Stop-Signal Test, a Negative Priming Task, and Directed Forgetting will form a battery of tests to yield a composite measure of prefrontal function. Data will be analyzed by MANOVA with Race and Sexual Abuse History as independent variables and prefrontal function as a dependent variable. The validity of the ASI is expected to reveal a significant

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frequency of false negatives when compared to comprehensive interview. No racial difference in the extent of CSA history or its effect on prefrontal function is expected and subjects with histories of CSA are expected to reveal relatively impaired prefrontal functioning irrespective of race. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN NOREPINEPHRINE AND STRESS REACTIVITY Principal Investigator & Institution: Morilak, David A.; 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-JUL-1996; Project End 31-JUL-2007 Summary: (provided by applicant): Stress is a factor in many psychopathological conditions, including depression, Post-Traumatic Stress Disorder and other anxiety disorders. Elucidating the reactivity and regulation of those brain systems responsible for modulating' the stress response is thus important for understanding the processes leading to such disorders, and possibly to developing novel or more effective treatment strategies- One such system is the brain noradrenergic system originating in the locus coeruleus (LC). Stress induces norepinephrine (NE) release in limbic regions such as the central amygdala (CeA) and bed nucleus of the stria terminalis (BSTL), enhancing behavioral activation and arousal. This system is also a target for antidepressant and mood-altering drugs used to treat stress-related disorders. However, while stress is a factor in many psychiatric disorders, not all individuals exposed to similar stress exhibit similar pathology. Thus, there is also a genetic component underlying a susceptibility to stress. This genetic predisposition, when combined with exposure to a sufficiently sensitizing environmental stimulus, results in stress-related psychopathology. In this project, we address these interacting genetic and environmental influences on the central noradrenergic system. Genetic predisposition will be studied by comparing rat strains differing in their reactivity and susceptibility to stress: Sprague-Dawley controls; Wistar-Kyoto (WKY) rats, which show behavioral inhibition to stress and increased susceptibility to stress pathology; and Lewis rats, which show blunted hormonal stress responses. We will investigate strain differences in reactivity of the brain NE system in response to acute immobilization stress, measured by changes in tyrosine hydroxylase (TH) mRNA in LC, and NE release in CeA and BSTL. We will compare endocrine and behavioral stress reactivity, measured by plasma ACTH and behavior on the social interaction and elevated plus maze tests. We will then compare the differential role played by NE in the CeA and BSTL of the three strains in modulating neuroendocrine and behavioral stress reactivity. In subsequent aims, we will investigate strain differences in the sensitizing effects of repeated cold stress exposure on noradrenergic, neuroendocrine and behavioral stress reactivity. Finally, we will determine how sensitization by repeated exposure to cold stress may alter the modulatory influence of NE in CeA and BSTL, and how this adaptive change in NE function may differ between the strains. Our hypothesis is that the behavioral inhibition shown by WKY rats results from reduced noradrenergic reactivity to stress, and that this may contribute to their stress susceptibility. We also hypothesize that cold sensitization will exacerbate the strain differences in noradrenergic reactivity that contribute to differences in behavioral and neuroendocrine reactivity. By comparing neurobiological differences between these strains, before and after sensitization, we hope to understand better the link between stress and disease states in vulnerable individuals Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CAMBODIAN REFUGEES: PROBLEM ALCOHOL USE AND COMORBIDITY Principal Investigator & Institution: Marshall, Grant N.; Rand Corporation 1700 Main St Santa Monica, Ca 90401 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): The proposed household survey of Cambodian refugees residing in the United States will constitute the first-ever community-based, epidemiologic study assessing the prevalence of alcohol use disorders in this population.The research would also assess the co morbidity between alcohol disorders and other psychological disorders and their relation to pre-migration torture/trauma. The proposed survey is to be conducted in conjunction with an ongoing NIMH-funded study of this population. The broad purpose of the ongoing study is to determine the mental health needs of this highly traumatized population, focusing on PTSD, anxiety disorders and depressive disorders. In addition to this assessment, the ongoing study aims to relate these disorders to the respondents' experience of trauma, as well as a number of economic, social, cultural, and physical health status measures. Using a twostage random sampling strategy, 500 adult male and female refugees, ages 35-70, will be recruited for participation from Cambodian residents in Long Beach, California. Study participants will complete a 120-minute, face-to- face interview in the Khmer language conducted by lay interviewers. As part of this interview, respondents will be given three measure to assess their alcohol use: a version of the Composite International Diagnostic Interview (CIDI, World Health Organization, 1997) will be used to measure alcohol disorders, the quantity-frequency-variability(QFV) scale (Cahatan, Cisin, & Crossley, 1969) will be used to assess consumption patterns, and a scale constructed from the Cambodian terms for alcohol use will be used assess respondents relative to their culturally defined typology of drinking. The bread aims of the proposed NIAAA research are: 1. to describe the alcohol consumption patterns and to estimate the prevalence of alcohol use disorders and problem drinking in a community-based sample of Cambodian refugees residing in the United States. 2. To identify the sociodemographic factors and environmental stressors associated with higher drinking. Factors of particular interest include those relatively unique to this Southeast Asian group's life experience (refugee standing, exposure to trauma/torture), those common to many new immigrants (e.g., acculturation status, and changes in family structure), as well as factors known to predict alcohol use and abuse more broadly (e.g., gender, and SES). 3. To examine the co morbidity between alcohol abuse and the psychological disorders associated with severe trauma exposure. More specifically, the study will investigate if alcohol use partially mediates the relationship between traumatic experiences and PTSD, depression and anxiety disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CBT AND VENLAFAXINE TREATMENTS FOR ANXIETY IN ALCOHOLISM Principal Investigator & Institution: Ciraulo, Domenic A.; Professor of Psychiatry; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Deficits in anxiety management skills are frequent causes of relapse to alcohol use. Empirical data support the role of anxiety in alcohol relapse. Psychosocial and pharmacological treatments for alcohol problems increasingly address the role of negative affect in alcohol use disorders. Due to the lack of large, well-

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controlled treatment outcome trials, the optimal treatment (or combination of treatments) remains unknown. Real world practice in the treatment of alcohol use disorders frequently begins brief, intensive detoxification and stabilization, and is often followed by some combination of CBT and pharmacotherapy for patients complaining of mood difficulties while attempting early abstinence from alcohol. The proposed project is written as a "typical clinical practice" test in response to the Program Announcement PA-98-003, and is a fully-controlled trial of a combined anxiety-focused CBT and pharmacotherapy (venlafaxine; CBT-VEN) delivered for patients with comorbid alcohol-use and anxiety disorders. The CBT-VEN package will be administered in three forms depending upon the primary presenting anxiety disorder (i.e., PD, GAD, or SP) and will be contrasted with two single-active treatment conditions (CBT-PLA and REL-VEN), and one fully-controlled condition (relaxation training and placebo medication; REL-PLAC). One hundred and twenty eight participants will be recruited and, subsequent to a platform of intensive outpatient treatment for alcoholism, will be randomly assigned to a 12-week treatment condition. Both conditions will begin with a 1-week placebo run-in, and conclude with a 3-week medication taper. Follow-up assessments will be conducted at post-treatment and at 3, 6, 9, and 12-months. The longterm objectives of this research are to develop a real-world combination of psychosocial and pharmacological treatments for patients with comorbid alcohol-use and anxiety disorders that compromise prognosis, and to evaluate the effectiveness of combined psychosocial and pharmacological treatments that target anxiety among patients with this comorbidity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CBT TREATMENT OF PANIC DISORDER IN COMORBID ALCOHOLICS Principal Investigator & Institution: Kushner, Matt G.; Associate Professor; Psychiatry; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): Alcohol use disorders are among the most serious and costly health problems of our time. Studies have been consistent in finding an increased risk of alcohol use disorder among those suffering with the anxiety syndrome, panic disorder "comorbidity". Further, studies suggest that panic disorder can contribute to risk for a new onset of alcohol disorder and to risk for relapse following alcoholism treatment. Both theory and research suggests that relapse in comorbid individuals stems, in part, from the tendency to drink as a means of coping with persistent anxiety and panic symptoms. These findings led us to hypothesize that addressing the panic symptoms of comorbid patients would improve the outcome of comorbid individuals undergoing alcoholism treatment Cognitive behavioral therapy (CBT) for panic disorder would appear to be an ideal intervention for testing this nypothesis; however, the effect of CBT treatment on panic disorder in comorbid individuals remains unknown. Further, conventional CBT treatments do not address the inter-relationship of panic symptoms and pathological alcohol use that is potentially relevant to the persistence of both disorders in comorbid individuals. Therefore, we are proposing an experimental/developmental program (P.21) with a series of research stages aimed at testing the value of CBT for panic among comorbid patients. In stage 1 (conducted in year 1), we will use approximately 4-6 comorbid alcoholism treatment patients as subjects in four separate pilot tests, each focused on one of the four core elements of the panic treatment program, Master your Anxiety and Panic (MAP), along with supplemental material pertinent to comorbidity. Pre- and post-tests along with

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expert consensus will be used to evaluate whether the material and techniques are working properly, with any problematic materials being modified as needed. In the stage 2 study (year 2 and 3), thirty comorbid patients undergoing a community-based alcoholism treatment will receive either the 10-session MAP program as modified in stage 1 (MMAP) or a 10-session control treatment (progressive muscle relaxation training; PMRT). (Note that PMRT is structured and credible but has been shown to have minimal effects on either alcoholism treatment outcome or panic disorder symptoms.) We hypothesize that those receiving fix MMAP program will demonstrate fewer panic attacks and less intense panic attacks following the study treatments. We also hypothesize that at a 3-month follow-up assessment, subjects in the MMAP group will demonstrate a lower overall rate of several standard alcohol use outcomes as well as time to those outcomes when present. Beyond these directional hypotheses, an important goal of the stage 2 study is to provide effect size parameters indicating the clinical importance of the MMAP intervention. It is expected that the stage 1 and 2 studies proposed here will provide the foundation for an RO1 application to conduct a larger-scale stage 3 study to confirm the value of supplementing standard alcoholism treatment with the MMAP program for comorbid patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CENTER FOR NEURAL SYSTEMS OF FEAR & ANXIETY Principal Investigator & Institution: Ledoux, Joseph E.; Professor; Center for Neural Science; New York University 15 Washington Place New York, Ny 10003 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: (Adapted from applicant's abstract): Considerable progress has been made in elucidating the neural pathways underlying conditioned fear in experimental animals. This work has implicated circuits centered around the amygdala, and interactions between the amygdala, hippocampus and medial frontal cortex (mPFC), in the acquisition and/or expression of different aspects of conditioned fear. New research in humans has confirmed essential aspects of the work in animals. These facts strongly suggest that studies of fear in animals can reveal important insights into the mechanisms of fear in humans, possibly including humans with pathological fear, such as occurs in anxiety disorders and paranoid psychosis. Further, given that threatening stimuli, which are prominent in the lives of patients with fear disorders, trigger stress reactions, that stress is believed to exacerbate symptoms in psychiatric patients, including those with pathological fear, and that the same brain regions implicated in normal fear are also strongly implicated in the regulation of stress hormones, we propose that stress-induced alterations in fear circuits may contribute to the development or maintenance of pathologic fear. The goals of this proposal, therefore, are to explore the relation between fear and stress in experimental animals and to examine whether the effects of stress on fear circuits mimics changes that occur in fearrelated disorders in humans. To do this, we will use the same behavioral paradigm, fear conditioning, to study rats, normal humans, and patients with fear disorders. The overall aim of the animal work is to examine the effects of stress on the behavioral functions, physiology, and morphology of fear circuits. The overall aim of the studies of normal humans is to use fMRI to both extend our understanding of fear mechanisms in the human brain and to develop new probes for testing patients with fear disorders. And the overall aim of the studies to determine whether the normal patterns of functional brain activation during fear are altered, and whether these alterations are consistent with the effects of stress on fear circuits, as determined in the animal work. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHD & ANXIETY: PREVALENCE, RELATIONSHIP Principal Investigator & Institution: Carmin, Cheryl N.; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): The goals of this career development award are designed enable the candidate to develop a program of independent research examining the relationship between anxiety disorders and coronary heart disease (CHD). This study would contribute to the investigator's long-term career goal of examining the relationship between anxiety disorders and medical illness, such as CHD. There is a relatively well-established link between emotional and behavioral variables and the risk for CHD. Despite the comorbidity of anxiety and depressive disorders, the lines of research investigating these conditions and CHD have remained largely independent of one another. Further, despite it being more prevalent than and often pre-dating the onset of depression, less attention has been paid to the relationship between anxiety and CHD. The existing research focusing on anxiety disorders in those at risk for or who have CHD is limited by the use of descriptive, rather than state-of-the-art diagnostic measures of psychopathology. It remains unclear to what extent clinically significant anxiety disorders serve as independent risk factors and may be influential in the development of CHD. In order to address the risk that anxiety disorders pose in CHD prone individuals, the initial phase of this award will allow the investigator to develop background in areas related to the interface between cardiology and psychology including psychosocial epidemiology, biostatistics, psychophysiological assessment, and scanning technology related to CHD. Existing epidemiological databases that assess CHD will be utilized to determine whether anxiety disorders are independently related to the development of CHD. The 2 nd phase of the award will be used to apply the skills acquired in coursework and in analyzing existing data to execute a study comparing a sample of anxiety disordered subjects to a matched control group based on anxiety symptoms (severity, frequency, duration), cardiac calcium as assessed by electron beam tomography, lipid levels, and heart rate variability. The investigator is in the unique position of having access to individuals who are being screened for CHD using EBT as well as having access mentors and collaborators involved in multicenter cardiovascular research (Drs. Lynda Powell, Peter Buttrick, Kiang IJu, George Kondos), psychophysiological research (Dr. Stephen Porges) and who are experienced in the psychopathology and treatment of anxiety disorders (Dr. Richard Heimberg). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHILD /ADOLESCENT ANXIETY MULTIMODAL TREATMENT STUDY Principal Investigator & Institution: Albano, Anne Marie.; Recanati Family Assistant Professor of p; Anesthesiology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-MAY-2006 Summary: (provided by applicant): With point prevalence estimates ranging from 12 percent to 20 percent, anxiety disorders are among the most common conditions affecting children and adolescents. The three most commonly impairing childhoodonset anxiety disorders are separation anxiety disorder, social phobia and generalized anxiety disorder. As a group, these disorders routinely co-occur and cause clinically significant distress and impairment affecting school, social, and family functioning. Left untreated, these disorders leave children at risk for anxiety disorders, major depression

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and, in some cases, substance abuse extending into late adolescence and adulthood. Hence, effective treatments for childhood-onset anxiety disorders promise to alleviate and perhaps to prevent long-term morbidity and even mortality. In randomized controlled trials, we have shown that two monotherapies, cognitive-behavioral therapy (CBT) and the selective serotonin reuptake inhibitor (SSRI), fluvoxamine (FLV), are effective treatments for separation anxiety, social phobia, and generalized anxiety disorders in children and adolescents. Even though the monotherapies are effective a substantial number of patients remain symptomatic following treatment and, might have benefited from combined treatment. There are as yet no systematic, controlled studies comparing CBT and an SSRI, alone or in combination, against a control condition in the same patient population. This revised application proposes a four-year, six site, randomized controlled efficacy trial comparing cognitive-behavioral (CBT) and pharmacological treatment for youth ages 7 to 16 years with anxiety disorders. Phase 1 is a 12-week, random assignment acute efficacy study comparing CBT, FLV, their combination (n=90, each condition), and pill placebo control (n=48) in 318 (53/site) youth with DSM-IV primary diagnoses of separation anxiety, social phobia, and/or generalized anxiety disorder. Phase II involves a 6-month treatment maintenance period for Phase I responders. All subjects regardless of response status will be evaluated at all scheduled assessment points. In addition to comprehensive parent, child, clinician, and teacher reports, the primary outcome variables will be assessed by blind independent evaluators. Manualized intervention and assessment protocols plus state-of-the-art quality assurance and adverse event monitoring procedures insure uniform cross-site administration of the study protocol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHILD AND ADOLESCENT ANXIETY MULTISITE STUDY (CAMS) Principal Investigator & Institution: March, John S.; Associate Professor; Psychiatry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 21-SEP-2002; Project End 31-MAY-2006 Summary: (provided by applicant): With point prevalence estimates ranging from 12 percent to 20 percent, anxiety disorders are among the most common conditions affecting children and adolescents. The three most commonly impairing childhoodonset anxiety disorders are separation anxiety disorder, social phobia and generalized anxiety disorder. As a group, these disorders routinely co-occur and cause clinically significant distress and impairment affecting school, social, and family functioning. Left untreated, these disorders leave children at risk for anxiety disorders, major depression and, in some cases, substance abuse extending into late adolescence and adulthood. Hence, effective treatments for childhood-onset anxiety disorders promise to alleviate and perhaps to prevent long-term morbidity and even mortality. In randomized controlled trials, we have shown that two monotherapies, cognitive-behavioral therapy (CBT) and the selective serotonin reuptake inhibitor (SSRI), fluvoxamine (FLV), are effective treatments for separation anxiety, social phobia, and generalized anxiety disorders in children and adolescents. Even though the monotherapies are effective a substantial number of patients remain symptomatic following treatment and, might have benefited from combined treatment. There are as yet no systematic, controlled studies comparing CBT and an SSRI, alone or in combination, against a control condition in the same patient population. This revised application proposes a four-year, six site, randomized controlled efficacy trial comparing cognitive-behavioral (CBT) and pharmacological treatment for youth ages 7 to 16 years with anxiety disorders. Phase 1 is a 12-week, random assignment acute efficacy study comparing CBT, FLV, their

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combination (n=90, each condition), and pill placebo control (n=48) in 318 (53/site) youth with DSM-IV primary diagnoses of separation anxiety, social phobia, and/or generalized anxiety disorder. Phase II involves a 6-month treatment maintenance period for Phase I responders. All subjects regardless of response status will be evaluated at all scheduled assessment points. In addition to comprehensive parent, child, clinician, and teacher reports, the primary outcome variables will be assessed by blind independent evaluators. Manualized intervention and assessment protocols plus state-of-the-art quality assurance and adverse event monitoring procedures insure uniform cross-site administration of the study protocol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHILD/ADOLESCENT ANXIETY MULTIMODAL TREATMENT STUDY Principal Investigator & Institution: Birmaher, Boris; Associate Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 18-SEP-2002; Project End 31-MAY-2006 Summary: (provided by applicant): With point prevalence estimates ranging from 12 percent to 20 percent, anxiety disorders are among the most common conditions affecting children and adolescents. The three most commonly impairing childhoodonset anxiety disorders are separation anxiety disorder, social phobia and generalized anxiety disorder. As a group, these disorders routinely co-occur and cause clinically significant distress and impairment affecting school, social, and family functioning. Left untreated, these disorders leave children at risk for anxiety disorders, major depression and, in some cases, substance abuse extending into late adolescence and adulthood. Hence, effective treatments for childhood-onset anxiety disorders promise to alleviate and perhaps to prevent long-term morbidity and even mortality. In randomized controlled trials, we have shown that two monotherapies, cognitive-behavioral therapy (CBT) and the selective serotonin reuptake inhibitor (SSRI), fluvoxamine (FLV), are effective treatments for separation anxiety, social phobia, and generalized anxiety disorders in children and adolescents. Even though the monotherapies are effective a substantial number of patients remain symptomatic following treatment and, might have benefited from combined treatment. There are as yet no systematic, controlled studies comparing CBT and an SSRI, alone or in combination, against a control condition in the same patient population. This revised application proposes a four-year, six site, randomized controlled efficacy trial comparing cognitive-behavioral (CBT) and pharmacological treatment for youth ages 7 to 16 years with anxiety disorders. Phase 1 is a 12-week, random assignment acute efficacy study comparing CBT, FLV, their combination (n=90, each condition), and pill placebo control (n=48) in 318 (53/site) youth with DSM-IV primary diagnoses of separation anxiety, social phobia, and/or generalized anxiety disorder. Phase II involves a 6-month treatment maintenance period for Phase I responders. All subjects regardless of response status will be evaluated at all scheduled assessment points. In addition to comprehensive parent, child, clinician, and teacher reports, the primary outcome variables will be assessed by blind independent evaluators. Manualized intervention and assessment protocols plus state-of-the-art quality assurance and adverse event monitoring procedures insure uniform cross-site administration of the study protocol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHILDHOOD COMORBIDITY

TRAUMA,

PARENTAL

ALCOHOLISM,AND

Principal Investigator & Institution: Nelson, Elliot C.; Assistant Professor; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This revised new investigator ROl application proposes an assessment of adult twin pairs, their full siblings, and parents ascertained via twins' participation in a recently completed survey of the Australian National Health and Medical Research Council '1989 cohort. The target sample will be: (1) a "childhood abuse" (CA) group (N=500 families) in which at least one twin reported having experienced childhood sexual abuse (CSA), physical abuse (PA), or both; and (2) a "control" group (N=500 families) in which neither twin reported a history of abuse, matched to the CA group on the basis of gender. zygosity, and age. The specific aims of this investigation are: AIM1 To examine parental alcoholism and other parental predictors of offspring CSA and PA, and the routes by which these associations are mediated. AIM2 To use data from non-abused co-twins and siblings to control for family background risk factors to permit: (i) improved estimation of the risks for negative outcomes associated with CSA and PA; (ii) examination of routes by which these risks are mediated and moderated. AIM3 To more comprehensively determine the contributions of CSA and PA, cluster B personality disorders, depression, and anxiety disorders, to the inheritance of alcohol dependence risk and to identify critical intervening variables. These aims will be accomplished by better assessing childhood abuse and neglect history and additional Axis I and II diagnoses in previously interviewed adult twin pairs and by obtaining comprehensive assessments of parents and other siblings (Axis I and H psychopathology as well as childhood abuse and neglect). Despite the limitations of retrospective data, this study population offers important advantages: 1) data available from the recently completed, extensive assessment of twins including history of early home environment, traumatic events, drug use, and parental alcohol problems in addition to psychiatric diagnostic assessments; 2) families with a demonstrated history of cooperation including the twins' willingness to allow telephone assessment of questions about CSA and PA history; 3) an established relationship between twin reports of childhood abuse and parental alcohol problems; 4) very low frequency of abstinence and high mean levels of alcohol consumption suggest that hypothesized relationships are likely to be expressed; 5) a powerful twin sibship design; 6) an ability to generalize findings to the twin panel as a whole. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL ANXIOLYTICS

ASSESSMENT

OF

NOVEL

ANTI-DEPRESSANT-

Principal Investigator & Institution: Charney, Dennis S.; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 11-AUG-2003; Project End 30-JUN-2008 Summary: New classes of medication for the treatment of serious mood and anxiety disorders have not been discovered for decades. Current medication treatment for these disorders is dominated by the selective serotonin reuptake inhibitors (SSRIs). However, SSRIs while an improvement in safety and tolerability over older medications such as the tricyclic antidepressants, have not resulted in improved efficacy. Advances in our understanding of the pathophysiology of mood and anxiety disorders, gleaned from

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both preclinical and clinical neuroscience research, have now set the state for testing the antidepressant and antianxiety efficacy of several new classes of medications. In the proposed project, investigators in the NIMH Intramural Mood and Anxiety Disorders Research Program, in collaboration with scientists from the Emory University School of Medicine and the pharmaceutical company GlaxoSmithKline, will evaluate the therapeutic potential of a CRF1 receptor antagonist (SB723620), a NK-1 receptor agonist (GW597599), a SSRI/5HT1A agonist (vilazodone), and a type IV phosphodiesterase inhibitor (SB207499) using an open trial proof of concept design in two patient groups, major depression and post traumatic stress disorder. Medications which show the potential for clinically relevant therapeutic effects will subsequently be tested in multicenter, placebo-controlled investigations. A major impediment to progress in the discovery and clinical trial testing of novel medications for serious psychiatric disorders is the lack of surrogate neurobiological markers predictive of therapeutic response. Identification of such markers could greatly facilitate drug discovery and may reduce the number of patients required for pivotal clinical trials. Therefore, in the proposed project we will also examine the usefulness of several potential neurobiological surrogate markers for antidepressant/antianxiety efficacy utilizing functional and receptor neuroimaging, psychophysiological and neuroendocrine techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL STUDIES OF HUMAN ANXIETY DISORDERS Principal Investigator & Institution: Weissman, Myrna M.; Professor; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): The overall aim of the Program Project Grant (PPG) is to understand the genetic basis for fear, anxiety and anxiety disorders in humans by identifying variant forms of genes that may contribute to pathological anxiety states. The underlying idea is that both learned and innate fear are tractable targets for genetic analyses in mice and humans. To accomplish this portion of the PPG dealing with human anxiety disorders Project 4 will provide well-characterized clinical samples and DNA from subjects with selected anxiety disorders (panic disorder, social anxiety disorder, and controls). Dimensional assessments of anxiety related temperaments, which cut across all clinical groups will provide another method for sample stratification. The clinical disorders have been selected where there is indication of heritability from family and/or twin studies; the clinical phenotypes are well defined and there is suggestive evidence for a relationship with fear conditioning and/or its neurobiological substrate and where hypotheses about candidate genes based on marker, treatment or pathophysiologic studies can be developed. To maximize the likelihood that we are selecting cases with genetic etiology, we will select cases from families with multiple affected individuals. The dimensional assessments have been selected because of prior promising associations with specific polymorphisms related to anxiety and evidence for heritability. Since issues of design and control groups have not been resolved, we will use both family based "triads" (probands and two biological parents) and population controls (matched for ethnicity). The central hypothesis is that there are similarities in fear conditioning circuitry between animal models and human and that genes involved in the pathways associated with fear conditioning or innate fear may be involved in the development of human anxiety disorders, particularly panic disorder, social anxiety disorder (social phobias), and/or neuroticism or anxiety sensitivity. The specific aims of this project are: identification, clinical characterization and DNA extraction of subjects with panic disorder (N= 150); social anxiety disorder

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Anxiety Disorders

(social phobia) (N=150); selected to be at high genetic risk for anxiety disorders; non ill matched controls also assessed on quantitative trait dimension (N=150). We will also collect bloods from the biological parents of the panic and social anxiety disorder probands. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGENT FOR MOOD AND ANXIETY DISORDER RESEARCH Principal Investigator & Institution: Papp, Laszlo A.; Assoc. Prof. of Clinical Psychiatry; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2004 Summary: (Adapted from the Applicant's Abstract): This is a request for a Core Grant to Enhance Neuroscience Transfer (CoGENT) from the New York State Psychiatric Institute. Ten qualifying Base Grants in the mood and anxiety disorders research area have been selected. These grants represent a diversity of expertise, technologies, and scientific approaches, ranging from basic to treatment studies. Included are studies involving neuroimaging, electrophysiology, genetic markers, study of CSF neurotransmitter metabolites and proteins, treatment of refractory patients, treatment of the elderly, and consideration of comorbid disorders and ecologically-valid research designs. The main goal of the proposed CoGENT is to link these technologies and diverse areas of expertise so that multiple studies can benefit. In particular, we are dedicated to neuroimaging, electrophysiology, applying modern neuroscience technologies such as advanced brain protein chemistry, and genetic marker analysis to treatment research. In so doing, we hope to be able to speed the effort toward placing our understanding of psychopathology and treatment on a firm neuroscience platform. The proposed CoGENT builds upon strengths accumulated during nearly two decades of funding through the Mental Health Clinical Research Center (MHCRC) program. Specifically, three cores that have proven both successful and invaluable from our MHCRC have been revised and are included in this proposal. They are the Laboratory and Technical Support (LTS) Core (formerly the Biological Studies Unit), the Centralized Normal Control Recruitment (CNCR) Core, and the Biostatistics, Data Management, and Networking (BDMN) Core. These three cores will support the ten Base Grants, provide common resources that will facilitate technology and knowledge transfer among scientists, and encourage the development of novel research studies and approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COGNITIVE THERAPY FOR PERSONALITY DISORDERS Principal Investigator & Institution: Hayes, Adele M.; Associate Professor; Psychology; University of Miami Coral Gables University Sta Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2005 Summary: (provided by applicant): The Cluster C personality disorders (obsessivecompulsive, avoidant, and dependent) are the most prevalent personality disorders (PDs) in outpatient samples. These PDs are highly comorbid with mood and anxiety disorders. Patients with comorbid PD and Axis I disorders present with more severe and chronic symptom profiles, and they do not respond well to psychotherapy or pharmacotherapy. It is particularly difficult to establish a therapeutic alliance, a welldocumented predictor of treatment outcome, and treatment retention and compliance are often compromised. Given the prevalence of Cluster C PDs and their significant impact on psychosocial functioning, treatment response, and health care utilization, it is

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surprising that little attention has been paid to treatment development for this population. Cognitive therapy has been demonstrated to be an effective treatment across a number of Axis I disorders and recently has been extended to PDs. In a sample of patients with obsessive-compulsive (OCPD) and avoidant (AVPD) PDs, the first open trial of cognitive therapy for PDs (CT-PD) demonstrated significant improvements in personality symptoms, as well as in symptoms of depression and anxiety. Because the therapy is in early stages of development, general principles and guidelines for treatment of PDs are provided, but there are few specific details on how to treat OCPD and AVPD. This lack of specificity limits the extent to which the manual can be used to conduct larger scale clinical trials outside of the Center for Cognitive Therapy, where the manual was developed. The goal of this R-21 treatment development research is to identify active ingredients of the therapy and to use this process research to improve the specificity of the manual. CT-PD is thought to have its effects by exposing patients to corrective information challenging existing personality patterns, identifying the historical roots of these patterns, and providing exercises to facilitate generalization. The proposed study will examine these interventions as predictors of three hypothesized precursors of change: turbulence in defensiveness and avoidance (protection), the therapeutic alliance, and in-session affect. Growth curve modeling will be used to examine sequencing and timing of therapist interventions and relations between these interventions and the hypothesized precursors of change, which will then be examined as predictors of symptom reduction. Quality of therapeutic alliance in early sessions will be examined as a predictor of treatment retention. With this information, sections of the treatment manual on OCPD and AVPD can be refined, strategies to facilitate therapeutic alliance and symptom change can be specified, and the refined manual can be used in future proposals examining treatment efficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITIVE TRAINING FOR SOCIAL ANXIETY Principal Investigator & Institution: Huppert, Jonathan D.; Assistant Professor of Psychology in Psy; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 11-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): This application proposes Jonathan D. Huppert, Ph.D. for a K23 Mentored Patient Oriented Research Career Development Award at the University of Pennsylvania. The overarching goal of this award is for the applicant to acquire expertise in information processing/cognitive science of anxiety disorders and to translate this knowledge to the treatment of anxiety disorders through an independent program of research funded by NIH. The four-year program discussed in this proposal is designed to accomplish this goal by through five aims: 1) to solidify his foundation in cognitive science and advanced research methods; 2) to establish a research program on cognitive training of social anxiety that will integrate cognitive science and clinical outcome research; 3) to write and publish empirical and theoretical papers about such an integration; 4) to create collaborative relationships with clinical and cognitive science faculty at the University of Pennsylvania as well as other experts in the field; and 5) to prepare for further funding for this programmatic line of research. These aims will be accomplished through a structured four-part plan: 1) to receive further formal instruction in cognitive science, advanced research design, and bioethics; 2) to obtain training and mentoring by a senior scientist experienced in this area (Edna B. Foa, Ph.D.) as well by a collaborator (Andrew M. Mathews, Ph.D.) and consultants (Colin M. MacLeod, Ph.D., Richard G. Heimberg, Ph.D., David M. Clark, Ph.D., and Xin

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Anxiety Disorders

Tu, Ph.D.); 3) to coordinate ongoing clinical research trials at the Center for the Treatment and Study of Anxiety; 4) to design and execute an original program of research. A series of studies examining the factors involved in the modification of interpretation and attentional biases in social anxiety will be conducted. The goal of these investigations is to create a cognitive training program that directly addresses the core biases involved in causing and maintaining social anxiety. First, a new measure of interpretation bias will be developed using contextual priming in order to have a measure that is less likely to be confounded by repeated administration. Simultaneously, the nature of attentional bias in social anxiety will be clarified in order to bring some resolution to conflicting findings in the literature. Then, potential for modifying interpretation bias will be examined. In parallel, parameters related to modifying attentional bias in social anxiety will be examined. In addition, the relationship between cognitive biases and cognitive-behavioral therapy outcome in patients diagnosed with social phobia will be evaluated. Based on these findings, a cognitive training program for social phobia will be developed and will be further evaluated in future research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLLABORATIVE LONGITUDINAL STUDY OF PERSONALITY DISORDER Principal Investigator & Institution: Gunderson, John G.; Professor; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2001; Project Start 01-MAR-1996; Project End 31-MAY-2005 Summary: APPLICANT'S ABSTRACT): This application is a revision of an application for 5 years continuation that was submitted in 1999. At that time a one year extension was awarded; this application is for four years. The overall aim of this study is to provide a comprehensive picture of the course and outcome of four specific personality disorders (PDs): schizotypal (STPD), borderline (BPD), avoidant (AVPD), and obsessivecompulsive (OCPD). The present application continues a multi-site collaborative effort to follow a carefully diagnosed sample of 668 subjects having either these representative PDs or major depressive disorder (MDD) (controls) for the period from 3 to a maximum of 6 years after recruitment. Sixty new minority subjects will be recruited and followed for at least 2 years. Using a prospective, longitudinal, repeated measures design, we will develop the same basic knowledge about course and outcome for the PDs that has previously resulted from similar investigations of affective and anxiety disorders, thus addressing an important gap in our knowledge. The extended period of follow-up is essential to discern clinically meaningful descriptions of course and outcome and their determinants. The sample is large enough and sufficiently diverse demographically to attain a unique array of results generalizable to most clinical settings. To accomplish our overall aim, we propose three approaches: I. descriptive, II. predictive, and III. validating. The descriptive approach will provide data on diagnostic stability of PDs, on presence and course of comorbid Axis I disorders, on persistence of functional impairment, and on utilization of health care resources that allow comparison between the PDs and to similar data on Axis I disorders. The predictive approach will identify clinically meaningful determinants of prognosis within and across PDs. The validating approach will examine the homogeneity of descriptive and longitudinal features for the PDs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COLLABORATIVE LONGITUDINAL STUDY OF PERSONALITY DISORDER Principal Investigator & Institution: Morey, Leslie C.; Professor; Psychology; Texas A&M University System College Station, Tx 778433578 Timing: Fiscal Year 2001; Project Start 01-MAR-1996; Project End 31-MAY-2005 Summary: (Adapted from Applicant's Abstract) The overall aim of this study is to provide a comprehensive picture of the course and outcome of four specific personality disorders (PDs): schizotypal (STPD), borderline (BPI), avoidant (AVPD), and obsessivecompulsive (OCPD). The present proposal continues a multi-site collaborative effort to follow a carefully diagnosed sample of 668 subjects having either these representative PDs or major depressive disorder (MDD) (controls) for the period from 2 to a minimum of 6 years after recruitment. Using a prospective, longitudinal, repeated measures design, we will develop the same basic knowledge about course and outcome for the PDs that has previously resulted from similar investigations of affective and anxiety disorders, thus addressing an important gap in our knowledge. The extended period of follow-up is essential to discern clinically meaningful descriptions of course and outcome and their determinants. The sample is large enough and sufficiently diverse demographically to attain a unique array of results generalized to most clinical settings. To accomplish our overall aim, we propose three approaches I. Descriptive, II. Predictive, and III. Validating. The descriptive approach will provide data on diagnostic stability of PDs, on presence and course of comorbid Axis I disorders, on persistence of functional impairment, and on utilization of health care resources that allow comparison between the PDs and similar data on Axis I disorders. The predictive approach will identify clinically meaningful determinants of prognosis within and across PDs. The validating approach will examine the homogeneity of descriptive and longitudinal features for the PDs, as defined by the DSM system, and how this compares with alternative schemes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMMON AND SPECIFIC RISK FACTORS FOR EMOTIONAL DISORDERS Principal Investigator & Institution: Zinbarg, Richard E.; Associate Professor; Psychology; Northwestern University 633 Clark St Evanston, Il 60208 Timing: Fiscal Year 2002; Project Start 18-JUN-2002; Project End 31-MAY-2007 Summary: This is a collaborative research effort of Northwestern University and the University of California, Los Angeles to evaluate common and specific risk factors for anxiety disorders and depression. Each site will work on a common protocol. We propose a prospective longitudinal study of 700 high school juniors, recruited in two cohorts over consecutive years at two high schools (Evanston and Santa Monica). Using a high-risk design, participants at high risk (according to Neuroticism cores) will be oversampled relative to medium and low risk groups. Their progression will be carefully tracked over the course of 8 to 10 assessments staggered over four to four and a half years of data collection. The participant sample will be geographically, ethnically, and socio-economically diverse. The proposal takes a comprehensive biopsychosocial approach to the conceptualization and measurement of risk factors, which include Neuroticism, depressogenic cognitive style, anxiety sensitivity, introversion and low positive affectivity, sociotropy and autonomy. Measures will include self report, parental report, as well as information processing tasks (modified Stroop, memory tasks), affective modulation of startle reactivity, and ambulatory cortisol assays. In

26

Anxiety Disorders

addition, diathesis-stress interactions will be evaluated on the basis of contextual assessment of chronic and episodic life stress. Outcome will be measured in terms of symptoms and diagnosis of anxiety and depression. Various models of commonalities and specificities of risk and their interaction with stress will be tested using hierarchical logistic regression and structural equation modeling. The findings may further our conceptualization of emotional disorders and provide the platform for prevention research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMMUNITY VIOLENCE & YOUTH: PREVENTING ANXIETY DISORDERS Principal Investigator & Institution: Cooley, Michele R.; Assistant Professor; Mental Hygiene; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2004 Summary: Community violence is a major public health problem most visible in lowincome, inner-city, predominantly ethnic minority communities. The public mental health impact of living in violent communities is significant, particularly for children. Most of the extant treatment and preventive interventions focus on the perpetrators of the violence, not on the youth who are its direct or indirect victims. Among the psychological correlates of community violence exposure are anxiety symptoms (e.g., fears, social withdrawal, intrusive thoughts, poor concentration, worry) and disorders (e.g., post-traumatic stress disorder, separation anxiety disorder). This is a request for a NIMH Pilot Effectiveness Trial for Mental Disorders Grant (R21) to support a 3- year pilot study of a school-based prevention and early intervention program with inner-city, primarily African American children at risk for anxiety disorders. This cognitivebehavioral intervention is based on the FRIENDS Anxiety Prevention Program that has demonstrated efficacy in reducing the rate of anxiety disorders and preventing the onset of new disorders in school samples of Australian children. Maintaining therapeutic integrity, the proposed project will broaden the FRIENDS target population by modifying the intervention to be culturally and contextually appropriate for innercity ethnic minority youth exposed to community violence. Four-hundred 3rd-5th graders will be screened to identify those at risk for anxiety symptoms and disorders. 180 elementary school students from low-SES, high crime communities will be randomly assigned to either an anxiety prevention and early intervention group or a non-intervention comparison group. Child, parent and teacher assessments will be made at pre- and post- intervention, and 6-month follow-up. This project will contribute to the applicant's goal of studying and preventing the mental health effects of community violence by achieving the following aims: 1) To broaden the target population of an existing efficacious preventive and early intervention program from Australian children to inner-city, low-SES primarily African American children; and 2) To maintain the therapeutic integrity of the modified FRIENDS preventive and early intervention program among children from schools located in inner- city, high crime, low-SES communities. The results of this R21 project will facilitate the design and later implementation of a full-scale NIMH R01 preventive intervention effectiveness trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMORBID CHILDHOOD ANXIETY AND ASTHMA Principal Investigator & Institution: Goodwin, Renee D.; Epidemiology; Columbia University Health Sciences New York, Ny 10032

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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by investigator): The applicant is requesting five years of funding through the Mentored Patient-Oriented Research Career Development Award (K23) program to enhance her technical and methodological skills in the investigation of the co-occurrence of anxiety disorders and asthma/allergy in youth. The ultimate goal is to gain expertise in the relationship between the co-occurrence of anxiety disorders and asthma/allergy and the risk of severe psychopathology among youth, using longitudinal, epidemiologic research methodology and ultimately to identify preventive interventions. The applicant's strong academic background in human development, clinical psychology, and psychiatric epidemiology, and her research experience using a developmental paradigm to study risk for severe psychopathology among individuals with early-onset anxiety disorders provide an excellent foundation for this work. The proposed training goals include (1) further training to increase the applicant's knowledge of the relationship between respiratory pathophysiology and anxiety disorders; (2) advanced statistical training and experience with longitudinal data analysis and survey methods, and; (3) investigation of potential interventions that integrate research on anxiety disorders and asthma/allergy. These goals will all facilitate the applicant's pursuit of innovative, comprehensive, technologically efficient approaches to study these comorbidities in youth. The research plan for this Award is divided into four investigations which complement the proposed sequence of training activities and offer the applicant the opportunity to explore important cross-sectional and longitudinal data from epidemiologic clinical and community samples, as well as hands-on experience, in the first two studies, the applicant will analyze previously collected data (MECA & SED and Dunedin). In the third study, the applicant will collect her own asthma data prospectively (Network study), in an ongoing longitudinal epidemiologic clinical (psychiatric) investigation, while learning how to conduct a study. The fourth investigation will involve developing measures and collecting pilot data on asthma and anxiety in a clinical (medical) sample. The applicant's resulting ROl will address the developmental paradigm described above, which will be further tested and will include early intervention strategies to facilitate the identification and treatment of children who are at risk for severe psychopathology. That study will involve a longitudinal epidemiologic preventive intervention study aimed at reducing the risk of anxiety disorders among pediatric asthma/allergy patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONDUCT DISORDER AND DEPRESSION IN CHILDHOOD Principal Investigator & Institution: Beauchaine, Theodore P.; Assistant Professor; Psychology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 07-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Conduct Disorder (CD) and depression are highly comorbid conditions in childhood and adolescence. This comorbidity is associated with increased risk for several adverse outcomes, including social rejection, substance use, anxiety disorders, and suicide. However, because much of the extant research in this area has been conducted at the symptom level, relatively little is known about the mechanisms of action that are responsible for the observed rates of comorbidity. Moreover, a number of plausible alternatives obtain. Identifying which of these mechanisms is at work is likely to require the application of several strategies that have generally not been employed in the comorbidity literature to date. These include (a) distinguishing between childhood-onset and adolescent-onset CD, (b) expanding the scope of comorbidity research to include biological and physiological measures, (c)

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Anxiety Disorders

generating and testing mechanistic theories of comorbidity, and (d) studying the development of comorbidity and its associated symptoms longitudinally. In the proposed research, each of these issues will be addressed in a study including childhood-onset conduct-disordered, depressed, comorbid (conduct-disordered + depressed), and control preadolescents, ages 8-12. Studies conducted within this age range are critical, as it represents a period of escalating delinquency, depression, and substance use, which often co-occur. Following from theories of emotion regulation (Porges, 1995) and motivation (Gray, 1 982a, 1 982b, 1 987a, 1 987b), patterns of psychophysiological responding will be assessed in participants during conditions of reward, punishment, and social threat. In addition, extensive family history interviews with be conducted with parents, and measures of child delinquency, symptoms of depression, and substance use will be obtained at each of three one-year intervals. Using these data, the following Specific Aims will be pursued: (1) elucidate patterns of autonomic nervous system activity within and across groups through assessment of appropriate psychophysiological markers of behavioral inhibition (electrodermal responding during punishment), behavioral activation (cardiac pre-ejection period during reward), and emotion regulation (respiratory sinus arrhythmia during social threat); (2) assess developmental trajectories in autonomic responding within and across disorders, and relate these trajectories to parental background characteristics and parenting practices; and (3) assess developmental trajectories in child substance use patterns, and examine the potential mediating roles of autonomic responding in relations between parental and child use. Findings obtained should further our understanding of the autonomic substrates of CD, depression, and their comorbidity, and may have differential treatment implications for depressed probands who do and do not present with comorbid CD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CROSS-CULTURAL EPIDEMIOLOGY

PSYCHIATRIC

ETHNOGRAPHY

AND

Principal Investigator & Institution: Howard, William T.; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2006 Summary: (Adapted from applicants abstract): Objective: This Mentored Clinical Scientist Development Award, K08, will enable the candidate to acquire training necessary to design, conduct, and analyze cross-cultural psychiatric ethnographic and epidemiologic research. Little is known regarding (1) the distribution and determinants of mental illness in the Philippines, in the millions of Asian-American in the U.S., and in the majority of the world's population who live in developing countries, and (2) to what degree DSM-IV and ICD-10 based psychiatric classification and methods of assessment are cross-culturally applicable. Career Development: The candidate proposes 12 months of career development that will include (1) additional training in epidemiology and statistics at The Johns Hopkins School of Public Health (JHSPH), (2) new interdisciplinary training, both in medical anthropology at JHSPH and in cross-cultural psychiatry at McGill University, and (3) mentorship and consultation with a panel of experts in psychiatric epidemiology, cross-cultural psychiatry, and world mental health. Proposed Study: The research plan will be conducted in Region IV and the National Capital Region (NCR) of Luzon, the largest of the Philippine islands. First, the candidate will conduct an ethnographic mental health study focusing on mood and anxiety symptoms and disorders. The candidate will interview approximately 75 adult Key Informants, including (1) medical and psychiatric patients, (2) non-patient community

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constituents, and (3) a variety of health care providers from Region IV and the NCR. Using information from the ethnography, a report will be prepared that (1) describes how Filipinos experience and express mental distress and illness; (2) describes how Filipinos explain the etiology, classification, and treatment of mental distress and illness; and (3) includes a dictionary of Filipino mental heath terms. Second, and after incorporating findings from the ethnography, an epidemiologic study will involve the administration of a structured interview to both adult psychiatric patients (150 + 50 reinterviews) primarily from the NCR and a representative community sample of adults (750 + 50 re-interviews) from Region IV. The core of the interview will consist of the mood and anxiety disorder sections of the World Health Organization's Composite International Diagnostic Interview (CIDI); however, the relatively shorter and more objective alcohol use disorder section will also be included. Goals of the epidemiologic study include (1) assessing the reliability, validity, and cross-cultural applicability of DSM-IV and ICD-10 based mood and anxiety disorders and methods of assessment in the Philippines and (2) determining what modifications may increase reliability and validity. Other goals include describing the relationship between anxiety, mood, and alcohol use disorders and (1) social and demographic characteristic; (2) patterns of health care services availability, utilization, and need; and (3) types and degrees of disability and functional impairment. Finally, the candidate will obtain Region IV community prevalence rate estimates for mood, anxiety, and alcohol use disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEMENTIA AND PSYCHIATRIC DISORDERS IN ASSISTED LIVING Principal Investigator & Institution: Lyketsos, Constantine G.; Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 25-SEP-2000; Project End 31-AUG-2003 Summary: (Applicant's abstract): Assisted living (AL) is a rapidly growing type of residence for the elderly, with approximately 1.3 million seniors as residents, and with an expected two-fold increase in occupancy over the next 10-15 years. Preliminary data presented here suggest that the elderly in AL have high rates of psychiatric disorders, with dementia being the most common. These conditions probably contribute to significant morbidity (such as functional impairments and caregiver burden), and to early discharge from AL, typically to a nursing home. Dementia and other psychiatric disorders are probably under-recognized and under-treated in AL, in part because of inadequate preparation of the AL care system to address them. There has never been a comprehensive study of dementia or of other psychiatric disorders in AL This study will gather information about the prevalence, detection, and treatment of dementia and other psychiatric disorders in AL residents. It will study a stratified, random sample of 275 AL residents in Maryland (100 from large facilities, 100 from small facilities and 75 from dementia special care units). Each resident will undergo a comprehensive evaluation for dementia and a standardized psychiatric diagnostic examination. S/he will also be rated on standardized scales quantifying dementia-associated behavioral disturbances, seriousness of general medical co-morbidity, severity of functional (IADL and ADL) impairments and caregiver burden. This will produce an estimate of the prevalence and morbidity associated with dementia in AL residents (Aim 1). It will also generate an estimate of the prevalence and morbidity associated with other psychiatric disorders, especially mood and anxiety disorders (Aim 2). Patient evaluations, chart reviews and interviews with family and professional caregivers will determine whether dementia or other psychiatric disorders are detected, or treated and how this affects clinical outcomes in assisted living (Aim 3). Study findings will likely have a substantial

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Anxiety Disorders

public health impact in gerontology, geriatric medicine and geriatric psychiatry. They will provide essential information about the prevalence and consequences of psychiatric morbidity among assisted living residents (projected to approach 3.9 million by 2025). This information is of great interest to healthcare providers, licensing agencies, policy makers, the assisted living industry and the general public. It is likely to affect clinical practices in assisted living resulting in the implementation of assisted living-based screening and treatment programs for dementia and other psychiatric disorders that will benefit residents, and may delay their discharge from assisted living facilities to nursing homes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF A GROUP CBT PROGRAM FOR PTSD AFTER A MVA Principal Investigator & Institution: Beck, J. Gayle.; Professor; Psychology; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2002; Project Start 19-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The goal of this application is to refine and pilot test a brief Group Cognitive Behavioral Treatment (CBT) to address the symptoms of Posttraumatic Stress Disorder (PTSD) following a motor vehicle accident. The application has 2 phases that encompass 3 specific aims. Phase 1 will Consist of completion of the treatment manual for Group CBT for PTSD in MVA survivors (Aim 1). Also included during Phase 1 will be efforts to finalize and empirically test procedures to ensure therapists' adherence and competence in using the treatment manual (including measures to assess adherence and competence - Aim 2). 15 individuals with MVA-reiated PTSD will participate in Phase 1. to be treated in 3 groups of 5 each. Participants will be diagnosed with the Clinician Administered PTSD Scale and will complete a battery of additional clinician and self-report measures before and after treatment. Phase 1 will be an iterative process across the 3 waves of 5 cases each. After each wave, the treatment manual and measures of adherence and competence will be refined. Phase 2 will involve a randomized pilot study, consisting of 2 treatment conditions: Group CBT and a Minimal Contact Control (MCC) condition. The aim of Phase 2 is to determine if Group CBT produces significant reductions in PTSD symptoms, anxiety, depression, health care use, and pain-related distress and impairment (Aim 3). 48 individuals with MVA-related PTSD will be randomly assigned to one of the 2 conditions. Outcome will be assessed using clinician measures of PTSD symptoms, anxiety disorders, and depressive disorders. As well, participants will complete questionnaires evaluating PTSD, anxiety, depression, health care utilization, and pain. It is hypothesized that patients with PTSD who receive Group CBT will show greater reductions in PTSD symptoms, anxiety, depression, health care use, and pain, relative to patients who receive MCC, at post-treatment assessment. Additionally, it is hypothesized that patients who receive Group CBT will maintain these gains at 3-month follow-up. Following participation, individuals in the MCC condition will be offered Group CBT, permitting uncontrolled replication. Examination of intent-to-treat participants will permit initial evaluation of the acceptability of Group CBT. Because MVAs are the single leading cause of PTSD in the general population, this application has the potential to provide a cost-efficient treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEVELOPMENTAL PRESCHOOLERS

EPIDEMIOLOGY

OF

Studies

31

ANXIETY

IN

Principal Investigator & Institution: Egger, Helen L.; Psychiatry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 16-JAN-2001; Project End 31-DEC-2005 Summary: The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) is to enable the candidate, a child psychiatrist, to became an independent research investigating the development pathways and causes of anxiety disorders in preschool children. The research goal is to place preschoolers' anxiety symptoms and disorders within the framework of developmental epidemiology by focusing on two questions: 1. What are the age-specific presentations of anxiety disorders in children ages 2 to 5 years old? (Nosology) 2. What are the relative contributions of genes and environment and their interaction in the early development of anxiety disorders? (etiology). This application details a program of training in infant/young child psychiatry, in behavioral and statistical genetics with an introduction to molecular genetics and genomics, and advanced training in pediatric anxiety disorders. The candidate is based in the Center for Developmental Epidemiology, Duke University Medical Center. Sponsors are child psychiatrists Adrian Angold MRCPsych (developmental psychopathology and measure development), Robert Emde MD, and Charles Zeanah MH (infant/young child psychiatry and assessment of young children), and John March MD (anxiety disorders). Lindon Eaves PhD, a leading behavioral geneticist, will provide mentoring in this area. The research plan includes: 1. A detailed review of current instrumentation for assessing preschool anxiety. 2. A pilot study of 60 children aged 36-72 months, using a multi-informant assessment protocol. DSM-IV and DC:0-3 diagnoses and symptoms will be assessed using the Preschool Age Psychiatric Assessment (PAPA), a structured parent interview developed by the candidate. 3. Analysis of data on 15,500 2-5 year-old twin pairs to examine the contributions of genes and shared and non-shared environmental factors to young children's anxiety symptoms. 4. Submission of an R01 application for a longitudinal, genetically-informed study of the development of anxiety disorders in preschool children. This work will make important contributions to the development of prevention and treatment interventions for young children and will contribute to our understanding of the etiology of childhood psychopathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENTAL PSYCHOPATHOLOGY

GENETIC

EPIDEMIOLOGY

OF

Principal Investigator & Institution: Eaves, Lindon J.; Distinguished Professor; Human Genetics; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): A five-year data analysis project is designed to yield a comprehensive understanding of the developmental interplay between genetic and social factors in the trajectory of mood and behavioral disorders from early adolescence into young adulthood. The study will use longitudinal data from the Virginia Twin Study of Adolescent Behavioral Development (8-16 yr) and its Young Adult Follow-Up (20+ yr). The data comprise intensive, juvenile and young adult longitudinal, multi-rater (child, parent, teacher), interview and questionnaire assessments of psychopathology, environment and psycho-social risk factors in 1412 families of like- and unlike-sex adolescent twin pairs and their parents. Outcomes assessed in twins and their parents

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Anxiety Disorders

include symptoms, severity, impairment and treatment relating to: anxiety disorders (AD); depression (MD); conduct disorder (CD); oppositional-defiant disorder (ODD); attention-deficit hyperactivity disorder (ADHD); Substance use disorders (SUD). Potential covariates and risk factors include: parental psychopathology; pre- and perinatal factors; life-events; home environment; socioeconomic and contextual variables; personality; interactions with peers, siblings and parents. The project will: 1) characterize the impact of age and sex on the contributions of genes, family environment and individual environment on principal mood and behavioral disorders and risk factors through adolescence into young adulthood.; 2) identify specific family and individual environmental variables that contribute to overall estimates of environmental components of variance; 3) analyze the interplay of genes and environment on development of mood and behavioral disorders, including the interaction (GxE) and correlation (rGE) of genotype with the impact of specific environmental factors at different stages of life history; 4) resolve heterogeneity in adolescent and young adult psychopathology expressed in differential patterns of genetic and environmental etiology, comorbidity, developmental trajectory, symptom pattern, severity, impairment and environmental risk; 5) establish the profile of early genetic and environmental risk factors and behaviors that best predict young adult psychopatholgy; 6) quantify the roles of parental psychopathology, family cohesion and communication that affect the consistency of assessments derived from parents, teachers and children and determine the combination of multiple ratings that best predict juvenile impairment and longerterm psychiatric outcomes in young adulthood. Where appropriate, the robustness of findings will be explored to minimize misleading claims and new analytical methods employed to reflect the new generation of questions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EARLY INTERVENTIONS FOR ANXIOUS CHILDREN Principal Investigator & Institution: Bernstein, Gail A.; Associate Professor; Psychiatry; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2005 Summary: (provided by applicant): This R21 application is in response to Program Announcement #PA-99-134 Exploratory/Development Grants for Mental Health Intervention Research. This project focuses on early identification of anxious children and pilot testing of school-based group interventions for anxious youth. Anxiety disorders are among the most prevalent psychiatric disorders in children. These disorders are strongly associated with risk for later developing mood disorders and other psychiatric disorders, academic failure, substance abuse problems, and other significant health problems. Up to 10-15% of the general youth population has an anxiety disorder. Anxiety disorders are associated with functional impairment and substantial morbidity. Longitudinal studies have demonstrated that untreated anxiety disorders in children may continue for years. For all these reasons, early identification and intervention are critical for preventing anxiety disorders and returning anxious children to the normal developmental trajectory. This R21 will employ a multiple gating procedure to identify children (ages 7-11) with features or diagnoses of separation anxiety disorder, generalized anxiety disorder, or social phobia. Schools will be randomly assigned to one of three conditions: (1) group cognitive-behavioral therapy (CBT) for children, (2) group CBT for children plus parent training, or (3) treatment as usual. Treatment as usual will consist of whatever the school would normally recommend for a child identified as anxious. Active treatments will utilize the FRIENDS Manual and will be provided at school. The FRIENDS manual will be expanded to

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provide a more intensive parent training component (i.e., parental anxiety management, understanding the child's anxiety in the family context, contracting and contingency management). All children will be followed prospectively with assessments at 3 months and 6 months post-treatment. Outcome measures will evaluate symptom severity, level of functioning, remission of baseline anxiety disorders, and incidence of new anxiety disorders. Data from this study will guide a large-scale school-based investigation of group interventions for anxious youth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF CONTEXT ON FEAR BEHAVIORS IN TODDLERS Principal Investigator & Institution: Buss, Kristin A.; Assistant Professor; Psychological Sciences; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): Young children with fearful temperaments have been a major focus of research on individual differences because these children are believed to be at risk for the development of internalizing problems, such as anxiety disorders. Research and theory on the etiology of these disorders has focused, in part, on individual differences in the intensity of fear behaviors. However, the mechanisms by which individual differences in fear put children at risk for developing behavioral problems have not been fully established. This proposal focuses on a model that posits the dysregulation of fear behavior as one potential mechanism to the development of internalizing problems. Historically, research on extremely fearful children has focused on observations during a limited variety of threatening contexts, situations in which most children are expected to show some level of fear. However, extreme fear during a fear-eliciting context may or may not reflect dysregulation. Therefore, the proposed study addresses whether different novel contexts, varying in their level of threat, result in an average pattern of change among all children, and individual patterns of change in the expression of fear-related behaviors. Specifically, the goal of the study is to evaluate two definitions of dysregulated fear behavior: cross-situational consistency in fear behavior and fear behavior in nonthreatening contexts (Aim 1). Participants will be 80, typically developing, 24-month-old children. Children will be observed in 12 situations, and fear behaviors will be assessed during each. Of particular interest is the identification of children who fail to regulate fear behavior based on contextual demands (i.e., dysregulated fear). Finally, the validity of the two definitions of dysregulated fear will be evaluated via associations with cortisol and maternal report of behavior problem symptoms, with particular focus on internalizing symptoms (Aim 2). These results are expected to further our understanding of the developmental risk factors and etiology of internalizing disorders in children, with particular focus on individual differences in emotion regulation. Better understanding of these risk factors will help to identify appropriate treatment and possible prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF NICOTINE IN SMOKERS WITH ANXIOUS MOOD Principal Investigator & Institution: Baker-Morissette, Sandra L.; Psychology; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This request for a Mentored Patient-Oriented Research Career Development Award (K23) is made by Dr. Sandra Baker-Morissette to foster her academic and research career development as a clinical scientist in smoking,

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nicotine dependence and psychiatric comorbidity. Dr. Baker-Morissette's career development plan spans 5 years, during which she will continue to work closely with her sponsor, Dr. Gulliver, as well as her co-mentors, Drs. David Barlow, David Spiegel, and Stephen Tiffany. Statistical consultation will be provided by the Boston University School of Medicine. Her career plan includes individual meetings with each mentor, mentorship team meetings, and coursework in statistical analysis and ethics. Her shortterm goals are to expand upon her theoretical, methodological, and statistical skills needed to become a highly productive clinical scientist and to develop an independent programmatic line of research. Dr. Baker-Morissette's plan should yield sufficient experience as defined by data collection, grant writing, and paper presentations to advance by the close of the award to Associate Professor. Dr. Baker-Morissette's overarching ambition is to make a meaningful contribution to the knowledge base on tobacco use and comorbid anxiety disorders across the lifespan. Her personal career goal is to progress to Full Professor within the Medical School of Boston University. The proposed study expands on Dr. Baker-Morissette's initial studies of anxiety and tobacco use research by examining the effects of nicotine and mood cue exposure on smoking urge and anxiety in cigarette smokers who have comorbid anxiety disorders. In a between- and within-subjects design, smokers will receive a nicotine (21 mg) or placebo patch in a counterbalanced order across two assessment days. During each assessment day, they will engage in a series of imaginal cue exposures that vary in content: smoking plus anxiety cues, smoking cues alone, anxiety cues alone, and neutral cues. Participants will complete self-report questionnaires prior to and following each exposure, including measures of smoking urge and anxiety. Understanding the effects of nicotine on smoking urge in a psychiatric population is particularly important in light of the difficulty that smokers with psychiatric comorbidity have with quitting smoking. Knowledge of such factors may assist our understanding of conditions that influence the relapse process, as well as the effect of certain cues on smoking urge when individuals are attempting to quit smoking and simultaneously using transdermal nicotine replacement therapy. In sum, this research will foster the career development of Dr. Baker- Morissette, and ensure the next step of her programmatic research, which has an excellent probabilit3-to increase our understanding of the links between nicotine, negative affect and tobacco use disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INITIATIVE

EMORY-GSK-NIMH

COLLABORATIVE

MOOD

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 2003; Project Start 11-AUG-2003; Project End 30-JUN-2008 Summary: This application, in response to RFA: MH-03-008 (National Cooperative Drug Discovery Groups for the Treatment of Mood Disorders or Nicotine Addiction, NC 336MD/NA), proposes the creation of"The Emory-GSK-NIMH Collaborative Mood Disorders Initiative." This unique opportunity to accererate antidepressant drug development brings together expertise of three complementary research groups: the Emory University School of Medicine Department of Psychiatry and Behavioral Sciences, the Mood and Anxiety Disorders Program at NIMH and the Center for Excellence in Drug Discovery (CEDD) in Psychiatry of GlaxoSmithKline (GSK), one of the largest multinational pharmaceutical companies. The two major goals of the current application are the development of innovative new models for basic and clinical

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research in mood disorders and the intensive scrutiny of 5 novel GSK antidepressant candidates in preclinical and clinical paradigms. In addition to an Administrative and Animal/Assay Core, 7 research projects are proposed. Of these, two are based in the intramural NIMH program; Neurogenesis, Synaptic Plasticity and Signal Transduction (Husseni Manji, M.D., PI) and Clinical Models to Assess Novel Antidepressants (Dennis S. Charney, M.D., PI). The remainder are based at Emory University led by established investigators including Jay M. Weiss, Ph.D. (Animal Models of Depression), Michael Davis, Ph.D. (Animal Models of Fear and Anxiety), Clinton D. Kilts, Ph.D. and Mark Goodman, Ph.D., (Functional Brain Imaging, with a focus on new PET ligand development), Michael J. Owens, Ph.D. and Charles B. Nemeroff, M.D., Ph.D. (Ex Vivo Assessment of Neurotransmitter Receptor and Transporter Occupancy of Antidepressants), and Andrew H. Miller, MD (Cytokine Induced Depression: A Rhesus Monkey Model). In conjunction with GSK, 5 novel GSK antidepressant candidates and others that become available via GSK Drug Discovery within the lifetime of the grant will be intensively scrutinized to synergize with the in-house GSK effort. This proposal encompasses virtually all of the major goals outlined in the RFA, namely, development of new neurochemical tools including novel PET ligands, exploration of new models of drug development and facilitation of a partnership between academia, NIMH and industry. 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 2001; 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 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

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Project Title: ETHANOL PREPARATION

ACTIONS

IN

THE

AMYGDALA

IN

VITRO

Principal Investigator & Institution: Moore, Scott D.; Psychiatry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-DEC-1996; Project End 30-NOV-2002 Summary: Ethanol abuse and dependence continue to be a serious public health issue, with much associated morbidity and mortality. The biopsychosocial causes of alcoholism are complex; however, the current literature indicates that anxiolysis is prominent in the reinforcing effect of alcohol. Many investigators are currently using animal models to elucidate the biological substrates of anxiogenesis and anxiolysis. These studies now indicate a significant role for the amygdala in mediating these phenomena, and suggest that the amygdala is the most appropriate model system for investigating the physiological substrates of ethanol-mediated anxiolysis. In spite of this groundwork, few studies have addressed effects of ethanol on amygdala physiology. As ethanol effects are specific for brain regions and neuron types, only a study of direct ethanol effects in the amygdala will provide this informa on. The present proposal will use state-of-the-art electrophysiological techniques to investigate effects of ethanol in the amygdala brain slice preparation. Although ethanol in relevant concentrations likely acts at multiple neuronal sites, it still retains a remarkably high degree of specificity. The most consistent findings are effects on synaptic transmission and voltage-sensitive ion channels. This proposal will include investigations of interactions between ethanol and voltage-dependent currents, synaptic transmission, and synaptic plasticity. The results of this proposal have potential applications in several areas. By examining physiological effects of alcohol with a specific focus on mechanisms underlying the anxiolytic and anxiogenic actions, this study may direct future clinical studies on causes and treatment of alcoholism. This study also may elucidate mechanisms involved in development of anxiety disorders and seizure disorders. Finally, the proposed work will provide critical groundwork needed to assess the role of specific neurotransmitters in ethanol-induced anxiolysis and to investigate the long-term effects associated with repeated ethanol use. 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

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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 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: EXPLORING DIABETES AND DEPRESSION IN YOUTH Principal Investigator & Institution: Mckeown, Robert E.; Graduate Director for Epidemiology; Epidemiology and Biostatistics; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2002; Project Start 24-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Exploring Diabetes and Depression in Youth (EDDY) is a response to RFA-DK-02-009: Depression and Mental Disorders in Diabetes, Renal Disease, and Obesity / Eating Disorders. EDDY will focus on depression and diabetes in 10 to 19 year old youth at two ethnically diverse sites: South Carolina and Colorado. EDDY is an ancillary study to SEARCH for Diabetes in Youth, a CDC- and NIDDK-funded, multisite investigation for population-based case ascertainment and classification of both prevalent and incident cases of diabetes in youth. This case-cohort will allow investigation of the complex association between diabetes and depression in three major ethnic groups, African American, Hispanic, and Non-Hispanic Whites. Diabetes mellitus (DM) is the third most prevalent severe chronic disease of childhood, and a major cause of morbidity, mortality, and compromised quality of life. Childhood DM is now acknowledged to be a complex and heterogeneous disorder, with increasing rates of type 2 DM. A few smaller studies have found that children with DM are at higher risk for depression and that depressed children with DM may be at increased risk of poor management and complications. Existing studies have been small, and restricted to type 1 diabetes. The overall aim of this application is to explore the complex associations of depression and diabetes, which may differ for type 1 and type 2, in the SEARCH case cohort in SC and CO. We will examine the mutual impact of depression on diabetes management, glucose control, quality of life, and complications, as well as the impact of DM disease burden on the risk for depression. Specifically, we will estimate the prevalence and incidence of depression and related affective and anxiety disorders among youth with DM, and explore the correlates and predictors for depression among children and teens with DM, including parenting, self-efficacy, body image, and self-esteem. We will also investigate the impact of depression on diabetes management, clinical course, and complications in both type 1 and type 2 DM, and examine the extent of effective treatment for depression, and the impact of treatment on

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DM outcomes. Finally, we will explore the pathways involved in the association between DM and co-morbid depression and recurrent depression, with particular attention to disease burden, self-concept, obesity, and parenting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GABAA RECEPTOR REGULATION AND TRAFFICKING IN C. ELEGANS Principal Investigator & Institution: Bamber, Bruce A.; Pharmacology and Toxicology; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2002; Project Start 10-DEC-2001; Project End 30-NOV-2003 Summary: (provided by applicant): The objective of this developmental/exploratory R21 proposal is to develop a new direction for studying GABAA receptor trafficking and regulation at synapses. A genetic model organism approach will be taken, using the nematode Caenorhabditis elegans. GABAA receptors are the major inhibitory neurotransmitter receptors in the brain, and play important roles in most brain functions. The abundance of GABAA receptors at synapses is an important factor in normal nervous system function, and in the progression of nervous system disease, particularly anxiety disorders. Studies in mammalian systems suggest that receptor abundance is regulated by controlling receptor biosynthesis, trafficking to synapses, and degradation. However, results to date have been largely descriptive. We lack an understanding of how these processes occur, and how they may be regulated. Progress has been slowed by the difficulty of perturbing mammalian gene expression, the anatomical complexity of the mammalian nervous system, and the structural heterogeneity of mammalian GABAA receptors. One solution is to take a genetic approach in a simple model organism. C. elegans is well suited for this purpose: GABAA receptors, and their regulation at synapses, are conserved in C. elegans; genetic manipulation of C. elegans is rapid and efficient; the C. elegans nervous system is relatively simple; and the C. elegans GABAA receptor is uniform and well characterized. The specific aims of this proposal are two-fold: First, the points along the biosynthetic, trafficking, and degradation pathways that control GABAA receptor abundance at synapses will be determined. To achieve this aim, these points will be perturbed genetically, and the effects on the regulation of receptor abundance will be determined. Measurements of receptor function (using electrophysiology), receptor subcellular localization, and receptor mRNA and protein levels will be performed. Second, the genes that are important at each of these potential regulatory points will be determined. This aim will be achieved by forward genetic screening using a functional GFP-tagged receptor. These initial data will form the basis of a substantial future research program to understand how GABAA receptor abundance at synapses is regulated. Because cellular processes are generally well-conserved between C. elegans and humans, insights from these studies could lead to improved treatments for anxiety disorders based on modulating GABAA receptor abundance at synapses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC AND BEHAVIORAL MODELS OF INNATE FEAR Principal Investigator & Institution: Hen, Rene; Associate Professor; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): While Project 1A is aimed at identifying genes that are modulated by an acute fear conditioning paradigm, Project 1B is aimed at

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identifying genes that are differentially expressed in mutant mice that display variable levels of innate fear. The main difference between these two projects is that the first one studies learned fear while the second one studies innate fear. One disadvantage of innate fear over learned fear is that the underlying brain circuitry is less well understood. Therefore our first aim will be to identify which brain regions are controlling innate fear responses. To facilitate that dissection we have chosen to use as a starting point knockout mice that display increased anxiety-like phenotypes in tests of innate fear rather than selected inbred strains. In the knockout strains, the phenotype results from the absence of a single known gene. As a result the phenotype can be further dissected by using tissue-specific ablations of that same gene. In contrast, in inbred strains the phenotype is likely to result from the combined effect of many unknown genes which makes it much more difficult to assess the relevant brain regions. Another difference between projects 1A and 1B resides in the nature of the genes that will be identified in these two projects. In Project 1A, genes will be identified that are involved in the acute expression of fear in the normal adult brain; in contrast in Project 1B, we will attempt to identify genes that are differentially expressed either during development or in adulthood in the brains of "chronically anxious" mice. Whether these two gene pools are overlapping or not is unknown; however, both gene pools should provide candidates for the genetic determinants of anxiety disorders or anxiety-related traits (Projects 2, 3 and 4). The first goal of this project is to identify the brain regions and genes that are involved in innate fear responses. We will use knockout strains that rate high or low in tests of innate fear such as the 5-HT1A and the NK1 receptor knockout mice and we will use tissue specific and inducible knockout and rescue strategies to determine which circuits and developmental time periods are responsible for the anxious-like phenotype of these mouse strains. The second goal of this project is to compare these animal models of innate fear to the models of learned fear studied in Project 1A. Specifically we will study the behavior of the various knockout and rescue mice in conflict tests and fear conditioning tests to establish whether there is a correlation between these two types of anxiety-related paradigms. These studies parallel the human studies aimed at establishing correlations between neuroticism, behavior in fear conditioning paradigms, and anxiety disorders (projects 3 and 4). The third goal of this project will be to identify candidate downstream effector genes of the 5-HT1A or NK1 receptors. To achieve this goal, we will perform gene expression profiling using mRNA of wild-type and knockout mice from the critical tissues and time periods identified in aim 1. From this list of genes, we will select for further study those candidates whose expression is altered in the knockout and rescue mice in a way that correlates with their anxiety-like behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF ADOLESCENT TOBACCO USE AND DEPENDENCE Principal Investigator & Institution: Madden, Pamela A.; Assistant Professor of Psychology; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: (Applicant's Abstract) Despite the importance of adolescent smoking from a public health perspective (including its association with teenage alcohol and drug involvement), and the evidence from adult twin studies for a strong genetic influence on smoking behavior, there has been little research designed specifically to understand the genetic contribution to risks of becoming a regular tobacco user, and of developing nicotine dependence, and to difficulties with quitting tobacco use. The classical twin

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study, comparing MZ and DZ twins reared together, is a powerful behavioral genetic design for analyzing the joint effects of genes and environment on behaviors such as the onset of regular tobacco use and transitions in the tobacco habit which are subject to rapid developmental and secular changes. Using a prospective cohort sequential design, we will ascertain cohorts of adolescent same sexed male twins, 11, 13, 15 and 17 years of age, including minority pairs, over a 2-year period, and continue to identify new cohorts of 11-year old twins in years 3, 4 and 5. Each twin and one parent or guardian (whenever possible the biological mother) will be sent a questionnaire and by telephone given an interview that includes assessments of patterns of tobacco use and nicotine dependence, alcohol use and dependence, illicit drug use, other axis I disorders, perceived tobacco, alcohol and drug use and attitudes towards use in peers and parents, and about other pertinent risk factors. There will be brief annual follow-up of the twins. Analyses will include data from an ongoing longitudinal study of female adolescent twins (AA09022; Heath, PI) using similar assessments, allowing us to examine the following issues for cigarette use in adolescent boys compared with girls: (i) genetic influences on tobacco use; (ii) possible mediators of genetic influences on use of and the development of dependence on nicotine; i.e., personality, lifetime depression and anxiety disorders, and adolescent conduct disorder; (iii) the relationship between genetic influences on smoking behavior, and genetic influences on alcohol and illicit drug- related problems; (iv) possible environmental mediators (e.g., perceived smoking in peers); and (v) protective factors (e.g., parental monitoring) which may modify a genetic predisposition to tobacco use and to nicotine dependence in adolescents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF FEAR AND ANXIETY DISORDERS Principal Investigator & Institution: Hettema, John M.; Assistant Professor of Psychiatry; Psychiatry; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 07-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): This K08 Mentored Clinical Scientist Development Award proposes to provide advanced research training in the genetics of fear and anxiety disorders for Dr. John M. Hettema, M.D., Ph.D. Dr. Kenneth S. Kendler, M.D., a world renowned researcher in psychiatric genetics, will serve as Dr. Hettema's primary sponsor. The training will take place at the Virginia Institute for Psychiatric and Behavioral Genetics of Virginia Commonwealth University, which provides a rich, stimulating environment for the conduct of training and research. Dr. Hettema proposes to receive training in epidemiology, statistical and molecular genetics, and experimental methods for measuring anxiety-related traits, including psychophysiology and neuroimaging. Specific research objectives include i) examining the stability, reliability, and heritability of self-report measures in anxiety disorders using a longitudinal design; ii) determine the extent to which the high comorbidity observed between the anxiety disorders is determined by genetic and environmental factors shared between them, including specific individual risk factors such as gender, early enviroment, stressful life events, etc.; iii) determine the genetic correlations between neuroticism and the anxiety disorders and the causal relations between them; iv) elucidate the genetic and environmental factors underlying the increased risk for major depression caused by preexisting anxiety disorders and what effects gender has on this relationship; v) understand the genetic structure of fear conditioning in humans and to what extent this is shared with phobias. In addition, Dr. Hettema intends to apply knowledge gained in training to design pilot studies that incorporate experimentally derived anxiety-related measures from a genetically informative sample of twins from the Virginia Twin

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Registry, combining this data with the existing database of self-report anxiety measures. This research training plan will allow Dr. Hettema to emerge at the end of the proposal period as an independent researcher in the genetics of anxiety disorders, seeking to extend this work further by combining self-report and experimentally derived anxietyrelated measures with linkage and association studies to identify genetic loci and brain mechanisms involved in the anxiety disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF MONOAMINE ENDOPHENOTYPES AND MENTAL HEALTH Principal Investigator & Institution: Rogers, Jeffrey A.; Group Leader, Genetics; Southwest Foundation for Biomedical Res San Antonio, Tx 782450549 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The available data strongly suggest that the causes of psychiatric illnesses are complex, and that the risk of suffering from depression, schizophrenia, anxiety disorder and other psychiatric diseases is influenced by genetic inheritance, nongenetic biological factors and external environmental factors such as social stress. In addition, it is clear that monoamine neurotransmitters (serotonin, dopamine and norepinephrine) are related to the onset and treatment of depression, anxiety disorders and other psychopathologies. Despite the evidence for genetic influences on psychiatric disorders, on levels of monoamine neurotransmitters, and on normal variation in temperament related to disease, the specific genes that affect these traits are not well known. Whole genome scanning using linkage analysis in multigeneration pedigrees is a powerful method for locating functional genes that influence complex traits such as these. Unfortunately, for several reasons, this approach cannot be used with human families to locate genes that influence cerebrospinal fluid (CSF) levels of monoamines, or to investigate normal variation in behavior. In this project, we propose to conduct a whole genome linkage scan in a nonhuman primate model (baboons, Papio hamadryas). We will search for genes that influence CSF levels of monoamine metabolites (5-HIAA, HVA and MHPG) and also investigate individual variation in temperament by subjecting each baboon to a behavioral challenge involving response to novel objects. All 650 study animals have already been genotyped for a linkage map consisting of 350 human microsatellite loci, with 7 cM resolution. We will also use gene expression array methods to assess the molecular effects of identified QTL loci in prefrontal cortex. Preliminary results from about 300 baboons indicate that all three monoamine metabolites and several behavioral responses to challenge are strongly heritable. Most significantly, the available genotypes permit a preliminary genome scan, and four LOD scores greater than 1.9 have been obtained, including a LOD score of 2.4 for the dopamine metabolite HVA, and 2.6 for an anxiety-related behavioral trait. Our preliminary data demonstrate the value of the baboon model and indicate that a larger sample from the same pedigrees would likely provide important new information about genes that influence both monoamine neurotransmitter levels and behavioral reactivity (i.e., temperament). Identification of these genes will be very significant for future studies of genetic risk factors for psychiatric illness in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HARVARD/BROWN ANXIETY RESEARCH PROJECT (HARP) Principal Investigator & Institution: Keller, Martin B.; Associate Professor; Psychiatry and Human Behavior; Brown University Providence, Ri 02912

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Timing: Fiscal Year 2004; Project Start 01-APR-1995; Project End 30-NOV-2008 Summary: (provided by applicant): We propose to continue the Harvard/Brown Anxiety Research Project (HARP), a unique, naturalistic, prospective, multicenter study of 711 subjects with anxiety disorders, who were enrolled when seeking treatment at mental health outpatient settings, for an additional 5 years of f/u. This will enable us to obtain a minimum of 15 years of f/u on subjects and to incorporate new assessments and data analysis methods in order to address important unanswered questions and develop a more comprehensive picture of the longitudinal course and outcome of common anxiety disorders: panic disorder with and without agoraphobia, generalized anxiety disorder, and social phobia. Enrollment of African-American and Hispanic subjects with anxiety disorders during the first three years of this proposal will enable us to obtain a representative sample and to examine the clinical characteristics, longitudinal course, and course mediators, in unstudied ethnic minority populations. Our specific aims are to 1) examine patterns, predictors and psychosocial outcomes of anxiety course; 2) examine factors associated with the clinical course of anxiety disorders in an aging population; 3) describe somatic and psychosocial treatment received and investigate the mediating effect of somatic treatment on course; 4) examine the course of anxiety disorders in African-Americans and Hispanics; and 5) examine the utility of dimensional approaches in characterizing and understanding the nature and course of the anxiety disorders and comorbid depressive disorders. Subjects will be evaluated at annual intervals with instruments that obtain detailed information on symptom status and severity, diagnostic status, treatment received, psychosocial functioning, stressful life events, and other domains. We have added a new assessment that will allow us to examine the effects of anxiety disorders on medical disorders and disability. We have also incorporated new data analysis methods to take maximum advantage of the new data. HARP is unique in its large number of subjects, comprehensiveness of assessment, and length of prospective f/u. This proposal will obtain meaningful new knowledge about anxiety disorders as described in a substantial revision of previous aims and hypotheses using new findings from HARP and other investigators during the past 4 years. Continuation of HARP should shed new light on clinically and theoretically important, innovative questions about a group of common and impairing disorders that have not been adequately addressed by previous research, particularly within African-Americans and Hispanics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IDENTIFICATION AND CHARACTERIZATION OF LATE LIFE PANIC Principal Investigator & Institution: Apfeldorf, William J.; Psychiatry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2003 Summary: The objective of this revised Academic Career Award, Development, application is to assist Dr. William Apfeldorf in his academic activities in the field of geriatric psychiatry and to develop a clinical research program in late life anxiety disorders at the New York Hospital - Cornell Medical Center. The award will free Dr. Apfeldorf from most of his present clinical responsibilities, allowing him to obtain the training and experience necessary to develop as an academician and scientist. The training plan focuses on forming strong collaborative relationships with experts in the fields of geriatric psychiatry, anxiety disorders, and behavioral neuroscience. The specific aims of the research plan are: 1) to describe the expression and course of late life panic disorder, and its impact on medical morbidity and functioning in elderly panic

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disorder patients and elderly normal controls, and 2) to describe the profile of panic symptoms and neuroendocrine responses to pentagastrin panic provocation in elderly panic disorder patients and elderly normal controls. The research plan addresses clinical concerns about the direct and indirect cost of late life panic disorder in term of morbidity, quality of life, and burden for patients and their families. The plan also introduces a biological model for evaluating late life panic symptoms, allowing pathophysiologic mechanisms implicated in late life panic disorder to be investigated. Academic and research activities will take place simultaneously throughout the award period. As a result of this program, hypotheses on the underlying relationships of aging, pathophysiologic mechanisms, and anxiety disorders will be formulated. Upon completion of the award period, Dr. Apfeldorf will function as a faculty scholar, as a principal investigator in late life anxiety disorders for NIMH-supported studies including R01 and First Award applications, and as mentor and resource to medical students, residents, fellows, and colleagues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVING QUALITY OF PRIMARY CARE FOR ANXIETY DISORDERS Principal Investigator & Institution: Rollman, Bruce L.; Associate Professor of Medicine; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 10-SEP-1999; Project End 31-MAY-2003 Summary: Panic and generalized anxiety disorders (PD/GAD) are prevalent in primary care practice; responsible for significant morbidity; inadequately recognized and treated; and associated with excessive health services utilization. Given the availability of efficacious treatments for PD/GAD, this effectiveness study hypothesizes that enabling patients to participate in their care while simultaneously disseminating guideline-based treatments to their primary care physicians (PCP) via electronic medical record (EMR) will produce superior clinical outcomes to those achieved by simply notifying the physician and patient of the diagnosis alone. Our patient intervention will be based on public-domain and commercially available information/self-management materials modified for local use. PCPs will receive treatment advice based on the American Psychiatric Association's anxiety guideline and other evidence-based treatment algorithms presented to them via EMR. Approximately 20 board-certified PCPs at two study sites will be randomized to either our intervention or control ( usual care ) group. Research assistants using a validated rapid screening and interview procedure will identify 247 patients experiencing PD/GAD upon presentation for primary care over an 18-month period. All study patients and PCPs will receive notification of the anxiety diagnosis from the investigators. Afterwards, according to PCP assignment: (1) patients may receive additional information on anxiety disorders and a structured anxiety selfmanagement program administered over the telephone by a trained facilitator; and (2) PCPs may be exposed to guideline advice presented via EMR at the time of the clinical encounter. A research assistant blinded to the PCPs randomization status will conduct standardized telephone assessments with each study patient at 0, 2, 4, 8, and 12 months. The primary outcome criterion, a 50 percent reduction in subjects' levels of anxiety symptomatology at 4 months, will be assessed using the Hamilton Rating Scale for Anxiety. Secondary outcome criteria, such as functional status and health services utilization, will be assessed using parallel analyses at 12 months. This study will enhance our understanding of new methods to implement guideline-based care and the magnitude of benefits that can be expected. Study findings can: identify process factors

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that contribute to appropriate and effective care; stimulate the development of other patient self-management strategies; and distinguish patient subgroups most likely to respond to a collaborative-management approach for treatment of a debilitating chronic mental disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MARKERS OF RISK FOR ANXIETY DISORDERS Principal Investigator & Institution: Craske, Michelle G.; Professor; Psychology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 13-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): The goals of this project are to evaluate risk factors for anxiety disorders. This proposal is a cross-sectional high-risk (HR) design, comparing children with anxiety disorders (AD) to non-disordered children who are at high-risk (HR) based on parental anxiety disorders and non-disordered children at low risk (LR) for anxiety disorders based on the absence of parental psychopathology. Markers of risk for anxiety disorders are hypothesized to include evaluated sympathetic state, lowered vagal tone, selectivity of attention, evaluated reactivity to aversive stimuli, and stronger learning and retention of aversive associations. Thus, the three groups of participants (N=80), aged 7-12 years (pre-pubertal) and matched on gender, will be evaluated in terms of resting sympathetic state and vagal tone, attention to negative facial expressions, startle blink and cardiac reactivity to high decibel tones, with potentiation by "lights off", and rates of acquiring aversive conditioned responses to novel geometric figures paired with airpuffs. In addition, replication of startle and selective attention to facial expressions as well as measurement of recovery of aversive associations will be assessed one week later. Conditioning will be measured in terms of autonomic responses as well as eye gaze movement, and selectivity of attention will be measured using eye gaze. Measurement of eye gaze in youths to gauge ongoing conditioning and attentional processes represents a new methodology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MEDICATION ADHERENCE IN LATINOS Principal Investigator & Institution: Diaz, Esperanza; Associate Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 15-DEC-1999; Project End 30-NOV-2004 Summary: This is a request for a Mentored Patient-Oriented Research Development Award (K23). The overall aim of the proposal is to provide the candidate, Esperanza Diaz MD., with a supervised patient oriented research and educational experience that will enable her to become an independent investigator in mental health services research with focus on the Latino population and cultural issues. Dr. Diaz is an experienced, bilingual, bicultural clinician. A K23 will free her time from clinical duties to obtain the skills and experience of an independent researcher. Dr. Diaz has chosen a distinguished set of mentors Robert Rosenheck MD., Joyce Cramer BS., and Scott W. Woods MD., from Yale University and Janis H. Jenkins Ph.D., from Case Western Reserve University. They are active mental health services and cultural researchers with excellent records of successful mentorships. The first aim of the study is to determine the medication adherence rates and differences in attitudes to medications in patients treated for Schizophrenia and other Psychotic Disorders, Mood disorders, Anxiety Disorders, and Somatoform Disorders in three groups. 1) Latinos treated at a culturally competent

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Latino Clinic, 2) Latinos treated by non Latinos in a standard Community Mental Health Center and 3) non Latino groups treated at the same Community Mental Health Center. Analysis of the data will be used to identify the role of cultural factors and other attitudes in medication compliance in Latinos to formulate a culturally sensitive intervention for enhancing medication adherence in Latinos. The second aim of the project will compare a previously tested intervention to enhance adherence to medicines, the Medication Usage Skills for Effectiveness, (MUSE) among Latino patients receiving the MUSE intervention alone, Latino patients receiving the MUSE plus a culturally sensitive enhancement and Latino patients receiving a non specific counseling intervention. The control group will provide data on medication adherence and outcome. Dr. Diaz's training experience includes a three year period of intense coursework at the school of Epidemiology and Public Health and at Case Western Reserve University. The plan includes developing skills in Statistics, Biostatistics, Epidemiology, Health Policy, Mental Health Services Research, Analysis of Data, etc., leading to a Masters in Public Health. Dr. Diaz will also develop skills in descriptive and qualitative research, Data collection, Data analysis. Dr. Diaz will have an R01 proposal ready by the end of funding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETIC STUDY OF FEAR AND ANXIETY Principal Investigator & Institution: Gilliam, T Conrad.; Borne Professor of Genetics and Developm; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): In this program project we present a novel strategy for the identification of genes important for psychiatric disorders. The studies are aimed at normal and pathological expressions of anxiety in humans, and focus specifically on learned and innate fear in mice. Because fear is a universal affect conserved throughout phylogeny, it is possible to model fear in mice - an organism that is suitable for both physiological and genetic analysis. Fear conditioning is a measure of an organism's basic ability to learn about new dangerous or threatening stimuli or environments, and to respond appropriately. The study of fear conditioning offers two very significant advantages for molecular genetic analysis: the behavioral paradigms can be closely mimicked in human subjects, and the neurocircuitry, and associated information processing systems that underlie these behaviors, are relatively well understood, and highly conserved among vertebrates. Since, in their most general sense, anxiety disorders represent a malfunction in the neural mechanisms that detect danger and mobilize adaptive responses to that danger, we propose that a subset of genes that harbor genetic determinants for learned or innate forms of fear will also harbor susceptibility alleles for human anxiety disorders. Thus, we propose a translational study of fear and anxiety that combines direct molecular genetic study of learned and innate forms of fear in mice with genetic analysis of anxiety related behaviors, traits, and disorders in humans. The Program Project consists of five independent Projects and a Training Component. 1. Genetic and Behavioral Models of Fear States in Mice- 1A. Learned Fear (Kandel) 2A. Innate Fear (Hen). 2.Translation from Mouse to Human Fear and Anxiety: Genetic and Genomic Approaches (Gilliam). 3. Clinical Studies of Human Fear and Anxiety (Fyer). 4. Clinical Studies of Human Anxiety Disorders (Weissman). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOOD AND ANXIETY DISORDERS IN PREGNANCY AND LACTATION Principal Investigator & Institution: Stowe, Zachary N.; Associate Professor and Director; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: The treatment of mental illness during pregnancy has gained considerable attention over the past decade. The majority of this attention has focused on antidepressants and major depression, with far less consideration of anxiety disorders and bipolar disorder. The treatment guidelines for mental illness during pregnancy and lactation remain empiric and continue to emphasize the risk/benefit assessment. The lack of data on the course of illness, the impact of pregnancy and lactation of the metabolism and distribution of pharmacological treatments, and the extent of fetal and neonatal medication exposure underscores the empiric nature and prematurity of such guidelines. The current project will enhance and extend the data derived from an ongoing collaborative R01 MH56555-01A2 (Stowe) focused on the relapse of major depression in pregnant women taking antidepressant proximate to conception and K23 MH 63507-01 (Newport) investigating psychosis during pregnancy. We will prospectively follow women with major depression (MID), bipolar disorder (BPD), panic disorder (PD), and obsessive-compulsive disorder (OCD) through pregnancy and the first postpartum year. Many of these women may chose to continue medications such as antidepressants, mood stabilizers, and antipsychotic medications either during pregnancy and/or take medications postpartum. Monthly serum sampling and GCRC admissions will provide novel data.regarding the metabolism, distribution, and fetal/neonatal exposure to these compounds. These PK/PD models will be expanded to include assessment of pharmacogenetic factors of metabolic capacity and protein binding. Similarly, prospective documentation of additional exposures, sex steroid concentrations, and psychosocial variables will further refine such models and provide preliminary assessment of factors (other than medication concentrations) that may influence the course of illness and obstetrical outcome. The current project will utilize the core components to address the deficits in the current literature, affords a diagnostically diverse group of women that may be germane to the results obtained in Project 2 with respect to co-morbidity and the use of similar medications in a nonepileptic population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEURAL BASIS OF PROCESSIVE STRESS Principal Investigator & Institution: Campeau, Serge; Psychology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This is an application for an Independent Scientist Award (K02) that would fundamentally enable the PI to devote at least 75 percent of his effort to research and career development. The PI's research has focused on animal models of processive stress to begin to trace and identify the neural circuits that mediate the activation of a specific stress responsive system, the hypothalamo-pituitaryadrenocortical (HPA) axis, and test the generality of the involvement of such a circuit across a variety of processive stressors. This work has been supported by a NARSAD Young Investigator Award, an NIMH B/START (R03 MH062471) award, and these studies will now be pursued through the recent award of a 5-year R01 (MH65327). This funded research provides the basis for the proposed Research Plan that examines in

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detail 1) which brain regions are specifically activated by exposure to two different processive stressors: audiogenic and predator odor stress; 2) whether any of the brain regions specifically activated by noise and predator odor project directly to the "motor" neurons (paraventricular nucleus of the hypothalamus) of the HPA axis, and will include tests of functional relevance by ablating the cell bodies of these projecting neurons; and 3) the basic neurochemical phenotypes of the cellular groups that project directly to the paraventricular hypothalamic nucleus and are necessary for HPA axis activation in response to processive stress. The PI's immediate objectives are to expand and facilitate his current research on the basic neural circuits that elaborate a central state of stress, which in the longer-term might provide insights into putative dysregulation within these circuits that may be responsible for the development or precipitation of a number of mood and anxiety disorders. The Career Development Plan targets several technical (neuroanatomical tracing and single cell expression profiling techniques) and conceptual (concept of "stress" and animal models of mood and anxiety disorders) areas of growth that will be achieved by enhanced scientific interactions, collaborations, and training, and will thus be vital in the attainment of the PI's shortand long-term career objectives. This will be done in an Institutional Environment with strong and continuing support to the PI's success via the provision of extensive laboratory space, physical resources, and accelerated growth of Neuroscience on campus. Through the Department approved teaching reduction, this award is unique in allowing the PI to devote a significantly greater amount of time and uninterrupted blocks of time to his research and career development, thereby assuring the success of the proposed growth initiatives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROGENETICS OF STRESS VULNERABILITY Principal Investigator & Institution: Gershenfeld, Howard K.; Associate Professor; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Depression and anxiety are common psychiatric illnesses in the U.S. with about 23 million and 28 million people suffering annually. In the1990's, the annual economic burden to society of depressive disorders and anxiety disorders were each estimated at $43 billion dollars. We aim to understand the neurobiology of "stress vulnerability," which leads to anxiety and depressive disorders. Stress is a well known "common factor" contributing to many disorders. While the causal association with stress is more direct for depressive and anxiety disorders, evidence has accumulated for stress aggravating cardiovascular and inflammatory diseases. Stress responses vary greatly among individuals. This project proposes to explore the mechanism of vulnerability to acute stress. The mouse tail suspension test (TST) reflects these individual differences in behavior to an uncontrollable stressor. This acute stress model has become a facile model of individual differences in stress reactivity (including psychogenic fever/hyperthermia) and antidepressant responses. This project focuses on the genetic factors predisposing to differences in stress responses induced by TST. The specific aims include: 1) positionally cloning a confirmed locus (Tsti1) on chromosome 5,2) performing secondary and tertiary screens of ENU mutagenized, mutant mice with altered TST behavior, and 3) dissecting the role of gender and cytokines in TST behaviors via selected transgenic mice. The ENU mutant screens will include TST-induced hyperthermia, antidepressant response, and neural activity mapping. Despite the effectiveness of antidepressants, we know little about how these treatments work. The goal is to define robust factors influencing the fundamental

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biology of individual differences in "stress reactivity," favoring assumption free genetic strategies. We hypothesize that the TST paradigm in mice may probe a genetic shared liability for "general distress," which is a risk factor for psychiatric disorders. An understanding of the molecular pathophysiology of the mammalian stress response will contribute to integration of established genes and pathways, attach functions to unknown genes, and define new pathways for improved therapy. Ultimately, this work may contribute to our etiological understanding of stress vulnerability, identifying individuals at high risk for stress-induced disorders, and provide rational drug design to sever the link between acute stress and pathological consequences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEW PET RADIOLIGAND FOR THE SEROTONIN TRANSPORTER Principal Investigator & Institution: Huang, Yiyun; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 19-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The goal of this application is to develop an F-18 labeled PET radiotracer to image the serotonin transporter (SERT) in discrete brain areas, especially areas with low density of SERT. The SERT, located on the cell bodies and terminals of the 5-HT neurons, is a marker of 5-HT innervation. Alterations in 5-HT transmission and SERT densities have been described in a number- of neuropsychiatric conditions, including major depression, anxiety disorders, schizophrenia, drug abuse, alcoholism, eating disorders, Alzheimer's and Parkinson's disease. The currently available PET radiotracer, [11C](+)-McN5652, suffers from many limitations, including high levels of nonspecific binding, poor in vivo signal to noise ratio, and slow brain kinetics. Due to these drawbacks, [11C](+)-McN5652 can only be used to image the brain regions with high SERT densities (midbrain, thalamus and striatum), but not those with lower SERT densities, such as hippocampus, amygdaIa and neocortex, where localized alterations in SERT densities have been identified in postmortem studies. In this application we propose to develop a new ligand, 2-[2-(dimethylaminomethyl) phenylsulfanyl)]-5-fluoromethylphenylamine, or AFM, into a PET ligand. AFN is a potent and selective SERT ligand that can be radiolabeled with either C-11 or F-18. Preliminary results indicate that [11C]AFM possesses high affinity and excellent binding specificity in vivo. Imaging studies in baboons demonstrates that [11CIAFM is a PET tracer with superior imaging properties, including faster kinetics and a higher signal-tonoise ratio compared to [11C](+)-McN5652. These characteristics make it possible to image brain regions with low SERT densities. We propose to develop [ 11C]AFM and [18F]AFM for clinical imaging applications. Experiments are designed to: 1) characterize fully the in vivo pharmacology and pharmacokinetics of [11C]AFM and [18F]AFM; 2) assess the potential and suitability of [11C]AFM and [18F]AFM to image the SERT in brain regions of both high and low SERT densities; and 3) characterize the imaging properties of [11C]AFM and [18F]AFM in healthy human subjects. The ultimate goal is to introduce [11C]AFM and [18F]AFM into the clinics to probe the role of SERT in neuropsychiatric disorders. Introduction of [18F]AFM would constitute the first PET tracer for the SERT that can be prepared in a central facility and distributed to various sites for clinical imaging purposes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHWAYS TO ADULT PSYCHOPATHOLOGY: ETIOLOGICAL FACTORS Principal Investigator & Institution: Silberg, Judy L.; Human Genetics; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-JUL-2002 Summary: We are proposing a telephone follow-up study of the psychiatric status of approximately 1300 male and female juvenile twin pairs as thy make the transition from late adolescence to early adulthood. Extensive psychiatric information is already available on these twins and their parents, having participated in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) a three wave, longitudinal study designed to investigate the influence of genetic and environmental factors on the development of childhood and adolescent psychopathology in the ages 8 through 16. The extensive array of psychopathological, environmental, and developmental data on this large epidemiologic twin sample represents and unprecedented opportunity to understand how hereditary and environmental factors in childhood may culminate in psychiatric problems in young adulthood. The availability of genetically informative data within a longitudinal framework from early childhood to young adulthood will enable us to address some of the most important questions about the various genetic and environmental pathways to Major Depression, Generalized Anxiety disorders, social, Situational, and Simple Phobias, Antisocial Personality Disorder, Alcoholism, Drug use, and Eating Disorder. These include: what salient risk factors, both genetic and environmental, contribute to an individuals; liability to psychiatric disorder in early adulthood? What are the mechanisms that can account for the continuity/discontinuity between juvenile and adult psychiatric outcomes? To what extent can behavioral continuity be attributable to an individuals selecting or creating environments that potentiate their genetic liability to certain behaviors? And finally, are the genetic and/or environmental factors that contribute to behavior in adolescence that same as those that influence psychiatric disorders later on in adulthood? We propose to utilize an extensive array of methodological strategies to both twin and family data to address these most fundamental questions concerning the pathways to adult psychiatric morbidity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PEDIATRIC ANXIETY DISORDERS IN PRIMARY CARE Principal Investigator & Institution: Wren, Frances J.; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2005 Summary: (Applicant's abstract): This proposal for a Mentored Clinical Scientist Career Development Award will prepare the candidate to independently design and conduct intervention studies for pediatric internalizing disorders in the primary care setting. Anxiety Disorders are the most common pediatric internalizing disorders. They are prevalent, impairing, often persistent, may be associated with increased health service use and are eminently treatable. Yet they are amongst the mental health disorders least likely to be recognized in primary care and, when recognized, are typically not optimally treated. Existing studies of community prevalence rates of Anxiety Disorders have not been linked to prognosis, functional impairment and treatment needs, with resultant difficulties in setting intervention thresholds for primary care. Over three and a half years, the proposed research study will recruit and follow for six months 200 school age children with anxiety disorder, identified by screening in a primary care practice. A detailed baseline evaluation will be obtained in order to study predictors of

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persistent anxiety disorder and of health service use and health care costs. A control group will also be recruited and followed in order to estimate group differences in health care costs between anxious children and non-anxious children: The study is the first to focus specifically on childhood Anxiety Disorders in primary care, the first to study predictors of the six month course of childhood Anxiety Disorders and the first to explore associated health service use and costs. The data generated will yield clinical profiles of children in primary care whose anxiety is likely to be persistent or costly. This is a necessary step towards the long-term goal of designing intervention protocols to improve outcomes for anxious children in primary care and of evaluating costeffectiveness and cost offsets. The candidate is a board certified Child and Adolescent psychiatrist with ten years of post-residency experience, currently Medical Director for Clinical Program Development in Primary Care in the Division of Child and Adolescent Psychiatry at the University of Pittsburgh. Dr. David Brent will serve as preceptor. The consultant panel includes experienced investigators both in the phenomenology and treatment of pediatric Mood and Anxiety Disorders, and in mental health intervention in adult primary care. Course work and guided readings in epidemiology; biostatistics; research design, methods, and ethics; health services research concepts and procedures; health economics and policy; and relevant applications of information technology will complement the research plan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREFRONTAL CONDITIONING

AMYGDALA

INTERACTIONS

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FEAR

Principal Investigator & Institution: Quirk, Gregory J.; Associate Professor; Physiology; Ponce School of Medicine G.P.O. Box 7004 Ponce, Pr 00731 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from applicant's abstract): Research into the neurobiology of emotion has advanced in recent years with studies of fear conditioning a neutral stimulus (the conditioned stimulus, CS) becomes associated with an aversive event (the unconditioned stimulus, US) so that subsequent exposure to the CS evokes physiological and behavioral fear responses. Repeated presentation of the CS without the US leads to a diminution of fear responses, a process known as extinction. Failure to extinguish fear responses may form the basis of anxiety disorders such as phobias and post traumatic stress disorder. While the neural circuitry for the acquisition of fear conditioning is becoming well understood, the circuitry of extinction is relatively unknown. The amygdala is crucial for fear conditioning. Cortical inputs to the amygdala, while not required for fear conditioning may modulate fear behavior. Recent data suggest that the medial prefrontal cortex (mPFC) and the basolateral nucleus of the amygdala (BLA), which are interconnected, may form part of the neural circuitry of extinction. Three experiments will test this central hypothesis. 1. Rats with lesions of the mPFC will be trained in conditioned suppression of bar pressing, followed by extinction and reinstatement (hypothesis: rats without mPFC will acquire, but not extinguish fear responses). 2. Tetrodes will be used to record from multiple mPFC neurons in behaving rats undergoing acquisition and extinction of fear conditioning (hypothesis: mPFC neurons will show extinction induced changes in tone responses and cell-cell correlations that did not occur during acquisition, suggesting a role of mPFC in learning new CS-US associations during extinction). 3. mPFC will be stimulated in anesthetized rats while recording from BL neurons (hypothesis: mPFC causes feed foward inhibition of BLA). And, 4. Tetrodes will be used to record from BLA neurons during fear conditioning, in animals with and without an intact mPFC (hypothesis: BLA cells from

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control animals will show rapid extinction of conditioned tone responses, while BLA cells from lesions animals will extinguish more slowly). This research will advance our understanding of fear processing in the brain. In particular, it will begin to tell us what circuits are important for extinction, and how extinguished stimuli are represented differently from non-extinguished stimuli in small groups of neurons. Ultimately, it will lead to more effective treatments for anxiety disorders, as our understanding of the neural mechanisms of fear increases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVENTION OF CIGARETTE SMOKING IN ADHD YOUTH Principal Investigator & Institution: Biederman, Joseph; Chief; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-AUG-2002 Summary: (Applicant's Description) There is no doubt that cigarette smoking is a substantial source of morbidity and premature morbidity the United States. Each year, cigarette smoking causes about 30 to 40 percent of coronary heart disease deaths and 30 percent of cancer deaths, leading to nearly half a million deaths each year. Yet, despite these statistics, there are more than 54 million smokers in the nation. Four million of these are adolescents and over 3,000 youth start smoking each day. If these rates of teenage smoking continue, the costs to society will be enormous. Cigarette smoking has become so widespread in youth that it is considered a "pediatric disease" by the Food and Drug Administration. Studies suggest that most adults could be prevented from becoming tobacco users if they could be kept tobacco-free during adolescence. This finding suggests that preventive efforts focus on adolescence, a known risk period for the initiation of smoking. This proposal seeks to apply a psychopharmacologic high risk paradigm to prevent regular smoking and nicotine dependence in adolescence. The work has three innovative features: 1) use of epidemiologic data to define a group of adolescents at high risk for smoking; 2) use of an anti-smoking medication that also addresses clinical features of the high-risk group and 3) implementation of procedure to facilitate the long-term follow-up of research participants. These features are defined by the three main aims of our proposal. Prior work shows that children with attention deficit hyperactivity disorder (ADHD), who also have comorbid conduct, mood or anxiety disorders, are at high risk for regular smoking and nicotine dependence. Thus, our first aim is to recruit a group of these adolescents into a preventative treatment protocol, before they have initiated regular smoking. Our second aim is to complete a double-blind clinical trial of bupropion for the prevention of smoking in high-risk ADHD adolescents. Bupropion is an appropriate agent for this group for several reasons. It is efficacious for the treatment of depression, one of the most common comorbid disorders in the high risk group. Moreover, prior research also shows that it reduces ADHD symptoms and is an effective treatment for smoking cessation. Moreover, its putative mechanism of action affects neural systems believed to mediate both ADHD and smoking. In addition to these main aims, we will assess the effects of bupropion on symptoms of ADHD and depression and will implement procedures that will allow us to study the outcome of this sample in future proposals, should that be warranted. We will use a balanced, double-blind, placebo-controlled study design. Sixty-five high risk adolescents will be given placebo and sixty-five bupropion. Subjects will he recruited over a 3-month period and will have varying lengths of follow-up based on when they were recruited into the study. The study is designed so that each subject will have at least one year of follow-up data. Some subjects will have as much as 3.5 years of follow-up data. The use of pharmacological agents, such as Bupropion, have

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not been explored in the prevention of cigarette smoking. Since this medication has been used for both the treatment of ADHD and cigarette smoking, it could aid in the prevention of cigarette smoking in this high-risk population. The number of cases that could he prevented is not trivial. Since there are estimated to be 3.5 million children with ADHD and 20% have been shown to be smokers, targeting this group could potentially impact 700,000 children and adolescents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PSYCHOBIOLOGY AND TREATMENT RESPONSE IN PRIMARY INSOMNIA Principal Investigator & Institution: Buysse, Daniel J.; Associate Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-DEC-1977; Project End 30-NOV-2006 Summary: Insomnia is a widely prevalent problem with serious consequences for mental and physical health, including risk for the development of major depressive and anxiety disorders. Fundamental questions persist regarding how affective disturbance is related to sleep disturbances; focusing on primary insomnia is a key to addressing these questions. The broad aim of this study is to better define the psychobiology of insomnia based on clues from its clinical phenomenology, responses to pharmacological treatment probes, and functional neuroimaging studies of sleep and wake states. Our model of primary insomnia emphasizes two major dimensions of dysfunction, affective disturbance and heightened central nervous system arousal. We propose that individuals with primary insomnia vary in their degree of affective disturbance and heightened arousal, leading to different individual profiles of sleep-wake behaviors. These different profiles may require pharmacotherapy specifically tailored to the individual's symptom constellation. In order to test our model, we will use innovative methods of clinical assessment (including mood and anxiety "spectrum" assessments and ecological momentary assessment of mood and arousal), pharmacological treatment problems, and [18F]-FDG positron emission tomography (PET) studies during wakefulness, NREM sleep to identify functional neuoanatomic correlates to affective disturbance and heightened arousal. We will address the following specific aims: Aim 1: To characterize the dimensions of affective disturbance and heightened arousal among patients with primary insomnia; the relationship of these dimensions to each other; and their relationships to insomnia symptoms. Aim 2: To determine the differential effects of treatment with an anti-depressant (nefazodone), a benzodiazepine receptor agonist (zolpidem), and placebo on the dimensions of affective disturbance and heightened arousal in patients with primary insomnia. Aim 3: To examine the functional neuroanatomy of primary insomnia during waking, NREM sleep, and REM sleep as related to the dimensions of affective disturbance and heightened arousal. Results from this study will lead to improved understanding of the psychobiology of primary insomnia and its relationship to mood and anxiety disorders; better recognition of relevant insomnia subgroups for future classifications; and the development of more targeted and effective treatments for primary insomnia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PSYCHOBIOLOGY OF ANXIETY DISORDERS Principal Investigator & Institution: Gorman, Jack M.; Professor; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-SEP-1987; Project End 31-AUG-2002

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Summary: (Adapted from applicant's abstract): A competing continuation of a Senior Scientist Award (formerly Research Scientist Award) is requested. The main focus is the study of the neurobiology and treatment of anxiety disorders, particularly panic. The candidate has held three successive five-year "K" award grants from NIMH. Four main areas of research are proposed: 1) studies of respiratory physiology in PD; 2) the relationships among respiratory, noradrenergic, and serotonergic function in PD; 3) developmental aspects of anxiety disorder including a preclinical model of anxiety, studies of anxious children, and development of a geriatric anxiety program; and 4) the role of CNS innervation in the cardiovascular response to acute and chronic stress. A hypothetical model is presented that will guide the candidate in studies attempting to elucidated biological aspects of PD and their relationship to cognitive and behavioral aspects. This includes placing respiratory abnormalities in panic in their proper perspective, testing relationships among several brain systems in the pathogenesis of panic, and studying the effects of early life traumatic stress on the biological and behavioral predisposition to anxiety disorder. Work on the "heart-brain" interaction includes studying heart transplant patients as a model of cardiac denervation in order to isolate the precise mechanisms by which the CNS controls cardiovascular function. In this proposed continuation period, particular attention will be placed on training in several neuroimaging techniques. Pilot single photon emission computerized tomography (SPECT) and positron emission tomography (PET) studies are described and plans for the use of functional magnetic resonance imaging to study carbon dioxide (C02) responsive zones of brain are also planned. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PSYCHOPHYSIOLOGY AND ANXIOGENESIS Principal Investigator & Institution: Berntson, Gary G.; Professor; Psychology; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 15-JAN-1995; Project End 30-SEP-2002 Summary: (applicant's abstract): The research proposed in this competitive renewal application would examine the role of the basal forebrain cortical cholinergic system in behavioral and cardiovascular features of fear and anxiety. The research is guided by two hypotheses: a) that rostral neurobehavioral mechanisms underlying fear and anxiety can modulate autonomic control, and b) that autonomically mediated visceral reactions can modulate the cortical processing of anxiety-related contexts via central ascending pathways. The latter includes the basal forebrain cortical cholinergic projection, which has been implicated in cardiovascular reactivity associated with fear and anxiety. The proposed work will further develop and test a neurobiological model of central systems underlying fear and anxiety. Specific emphasis is on the basal forebrain cholinergic system and its role in integrating behavioral and cardiovascular reactions. The work will identify relevant target sites of the basal forebrain cholinergic system in rats, by central infusions of a cholinergic-specific immunotoxin (192IgGsaporin), as well as cholinergic and adrenergic drugs and benzodiazepine receptor agonists, antagonists, and inverse agonists. Other proposed studies will clarify the behavioral conditions in which the basal forebrain cholinergic system is operative, and will test hypotheses concerning the ascending components of the model. These include an examination of the role of visceral afference in modulating behavioral and autonomic reactivity in anxiogenic contexts, by means of subdiaphragmatic vagotomy and other approaches. The proposed studies bear on the fundamental nature of anxiety and the underlying neural mechanisms that link behavioral processes and autonomic functions. These are important issues given the prevalence of anxiety disorders, and the fact that

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anxiolytic benzodiazepine receptor agonists are the most widely prescribed psychopharmacological agents worldwide. Because anxiety disorders are often associated with abnormal autonomic regulation, they represent a clear risk factor for cardiovascular disease and sudden cardiac death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESEARCH TRAINING - PSYCHOBIOLOGICAL SCIENCES Principal Investigator & Institution: Hofer, Myron A.; Professor; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-JUL-1984; Project End 30-JUN-2008 Summary: (provided by applicant): This program has been training M.D. and Ph.D. investigators to pursue careers in the psychobiological sciences related to mental disorders for nearly two decades. Clinical researchers and those working in the laboratory on animal models in the basic sciences are united by a common interest in the interplay of psychological and biological processes as these contribute to increased understanding of clinical disease. We emphasize training in an analytic experimental approach to elucidate the processes and mechanisms underlying the development of abnormal neural functioning and behavior. Specific areas of research interests of the 20 sponsoring faculty include: developmental psychobiology, chronobiology, perinatal physiology and behavior, psychosexual differentiation, anxiety disorders, brain imaging, psychopharmacology of pain systems, attachment and separation, epidemiology of psychiatric disorders, behavioral medicine, and genetic models of abnormal brain function. The research ideas and career goals of the trainee candidates are carefully matched with particular faculty member's expertise. Training focuses primarily on conducting research designed by the fellow with the guidance from faculty mentors. This hands-on research training is supplemented with 1) a weekly seminar in which the processes of research are intensively discussed with a core group of sponsoring faculty, and 2) personalized didactic study programs consisting of courses in statistics, lectures from medical school courses and a rich variety of seminars and rounds in psychiatry and psychobiology. The goal of the program is to promote the development of successful independent researchers. Toward this end, all fellows receive instruction in how to design and write competitive grant proposals. Funds are requested for six postdoctoral trainees. M.D.s are usually psychiatric residents with several years of postdoctoral experience. Ph.D.s usually begin their training with a year or two following completion of the graduate training. Selection is based on the applicants' potential for original and creative research; on their motivation and the perseverance required to complete 2-3 years of intensive research training. Creative selfstarters with their own ideas are sought and then matched with faculty mentors who can best guide this research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF CENTRAL CRF SYSTEMS IN CHRONIC STRESS RESPONSES Principal Investigator & Institution: Jaferi, Azra; Psychology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: The long term goals of this project are to characterize the role of central corticotropin releasing factor (CRF) systems in physiology and behavior under chronic stress conditions. The CRF system has recently been recieving increasing attention for its

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role in coordinating behavioral, autonomic and endocrine responses to stress. Changes in central CRF activity has been linked to stress-related disorders such as depression, post-traumatic stress disorder, and anxiety disorders. While it is well known that chronic stress is associated with the onset of stress related disorders such as depression, little is known regarding changes in central CRF systems under chronic stress conditions. The specific aims of this project are to examine CRF receptor expression in the neural circuitry that may underlie chronic stress responses using insitu hybridization. Secondly, this project aims to investigate which sites within this circuitry mediate differential effects of CRF receptor antagonists on stress-induced anxiety behavior as well as on activity in the stress-sensitive hypothalamic-pituitary-adrenal axis. Lasty, we aim to examine corticosterone-mediated regulation of CRF receptors in the circuitry underlying chronic sress responses after acute and chronic stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RUPP-PI IN NEW YORK CITY Principal Investigator & Institution: Greenhill, Laurence L.; Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): This U10 proposal responds is to establish an NIMH Research Unit for Pediatric Psychopharmacology --Psychosocial Intervention (RUPP-PI) in New York City. The proposed unit combines the recruiting strengths and expertise of two urban university medical centers -New York State Psychiatric Institute and New York University's Child Study Center -in clinical epidemiology of suicidal behavior, psychosocial treatment development, pharmaco- kinetics of stimulants, and participation in numerous successfully performed, single and multi-site clinical trials involving psychosocial interventions, selective serotonin reuptake inhibitors, and their combination for mood and anxiety disorders. Resources to support this program of research and training include T32 postdoctoral training grants in child psychiatry research, an Intervention Research Center on child psychiatric disorders, and a RUPP devoted to treatment of anxiety disorders. This application's exemplar research protocol, "Treatment of Suicidal Adolescent Attempters" (TASA), targets a major public health issue: although adolescents in this country suffer 2 million suicide attempts annually, no large scale, multimodal 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 further reattempts in 480 depressed adolescent attempters, ages 12 to 18, at 8 sites. Eligible subjects will be recruited, carefully assessed, and then randomized equally to two treatment conditions. The Experimental Treatment group will receive a 24 week course integrating antidepressant medication management (MM) with cognitive behavioral therapy. The Control Treatment group will be referred to a community provider for standard clinical care plus enhanced clinical monitoring and case management to encourage treatment adherence. Both groups will be assessed at baseline 2, 4, 8, 12, 24, 36 and 48 weeks by an independent evaluator blind to treatment assignment. We hypothesize that the experimental treatment will result in fewer suicide attempts, diminished depression and severity of suicidal ideation, and greater global improvement scores than in the control group over a one year period of observation. The expertise and experience at this RUPPPI site also will be directed to train new investigators. In creating TASA, a collaborative group of 8 RUPP-PI applicants forged the ability to work together. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SELECTIVE ANXIOLYTICS VIA BZR SUBTYPE SPECIFIC LIGANDS Principal Investigator & Institution: Cook, James M.; Professor; Chemistry; University of Wisconsin Milwaukee Box 413, 2200 Kenwood Blvd Milwaukee, Wi 53201 Timing: Fiscal Year 2001; Project Start 01-SEP-1991; Project End 30-NOV-2005 Summary: Adapted from applicant's abstract): The understanding and treatment of pathological anxiety have long been a prime concern in regard to mental health. Alterations in GABAA function from controls are known to occur in anxiety disorders,6 including panic disorder, epilepsy,7 hypersensitive behavior,7b phobias,6 schizophrenia,8 alcoholism,9 Anglemans syndrome,7b and Rhetts syndrome,10 as well as effects which lead to/or complicate drug abuse.11 The 1,4-benzodiazepines, employed to treat anxiety disorders as well as sleep disorders exhibit anxiolytic, anticonvulsant, muscle relaxant/ataxic and sedative-hypnotic effects.5-12 Despite the clinical effectiveness of these drugs there is a need for selective anxiolytics and anticonvulsants which are devoid of myorelaxant/ataxic and sedative-hypnotic effects.5 Since BzR (benzodiazepine receptor) ligands allosterically modulate this system,1-5 the design of BzR subtype selective ligands5,25 is one means to generate better therapeutic agents.5 The combination of ligand affinities, molecular modeling and CoMFA analysis has been employed to determine the similarities and differences between BzR subtypes.25,26 This approach has permitted the synthesis of the most alpha5beta2gamma2 subtype selective agonist 5a reported to date,29 as well as several potent alpha5 selective inverse agonists 1a and 2a (50-75 fold more selective).25,28 Moreover, BCCt 6a (a neutral antagonist)31,32 and 3PBC 7a have been shown to be selective for alpha1beta2gamma2 subtypes, the former t-butylester is the most alpha1 selective agent in vitro reported to date.31,32 The alpha4/alpha6 "diazepaminsensitive" ligands 3a,b and 4a,b are again the most potent selective DI ligands reported to date. These ligands serve as lead compounds in the search for BzR subtype specific agents. Based on modeling, variation of the ligand substituents (chiral or achiral; polar or nonpolar) which occupy lipophilic pockets L1, L2, L3, or Ldi of the pharmacophore/receptor model will provide the desired subtype selectivity. The lead compounds are illustrated in Schemes I and II, while the target compounds are depicted in Schemes III-XI. The goal is to develop ligands that are > 150 times more selective for either alpha1,alpha5,alpha4, or alpha6 (later alpha2,alpha3) subtypes in order to determine which biological function is mediated by which subtype(s). Characterization of the pharmacology of BzR at the subtype level is crucial for understanding the physiological processes which underlie anxiety, including panic disorder,6 convulsions,7 sleep disorders and cognition,16 as well as the design of selective agents to treat these disease states with reduced abuse potential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP IN PTSD/PANIC: A MULTIMODAL NATURALISTIC STUDY Principal Investigator & Institution: Sheikh, Javaid I.; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): The past decade has seen exciting advances in our understanding of central fear systems, information regarding the extended amygdala, the broader limbic system, their targets and modulating structures, is providing new avenues for the formation of testable models of anxiety disorders that are amongst the most common psychiatric illnesses. Panic disorder (PD) and posttraumatic stress disorder (PTSD) are prime candidates for explication by reference to central fear

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systems. Further, because they converge and diverge in important ways, PD and PTSD challenge our understanding of how central fear systems can support related yet distinct anxiety syndromes. A strong version of this challenge is presented by the sleep disturbances of PD and PTSD. Both are associated with subjectively disturbed sleep continuity, nocturnal paroxysmal episodes (nocturnal panic attacks and trauma-related nightmares, respectively), and, our data would suggest, suppression of sleep movement. Nevertheless, these two anxiety disorders appear to exhibit divergent modifications of nocturnal respiration, elevated tidal volume variability in PD, versus accelerated respiration in association with nightmares in PTSD. The aim of this project is to lay the foundation for a more comprehensive account of the interaction of sleep and fear systems in PD and PTSD by optimally quantifying domains in which they converge and diverge: arousals from sleep, sleep movements and sleep respiration. In this study, sleep data will be obtained from 180 community-residents, unmedicated, female and male subjects with PD (30 with and 30 without a history of nocturnal panic attacks), PTSD (30 with and 30 without a history of trauma-related nightmares), comorbid PD and PTSD (30), and normal controls. The proposed methods represent an advanced approach to naturalistic sleep data acquisition, combining an initial phase of ambulatory polysomnography (PSG) with extended (21+days) actigraphy and auditory sonography. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRESSOR CONTROLLABILITY: ANXIETY AND SEROTONIN Principal Investigator & Institution: Maier, Steven F.; Professor; Psychology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2001; Project Start 01-APR-1993; Project End 31-MAR-2002 Summary: The degree of behavioral control which an organism has over a stressor (ability to alter the onset, termination, duration, intensity, or temporal pattern of the event) is an important determinant of the behavioral and physiological impact of the stressor. Numerous behavioral, neurochemical, hormonal, and immunological changes follow exposure to a stressor if it is uncontrollable, but not if the identical stressor is controllable. Effects such as these which depend on the uncontrollability of a stressor have been called "learned helplessness effects." They have played an important role in psychological theory, in understanding the physiology of stress, in understanding the environmental regulation of endogenous pain modulation mechanisms and immune function, and have been proposed to be involved in the etiology of numerous human disorders. Depression, anxiety disorders, and post-traumatic stress disorder are but examples. Despite the seeming importance of stressor controllability and the considerable amount of research that has ben directed at explaining its operation, there is still no adequate general explanation at either the behavioral or physiological level. The present proposal is designed to directly test an integrated behavioral and physiological explanation of learned helplessness effects that has emerged during the previous grant period. This hypothesis includes both a description of the immediate neurochemical effects of uncontrollable stressors as well as a putative set of mechanisms for how the behavioral sequalae of such stressors are produced. At a behavioral level the critical argument is that uncontrollable stressors produce intense "anxiety" that dissipates over a 3-5 day period, and that many of the behavioral consequences of these stressors reflect this state of anxiety. At a physiological level it is argued that this state of anxiety involves a temporarily hyper-responsive serotonergic (5-HT) system originating from the dorsal raphe nucleus (DRN) and that the diverse behavioral outcomes of exposure to uncontrollable stressors are produced by excessive 5-HT released in projections of the DRN.

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

Project Title: SYNERGY BETWEEN SSRIS AND OVARIAN HORMONES Principal Investigator & Institution: Van De Kar, Louis D.; Professor; Pharmacol & Exper Therapeutics; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 05-AUG-1999; Project End 31-JUL-2004 Summary: Women suffer from disorders associated with serotonin (5-HT) deficiency, such as premenstrual syndrome (PMS) post-partum and post-menopausal depression, anxiety and bulimia. These mood and impulse control disorders are also associated with fluctuations in ovarian hormone levels. Estrogen can be used to treat some of these disorders, but serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac ) are the most effective drugs currently available. A major problem with SSRIs is the delay (2-3 weeks) in onset of clinical improvement of depression, a time which is associated with increased danger of suicide. Treatment with either fluoxetine or estrogen decreases the sensitivity of hypothalamic 5-HT1A receptor systems. These observations suggest that desensitization of 5-HT1A receptor signalling may underlie the therapeutic effectiveness of estrogen and SSRI treatments. Ovarian hormones act predominantly via genomic mechanisms, while fluoxetine induces adaptive responses via membrane proteins. Therefore, our central hypothesis is that estrogen will act synergistically with fluoxetine via complementary mechanisms to desensitize hypothalamic 5-HT1A receptor systems. Based on this hypothesis, we predict that estrogen or estrogen + progesterone will shorten the delay in the effects of SSRIs. The proposed studies will examine the mechanisms by which estrogen: 1) inhibits 5-HT1A signal transduction systems, and 2) reduces the delay in fluoxetine-induced desensitization of hypothalamic 5-HT1A receptor signalling. The proposed studies will use neuroendocrine, biochemical and molecular approaches to study the following specific aims: Specific Aim 1 will determine the doses of estrogen and progesterone that reduce hypothalamic 5-HT1A receptor function in ovariectomized rats. Specific Aim 2 will identify the estrogen receptor subtype(s) which mediate the effect of estrogen on 5-HT1A receptor systems in the hypothalamus. Specific Aim 3 will determine if estrogen shortens the delay in fluoxetine's effects on 5-HT1A receptor signalling. Specific Aim 4 will determine if progesterone increases estrogen's effectiveness in shortening the delay in fluoxetineinduced 5-HT1A receptor sub-sensitivity. The proposed studies will provide the scientific basis for the development of improved therapeutic regimens and novel drugs that provide faster clinical improvement in women suffering from PMS, depression, bulimia and anxiety disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE CLASSIFICATION OF ANXIETY DISORDER Principal Investigator & Institution: Brown, Timothy A.; Research Associate Professor; Psychology; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-APR-1984; Project End 30-NOV-2006 Summary: Most empirical evaluation of diagnostic systems of emotional disorders (e.g., DSM-IV) has occurred at the categorical/descriptive level (e.g., diagnostic reliability and comorbidity) or has examined categories in isolation of related disorders. These findings provide little information on the validity of our nosology and the validity of conceptual models of the etiology, nature, and course of emotional disorders. Expanding on our

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recent work, research in the next project phase will test hypotheses pertaining to structural models of anxiety and mood disorders and trait variables implicated in the etiology, comorbidity, expression, and course of these disorders. Over 1,750 patients will be assessed using the Anxiety Disorders Interview Schedule: Lifetime version and associated instruments of key features of anxiety and mood disorders and measures of core temperament and personality (e.g., negative affect, behavioral inhibition). Dimensional measures of DSM-IV disorder features and personality, collected crosssectionally and longitudinally, will be submitted to structural equation modeling to test competing models of the latent structure of DSM-IV emotional disorders, trait personality constructs, and their interrelationships. These studies will provide the first large- scale comparative evaluations of models of trait vulnerability and the influence of such constructs on the course of emotional disorders. Further analyses will evaluate the generalizability of the DSM-IV structure and its relationships with higher-order personality dimensions across races, sexes, and ages. Longitudinal analyses will examine the covariation of disorder and personality constructs as a function of psychosocial treatment and across two-year follow-up. Collectively, findings will indicate: (a) the shared, and specific dimensions of anxiety and mood disorders; (b) the possible treatment resiliency of higher-order personality dimensions influencing the course of disorders; (c) important reconceptualizations of personality models of emotional disorders; (d) refinements to the diagnostic definitions of emotional disorders and their cross-cultural aspects in DSM-V. This work will enhance and complement biological approaches to these issues by suggesting a more valid and robust set of disorder and personality constructs on which to base investigations such as familial, genetic, and etiologic studies-these data will foster a fuller integration of biological and psychological approaches to the structure and pathogenesis of emotional disorders. Taxometric studies will be conducted on selected DSM-IV disorders and personality constructs to examine whether these phenomena operate on a continuum or as taxa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE SOCIAL NEUROSCIENCE OF AUTISM AND RELATED DISORDERS Principal Investigator & Institution: Volkmar, Fred R.; Associate Professor; Child Study Center; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): This application requests five years of support for a collaborative, multidisciplinary program of research on social neuroscience in autism and related disorders. This application, submitted as a STAART autism center, builds on important resources and research programs. It is concerned with increasing the understanding of the processes underlying the social-communicative and socialaffective functioning of individuals with autism and related conditions. The focus of the grant is on integrating advances in neuroscience and genetics in understanding specific neurodevelopmental processes and risk factors and using this understanding in treatment studies. Objectives include characterization of visual scanning patterns of social stimuli, development of simple behavioral screening methods for young children at risk for autism, to determine whether young children with symptoms of autism display distinctive listening preferences as compared to developmentally delayed children, to assess the potential utility of computer assisted face training in autism with a goal of improving face perception skills and enhancing fusiform face area activity as seen on fMRI facial expression and normalization of visual scanning. In addition we propose to characterize the nature of anxiety disorders, particularly social anxiety

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disorder, in children and adolescents with PDD and to evaluate the effects of the selective serotonin reuptake inhibitor, fluvoxamine, in a randomized double-blind, placebo-controlled trial. Finally we plan to conduct a series of interrelated genetic studies with the overarching aim of identifying genetic mechanisms of social disability. Six projects and two core resources are proposed. Projects include: (I) Eye tracking studies of social engagement in infants and toddlers with autism, (II) Behavioral indices of joint attention in autism in young children, (III) Precursors to social communication in autism and related disorder, (IV) Molecular and family genetic studies of social phenotypes in autism, (V) Behavioral and neural plasticity in face recognition, and (VI) Fluvoxamine in the treatment of children and adolescents with social anxiety disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE USE OF ELECTROACUPUNCTURE TO MODULATE AROUSAL Principal Investigator & Institution: Garcia-Rill, Edgar E.; Director; Anatomy; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, Ar 72205 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-DEC-2002 Summary: (APPLICANT'S ABSTRACT): The vertex-recorded midlatency auditory evoked P50 potential is a measure of the output of the reticular activating system (RAS). This rapidly-habituating, sleep state-dependent potential is present during waking and paradoxical sleep but absent during slow-wave sleep, i.e. is present only during cortical EEC "desynchronization" or arousal. The amplitude of the P50 potential is decreased in narcolepsy and autism, that is, in diseases in which there appears to be downregulation of the output of the RAS. Using a paired stimulus paradigm, sensory gating of the P50 potential (the ability to habituate to or "filter" repetitive stimuli) can be assessed. There is a deficit in sensory gating of this potential in schizophrenia and anxiety disorders, that is, it diseases in which there appears to be an upregulation of the output of the RAS. We have preliminary data suggesting that electroacupuncture (EA) applied at three specific points may modulate the manifestation of the P50 potential. In a small number of subjects, we found that stimulation using needles was as effective a., stimulation using surface electrodes (an important innovation in the therapeutic use of EA), that stimulation a low frequencies may be more efficacious than stimulation at medium or high frequencies, that stimulation at only two of these points or three unrelated "control" points may be ineffective, and that using multiple episodes o1 stimulation may have additive effects in modulating P50 potential amplitude, suggesting important clinical applications in a number of disorders. The proposed feasibility studies will use larger samples of subjects comparing male vs female, and Caucasian vs African-American, populations to determine with sufficient power that a statistically significant effect on the amplitude of the P50 potential is present or absent under each of these experimental conditions. In addition, sensory gating of the P50 potential will be assessed for each experiments condition, allowing predictions of the effects of such treatment on either the initial manifestation (amplitude o1 the P50 potential induced by the first stimulus of a pair) or the sensory gating (ratio of the amplitudes of the PM potentials induced by the paired stimuli) of this non-invasive measure of RAS function. It may be possible in the future, to use this novel treatment methodology as an adjunct/replacement therapy for disorders of arousal, especially if the effects of multiple episodes of stimulation can be found to affect amplitude and/or sensory gating of the P50 potential for prolonged periods of time. However, the optimal stimulation sites and paradigms muse be identified and proven effective, first, in control populations, and later, in pathological populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THERAPY SPECIFICITY AND MEDIATION IN FAMILY & GROUP CBT Principal Investigator & Institution: Silverman, Wendy K.; Professor; Psychology; Florida International University Division of Sponsored Research and Training Miami, Fl 33199 Timing: Fiscal Year 2002; Project Start 09-JUL-2002; Project End 30-JUN-2007 Summary: Considerable evidence has now accumulated demonstrating the efficacy of Individual Child Cognitive Behavior Therapy for reducing anxiety disorders in children. In growing recognition that the child's context affects the development, course, and outcome of childhood psychopathology and functional status, recent clinical research efforts have been directed toward evaluating whether cognitive behavior therapy when used with anxious children also is efficacious when particular contexts (i.e., family/parents, group/peer) are incorporated in the treatment program. As a result, there now exists considerable empirical evidence that childhood anxiety disorders also can be reduced in cognitive behavioral treatment programs that incorporate family/parents and peer/group contexts and target specific domains/content areas relevant to these contexts. Despite the above, there have been no studies that have directly evaluated whether family/parents and peer/group interventions that target specific domains/variables and content areas relevant to that respective intervention context actually produce specific effects on these domains/variables and, more importantly, whether changes produced on these variables mediate treatment response. Consequently, claims regarding the importance of incorporating (or not incorporating) family/parents and peer/groups and targeting respective variables relevant to each context in order to produce child treatment response are based more on speculation than on empirical data. Investigating whether incorporating family/parents or peer/group contexts and targeting specific domains/variables and content areas relevant to these respective contexts, and whether changes on these variables mediate treatment response in two cognitive behavioral treatments that each represent these distinct contexts (i.e., family/parents and peer/group) among children with anxiety disorders, thus comprise the specific aims of this project. The study targets the same DSM-IV anxiety disorders targeted in previous clinical trials and that are most common in children: social phobia, generalized anxiety disorder, and separation anxiety disorder. Using a controlled clinical trial design, 252 children (ages 8-14 years) and their parents will be admitted to treatment over the five years of the study, yielding an estimated 216 treatment completers at post-test and 180 at one year follow- up. Children and their parents will be randomly assigned to one of two treatment conditions: Family/Parents Cognitive Behavior Therapy (FCBT) and Peer/Group Cognitive Behavior Therapy (GCBT). All participants will be assessed at pretreatment, posttest, and one-year followup. Two sets of hypotheses will be tested. Because each condition represents a distinct treatment context (family/parents and peer/group) that targets the same two domains (skills and relationships) but in two different content areas within each domain (i.e., parenting skills and parent-child relationships in FCBT versus child social skills and peer-child relationships in GCBT), the first set of hypotheses is designed to establish empirically whether there are in fact treatment specific effects. Thus, the first set of hypotheses to be tested is that FCBT will produce significantly greater specific effects on parenting skills and parent-child relationships than on child social skills and peer-child relationships. GCBT, on the other hand, will produce significantly greater specific effects on child social skills and peerchild relationships than on parenting skills and parent-child relationships. The second and more theoretically and practically significant set of hypotheses will test whether or not it is the changes that are produced on these variables that mediate treatment

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response. Thus, the second set of hypotheses to be tested is that parenting skills, parentchild relationships, child social skills and/or peer-child relationships will be significant mediators of treatment response, i.e., anxiety reduction. To test the study's mediational models and to fully examine specificity effects, a multi-analytic approach that includes structural equational modeling and other complex data analytic strategies (e.g., growth curve modeling) will be used. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRAINING IN COMORBIDITY OF ALCOHOLISM AND MENTAL ILLNESS Principal Investigator & Institution: Book, Sarah W.; Psychiatry and Behavioral Scis; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 29-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): This application is designed to provide the candidate, Dr. Sarah Book, with skills and expertise in the treatment of alcoholism and co-occurring psychiatric disorders (psychiatric comorbidity), in general, and cooccurring alcoholism and social phobia, in particular. Psychiatric comorbidity is an area of recent interest to NIAAA, and one where well trained psychiatric researchers are needed. Perhaps more than 60% of individuals with alcoholism suffer from psychiatric comorbidity. This population is more likely to seek alcoholism treatment, their alcohol problems are more severe, and their outcomes tend to be more complicated and less favorable than for those without psychiatric comorbidity. In the past decade, there has been interest in using psychiatric comorbidity to sub-group alcoholics for treatment matching. The anxiety area has received considerably less attention than depression comorbidity, and more research is needed. Dr. Book's goal is to be a clinical-scientist with unique expertise in the treatment of alcoholism and anxiety disorder comorbidity. She desires K23 training to permit the development of a research program to enable her to conduct research, treat patients, and educate future medical professionals about the challenges faced in treating alcoholic individuals with comorbidity. The proposed research integrates her skills developed in clinical treatment of anxiety disorders with more recently acquired ones in treatment of alcohol dependence as inpatient attending in the Center for Drug and Alcohol Programs. The training plan identifies areas to be developed, including mastery of the literature, delivery of cognitive behavioral therapy for alcohol treatment, and exploration of gender differences in alcohol use disorders and psychiatric comorbidity. She will refine skills in critical reasoning, and develop skills in quantitative methods and grant writing. This award will allow Dr. Book protected time from her extensive clinical, education, and administrative responsibilities as an inpatient attending to further develop her research skills. Her ultimate goal is to become an independent clinical researcher, while still treating patients and providing didactic substance abuse education to future generations of medical professionals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TREATING ANXIETY IN PUBLIC SECTOR MEDICAL SETTINGS Principal Investigator & Institution: Roy-Byrne, Peter P.; Professor; Psychiatry and Behavioral Scis; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: (provided by candidate): This is a mid-career investigator award in patientoriented research that is designed to strengthen my research and further the development and growth of young investigators in the application of evidence based

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treatments, especially for anxiety disorders, in public sector medical settings. Poor and medically disadvantaged populations are clearly underrepresented in research studies, especially in treatment studies. We clearly need more clinical investigators to work in these settings and with these populations. There also is a need for public sector research infrastructures that will support state-of-the-art research. Finally, given the deficiencies in quality of care for anxiety disorders in most medical settings, but especially the public sector, we need to know how to best tailor and deliver evidence-based treatments. My three goals for this Mid-Career Investigator Award in Patient-Oriented Research (K24) are therefore (1) to crystallize a new career research focus in translational research that would increase the relevance, speed the development, and facilitate the utilization of research-focused treatments and services interventions for anxiety disorders in the public sector medical setting; (2) to create a practice infrastructure that supports state-of-the-art research on the application of evidence based treatments in public sector medical settings; (3) to mentor junior investigators interested in research on the application of evidence-based treatments in the public sector. My broad background in clinical research will allow me to relate to the developing clinicianscientist across multiple levels of research interest and to steer them toward the field of services research. As my skills in this latter area evolve over the course of this award, I hope to be able to mentor them even more effectively in this specific area as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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

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(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 •

Project Title: TREATMENT CHILDHOOD

OF

SEPARATION

ANXIETY

DISORDER

IN

Principal Investigator & Institution: Pincus, Donna B.; Psychologist; Psychology; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 07-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): This application is a request for a Mentored PatientOriented Research Career Development Award (K23) from the NIMH to foster the academic career development of the applicant, Donna B. Pincus, Ph.D. The applicant will work closely with her primary mentor, Dr. David Barlow, and co-mentors, Dr. Sheila Eyberg, Dr. Thomas Ollendick, Dr. Anne Marie Albano, and Dr. Simon Budman, to develop expertise in conducting clinical research to establish innovative and efficacious interventions for young children with anxiety disorders. In a career development plan spanning five years, the applicant has delineated specific short-term and long-term goals to prepare her for a patient-oriented research career. Short term goals include obtaining additional didactic training and mentoring in several "core" areas that have been chosen to deepen her existing skills as well as expand her skills into new areas. The applicant's long term goals are to develop a programmatic line of research that is focused on developing efficacious, innovative treatments for childhood anxiety disorders, and to launch a highly productive research career as a clinical scientist. A formal research plan is proposed to investigate the most prevalent, yet most under-researched anxiety disorder in childhood: Separation Anxiety Disorder (SAD). Despite growing evidence that SAD is prevalent in young children and linked to later psychopathology, there have been few treatment studies investigating the efficacy of interventions for SAD; those that do exist typically have not included young children. Recent experimental evidence highlights the potential clinical utility of incorporating parents more centrally in the treatment of childhood anxiety disorders. The primary goal of the proposed research plan is to apply an existing, empirically supported parent training intervention (Parent-Child Interaction Therapy; PCIT) to the treatment of children ages 4-8 with SAD. Although originally designed as a treatment of oppositional children, PCIT incorporates each of the skills anxiety researchers have indicated as essential training components for reducing child anxiety, and thus, is expected to be effective in reducing children's separation fearful behaviors and in promoting improved parent-child interactions. The specific goals of this project are: (1) to evaluate the efficacy of PCIT for reducing separation anxious behaviors in young children (2) to assess long term maintenance of change at 3, 6, and 12 months following treatment (3) to investigate potential mechanisms of improvement. This research project will be the first controlled clinical trial that has been conducted with very young children with separation anxiety, and thus, will begin to fill in a significant gap in our knowledge of this at-risk population. This project will provide the applicant with a solid foundation of skills for the continued development of innovative, empirically validated interventions for children with anxiety disorders and their families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TREATMENT OUTCOMES FOR CHILDREN WITH ANXIETY DISORDERS Principal Investigator & Institution: Rynn, Moira A.; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 02-AUG-2000; Project End 31-JUL-2005 Summary: This application proposes Moira A. Rynn, M.D. for a Mentored PatientOriented Research Career Development Award at the University of Pennsylvania. The aims of this program include: 1) to support my development into an independent research scientist; 2) to support and enhance my development as an investigator in anxiety disorders in children and adolescents; 3) to develop my ability to use my clinical experience to design and execute a protocol that will answer a proposed research question; and 4) to provide the groundwork for the preparation of an RO1 grant application based on the research performed during the award period. These aims will be accomplished through a structured four-part plan: 1) to complete a Master's of Science of Clinical Epidemiology, a program of formal academic courses and tutorials to enhance my research skills, under the supervision of Dr. Brian Strom; 2) to obtain research training and mentoring by a senior scientist who will serve as my sponsor (Karl Rickels, M.D.) as well as by a co-sponsor (Edna Foa, Ph.D) and collaborators (Elizabeth Weller, M.D., Irwin Lucki, Ph.D., John March, M.D., M.P.H., Brian Strom, M.D., M.P.H., and Philip C. Kendall, Ph.D., ABPP); 3) to participate in several ongoing psychopharmacological trials for anxiety and depression in both children and adults in the Mood and Anxiety Disorders Section; and 4) to design and execute an original clinical research treatment protocol. Children aged 8 to 12 years and 11 months who meet the diagnosis of generalized anxiety disorder, separation anxiety disorder, or anxiety disorder nos will enter a randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of 50 mg sertraline per day (Pt N = 60). I also will evaluate the moderating effect the presence of parental psychopathology has on the child's level of impairment, onset of disorder and response to medication treatment. Families will be followed for one year to collect for further research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TWIN COMORBIDITY

STUDY

OF

SEPARATION

ANXIETY

DISORDER

Principal Investigator & Institution: Cronk, Nikole J.; Psychological Sciences; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Comorbidity among anxiety and depressive disorders has been well documented, yet the etiological pathways contributing to this comorbidity are not clearly understood. Most of the research regarding the genetic and environmental sources of comorbidity among these disorders has been conducted using adult samples and suggests that genetic and nonshared environmental sources of covariation are important. Relatively little is known about the behavioral genetic aspects of comorbidity among anxiety and depressive disorders in children and adolescents. In an effort to extend the current knowledge regarding the comorbidity of internalizing disorders to younger populations, the proposed research will employ data from a large population-based sample of female twins to explore the comorbidity among Separation Anxiety Disorder (SAD), Depression (DEP) and Generalized Anxiety Disorder (GAD) and parse the sources of comorbidity into latent genetic and environmental factors using multivariate genetic analyses. In addition, the proposed research seeks to further clarify

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the nature of comorbidity of SAD with DEP and GAD by including measured personality (introversion and neuroticism) and environmental characteristics (socioeconomic disadvantage and paternal absence) in multivariate genetic analyses. Advances have been made in the study of comorbidity as well as personality and environmental characteristics as risk factors for internalizing disorders among youth; yet, these areas of study remain largely independent of one another. The proposed project seeks to integrate these areas of investigation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VESTIBULO-CEREBELLAR CIRCUITS Principal Investigator & Institution: Balaban, Carey D.; Professor; Otolaryngology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-MAR-1990; Project End 31-MAY-2008 Summary: (provided by applicant): The proposed neuroanatomical and electrophysiological studies continue investigations of the organization of pathways that mediate vestibular influences on autonomic and limbic pathways, particularly in pathways that mediate the linkage between balance disorders and anxiety disorders. Three circuitry networks appear to be critical for balance-anxiety link: a vestibuloparabrachial nucleus (PBN) network, coeruleo-vestibular (noraderenergic) network and raphe-vestibular (serotonergic and non-serotonergic) networks. The physiology and connections of the PBN network will be studied in primates; the organization of the noradrenergic and raphe pathways will be explored in rats. Our on-going primate studies have shown that a caudal region of PBN contains neurons that receive vestibular nuclear input and are sensitive to whole body rotation. New electrophysiologic studies in alert primates are directed at elucidating the spatial organization of responses of parabrachial nucleus neurons during whole body rotation. Two main foci will be characterization of otolith-related responses and a test of the hypothesis that responses will differ for predictable and unpredictable whole body rotation in three dimensions. Anatomical studies in primates are also designed elucidate the afferent and efferent connections of this vestibulo-recipient region of PBN. Our on-going studies have shown that the dorsal raphe nucleus, nucleus raphe obscurus and nucleus raphe pallidus provide serotonergic input to the vestibular nuclei. Anatomical studies will elucidate the topography of these projections, the distribution of immunoreactive serotonin receptors in the vestibular nuclei and test specific hypotheses regarding the organization of collateralized raphe projections to the vestibular nuclei and other sites. Finally, anatomical studies in rats will test specific hypotheses regarding the organization of collateralized noradrenergic projections to the vestibular nuclei and other sites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and 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.

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unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “anxiety 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 anxiety disorders in the PubMed Central database: •

Neuroactive steroids and anxiety disorders. by Melledo JM, Baker GB.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161645

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Persistent Elevations of Cerebrospinal Fluid Concentrations of CorticotropinReleasing Factor in Adult Nonhuman Primates Exposed to Early-Life Stressors: Implications for the Pathophysiology of Mood and Anxiety Disorders. by Coplan JD, Andrews MW, Rosenblum LA, Owens MJ, Friedman S, Gorman JM, Nemeroff CB.; 1996 Feb 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39991

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Rapid resolution of social anxiety disorder, selective mutism, and separation anxiety with paroxetine in an 8-year-old girl. by Lehman RB.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161642

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Treatment Plans and Interventions for Depression and Anxiety Disorders. by Antony MM.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=167202

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

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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•

A comparison of completers and noncompleters of exposure-based cognitive and behavioral treatment for phobic and anxiety disorders in youth. Author(s): Pina AA, Silverman WK, Weems CF, Kurtines WM, Goldman ML. Source: Journal of Consulting and Clinical Psychology. 2003 August; 71(4): 701-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924675&dopt=Abstract

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A contemporary protocol to assist primary care physicians in the treatment of panic and generalized anxiety disorders. Author(s): Rollman BL, Herbeck Belnap B, Reynolds CF, Schulberg HC, Shear MK. Source: General Hospital Psychiatry. 2003 March-April; 25(2): 74-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676419&dopt=Abstract

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A descriptive and comparative study of the prevalence of depressive and anxiety disorders in low-income adults with type 2 diabetes and other chronic illnesses. Author(s): Thomas J, Jones G, Scarinci I, Brantley P. Source: Diabetes Care. 2003 August; 26(8): 2311-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882854&dopt=Abstract

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A general anxiety-prone cognitive style in anxiety disorders. Author(s): Uhlenhuth EH, Starcevic V, Warner TD, Matuzas W, McCarty T, Roberts B, Jenkusky S. Source: Journal of Affective Disorders. 2002 August; 70(3): 241-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12128236&dopt=Abstract

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A Web-based screening instrument for depression and anxiety disorders in primary care. Author(s): Farvolden P, McBride C, Bagby RM, Ravitz P. Source: Journal of Medical Internet Research [electronic Resource]. 2003 July-September; 5(3): E23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517114&dopt=Abstract

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Amygdaloid regional cerebral blood flow and subjective fear during symptom provocation in anxiety disorders. Author(s): Fredrikson M, Furmark T. Source: Annals of the New York Academy of Sciences. 2003 April; 985: 341-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724169&dopt=Abstract

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Anatomical MRI findings in mood and anxiety disorders. Author(s): Brambilla P, Barale F, Caverzasi E, Soares JC. Source: Epidemiol Psichiatr Soc. 2002 April-June; 11(2): 88-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12212470&dopt=Abstract

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•

Anxiety and anxiety disorders. Author(s): Karasic D. Source: Focus. 1996 November; 11(12): 5-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206111&dopt=Abstract

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Anxiety disorders and disability secondary to urinary incontinence among adults over age 50. Author(s): Bogner HR, Gallo JJ, Swartz KL, Ford DE. Source: International Journal of Psychiatry in Medicine. 2002; 32(2): 141-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269595&dopt=Abstract

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Anxiety disorders and other psychiatric subgroups in patients complaining of dizziness. Author(s): Eckhardt-Henn A, Breuer P, Thomalske C, Hoffmann SO, Hopf HC. Source: Journal of Anxiety Disorders. 2003; 17(4): 369-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826087&dopt=Abstract

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Anxiety disorders and the onset of depression among adults in the community. Author(s): Goodwin RD. Source: Psychological Medicine. 2002 August; 32(6): 1121-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12214791&dopt=Abstract

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Anxiety disorders associated with traumatic brain injuries. Author(s): Hiott DW, Labbate L. Source: Neurorehabilitation. 2002; 17(4): 345-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547982&dopt=Abstract

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Anxiety disorders in 318 bipolar patients: prevalence and impact on illness severity and response to mood stabilizer. Author(s): Henry C, Van den Bulke D, Bellivier F, Etain B, Rouillon F, Leboyer M. Source: The Journal of Clinical Psychiatry. 2003 March; 64(3): 331-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716276&dopt=Abstract

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Anxiety disorders in children: intervention strategies for the primary care setting. Author(s): Clift G. Source: Journal of Pediatric Health Care : Official Publication of National Association of Pediatric Nurse Associates & Practitioners. 2002 September-October; 16(5): 253-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226594&dopt=Abstract

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Anxiety disorders in subjects seeking treatment for eating disorders: a DSM-IV controlled study. Author(s): Godart NT, Flament MF, Curt F, Perdereau F, Lang F, Venisse JL, Halfon O, Bizouard P, Loas G, Corcos M, Jeammet P, Fermanian J. Source: Psychiatry Research. 2003 March 25; 117(3): 245-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686367&dopt=Abstract

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Anxiety disorders in women: a developmental and lifecycle perspective. Author(s): Halbreich U. Source: Depression and Anxiety. 2003; 17(3): 107-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768644&dopt=Abstract

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Anxiety disorders. Author(s): Chen JP, Reich L, Chung H. Source: The Western Journal of Medicine. 2002 September; 176(4): 249-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208831&dopt=Abstract

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Behavioral and cerebrovascular effects of caffeine in patients with anxiety disorders. Author(s): Mathew RJ, Wilson WH. Source: Acta Psychiatrica Scandinavica. 1990 July; 82(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2399815&dopt=Abstract

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Behavioral inhibition in childhood: a risk factor for anxiety disorders. Author(s): Rosenbaum JF, Biederman J, Bolduc-Murphy EA, Faraone SV, Chaloff J, Hirshfeld DR, Kagan J. Source: Harvard Review of Psychiatry. 1993 May-June; 1(1): 2-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9384823&dopt=Abstract

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Behavioral, psychotic, and anxiety disorders in epilepsy: etiology, clinical features, and therapeutic implications. Author(s): Torta R, Keller R. Source: Epilepsia. 1999; 40 Suppl 10: S2-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10609602&dopt=Abstract

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Behavioural approaches to anxiety disorders. Author(s): Drummond LM. Source: Postgraduate Medical Journal. 1993 March; 69(809): 222-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8497438&dopt=Abstract

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Behavioural inhibition, attachment and anxiety in children of mothers with anxiety disorders. Author(s): Manassis K, Bradley S, Goldberg S, Hood J, Swinson RP. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1995 March; 40(2): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7788623&dopt=Abstract

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Benefits of a nurse-psychiatrist collaborative practice in an anxiety disorders unit. Author(s): Schurmans K, McCrank E. Source: Journal of Psychosocial Nursing and Mental Health Services. 1997 November; 35(11): 26-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9395986&dopt=Abstract

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Benzodiazepine receptor function in anxiety disorders. Author(s): Malizia AL, Coupland NJ, Nutt DJ. Source: Adv Biochem Psychopharmacol. 1995; 48: 115-33. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7653322&dopt=Abstract

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Benzodiazepines for anxiety disorders. Are the concerns justified? Author(s): Rifkin A. Source: Postgraduate Medicine. 1990 January; 87(1): 209-11, 215-6, 219. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2404265&dopt=Abstract

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Benzodiazepines in anxiety disorders: managing therapeutics and dependence. Author(s): Norman TR, Ellen SR, Burrows GD. Source: The Medical Journal of Australia. 1997 November 3; 167(9): 490-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9397065&dopt=Abstract

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Beta-blockers in anxiety disorders. Author(s): Hayes PE, Schulz SC. Source: Journal of Affective Disorders. 1987 September-October; 13(2): 119-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2890677&dopt=Abstract

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Betaxolol in anxiety disorders. Author(s): Swartz CM. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1998 March; 10(1): 9-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9622045&dopt=Abstract

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Biased attention in childhood anxiety disorders: a preliminary study. Author(s): Vasey MW, Daleiden EL, Williams LL, Brown LM. Source: Journal of Abnormal Child Psychology. 1995 April; 23(2): 267-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7642837&dopt=Abstract

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Biological dissection of anxiety disorders: the clinical role of selective serotonin reuptake inhibitors with particular reference to fluvoxamine. Author(s): den Boer JA, Westenberg HG, De Leeuw AS, van Vliet IM. Source: International Clinical Psychopharmacology. 1995 January; 9 Suppl 4: 47-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7622824&dopt=Abstract

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Body dysmorphic disorder in patients with anxiety disorders and major depression: a comorbidity study. Author(s): Brawman-Mintzer O, Lydiard RB, Phillips KA, Morton A, Czepowicz V, Emmanuel N, Villareal G, Johnson M, Ballenger JC. Source: The American Journal of Psychiatry. 1995 November; 152(11): 1665-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7485632&dopt=Abstract

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Brain blood flow in anxiety disorders. OCD, panic disorder with agoraphobia, and post-traumatic stress disorder on 99mTcHMPAO single photon emission tomography (SPET). Author(s): Lucey JV, Costa DC, Adshead G, Deahl M, Busatto G, Gacinovic S, Travis M, Pilowsky L, Ell PJ, Marks IM, Kerwin RW. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1997 October; 171: 346-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9373423&dopt=Abstract

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Brain imaging studies in mood and anxiety disorders: special emphasis on the amygdala. Author(s): Anand A, Shekhar A. Source: Annals of the New York Academy of Sciences. 2003 April; 985: 370-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724172&dopt=Abstract

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Buspirone for anxiety disorders in patients with severe lung disease. Author(s): Craven J, Sutherland A. Source: Lancet. 1991 July 27; 338(8761): 249. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1676794&dopt=Abstract

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Capsulotomy for refractory anxiety disorders: long-term follow-up of 26 patients. Author(s): Ruck C, Andreewitch S, Flyckt K, Edman G, Nyman H, Meyerson BA, Lippitz BE, Hindmarsh T, Svanborg P, Mindus P, Asberg M. Source: The American Journal of Psychiatry. 2003 March; 160(3): 513-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611833&dopt=Abstract

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Characteristics of patients with social phobia and their treatment in specialized clinics for anxiety disorders in the Netherlands. Author(s): Dingemans AE, van Vliet IM, Couvee J, Westenberg HG. Source: Journal of Affective Disorders. 2001 July; 65(2): 123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11356235&dopt=Abstract

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Childhood adversities associated with major depression and/or anxiety disorders in a community sample of Ontario: issues of co-morbidity and specificity. Author(s): Levitan RD, Rector NA, Sheldon T, Goering P. Source: Depression and Anxiety. 2003; 17(1): 34-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577276&dopt=Abstract

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Childhood anxiety disorders: etiology, assessment, and treatment in the new millennium. Author(s): Morris TL. Source: Current Psychiatry Reports. 2001 August; 3(4): 267-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11470032&dopt=Abstract

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Childhood anxiety disorders: parent-child (dis)agreement using a structured interview for the DSM-IV. Author(s): Choudhury MS, Pimentel SS, Kendall PC. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 August; 42(8): 957-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874498&dopt=Abstract

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Childhood history of anxiety disorders among adults with social phobia: rates, correlates, and comparisons with patients with panic disorder. Author(s): Otto MW, Pollack MH, Maki KM, Gould RA, Worthington JJ 3rd, Smoller JW, Rosenbaum JF. Source: Depression and Anxiety. 2001; 14(4): 209-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754127&dopt=Abstract

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Clinician recognition of anxiety disorders in depressed outpatients. Author(s): Zimmerman M, Chelminski I. Source: Journal of Psychiatric Research. 2003 July-August; 37(4): 325-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765855&dopt=Abstract

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Cognitive behavior therapy (CBT) in anxiety disorders. Author(s): Marom S, Hermesh H. Source: The Israel Journal of Psychiatry and Related Sciences. 2003; 40(2): 135-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509204&dopt=Abstract

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Cognitive ERPs in depressive and anxiety disorders during tonal and phonetic oddball tasks. Author(s): Bruder GE, Kayser J, Tenke CE, Leite P, Schneier FR, Stewart JW, Quitkin FM. Source: Clin Electroencephalogr. 2002 July; 33(3): 119-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192661&dopt=Abstract

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Comorbid anxiety disorders in civilians seeking treatment for posttraumatic stress disorder. Author(s): Zayfert C, Becker CB, Unger DL, Shearer DK. Source: Journal of Traumatic Stress. 2002 February; 15(1): 31-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936720&dopt=Abstract

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Comorbidity between eating disorders and anxiety disorders: a review. Author(s): Godart NT, Flament MF, Perdereau F, Jeammet P. Source: The International Journal of Eating Disorders. 2002 November; 32(3): 253-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210640&dopt=Abstract

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Comorbidity fails to account for the relationship of expressed emotion and perceived criticism to treatment outcome in patients with anxiety disorders. Author(s): Renshaw KD, Chambless D, Steketee G. Source: Journal of Behavior Therapy and Experimental Psychiatry. 2001 September; 32(3): 145-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934127&dopt=Abstract

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Comorbidity in childhood anxiety disorders and treatment outcome. Author(s): Kendall PC, Brady EU, Verduin TL. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 July; 40(7): 787-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11437017&dopt=Abstract

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Comorbidity of depression and anxiety disorders in later life. Author(s): Lenze EJ, Mulsant BH, Shear MK, Alexopoulos GS, Frank E, Reynolds CF 3rd. Source: Depression and Anxiety. 2001; 14(2): 86-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668661&dopt=Abstract

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Comorbidity of mood and anxiety disorders: the rule, not the exception? Author(s): Nemeroff CB. Source: The American Journal of Psychiatry. 2002 January; 159(1): 3-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772680&dopt=Abstract

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Comparing anxiety disorders and anxiety-related traits in bipolar disorder and unipolar depression. Author(s): Simon NM, Smoller JW, Fava M, Sachs G, Racette SR, Perlis R, Sonawalla S, Rosenbaum JF. Source: Journal of Psychiatric Research. 2003 May-June; 37(3): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650739&dopt=Abstract

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Concurrent validity of the anxiety disorders section of the Anxiety Disorders Interview Schedule for DSM-IV: child and parent versions. Author(s): Wood JJ, Piacentini JC, Bergman RL, McCracken J, Barrios V. Source: Journal of Clinical Child and Adolescent Psychology : the Official Journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53. 2002 September; 31(3): 335-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149971&dopt=Abstract

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Considerations in the treatment of anxiety disorders: a pharmacoeconomic review. Author(s): Grudzinski AN. Source: Expert Opinion on Pharmacotherapy. 2001 October; 2(10): 1557-69. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11825299&dopt=Abstract

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Consumers who call the Anxiety Disorders Association of America: characteristics and satisfaction. Author(s): Kramer ML, Ross J, Davidson JR. Source: The Journal of Nervous and Mental Disease. 2001 May; 189(5): 328-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11379978&dopt=Abstract

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Course and outcome of anxiety disorders in adolescents. Author(s): Essau CA, Conradt J, Petermann F. Source: Journal of Anxiety Disorders. 2002; 16(1): 67-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171214&dopt=Abstract

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Datapoints: prescription patterns for mood and anxiety disorders in a community sample. Author(s): Mojtabai R. Source: Psychiatric Services (Washington, D.C.). 1999 December; 50(12): 1557. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10577871&dopt=Abstract

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Death obsession in Egyptian samples: differences among people with anxiety disorders, schizophrenia, addictions, and normals. Author(s): Abdel-Khalek AM. Source: Death Studies. 2002 June; 26(5): 413-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12046617&dopt=Abstract

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Delayed posttraumatic stress disorder (PTSD) and predictors of first onset of PTSD in patients with anxiety disorders. Author(s): Zlotnick C, Bruce SE, Shea MT, Keller MB. Source: The Journal of Nervous and Mental Disease. 2001 June; 189(6): 404-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434644&dopt=Abstract

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Depression and anxiety disorders among Jews from the former Soviet Union five years after their immigration to Israel. Author(s): Zilber N, Lerner Y, Eidelman R, Kertes J. Source: International Journal of Geriatric Psychiatry. 2001 October; 16(10): 993-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11607945&dopt=Abstract

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Depression and anxiety disorders associated with headache frequency. The NordTrondelag Health Study. Author(s): Zwart JA, Dyb G, Hagen K, Odegard KJ, Dahl AA, Bovim G, Stovner LJ. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2003 March; 10(2): 147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603289&dopt=Abstract

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Depression and anxiety disorders. Author(s): Brown CS. Source: Obstetrics and Gynecology Clinics of North America. 2001 June; 28(2): 241-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430175&dopt=Abstract

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Depressive and anxiety disorders in women with HIV infection. Author(s): Morrison MF, Petitto JM, Ten Have T, Gettes DR, Chiappini MS, Weber AL, Brinker-Spence P, Bauer RM, Douglas SD, Evans DL. Source: The American Journal of Psychiatry. 2002 May; 159(5): 789-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986133&dopt=Abstract

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Development and vulnerability: new perspectives for anxiety disorders. Author(s): Foote SL. Source: Biological Psychiatry. 1999 December 1; 46(11): 1457-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599475&dopt=Abstract

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Diagnosis at the first episode to differentiate antidepressant treatment responses in patients with mood and anxiety disorders. Author(s): de Kemp EC, Moleman P, Hoogduin CA, Broekman TG, Goedhart A, Schaap CP, van den Berg PC. Source: Psychopharmacology. 2002 February; 160(1): 67-73. Epub 2001 November 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862375&dopt=Abstract

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Dichotic listening and response inhibition in children with comorbid anxiety disorders and ADHD. Author(s): Manassis K, Tannock R, Barbosa J. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2000 September; 39(9): 1152-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10986812&dopt=Abstract

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Differential carbon dioxide sensitivity in childhood anxiety disorders and nonill comparison group. Author(s): Pine DS, Klein RG, Coplan JD, Papp LA, Hoven CW, Martinez J, Kovalenko P, Mandell DJ, Moreau D, Klein DF, Gorman JM. Source: Archives of General Psychiatry. 2000 October; 57(10): 960-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11015814&dopt=Abstract

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Differential metabolization of the impact of life events on subjects hospitalized for depressive and anxiety disorders: case-control study. Author(s): Amiel-Lebigre F, Chevalier A. Source: Social Psychiatry and Psychiatric Epidemiology. 2002 February; 37(2): 74-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931091&dopt=Abstract

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Differential occurrence of comorbidity within childhood anxiety disorders. Author(s): Verduin TL, Kendall PC. Source: Journal of Clinical Child and Adolescent Psychology : the Official Journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53. 2003 June; 32(2): 290-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679288&dopt=Abstract

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Differentiating anxious and depressive self-statements in youth: factor structure of the Negative Affect Self-Statement Questionnaire among youth referred to an anxiety disorders clinic. Author(s): Lerner J, Safren SA, Henin A, Warman M, Heimberg RG, Kendall PC. Source: Journal of Clinical Child Psychology. 1999 March; 28(1): 82-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10070609&dopt=Abstract

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Disability measurement in the anxiety disorders: comparison of three brief measures. Author(s): Sanderson K, Andrews G, Jelsma W. Source: Journal of Anxiety Disorders. 2001 July-August; 15(4): 333-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474818&dopt=Abstract

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Disgust sensitivity, trait anxiety and anxiety disorders symptoms in normal children. Author(s): Muris P, Merckelbach H, Schmidt H, Tierney S. Source: Behaviour Research and Therapy. 1999 October; 37(10): 953-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10472712&dopt=Abstract

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Drug treatment of anxiety disorders in children. Author(s): Coyle JT. Source: The New England Journal of Medicine. 2001 April 26; 344(17): 1326-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11320394&dopt=Abstract

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Drug treatment of anxiety disorders: update 1987. Author(s): Noyes R Jr. Source: Journal of Affective Disorders. 1987 September-October; 13(2): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2890680&dopt=Abstract

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DSM-III classification of the anxiety disorders: a psychometric study. Author(s): Turner SM, McCann BS, Beidel DC, Mezzich JE. Source: Journal of Abnormal Psychology. 1986 May; 95(2): 168-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3711441&dopt=Abstract

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Early childhood predictors of adult anxiety disorders. Author(s): Kagan J, Snidman N. Source: Biological Psychiatry. 1999 December 1; 46(11): 1536-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599481&dopt=Abstract

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Early intervention and prevention of anxiety disorders in children: results at 2-year follow-up. Author(s): Dadds MR, Holland DE, Laurens KR, Mullins M, Barrett PM, Spence SH. Source: Journal of Consulting and Clinical Psychology. 1999 February; 67(1): 145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10028219&dopt=Abstract

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Eating disorders and antecedent anxiety disorders: a controlled study. Author(s): Bulik CM, Sullivan PF, Fear JL, Joyce PR. Source: Acta Psychiatrica Scandinavica. 1997 August; 96(2): 101-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9272193&dopt=Abstract

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Economic costs of anxiety disorders. Author(s): DuPont RL, Rice DP, Miller LS, Shiraki SS, Rowland CR, Harwood HJ. Source: Anxiety. 1996; 2(4): 167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9160618&dopt=Abstract

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Effect of a serotonin precursor and uptake inhibitor in anxiety disorders; a doubleblind comparison of 5-hydroxytryptophan, clomipramine and placebo. Author(s): Kahn RS, Westenberg HG, Verhoeven WM, Gispen-de Wied CC, Kamerbeek WD. Source: International Clinical Psychopharmacology. 1987 January; 2(1): 33-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3312397&dopt=Abstract

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Effect of serotonin uptake inhibitors in anxiety disorders; a double-blind comparison of clomipramine and fluvoxamine. Author(s): den Boer JA, Westenberg HG, Kamerbeek WD, Verhoeven WM, Kahn RS. Source: International Clinical Psychopharmacology. 1987 January; 2(1): 21-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3117876&dopt=Abstract

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Effects of alcohol on baseline startle and prepulse inhibition in young men at risk for alcoholism and/or anxiety disorders. Author(s): Grillon C, Sinha R, Ameli R, O'Malley SS. Source: J Stud Alcohol. 2000 January; 61(1): 46-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10627096&dopt=Abstract

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Efficacy of fluvoxamine in the treatment of major depression with comorbid anxiety disorders. Author(s): Sonawalla SB, Spillmann MK, Kolsky AR, Alpert JE, Nierenberg AA, Rosenbaum JF, Fava M. Source: The Journal of Clinical Psychiatry. 1999 September; 60(9): 580-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10520975&dopt=Abstract

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Electroencephalographic asymmetries in adolescents with major depression: influence of comorbidity with anxiety disorders. Author(s): Kentgen LM, Tenke CE, Pine DS, Fong R, Klein RG, Bruder GE. Source: Journal of Abnormal Psychology. 2000 November; 109(4): 797-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11196007&dopt=Abstract

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Empirically supported treatments for children with phobic and anxiety disorders: current status. Author(s): Ollendick TH, King NJ. Source: Journal of Clinical Child Psychology. 1998 June; 27(2): 156-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9648033&dopt=Abstract

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Enhanced stress reactivity in paediatric anxiety disorders: implications for future cardiovascular health. Author(s): Monk C, Kovelenko P, Ellman LM, Sloan RP, Bagiella E, Gorman JM, Pine DS. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2001 June; 4(2): 199-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11468091&dopt=Abstract

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Escitalopram : a review of its use in the management of major depressive and anxiety disorders. Author(s): Waugh J, Goa KL. Source: Cns Drugs. 2003; 17(5): 343-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665392&dopt=Abstract

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Etiology and pathogenesis of anxiety disorders. Author(s): Sher L. Source: Medical Hypotheses. 2001 July; 57(1): 101-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421635&dopt=Abstract

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Evaluating and treating anxiety disorders in medical settings. Author(s): Ball S, Goddard A, Shekhar A. Source: Journal of Postgraduate Medicine. 2002 October-December; 48(4): 317-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571395&dopt=Abstract

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Evaluation of cognitive-behavioral group treatments for childhood anxiety disorders. Author(s): Barrett PM. Source: Journal of Clinical Child Psychology. 1998 December; 27(4): 459-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9866083&dopt=Abstract

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Explicit memory in anxiety disorders. Author(s): Becker ES, Roth WT, Andrich M, Margraf J. Source: Journal of Abnormal Psychology. 1999 February; 108(1): 153-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10067001&dopt=Abstract

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Exposure-based cognitive-behavioral treatment for phobic and anxiety disorders: treatment effects and maintenance for Hispanic/Latino relative to European-American youths. Author(s): Pina AA, Silverman WK, Fuentes RM, Kurtines WM, Weems CF. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 October; 42(10): 1179-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14560167&dopt=Abstract

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Extralinguistic speech characteristics of children with conduct and anxiety disorders. Author(s): Kotsopoulos S, Mellor C. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 1986 January; 27(1): 99-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3949911&dopt=Abstract

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Facial expression recognition in adolescents with mood and anxiety disorders. Author(s): McClure EB, Pope K, Hoberman AJ, Pine DS, Leibenluft E. Source: The American Journal of Psychiatry. 2003 June; 160(6): 1172-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777278&dopt=Abstract

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Fact or artifact--a comment on “Subpopulations of early separation anxiety: relevance to risk of adult anxiety disorders”. Author(s): Stravynski A, Amado D. Source: Journal of Affective Disorders. 2001 October; 66(2-3): 281. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11578683&dopt=Abstract

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Failure to find DUP25 in patients with anxiety disorders, in control individuals, or in previously reported positive control cell lines. Author(s): Tabiner M, Youings S, Dennis N, Baldwin D, Buis C, Mayers A, Jacobs PA, Crolla JA. Source: American Journal of Human Genetics. 2003 March; 72(3): 535-8. Epub 2003 January 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548501&dopt=Abstract

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Familial predictors of treatment outcome in childhood anxiety disorders. Author(s): Crawford AM, Manassis K. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 October; 40(10): 1182-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589531&dopt=Abstract

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Familial psychiatric illness and posttraumatic stress disorder: findings from a family study of substance abuse and anxiety disorders. Author(s): Dierker LC, Merikangas KR. Source: The Journal of Clinical Psychiatry. 2001 September; 62(9): 715-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11681768&dopt=Abstract

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Family study of co-morbidity between major depressive disorder and anxiety disorders. Author(s): Klein DN, Lewinsohn PM, Rohde P, Seeley JR, Shankman SA. Source: Psychological Medicine. 2003 May; 33(4): 703-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785472&dopt=Abstract

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First onset of depressive or anxiety disorders predicted by the longitudinal course of internalizing symptoms and parent-adolescent disagreements. Author(s): Rueter MA, Scaramella L, Wallace LE, Conger RD. Source: Archives of General Psychiatry. 1999 August; 56(8): 726-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10435607&dopt=Abstract

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First-time hospitalisation for depressive and/or anxiety disorders and severe life events. Author(s): Amiel-Lebigre F, Lacalmontie E, Menard F. Source: Social Psychiatry and Psychiatric Epidemiology. 2002 December; 37(12): 586-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12545236&dopt=Abstract

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FISH, flexible joints and panic: are anxiety disorders really expressions of instability in the human genome? Author(s): Collier DA. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2002 December; 181: 457-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456511&dopt=Abstract

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Five group comparisons of treatments for anxiety disorders. Author(s): Sharp DM, Power KG, Simpson RJ. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1995 December; 167(6): 820-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8829755&dopt=Abstract

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Fluoxetine for the treatment of childhood anxiety disorders. Author(s): Birmaher B, Axelson DA, Monk K, Kalas C, Clark DB, Ehmann M, Bridge J, Heo J, Brent DA. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 April; 42(4): 415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649628&dopt=Abstract

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Fluoxetine treatment of depressed patients with comorbid anxiety disorders. Author(s): Sonawalla SB, Farabaugh A, Johnson MW, Morray M, Delgado ML, Pingol MG, Rosenbaum JF, Fava M. Source: Journal of Psychopharmacology (Oxford, England). 2002 September; 16(3): 2159. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236627&dopt=Abstract

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Fluvoxamine for the treatment of anxiety disorders in children and adolescents. Author(s): Isaacs E. Source: The New England Journal of Medicine. 2001 August 9; 345(6): 466-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11496864&dopt=Abstract

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Fluvoxamine pharmacotherapy of anxiety disorders in later life: preliminary opentrial data. Author(s): Wylie ME, Miller MD, Shear MK, Little JT, Mulsant BH, Pollock BG, Reynolds CF 3rd. Source: Journal of Geriatric Psychiatry and Neurology. 2000 Spring; 13(1): 43-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10753007&dopt=Abstract

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Fluvoxamine. An updated review of its use in the management of adults with anxiety disorders. Author(s): Figgitt DP, McClellan KJ. Source: Drugs. 2000 October; 60(4): 925-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11085201&dopt=Abstract

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Fluvoxamine: a review of its therapeutic potential in the management of anxiety disorders in children and adolescents. Author(s): Cheer SM, Figgitt DP. Source: Paediatric Drugs. 2001; 3(10): 763-81. Review. Erratum In: Paediatr Drugs 2001; 3(11): 801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706925&dopt=Abstract

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Frequency of anxiety disorders in psychiatric outpatients with major depressive disorder. Author(s): Zimmerman M, McDermut W, Mattia JI. Source: The American Journal of Psychiatry. 2000 August; 157(8): 1337-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10910803&dopt=Abstract

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Frequency, comorbidity, and psychosocial impairment of anxiety disorders in German adolescents. Author(s): Essau CA, Conradt J, Petermann F. Source: Journal of Anxiety Disorders. 2000 May-June; 14(3): 263-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10868984&dopt=Abstract

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Future directions in anxiety disorders: profiles and perspectives of leading contributors. Author(s): Norton PJ, Asmundson GJ, Cox BJ, Norton GR. Source: Journal of Anxiety Disorders. 2000 January-February; 14(1): 69-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770237&dopt=Abstract

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Future directions in the treatment of anxiety disorders: an examination of theory, basic science, public policy, psychotherapy research, clinical training, and practice. Author(s): Newman MG, Borkovec TD, Hope DA, Kozak MJ, McNally RJ, Taylor CB. Source: Journal of Clinical Psychology. 1999 November; 55(11): 1325-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599824&dopt=Abstract

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GABAergic function in detoxified heroin addicts: relationship to anxiety disorders. Author(s): Gerra G, Ferri M, Zaimovic A, Giucastro G, Palladino M, Sartori R, Delsignore R, Maestri D, Marzocchi G, Brambilla F. Source: Psychiatry Research. 1998 February 9; 77(2): 89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9541144&dopt=Abstract

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Gabapentin as a potential treatment for anxiety disorders. Author(s): Pollack MH, Matthews J, Scott EL. Source: The American Journal of Psychiatry. 1998 July; 155(7): 992-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9659873&dopt=Abstract

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Gender differences in anxiety disorders and anxiety symptoms in adolescents. Author(s): Lewinsohn PM, Gotlib IH, Lewinsohn M, Seeley JR, Allen NB. Source: Journal of Abnormal Psychology. 1998 February; 107(1): 109-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9505043&dopt=Abstract

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Gender differences in risk factors for mood and anxiety disorders: implications for clinical treatment research. Author(s): Blehar MC. Source: Psychopharmacology Bulletin. 1995; 31(4): 687-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8851641&dopt=Abstract

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Gender differences in the epidemiology and treatment of anxiety disorders. Author(s): Pigott TA. Source: The Journal of Clinical Psychiatry. 1999; 60 Suppl 18: 4-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10487250&dopt=Abstract

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Gender role orientation and fearfulness in children with anxiety disorders. Author(s): Ginsburg GS, Silverman WK. Source: Journal of Anxiety Disorders. 2000 January-February; 14(1): 57-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770236&dopt=Abstract

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Generalized anxiety disorders three to four months after ischemic stroke. Author(s): Leppavuori A, Pohjasvaara T, Vataja R, Kaste M, Erkinjuntti T. Source: Cerebrovascular Diseases (Basel, Switzerland). 2003; 16(3): 257-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865614&dopt=Abstract

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Generalized anxiety disorders. Author(s): Gorman JM. Source: Mod Probl Pharmacopsychiatry. 1987; 22: 127-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3299062&dopt=Abstract

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Genetic factors in anxiety disorders. Author(s): Torgersen S. Source: Archives of General Psychiatry. 1983 October; 40(10): 1085-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6625857&dopt=Abstract

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Genetic factors in early separation anxiety: implications for the genesis of adult anxiety disorders. Author(s): Silove D, Manicavasagar V, O'Connell D, Morris-Yates A. Source: Acta Psychiatrica Scandinavica. 1995 July; 92(1): 17-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7572243&dopt=Abstract

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Genetics of fear and anxiety disorders. Author(s): Marks IM. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1986 October; 149: 406-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3545353&dopt=Abstract

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Group and individual cognitive-behavioral therapy for childhood anxiety disorders: a randomized trial. Author(s): Manassis K, Mendlowitz SL, Scapillato D, Avery D, Fiksenbaum L, Freire M, Monga S, Owens M. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 December; 41(12): 1423-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447028&dopt=Abstract

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Group therapy for anxiety disorders using rational emotive behaviour therapy. Author(s): Cowan D, Brunero S. Source: The Australian and New Zealand Journal of Mental Health Nursing. 1997 December; 6(4): 164-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9479090&dopt=Abstract

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Health care costs associated with depressive and anxiety disorders in primary care. Author(s): Simon G, Ormel J, VonKorff M, Barlow W. Source: The American Journal of Psychiatry. 1995 March; 152(3): 352-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7864259&dopt=Abstract

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Health functioning impairments associated with posttraumatic stress disorder, anxiety disorders, and depression. Author(s): Zayfert C, Dums AR, Ferguson RJ, Hegel MT. Source: The Journal of Nervous and Mental Disease. 2002 April; 190(4): 233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960084&dopt=Abstract

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Health-related quality of life in primary care patients with recognized and unrecognized mood and anxiety disorders. Author(s): Cass AR, Volk RJ, Nease DE Jr. Source: International Journal of Psychiatry in Medicine. 1999; 29(3): 293-309. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10642904&dopt=Abstract

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Heart rate and plasma norepinephrine responsivity to orthostatic challenge in anxiety disorders. Comparison of patients with panic disorder and social phobia and normal control subjects. Author(s): Stein MB, Tancer ME, Uhde TW. Source: Archives of General Psychiatry. 1992 April; 49(4): 311-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1558465&dopt=Abstract

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Heart rate and QT variability in children with anxiety disorders: a preliminary report. Author(s): Yeragani VK, Rao KA, Pohl R, Jampala VC, Balon R. Source: Depression and Anxiety. 2001; 13(2): 72-7. Erratum In: Depress Anxiety 2001; 13(4): 198. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11301923&dopt=Abstract

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Heart rate variability in depressive and anxiety disorders. Author(s): Gorman JM, Sloan RP. Source: American Heart Journal. 2000 October; 140(4 Suppl): 77-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11011352&dopt=Abstract

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Hemispheric laterality and memory bias for threat in anxiety disorders. Author(s): Otto MW, McNally RJ, Pollack MH, Chen E, Rosenbaum JF. Source: Journal of Abnormal Psychology. 1994 November; 103(4): 828-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7822587&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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History of anxiety disorders is associated with a decreased likelihood of angiographic coronary artery disease in women with chest pain: the WISE study. Author(s): Rutledge T, Reis SE, Olson M, Owens J, Kelsey SF, Pepine CJ, Reichek N, Rogers WJ, Merz CN, Sopko G, Cornell CE, Sharaf B, Matthews KA; Women's Ischemia Syndrome Evaluation (WISE). Source: Journal of the American College of Cardiology. 2001 March 1; 37(3): 780-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693752&dopt=Abstract

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HIV-1 associated mood and anxiety disorders. Author(s): Riccio M. Source: Clinical Neuropharmacology. 1992; 15 Suppl 1 Pt A: 366A-367A. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1498875&dopt=Abstract

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How does premenstrual dysphoric disorder relate to depression and anxiety disorders? Author(s): Landen M, Eriksson E. Source: Depression and Anxiety. 2003; 17(3): 122-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768646&dopt=Abstract

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Hypochondriasis vs. anxiety disorders: why should we care? Author(s): Fallon B. Source: General Hospital Psychiatry. 1999 January-February; 21(1): 5-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10068914&dopt=Abstract

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Hypothyroidism and hyperthyroidism in anxiety disorders revisited: new data and literature review. Author(s): Simon NM, Blacker D, Korbly NB, Sharma SG, Worthington JJ, Otto MW, Pollack MH. Source: Journal of Affective Disorders. 2002 May; 69(1-3): 209-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12103468&dopt=Abstract

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Identifying anxiety disorders in adolescents hospitalized for alcohol abuse or dependence. Author(s): Clark DB, Bukstein OG, Smith MG, Kaczynski NA, Mezzich AC, Donovan JE. Source: Psychiatric Services (Washington, D.C.). 1995 June; 46(6): 618-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7641008&dopt=Abstract

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Imipramine and chlordiazepoxide in depressive and anxiety disorders. I. Efficacy in depressed outpatients. Author(s): Lipman RS, Covi L, Rickels K, McNair DM, Downing R, Kahn RJ, Lasseter VK, Faden V. Source: Archives of General Psychiatry. 1986 January; 43(1): 68-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3510601&dopt=Abstract

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Imipramine and chlordiazepoxide in depressive and anxiety disorders. II. Efficacy in anxious outpatients. Author(s): Kahn RJ, McNair DM, Lipman RS, Covi L, Rickels K, Downing R, Fisher S, Frankenthaler LM. Source: Archives of General Psychiatry. 1986 January; 43(1): 79-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3510602&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 rates of drug abuse and dependence after onset of mood or anxiety disorders in adolescence. Author(s): Burke JD Jr, Burke KC, Rae DS. Source: Hosp Community Psychiatry. 1994 May; 45(5): 451-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8045539&dopt=Abstract

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Individual and familial predictors of impairment in childhood anxiety disorders. Author(s): Manassis K, Hood J. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1998 April; 37(4): 428-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9549964&dopt=Abstract

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Influence of breathing therapy on complaints, anxiety and breathing pattern in patients with hyperventilation syndrome and anxiety disorders. Author(s): Han JN, Stegen K, De Valck C, Clement J, Van de Woestijne KP. Source: Journal of Psychosomatic Research. 1996 November; 41(5): 481-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9032712&dopt=Abstract

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Influence of exercise on anxiety level in patients with anxiety disorders. Author(s): Cameron OG, Hudson CJ. Source: Psychosomatics. 1986 October; 27(10): 720-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3774945&dopt=Abstract

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Insight and outcome in bipolar, unipolar, and anxiety disorders. Author(s): Ghaemi SN, Boiman E, Goodwin FK. Source: Comprehensive Psychiatry. 2000 May-June; 41(3): 167-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10834624&dopt=Abstract

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International study of expert judgement on therapeutic use of benzodiazepines and other psychotherapeutic medications: II. Pharmacotherapy of anxiety disorders. Author(s): Uhlenhuth EH, Balter MB, Ban TA, Yang K. Source: Journal of Affective Disorders. 1995 December 18; 35(4): 153-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8749980&dopt=Abstract

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International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications: III. Clinical features affecting experts' therapeutic recommendations in anxiety disorders. Author(s): Uhlenhuth EH, Balter MB, Ban TA, Yang K. Source: Psychopharmacology Bulletin. 1995; 31(2): 289-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7491381&dopt=Abstract

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International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications: IV. Therapeutic dose dependence and abuse liability of benzodiazepines in the long-term treatment of anxiety disorders. Author(s): Uhlenhuth EH, Balter MB, Ban TA, Yang K. Source: Journal of Clinical Psychopharmacology. 1999 December; 19(6 Suppl 2): 23S-29S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10587281&dopt=Abstract

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International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications: VI. Trends in recommendations for the pharmacotherapy of anxiety disorders, 1992-1997. Author(s): Uhlenhuth EH, Balter MB, Ban TA, Yang K. Source: Depression and Anxiety. 1999; 9(3): 107-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10356648&dopt=Abstract

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Introduction to the special issue: the role of disgust in anxiety disorders. Author(s): McKay D. Source: Journal of Anxiety Disorders. 2002; 16(5): 475-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396206&dopt=Abstract

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Introduction. New treatments for anxiety disorders: clinical approaches for successful outcomes. Author(s): Sheehan DV. Source: The Journal of Clinical Psychiatry. 1999; 60 Suppl 18: 3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10487249&dopt=Abstract

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Is any female preponderance in depression secondary to a primary female preponderance in anxiety disorders? Author(s): Parker G, Hadzi-Pavlovic D. Source: Acta Psychiatrica Scandinavica. 2001 April; 103(4): 252-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328237&dopt=Abstract

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Mesial temporal lobe seizures presenting as anxiety disorders. Author(s): Young GB, Chandarana PC, Blume WT, McLachlan RS, Munoz DG, Girvin JP. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 1995 Summer; 7(3): 352-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7580198&dopt=Abstract

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Neuroendocrine effects of diazepam in panic and generalized anxiety disorders. Author(s): Roy-Byrne PP, Cowley DS, Hommer D, Ritchie J, Greenblatt D, Nemeroff C. Source: Biological Psychiatry. 1991 July 1; 30(1): 73-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1654136&dopt=Abstract

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New developments in childhood affective and anxiety disorders. Author(s): Swedo SE, Leonard HL, Allen AJ. Source: Curr Probl Pediatr. 1994 January; 24(1): 12-38. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8174389&dopt=Abstract

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New findings in mood and anxiety disorders are important for health insurers. Author(s): Lieber AL. Source: J Insur Med. 1992 Summer; 24(2): 97-101. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10171567&dopt=Abstract

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Normalization of personality characteristics in patients with incapacitating anxiety disorders after capsulotomy. Author(s): Mindus P, Nyman H. Source: Acta Psychiatrica Scandinavica. 1991 April; 83(4): 283-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2028804&dopt=Abstract

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Object relations theory and pharmacopsychotherapy of anxiety disorders. Author(s): Hamilton NG, Sacks LH, Hamilton CA. Source: American Journal of Psychotherapy. 1994 Summer; 48(3): 380-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7992869&dopt=Abstract

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Open fluoxetine treatment of mixed anxiety disorders in children and adolescents. Author(s): Fairbanks JM, Pine DS, Tancer NK, Dummit ES 3rd, Kentgen LM, Martin J, Asche BK, Klein RG. Source: Journal of Child and Adolescent Psychopharmacology. 1997 Spring; 7(1): 17-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9192539&dopt=Abstract

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Outcomes in a referral cohort of patients with anxiety disorders. Author(s): McCusker J, Boulenger JP, Bellavance F, Boyer R, Miller JM. Source: The Journal of Nervous and Mental Disease. 2000 January; 188(1): 3-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10665454&dopt=Abstract

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Outcomes of a brief inpatient treatment program for mood and anxiety disorders. Author(s): Tucker S, Moore W, Luedtke C. Source: Outcomes Management for Nursing Practice. 2000 July-September; 4(3): 117-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299580&dopt=Abstract

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Overview of antidepressants currently used to treat anxiety disorders. Author(s): Feighner JP. Source: The Journal of Clinical Psychiatry. 1999; 60 Suppl 22: 18-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10634351&dopt=Abstract

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Parental anxiety disorders, child anxiety disorders, and the perceived parent-child relationship in an Australian high-risk sample. Author(s): McClure EB, Brennan PA, Hammen C, Le Brocque RM. Source: Journal of Abnormal Child Psychology. 2001 February; 29(1): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316331&dopt=Abstract

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Parenting behaviors in parents with anxiety disorders. Author(s): Turner SM, Beidel DC, Roberson-Nay R, Tervo K. Source: Behaviour Research and Therapy. 2003 May; 41(5): 541-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711263&dopt=Abstract

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Parsing the comorbidity between bipolar disorder and anxiety disorders: a familial risk analysis. Author(s): Wozniak J, Biederman J, Monuteaux MC, Richards J, Faraone SV. Source: Journal of Child and Adolescent Psychopharmacology. 2002 Summer; 12(2): 10111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188979&dopt=Abstract

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Personality and anxiety disorders: a review. Author(s): Bienvenu OJ, Stein MB. Source: Journal of Personality Disorders. 2003 April; 17(2): 139-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755327&dopt=Abstract

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Pharmacologic treatment of anxiety disorders in 1989 versus 1996: results from the Harvard/Brown anxiety disorders research program. Author(s): Salzman C, Goldenberg I, Bruce SE, Keller MB. Source: The Journal of Clinical Psychiatry. 2001 March; 62(3): 149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305698&dopt=Abstract

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Pharmacotherapy of childhood anxiety disorders. Author(s): Kratochvil CJ, Harrington MJ, Burke WJ, March JS. Source: Current Psychiatry Reports. 2002 August; 4(4): 264-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126594&dopt=Abstract

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Physician office visits of adults for anxiety disorders in the United States, 1985-1998. Author(s): Harman JS, Rollman BL, Hanusa BH, Lenze EJ, Shear MK. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2002 March; 17(3): 165-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929501&dopt=Abstract

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Place of chronic insomnia in the course of depressive and anxiety disorders. Author(s): Ohayon MM, Roth T. Source: Journal of Psychiatric Research. 2003 January-February; 37(1): 9-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482465&dopt=Abstract

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Practitioner review: psychological management of anxiety disorders in childhood. Author(s): Dadds MR, Barrett PM. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 2001 November; 42(8): 999-1011. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11806693&dopt=Abstract

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Prediction of anxiety disorders using the state-trait anxiety inventory for multiethnic adolescents. Author(s): Hishinuma ES, Miyamoto RH, Nishimura ST, Goebert DA, Yuen NY, Makini GK Jr, Andrade NN, Johnson RC, Carlton BS. Source: Journal of Anxiety Disorders. 2001 November-December; 15(6): 511-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764310&dopt=Abstract

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Predictors of response in anxiety disorders. Author(s): Solvason HB, Ernst H, Roth W. Source: The Psychiatric Clinics of North America. 2003 June; 26(2): 411-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778841&dopt=Abstract

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Predominance of anger in depressive disorders compared with anxiety disorders and somatoform disorders. Author(s): Koh KB, Kim CH, Park JK. Source: The Journal of Clinical Psychiatry. 2002 June; 63(6): 486-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088159&dopt=Abstract

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Prevalence and relationship to delusions and hallucinations of anxiety disorders in schizophrenia. Author(s): Tibbo P, Swainson J, Chue P, LeMelledo JM. Source: Depression and Anxiety. 2003; 17(2): 65-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621594&dopt=Abstract

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Psychological comorbidity and stress reactivity in children and adolescents with recurrent abdominal pain and anxiety disorders. Author(s): Dorn LD, Campo JC, Thato S, Dahl RE, Lewin D, Chandra R, Di Lorenzo C. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 January; 42(1): 66-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500078&dopt=Abstract

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Quality of life and the anxiety disorders. Author(s): Quilty LC, Van Ameringen M, Mancini C, Oakman J, Farvolden P. Source: Journal of Anxiety Disorders. 2003; 17(4): 405-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826089&dopt=Abstract

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Quality of life in depression and anxiety disorders: an exploratory follow-up study after intensive inpatient cognitive behaviour therapy. Author(s): Lenz G, Demal U. Source: Psychopathology. 2000 November-December; 33(6): 297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11060512&dopt=Abstract

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Quality of life in individuals with anxiety disorders. Author(s): Mendlowicz MV, Stein MB. Source: The American Journal of Psychiatry. 2000 May; 157(5): 669-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10784456&dopt=Abstract

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Quality of life in the anxiety disorders. Author(s): Mogotsi M, Kaminer D, Stein DJ. Source: Harvard Review of Psychiatry. 2000 December; 8(6): 273-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11133822&dopt=Abstract

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Quick rating of depressed mood in patients with anxiety disorders. Author(s): McKenzie N, Marks I. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1999 March; 174: 266-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10448454&dopt=Abstract

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Rationale and principles for early intervention with young children at risk for anxiety disorders. Author(s): Hirshfeld-Becker DR, Biederman J. Source: Clinical Child and Family Psychology Review. 2002 September; 5(3): 161-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12240705&dopt=Abstract

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Rationing of health care: clinical decision making in an outpatient clinic for anxiety disorders. Author(s): Issakidis C, Andrews G. Source: Journal of Anxiety Disorders. 2003; 17(1): 59-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464289&dopt=Abstract

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Recognizing and treating childhood anxiety disorders. Author(s): Piacentini J, Roblek T. Source: The Western Journal of Medicine. 2002 May; 176(3): 149-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12016234&dopt=Abstract

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Relationship between alcohol problems and anxiety disorders. Author(s): Kushner MG. Source: The American Journal of Psychiatry. 1996 January; 153(1): 139-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8540583&dopt=Abstract

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Relationship of genetically transmitted alpha EEG traits to anxiety disorders and alcoholism. Author(s): Enoch MA, Rohrbaugh JW, Davis EZ, Harris CR, Ellingson RJ, Andreason P, Moore V, Varner JL, Brown GL, Eckardt MJ, et al. Source: American Journal of Medical Genetics. 1995 October 9; 60(5): 400-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8546153&dopt=Abstract

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Relationship of parental trauma exposure and PTSD to PTSD, depressive and anxiety disorders in offspring. Author(s): Yehuda R, Halligan SL, Bierer LM. Source: Journal of Psychiatric Research. 2001 September-October; 35(5): 261-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591428&dopt=Abstract

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Relationships of premenstrual dysphoric disorder to major depression and anxiety disorders: a re-examination. Author(s): Breaux C, Hartlage S, Gehlert S. Source: Journal of Psychosomatic Obstetrics and Gynaecology. 2000 March; 21(1): 17-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10907211&dopt=Abstract

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Retrospective self-reports of therapist flexibility in a manual-based treatment for youths with anxiety disorders. Author(s): Kendall PC, Chu BC. Source: Journal of Clinical Child Psychology. 2000 June; 29(2): 209-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10802830&dopt=Abstract

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Revisiting the association between attention-deficit/hyperactivity disorder and anxiety disorders: a familial risk analysis. Author(s): Braaten EB, Beiderman J, Monuteaux MC, Mick E, Calhoun E, Cattan G, Faraone SV. Source: Biological Psychiatry. 2003 January 1; 53(1): 93-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513949&dopt=Abstract

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Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Author(s): Ressler KJ, Nemeroff CB. Source: Depression and Anxiety. 2000; 12 Suppl 1: 2-19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11098410&dopt=Abstract

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Schemata as moderators of clinical effectiveness of a comprehensive cognitive behavioral program for patients with depression or anxiety disorders. Author(s): Halford WK, Bernoth-Doolan S, Eadie K. Source: Behavior Modification. 2002 October; 26(5): 571-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375375&dopt=Abstract

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Screening and assessing adult asthmatics for anxiety disorders. Author(s): Davis TM, Ross CJ, MacDonald GF. Source: Clinical Nursing Research. 2002 May; 11(2): 173-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991171&dopt=Abstract

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Searching for moderators and mediators of pharmacological treatment effects in children and adolescents with anxiety disorders. Author(s): Walkup JT, Labellarte MJ, Riddle MA, Pine D, Greenhill L, Klein R, Davies M, Sweeney M, Fu C, Abikoff H, Hack S, Klee B, McCracken J, Bergman L, Piacentini J, March J, Compton S, Robinson J, O'Hara T, Baker S, Vitiello B, Ritz L, Roper M; Research Units on Pediatric Psychopharmacology Anxiety Study Group. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 January; 42(1): 13-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500072&dopt=Abstract

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Showing you can do it: homework in therapy for children and adolescents with anxiety disorders. Author(s): Hudson JL, Kendall PC. Source: Journal of Clinical Psychology. 2002 May; 58(5): 525-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11967878&dopt=Abstract

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Specificity of conditional associative-learning deficits in obsessive-compulsive disorder (OCD) and non-OCD anxiety disorders. Author(s): Leplow B, Murphy R, Nutzinger DO. Source: J Clin Exp Neuropsychol. 2002 September; 24(6): 792-805. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424653&dopt=Abstract

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Spotlight on fluvoxamine in anxiety disorders in children and adolescents. Author(s): Cheer SM, Figgitt DP. Source: Cns Drugs. 2002; 16(2): 139-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11825104&dopt=Abstract

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Startle reactivity and anxiety disorders: aversive conditioning, context, and neurobiology. Author(s): Grillon C. Source: Biological Psychiatry. 2002 November 15; 52(10): 958-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437937&dopt=Abstract

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Suicide risk in patients with anxiety disorders: a meta-analysis of the FDA database. Author(s): Khan A, Leventhal RM, Khan S, Brown WA. Source: Journal of Affective Disorders. 2002 April; 68(2-3): 183-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12063146&dopt=Abstract

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Symptoms of anxiety disorders and teacher-reported school functioning of normal children. Author(s): Muris P, Meesters C. Source: Psychological Reports. 2002 October; 91(2): 588-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416853&dopt=Abstract

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The development and modification of temperamental risk for anxiety disorders: prevention of a lifetime of anxiety? Author(s): Rapee RM. Source: Biological Psychiatry. 2002 November 15; 52(10): 947-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437936&dopt=Abstract

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The epidemiology of anxiety disorders: prevalence and societal costs. Author(s): Lepine JP. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 14: 4-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562112&dopt=Abstract

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The influence of comorbidity on treatment outcome for children and adolescents with anxiety disorders. Author(s): Rapee RM. Source: Behaviour Research and Therapy. 2003 January; 41(1): 105-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488123&dopt=Abstract

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The other side of the coin: using intervention research in child anxiety disorders to inform developmental psychopathology. Author(s): Hudson JL, Kendall PC, Coles ME, Robin JA, Webb A. Source: Development and Psychopathology. 2002 Fall; 14(4): 819-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549705&dopt=Abstract

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The role of GABA in anxiety disorders. Author(s): Lydiard RB. Source: The Journal of Clinical Psychiatry. 2003; 64 Suppl 3: 21-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662130&dopt=Abstract

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Threat perception abnormalities in children: the role of anxiety disorders symptoms, chronic anxiety, and state anxiety. Author(s): Muris P, Rapee R, Meesters C, Schouten E, Geers M. Source: Journal of Anxiety Disorders. 2003; 17(3): 271-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727122&dopt=Abstract

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Topiramate treatment for SSRI-induced weight gain in anxiety disorders. Author(s): Van Ameringen M, Mancini C, Pipe B, Campbell M, Oakman J. Source: The Journal of Clinical Psychiatry. 2002 November; 63(11): 981-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444810&dopt=Abstract

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Treatment of childhood anxiety disorders: a preliminary comparison between cognitive-behavioral group therapy and a psychological placebo intervention. Author(s): Muris P, Meesters C, van Melick M. Source: Journal of Behavior Therapy and Experimental Psychiatry. 2002 SeptemberDecember; 33(3-4): 143-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628633&dopt=Abstract

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Treatment of depression with comorbid anxiety disorders: differential efficacy of paroxetine versus moclobemide. Author(s): Pini S, Amador XF, Dell'Osso L, Baldini Rossi N, Cassano P, Savino M, Cassano GB. Source: International Clinical Psychopharmacology. 2003 January; 18(1): 15-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490770&dopt=Abstract

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Treatment of pediatric anxiety disorders: an open-label extension of the research units on pediatric psychopharmacology anxiety study. Author(s): Walkup J, Labellarte M, Riddle MA, Pine DS, Greenhill L, Fairbanks J, Klein R, Davies M, Sweeney M, Abikoff H, Hack S, Klee B, Bergman RL, Lynn D, McCracken J, March J, Gammon P, Vitiello B, Ritz L, Roper M; Research Units on Pediatric Psychopharmacology Anxiety Study Group. Source: Journal of Child and Adolescent Psychopharmacology. 2002 Fall; 12(3): 175-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427292&dopt=Abstract

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UCS inflation in the aetiology of a variety of anxiety disorders: some case histories. Author(s): Davey GC, de Jong PJ, Tallis F. Source: Behaviour Research and Therapy. 1993 June; 31(5): 495-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8333824&dopt=Abstract

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Unsteadiness of breathing in patients with hyperventilation syndrome and anxiety disorders. Author(s): Han JN, Stegen K, Simkens K, Cauberghs M, Schepers R, Van den Bergh O, Clement J, Van de Woestijne KP. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1997 January; 10(1): 167-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9032511&dopt=Abstract

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Update on anxiety disorders. Author(s): Ballenger JC. Source: Archives of Internal Medicine. 1991 May; 151(5): 857-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2025132&dopt=Abstract

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Use of a structured interview to diagnose anxiety disorders in a minority population. Author(s): Paradis CM, Friedman S, Lazar RM, Grubea J, Kesselman M. Source: Hosp Community Psychiatry. 1992 January; 43(1): 61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1544652&dopt=Abstract

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Use of benzodiazepines in anxiety disorders. Author(s): Gross HS. Source: The New England Journal of Medicine. 1993 November 11; 329(20): 1501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8105381&dopt=Abstract

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Use of benzodiazepines in anxiety disorders. Author(s): Powell G. Source: The New England Journal of Medicine. 1993 November 11; 329(20): 1500-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8105380&dopt=Abstract

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Use of benzodiazepines in anxiety disorders. Author(s): Shader RI, Greenblatt DJ. Source: The New England Journal of Medicine. 1993 May 13; 328(19): 1398-405. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8292115&dopt=Abstract

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Use of health services for anxiety disorders: a multisite study in Quebec. Author(s): McCusker J, Boulenger JP, Boyer R, Bellavance F, Miller JM. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1997 September; 42(7): 730-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9307833&dopt=Abstract

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Use of paroxetine for the treatment of depression and anxiety disorders in the elderly: a review. Author(s): Bourin M. Source: Human Psychopharmacology. 2003 April; 18(3): 185-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672169&dopt=Abstract

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Utilization of behavioral methods in a multicenter anxiety disorders study. Author(s): Goisman RM, Rogers MP, Steketee GS, Warshaw MG, Cuneo P, Keller MB. Source: The Journal of Clinical Psychiatry. 1993 June; 54(6): 213-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8101186&dopt=Abstract

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Value and effectiveness of consumer advocacy groups: a survey of the anxiety disorders support group in South Africa. Author(s): Stein DJ, Wessels C, Zungu-Dirwayi N, Berk M, Wilson Z. Source: Depression and Anxiety. 2001; 13(2): 105-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11301921&dopt=Abstract

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Variables associated with disparities in treatment of patients with schizophrenia and comorbid mood and anxiety disorders. Author(s): Dixon L, Green-Paden L, Delahanty J, Lucksted A, Postrado L, Hall J. Source: Psychiatric Services (Washington, D.C.). 2001 September; 52(9): 1216-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533396&dopt=Abstract

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Ventilatory physiology of children and adolescents with anxiety disorders. Author(s): Pine DS, Coplan JD, Papp LA, Klein RG, Martinez JM, Kovalenko P, Tancer N, Moreau D, Dummit ES 3rd, Shaffer D, Klein DF, Gorman JM. Source: Archives of General Psychiatry. 1998 February; 55(2): 123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9477925&dopt=Abstract

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Voluntary breath holding in panic and generalized anxiety disorders. Author(s): Roth WT, Wilhelm FH, Trabert W. Source: Psychosomatic Medicine. 1998 November-December; 60(6): 671-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9847025&dopt=Abstract

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Vulnerability factors among children at risk for anxiety disorders. Author(s): Merikangas KR, Avenevoli S, Dierker L, Grillon C. Source: Biological Psychiatry. 1999 December 1; 46(11): 1523-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599480&dopt=Abstract

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Vulnerability factors in the anxiety disorders. Author(s): Bennet A, Stirling J. Source: The British Journal of Medical Psychology. 1998 September; 71 ( Pt 3): 311-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9733425&dopt=Abstract

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What do brain imaging studies tell us about anxiety disorders? Author(s): Malizia AL. Source: Journal of Psychopharmacology (Oxford, England). 1999 December; 13(4): 372-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10667613&dopt=Abstract

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What do the neurosciences tell us about anxiety disorders? A comment. Author(s): Marks I, Tobena A. Source: Psychological Medicine. 1986 February; 16(1): 9-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2870530&dopt=Abstract

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What do youth referred for anxiety problems worry about? Worry and its relation to anxiety and anxiety disorders in children and adolescents. Author(s): Weems CF, Silverman WK, La Greca AM. Source: Journal of Abnormal Child Psychology. 2000 February; 28(1): 63-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10772350&dopt=Abstract

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Why do people with anxiety disorders become depressed? A prospective-longitudinal community study. Author(s): Wittchen HU, Kessler RC, Pfister H, Lieb M. Source: Acta Psychiatrica Scandinavica. Supplementum. 2000; (406): 14-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11131466&dopt=Abstract

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Women's health. Anxiety disorders. Author(s): Pennington A. Source: Primary Care. 1997 March; 24(1): 103-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9082465&dopt=Abstract

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Worry themes in primary GAD, secondary GAD, and other anxiety disorders. Author(s): Dugas MJ, Freeston MH, Ladouceur R, Rheaume J, Provencher M, Boisvert JM. Source: Journal of Anxiety Disorders. 1998 May-June; 12(3): 253-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9653683&dopt=Abstract

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Yohimbine challenge in children with anxiety disorders. Author(s): Sallee FR, Sethuraman G, Sine L, Liu H. Source: The American Journal of Psychiatry. 2000 August; 157(8): 1236-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10910785&dopt=Abstract

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Yohimbine for anxiety disorders. Author(s): Watson S, Young AH. Source: The American Journal of Psychiatry. 2001 August; 158(8): 1340. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11481195&dopt=Abstract

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CHAPTER 2. NUTRITION AND ANXIETY DISORDERS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and anxiety disorders.

Finding Nutrition Studies on Anxiety 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 “anxiety disorders” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “anxiety disorders” (or a synonym): •

A placebo-controlled study of Kava kava in generalized anxiety disorder. Author(s): Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA. [email protected] Source: Connor, K M Davidson, J R Int-Clin-Psychopharmacol. 2002 July; 17(4): 185-8 0268-1315

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Acute inositol does not attenuate m-CPP-induced anxiety, mydriasis and endocrine effects in panic disorder. Author(s): Soroka Medical Center, Kupat Holim Sick Fund, Ben Gurion University of the Negev, Beer-sheba, Israel. Source: Benjamin, J Nemetz, H Fux, M Bleichman, I Agam, G J-Psychiatr-Res. 1997 JulAugust; 31(4): 489-95 0022-3956

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Caffeine abstention in the management of anxiety disorders. Author(s): Department of Psychiatry, Institute of Psychiatry, London. Source: Bruce, M S Lader, M Psychol-Med. 1989 February; 19(1): 211-4 0033-2917

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Effect of a serotonin precursor and uptake inhibitor in anxiety disorders; a doubleblind comparison of 5-hydroxytryptophan, clomipramine and placebo. Author(s): Department of Biological Psychiatry, University Hospital, Utrecht, The Netherlands. Source: Kahn, R S Westenberg, H G Verhoeven, W M Gispen de Wied, C C Kamerbeek, W D Int-Clin-Psychopharmacol. 1987 January; 2(1): 33-45 0268-1315

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Facing the challenge of social anxiety disorder. Author(s): Department of Biological Psychiatry, Academic Hospital Utrecht, The Netherlands. Source: Westenberg, H G Eur-Neuropsychopharmacol. 1999 July; 9 Suppl 3S93-9 0924977X

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Somatic sensations, anxiety, and control in panic disorder. Author(s): Department of Psychology, University of Illinois, Champaign 61820. Source: Salzer, M S Berenbaum, H J-Behav-Ther-Exp-Psychiatry. 1994 March; 25(1): 7580 0005-7916

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The MSH/ACTH analog ORG 2766 in anxiety disorders. Author(s): Department of Biological Psychiatry, University Hospital Utrecht, The Netherlands. Source: Den Boer, J A Westenberg, H G De Vries, H Peptides. 1992 Jan-February; 13(1): 109-12 0196-9781

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The role of corticotropin-releasing factor in the pathophysiology of affective and anxiety disorders: laboratory and clinical studies. Author(s): Department of Psychiatry, Emory University School of Medicine, Atlanta, GA 30322. Source: Owens, M J Nemeroff, C B Ciba-Found-Sympage 1993; 172296-308; discussion 308-16 0300-5208

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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/

•

Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

•

Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

•

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

•

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

•

Google: http://directory.google.com/Top/Health/Nutrition/

•

Healthnotes: http://www.healthnotes.com/

•

Open Directory Project: http://dmoz.org/Health/Nutrition/

•

Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

•

WebMDHealth: http://my.webmd.com/nutrition

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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The following is a specific Web list relating to anxiety 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: •

Minerals Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND ANXIETY DISORDERS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to anxiety 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 anxiety 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 “anxiety 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 anxiety disorders: •

A 28-year-old woman with panic disorder, 1 year later. Author(s): Burns RB, Hartman EE. Source: Jama : the Journal of the American Medical Association. 2002 July 24-31; 288(4): 494. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132981&dopt=Abstract

•

A 28-year-old woman with panic disorder. Author(s): Gorman JM. Source: Jama : the Journal of the American Medical Association. 2001 July 25; 286(4): 450-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11466124&dopt=Abstract

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A component analysis of cognitive-behavioral therapy for generalized anxiety disorder and the role of interpersonal problems. Author(s): Borkovec TD, Newman MG, Pincus AL, Lytle R. Source: Journal of Consulting and Clinical Psychology. 2002 April; 70(2): 288-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952187&dopt=Abstract

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A placebo-controlled study of Kava kava in generalized anxiety disorder. Author(s): Connor KM, Davidson JR. Source: International Clinical Psychopharmacology. 2002 July; 17(4): 185-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131602&dopt=Abstract

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A randomized, double-blind, placebo-controlled study of classical homeopathy in generalized anxiety disorder. Author(s): Bonne O, Shemer Y, Gorali Y, Katz M, Shalev AY. Source: The Journal of Clinical Psychiatry. 2003 March; 64(3): 282-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716269&dopt=Abstract

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A review of EEG biofeedback treatment of anxiety disorders. Author(s): Moore NC. Source: Clin Electroencephalogr. 2000 January; 31(1): 1-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10638346&dopt=Abstract

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Alternative psychotherapy approaches for social anxiety disorder. Author(s): Lipsitz JD, Marshall RD. Source: The Psychiatric Clinics of North America. 2001 December; 24(4): 817-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723635&dopt=Abstract

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Anxiety disorders in the child and teen. Author(s): Varley CK, Smith CJ. Source: Pediatric Clinics of North America. 2003 October; 50(5): 1107-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14558683&dopt=Abstract

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Applied relaxation vs. cognitive therapy in the treatment of generalized anxiety disorder. Author(s): Ost LG, Breitholtz E. Source: Behaviour Research and Therapy. 2000 August; 38(8): 777-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10937426&dopt=Abstract

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Breathing training for treating panic disorder. Useful intervention or impediment? Author(s): Meuret AE, Wilhelm FH, Ritz T, Roth WT.

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Source: Behavior Modification. 2003 October; 27(5): 731-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14531164&dopt=Abstract •

Cognitive therapy versus applied relaxation as treatment of generalized anxiety disorder. Author(s): Arntz A. Source: Behaviour Research and Therapy. 2003 June; 41(6): 633-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732372&dopt=Abstract

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Cognitive-behavioral therapy for generalized anxiety disorder with integrations from interpersonal and experiential therapies. Author(s): Borkovec TD, Newman MG, Castonguay LG. Source: Cns Spectr. 2003 May; 8(5): 382-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766694&dopt=Abstract

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Cognitive-behavioral therapy for social anxiety disorder: current status and future directions. Author(s): Heimberg RG. Source: Biological Psychiatry. 2002 January 1; 51(1): 101-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801235&dopt=Abstract

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Comparison between two models of experimental anxiety in healthy volunteers and panic disorder patients. Author(s): Graeff FG, Silva M, Del Ben CM, Zuardi AW, Hetem LA, Guimaraes FS. Source: Neuroscience and Biobehavioral Reviews. 2001 December; 25(7-8): 753-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801299&dopt=Abstract

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Current perspectives on the pathophysiology of schizophrenia, depression, and anxiety disorders. Author(s): Krystal JH, D'Souza DC, Sanacora G, Goddard AW, Charney DS. Source: The Medical Clinics of North America. 2001 May; 85(3): 559-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349473&dopt=Abstract

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Effect of kava extract on vagal cardiac control in generalized anxiety disorder: preliminary findings. Author(s): Watkins LL, Connor KM, Davidson JR. Source: Journal of Psychopharmacology (Oxford, England). 2001 December; 15(4): 283-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11769822&dopt=Abstract

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Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot study. Author(s): Andreatini R, Sartori VA, Seabra ML, Leite JR.

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Source: Phytotherapy Research : Ptr. 2002 November; 16(7): 650-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410546&dopt=Abstract •

Effects of a traditional herbal supplement on anxiety in patients with generalized anxiety disorder. Author(s): Mills PJ, Farag NH, Newton RP, Parry BL. Source: Journal of Clinical Psychopharmacology. 2002 August; 22(4): 443-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172353&dopt=Abstract

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EMDR for panic disorder with agoraphobia: comparison with waiting list and credible attention-placebo control conditions. Author(s): Goldstein AJ, de Beurs E, Chambless DL, Wilson KA. Source: Journal of Consulting and Clinical Psychology. 2000 December; 68(6): 947-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11142547&dopt=Abstract

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Evidence for disturbed cortical signal processing and altered serotonergic neurotransmission in generalized anxiety disorder. Author(s): Senkowski D, Linden M, Zubragel D, Bar T, Gallinat J. Source: Biological Psychiatry. 2003 February 15; 53(4): 304-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586449&dopt=Abstract

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Eye Movement Desensitization and Reprocessing (EMDR) and the anxiety disorders: clinical and research implications of an integrated psychotherapy treatment. Author(s): Shapiro F. Source: Journal of Anxiety Disorders. 1999 January-April; 13(1-2): 35-67. Review. Erratum In: J Anxiety Disord 1999 November-December; 13(6): 621. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10225500&dopt=Abstract

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Four cases of panic disorder successfully treated with Kampo (Japanese herbal) medicines: Kami-shoyo-san and Hange-koboku-to. Author(s): Mantani N, Hisanaga A, Kogure T, Kita T, Shimada Y, Terasawa K. Source: Psychiatry and Clinical Neurosciences. 2002 December; 56(6): 617-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485303&dopt=Abstract

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Generalized anxiety disorder in primary care: emerging issues in management and treatment. Author(s): Culpepper L. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 8: 35-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044106&dopt=Abstract

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Generalized anxiety disorder. Author(s): Gale CK, Oakley-Browne M.

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Source: American Family Physician. 2003 January 1; 67(1): 135-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537176&dopt=Abstract •

Generalized anxiety disorder. An important clinical concern. Author(s): Hidalgo RB, Davidson JR. Source: The Medical Clinics of North America. 2001 May; 85(3): 691-710. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349480&dopt=Abstract

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Kava kava in the treatment of generalized anxiety disorder, simple phobia and specific social phobia. Author(s): Boerner RJ. Source: Phytotherapy Research : Ptr. 2001 November; 15(7): 646-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746854&dopt=Abstract

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Kava-Kava extract LI 150 is as effective as Opipramol and Buspirone in Generalised Anxiety Disorder--an 8-week randomized, double-blind multi-centre clinical trial in 129 out-patients. Author(s): Boerner RJ, Sommer H, Berger W, Kuhn U, Schmidt U, Mannel M. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2003; 10 Suppl 4: 38-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807341&dopt=Abstract

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Laboratory psychophysiological assessment and imagery exposure in panic disorder patients. Author(s): Bystritsky A, Maidenberg E, Craske MG, Vapnik T, Shapiro D. Source: Depression and Anxiety. 2000; 12(2): 102-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11091934&dopt=Abstract

•

Marijuana and panic disorder. Author(s): Deas D, Gerding L, Hazy J. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2000 December; 39(12): 1467. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11128322&dopt=Abstract

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Mirtazapine in the treatment of panic disorder. Author(s): Carli V, Sarchiapone M, Camardese G, Romano L, DeRisio S. Source: Archives of General Psychiatry. 2002 July; 59(7): 661-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090820&dopt=Abstract

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Plasma anti-serotonin and serotonin anti-idiotypic antibodies are elevated in panic disorder. Author(s): Coplan JD, Tamir H, Calaprice D, DeJesus M, de la Nuez M, Pine D, Papp LA, Klein DF, Gorman JM.

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Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1999 April; 20(4): 386-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10088140&dopt=Abstract •

Prepulse inhibition deficits in patients with panic disorder. Author(s): Ludewig S, Ludewig K, Geyer MA, Hell D, Vollenweider FX. Source: Depression and Anxiety. 2002; 15(2): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11891993&dopt=Abstract

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Priming panic interpretations in children of patients with panic disorder. Author(s): Schneider S, Unnewehr S, Florin I, Margraf J. Source: Journal of Anxiety Disorders. 2002; 16(6): 605-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405521&dopt=Abstract

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Psychological and physiological predictors of response to carbon dioxide challenge in individuals with panic disorder. Author(s): Rassovsky Y, Kushner MG, Schwarze NJ, Wangensteen OD. Source: Journal of Abnormal Psychology. 2000 November; 109(4): 616-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11195985&dopt=Abstract

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Psychosocial treatment prescriptions for generalized anxiety disorder, panic disorder, and social phobia, 1991-1996. Author(s): Goisman RM, Warshaw MG, Keller MB. Source: The American Journal of Psychiatry. 1999 November; 156(11): 1819-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10553751&dopt=Abstract

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Psychotherapy for generalized anxiety disorder. Author(s): Borkovec TD, Ruscio AM. Source: The Journal of Clinical Psychiatry. 2001; 62 Suppl 11: 37-42; Discussion 43-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11414549&dopt=Abstract

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Respiratory biofeedback-assisted therapy in panic disorder. Author(s): Meuret AE, Wilhelm FH, Roth WT. Source: Behavior Modification. 2001 September; 25(4): 584-605. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530717&dopt=Abstract

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Responses to panic induction procedures in subjects with multiple chemical sensitivity/idiopathic environmental intolerance: understanding the relationship with panic disorder. Author(s): Tarlo SM, Poonai N, Binkley K, Antony MM, Swinson RP.

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Source: Environmental Health Perspectives. 2002 August; 110 Suppl 4: 669-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194904&dopt=Abstract •

Self-help and minimal-contact therapies for anxiety disorders: Is human contact necessary for therapeutic efficacy? Author(s): Newman MG, Erickson T, Przeworski A, Dzus E. Source: Journal of Clinical Psychology. 2003 March; 59(3): 251-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579544&dopt=Abstract

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Social anxiety disorder: common, disabling, and treatable. Author(s): Zamorski MA, Ward RK. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2000 July-August; 13(4): 251-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10933289&dopt=Abstract

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St. John's wort in generalized anxiety disorder: three case reports. Author(s): Davidson JR, Connor KM. Source: Journal of Clinical Psychopharmacology. 2001 December; 21(6): 635-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11763024&dopt=Abstract

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The somatic symptom paradox in DSM-IV anxiety disorders: suggestions for a clinical focus in psychophysiology. Author(s): Wilhelm FH, Roth WT. Source: Biological Psychology. 2001 July-August; 57(1-3): 105-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454436&dopt=Abstract

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Therapeutic potential of kava in the treatment of anxiety disorders. Author(s): Singh YN, Singh NN. Source: Cns Drugs. 2002; 16(11): 731-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383029&dopt=Abstract

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Treating generalised anxiety disorder. Author(s): Tonks A. Source: Bmj (Clinical Research Ed.). 2003 March 29; 326(7391): 700-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663409&dopt=Abstract

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Treatment of generalized anxiety disorder. Author(s): Gorman JM. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 8: 17-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044104&dopt=Abstract

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Two-year follow-up after a randomised controlled trial of self- and clinicianaccompanied exposure for phobia/panic disorders. Author(s): Park JM, Mataix-Cols D, Marks IM, Ngamthipwatthana T, Marks M, Araya R, Al-Kubaisy T. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2001 June; 178: 543-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388971&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

•

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 anxiety 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 Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Anxiety Source: Healthnotes, Inc.; www.healthnotes.com Anxiety Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine 123

Anxiety and Panic Attacks Source: Prima Communications, Inc.www.personalhealthzone.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Post Traumatic Stress Disorder Source: Integrative Medicine Communications; www.drkoop.com Ptsd Source: Integrative Medicine Communications; www.drkoop.com Stress Source: Integrative Medicine Communications; www.drkoop.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com •

Alternative Therapy Autoregulation Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/a.html Herbal Medicine Source: Integrative Medicine Communications; www.drkoop.com Hypnotherapy Source: Integrative Medicine Communications; www.drkoop.com Mind&body Medicine Source: Integrative Medicine Communications; www.drkoop.com Relaxation Techniques Source: Integrative Medicine Communications; www.drkoop.com Trager Approach Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,741,00.html

•

Herbs and Supplements Alprazolam Source: Healthnotes, Inc.; www.healthnotes.com Antidepressants Source: Healthnotes, Inc.; www.healthnotes.com

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Ava Source: Integrative Medicine Communications; www.drkoop.com Ephedra (ma Huang) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,777,00.html Gaba (gamma-amino Butyric Acid) Source: Healthnotes, Inc.; www.healthnotes.com Inositol Source: Healthnotes, Inc.; www.healthnotes.com Inositol Source: Prima Communications, Inc.www.personalhealthzone.com Kava Alternative names: Piper methysticum Source: Healthnotes, Inc.; www.healthnotes.com Kava Source: Prima Communications, Inc.www.personalhealthzone.com Kava Kava Alternative names: Piper methysticum, Ava Source: Integrative Medicine Communications; www.drkoop.com Piper Alternative names: Kava; Piper methysticum Forst.f Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piper Methysticum Source: Integrative Medicine Communications; www.drkoop.com Yohimbe Alternative names: Pausinystalia yohimbe Source: Healthnotes, Inc.; www.healthnotes.com

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 ANXIETY DISORDERS Overview In this chapter, we will give you a bibliography on recent dissertations relating to anxiety 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 “anxiety disorders” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on anxiety disorders, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Anxiety 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 anxiety 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: •

A Reliability and Validity Study of the Brief Screen for Anxiety Disorders: a Screening Questionnaire for Use by Primary Care Physicians (anxiety Disorders) by Mirise, Beverly Anne, Phd from California School of Professional Psychology - Fresno, 1993, 150 pages http://wwwlib.umi.com/dissertations/fullcit/9408182

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An Empirical Investigation of the Bowenian Concept of Triangulation and Its Relationship to Separation Anxiety Disorder (murray Bowen) by Werman, Amy; Dsw from Adelphi University, School of Social Work, 2001, 87 pages http://wwwlib.umi.com/dissertations/fullcit/3036935

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An Investigation of the Relationship between Irrational Cognitions and Anxiety Disorders by Dodd, Deborah Jean, Phd from The Florida State University, 1987, 185 pages http://wwwlib.umi.com/dissertations/fullcit/8803366

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Analysis of Gaba(a) Receptor Subunit Genes in Alcohol Dependence and Anxiety Disorders by Radel, Marta Quintas; Phd from The George Washington University, 2002, 157 pages http://wwwlib.umi.com/dissertations/fullcit/3045184

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Cognitive Behavioral Therapy for Childhood Anxiety Disorders: Individual Differences in Response to Treatment by Wolfe, Janis Lynn; Phd from University of Toronto (canada), 2003, 234 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78373

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Cognitive Behavioral Treatment Efficacy for Anxiety Disorders: a Meta-analytic Review by Ghahramanlou, Marjan; Phd from Fairleigh Dickinson University, 2003, 240 pages http://wwwlib.umi.com/dissertations/fullcit/3089061

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Cognitive-behavioral Therapy Efficacy Via Videoconferencing for Social (public Speaking) Anxiety Disorder: Single Case Design by Pelletier, Marie Helene; Phd from The University of British Columbia (canada), 2002, 279 pages http://wwwlib.umi.com/dissertations/fullcit/NQ75066

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Differences in Cognitive Responses to Fear among Individuals Diagnosed As Panic Disorder, Generalized Anxiety Disorder, Agoraphobia with Panic Attacks, and Simple Phobia by Dattilio, Frank Mark, Phd from Temple University, 1987, 232 pages http://wwwlib.umi.com/dissertations/fullcit/8711320

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Efficacy of Eye Movement Desensitization and Reprocessing in the Treatment of Trauma and Anxiety Disorders by Hollwig, Kathleen Elizabeth; Ms from California State University, Long Beach, 2002, 77 pages http://wwwlib.umi.com/dissertations/fullcit/1409202

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Expressed Emotion and Interaction Patterns in Mothers with Anxiety Disorders and Their Children by Stern, Emily Hoffman; Phd from Boston University, 2002, 198 pages http://wwwlib.umi.com/dissertations/fullcit/3043327

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Family Dynamics and the Anxiety Disorders of Childhood by Moore, Phoebe Sylvina; Phd from University of California, Los Angeles, 2003, 167 pages http://wwwlib.umi.com/dissertations/fullcit/3081154

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Fear Conditioning in the Anxiety Disorders: a Meta-analysis by Lissek, Shmuel Mordechai; Phd from St. John's University (new York), 2002, 70 pages http://wwwlib.umi.com/dissertations/fullcit/3082049

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Panic Disorder with Dissociation: a Comparative Study by Schimmel, Tara Faith; Psyd from Carlos Albizu University, 2002, 73 pages http://wwwlib.umi.com/dissertations/fullcit/3070511

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Self-perception of Memory Confidence among Individuals with Anxiety Disorders: a Comparison of Obsessive-compulsive Disorder and Social Phobia by Zarro, Jacqueline M.; Phd from Drexel University College of Nursing and Health Professions, 2002, 154 pages http://wwwlib.umi.com/dissertations/fullcit/3061996

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Separation Anxiety Disorder in Adults with Borderline Personality Disorder by Aaronson, Cindy J.; Phd from Columbia University, 2001, 114 pages http://wwwlib.umi.com/dissertations/fullcit/3028492

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The Wisconsin Anxiety Disorders Schedule: a Study of a Computer-administered Structured Clinical Interview by Conrady, Linda Jule, Phd from The University of Wisconsin - Madison, 1992, 207 pages http://wwwlib.umi.com/dissertations/fullcit/9306448

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 ANXIETY DISORDERS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning anxiety disorders.

Recent Trials on Anxiety Disorders The following is a list of recent trials dedicated to anxiety disorders.8 Further information on a trial is available at the Web site indicated. •

Brain Changes in Fear Condition(s): Anxiety Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to use brain imaging technology to investigate brain changes in people exposed to predictable versus unpredictable unpleasant stimuli. Unpleasant events that can be predicted evoke a response of fear, whereas unpredictable, unpleasant stimuli cause chronic anxiety not associated with a specific event. Information gained from this study may help in the development of more effective treatments for anxiety disorders. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047853

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Brain Chemical Receptor Effects in Patients with Panic Disorder and Post-Traumatic Stress Disorder Condition(s): Panic Disorder; Posttraumatic Stress Disorder; Major Depressive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH)

8

These are listed at www.ClinicalTrials.gov.

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Purpose - Excerpt: The purpose of this study is to examine how certain brain chemicals work in patients with Panic Disorder (PD) and Post-Traumatic Stress Disorder (PTSD) with and without major depressive disorder (MDD). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025974 •

Child and Adolescent Anxiety Disorders Condition(s): Anxiety Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to compare the effectiveness of interventions for children and adolescents with separation anxiety disorder, social phobia, and/or generalized anxiety disorder. This study will also determine how long the treatment effects last. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052078

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Clinical Trial of Fluoxetine in Anxiety and Depression in Children, and Associated Brain Changes Condition(s): Depression; Mood Disorder; Anxiety Disorder; Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will determine if fluoxetine (Prozac(r) (Registered Trademark)) is effective for treating anxiety or depression in children and adolescents. The study will also use functional magnetic resonance imaging (fMRI) to learn more about how the brain functions in children/adolescents taking this medication for anxiety or depression. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018057

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Effects of Arousal and Stress in Anxiety Condition(s): Anxiety Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study has several parts. One part will examine the influence of factors such as personality and past experience on reactions to unpleasant stimuli. Others will examine the effect of personality and emotional and attentional states on learning and memory. Study Type: Observational

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026559 •

Evaluation of Clonazepam and Paroxetine for Panic Disorder with Depression Condition(s): Panic Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to examine the safety and effectiveness of the drug combination paroxetine and clonazepam in treating people with panic disorder (PD) and major depression. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031317

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Evaluation of the Genetics of Bipolar Disorder Condition(s): Anxiety Schizophrenia

Disorder;

Bipolar

Disorder;

Healthy;

Mood

Disorder;

Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to identify genes that may affect a person's chances of developing bipolar (BP) disorder and related conditions. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001174 •

Expectation of Unpleasant Events in Anxiety Disorders Condition(s): Anxiety Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Fear and anxiety are normal responses to a threat. However, anxiety is considered abnormal when the response to the threat is excessive or inappropriate. This study will examine changes in the body and brain that occur during unpleasant learning experiences in healthy volunteers with high, moderate, and low levels of anxiety. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055224

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Fear Conditioning Using Computer-Generated Virtual Reality Condition(s): Anxiety Disorder

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Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to use a computer-generated virtual reality environment to study fear conditioning. Fear conditioning is used to explore the causes and persistence of anxiety and anxiety disorders. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025844 •

Generalized Anxiety Disorder and Social Anxiety Disorder: Their Impact on the Processing of Information and Learning Condition(s): Anxiety Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to increase researchers' understanding of the biological basis of generalized anxiety disorder and social anxiety disorder. They will investigate how the brain activity associated with specific thoughts and feelings may play a role in these anxiety disorders. This knowledge will be used to design interventions to help those with these illnesses. To qualify for this study, participants must be evaluated via an initial telephone screening interview and material sent through the mail. Participants will then be required to make three visits to NIH. During the first visit, they will be asked questions about their general mood, degree of nervousness, thinking skills, and behavior. They will undergo a thorough physical exam, including an EKG, blood work, urinalysis, and a pregnancy test for women of childbearing potential. During the second visit, participants will spend about 2.5 hours doing various tasks while sitting and looking at a computer screen. These tasks will guide them to experience specific kinds of thoughts and emotions. Researchers will attach electrodes to the participants' hands to monitor the amount of electricity conducted by the skin. The third visit will be similar to the second visit, but participants will perform the tasks while lying in a MRI scanner. Participants will be compensated up to $400 for their involvement in this study. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062517

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Interactive Computer Treatment for Panic Disorder Condition(s): Panic Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to develop an interactive computer based version of cognitive behavioral therapy (CBT) and compare its effectiveness to book based CBT for the treatment of panic disorder. Phase(s): Phase I Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063375 •

Lorazepam- Induced Toxicity in the Aged Condition(s): Anxiety Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to compare the effects of an acute dose of lorazepam to an acute dose of placebo in elderly patients with Generalized Anxiety Disorder (GAD). Phase(s): Phase IV Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044642

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MRI Study of Brain Activity and Risk for Depression in Adolescents Condition(s): Involutional Depression; Anxiety Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will use magnetic resonance imaging (MRI) to investigate brain changes in adolescents at risk for Major Depressive Disorder. It also calls for healthy volunteers to compare to children at risk for major depression. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047944

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Music Therapy to Ease Pain and Emotional Distress in Patients With Hematologic Cancer Who Are Undergoing High-Dose Therapy and Stem Cell Transplantation Condition(s): adult Hodgkin's lymphoma; adult non-Hodgkin's lymphoma; Anxiety Disorder; childhood acute myeloid leukemia and other myeloid malignancies; chronic idiopathic myelofibrosis; Depression; mycosis fungoides and Sezary syndrome; Pain; recurrent cutaneous T-cell lymphoma; refractory plasma cell neoplasm; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Music therapy may be effective in relieving pain and emotional distress in patients who are undergoing cancer therapy. PURPOSE: Randomized trial to determine the effectiveness of music therapy to ease pain and emotional distress in patients with hematologic cancer who are undergoing high-dose therapy and stem cell transplantation. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00014482

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Neuropsychological Evaluation of Psychiatric and Neurological Patients Condition(s): Anxiety Disorder; Head Injury; Mood Disorder; Schizophrenia; Seizures Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will allow researchers to use various types of tests to evaluate cognitive and sensory functions. These tests, referred to as "batteries" will evaluate attention, executive functions, general intellectual functioning, language, memory, motor functions, orientation, personality, selected sensory and perceptual functions, vigilance (alertness), and visual-spatial functions. Children and adult patient will receive different test batteries. The goals of this research study are to; 1. Create descriptions based on the performance of each patient on the test batteries. Then use this information to relate patient behavior to their neurophysiological, neuroradiological, and biochemical descriptions. 2. Define subgroups of patients based on their neurobehavior in order to decrease the variability of psychiatric diagnoses, treatments, and prognoses. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001192

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Panic Disorder Study Condition(s): Panic Disorder Study Status: This study is currently recruiting patients. Sponsor(s): Wyeth-Ayerst Research Purpose - Excerpt: The primary objective of this study is to determine the efficacy, safety, and tolerability of a flexible dose of venlafaxine extended-release (ER) capsules administered for 10 weeks in the treatment of adult outpatients with panic disorder (PD) in a placebo-controlled phase III study. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00038896

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Reward-Related Processes and Brain Function Condition(s): Depression; Anxiety Disorders; Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will examine and compare brain changes during decisionmaking in healthy adolescents and adolescents who are anxious or depressed. The findings may provide a better understanding of mechanisms that lead to depression or anxiety. Adolescents between 9 and 17 years of age and adults between 20 and 40 years of age in the following categories will be enrolled in this study: - Healthy adults Healthy adolescents - Adolescents with major depression - Adolescents with anxiety disorder (generalized anxiety disorder, social phobia, or/and separation anxiety disorder) The study involves three visits, as follows: Visit 1 Visit 1 consists of three parts

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for both child and adult participants: - Part 1: Staff will meet with participants for a standard psychiatric interview, which will include questions about the participants' feelings, experiences and behavior-both past and present. For adolescent participants, staff will meet with the child alone, the parent alone, and the child and parent together. Part 2: Participants will perform a series of simple tasks involving shapes, letters, and numbers. They will have a medical history, physical examination and blood draw. In addition, adolescents will have a urine drug test. - Part 3: Adults and those adolescents who will undergo magnetic resonance imaging (MRI) in Visit 3 will receive training to familiarize them with the procedure. Visit 2 - Adolescents will again be asked standardized questions regarding their feelings, experiences and behavior, and will then perform a series of simple decision-making tasks on a computer. - Adults will undergo MRI scanning, as described below in Visit 3 for adolescents. This concludes the participation of adults in the study. Visit 3 Adolescents will have one of the following two procedures: - Decision-making task using a computer. Small electrodes will be placed on the child's wrists, face and fingers to monitor muscle tone and skin humidity during the task. Or - - MRI, a test that uses a strong magnetic field and radio waves to show changes in brain function. During the scan, the participant lies on a table in a space enclosed by a metal cylinder (the MRI scanner). The procedure takes 60-90 minutes; subjects must lie still for 10-15 minutes at a time. During imaging, the subject will be asked to perform a decision-making task on a computer. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029588 •

Stress Management Training in Patients Undergoing Radiation Therapy for Cancer Condition(s): Quality of Life; Anxiety Disorder; Depression; unspecified adult solid tumor, protocol specific Study Status: This study is currently recruiting patients. Sponsor(s): H. Lee Moffitt Cancer Center and Research Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Stress management techniques such as muscle relaxation, guided imagery, and abdominal breathing may improve quality of life and decrease emotional distress in patients who are undergoing radiation therapy for cancer. PURPOSE: Randomized clinical trial to determine the effectiveness of stress management training in helping cancer patients cope with the emotional distress of radiation therapy. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057733

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The Psychobiology of Childhood Temperament Condition(s): Mood Disorders; Anxiety Disorders; Adolescents Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to use brain imaging technology to examine brain changes that occur in children when they are exposed to various kinds of

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emotional tasks and to determine if these changes are related to the child's temperament. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00060775 •

Therapeutic Processes and Treatment Outcome in Adolescents with Anxiety Disorders Condition(s): Anxiety Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to examine the relationship between different aspects of cognitive behavior therapy (CBT) and treatment outcome. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00071630

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Therapy for Depression with Co-occurring Panic or Anxiety Symptoms Condition(s): Depression; Mood Disorder; Anxiety Disorder; Panic Disorder; Major Depressive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to develop and test a new therapy designed to treat depressed patients with co-occurring symptoms of panic or anxiety. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051207

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Treatment of Panic Disorder: Long Term Strategies Condition(s): Panic Disorder; Agoraphobia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Cognitive behavior therapy (CBT) with or without medication has been used in the treatment of panic disorder (PD). The purpose of this study is 1) to determine whether nine months of maintenance cognitive-behavior therapy (CBT) significantly improves the likelihood of sustained improvement; and 2) to determine the acute acceptability and efficacy of medication therapy or continued CBT alone among patients who fail to respond sufficiently to an initial course of CBT alone. It has been found that patients with PD respond as well to CBT or medication alone as they do to a combination of the two. Since the combined treatments are expensive and CBT is associated with less risk of medical toxicity compared to medications, CBT alone will be

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used first. All patients will first receive CBT alone. If the patient responds to this therapy, the patient will be assigned randomly (like tossing a coin) to 1 of 2 groups. One group will continue to receive CBT (maintenance therapy) for 9 months. The other group of responders will not receive any further therapy. If a patient does not respond to CBT alone, he/she will be assigned randomly to 1 of 2 different groups. One group will receive paroxetine; the other will continue to receive CBT for a longer period. The response to treatment will be evaluated to see which regimen works best to treat PD. The study will last approximately 3 years. An individual may be eligible for this study if he/she has panic disorder with no more than mild agoraphobia (fear of being in public places) and is at least 18 years old. Phase(s): Phase III Study Type: Interventional Contact(s): Katherine Shear, PhD 1-412-624-1340 [email protected]; Susan Ray, PhD [email protected] or [email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00000368 •

Vestibular Dysfunction In Adult Patients With Panic Disorder With or Without Agoraphobia Condition(s): Anxiety Disorder; Panic Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); University of Pittsburgh Purpose - Excerpt: Objectives: I. Determine whether the prevalence of abnormalities on clinical vestibular (balance) tests is higher in panic disorder with agoraphobia than in uncomplicated panic disorder and nonpanic anxiety disorder. II. Determine whether the prevalence of abnormalities on audiological tests of cochlear or brainstem function is elevated in panic disorder without agoraphobia or nonpanic anxiety disorder. III. Determine whether symptom patterns can be identified that are indicative of vestibular abnormalities in panic disorder. IV. Determine whether vestibular dysfunction can be induced by psychosomatic mechanisms. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004367

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Cognitive and Drug Therapy for Drug-Resistant Depression Condition(s): Depression; Anxiety Disorders; Personality Disorders; Drug-resistant depression Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: To develop an effective combined cognitive therapy (CT) plus drug treatment for patients with drug-resistant depression (DRD) (i.e., depression that is refractory to medication). To develop a manual for combined treatment for DRD that integrates three existing forms of CT (CT for depression, CT for personality disorders, and CT for anxiety disorders), and that specifies interventions for combining CT and medication when two therapists (psychotherapist and pharmacotherapist) provide the treatment. To obtain outpatient, randomized control, pilot data on the clinical value of the combined CT plus drug treatment, using the standard antidepressant desipramine

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(DMI), to obtain effect sizes and to determine if the treatment merits further investigation in a clinical trial. To develop a therapist adherence measure for the combined treatment. Patients receive 1 of 2 treatments: CT plus DMI (n = 18) or DMI plus Clinical Management (n = 12). The first 6 of the 18 CT plus DMI patients are treated in a pre-pilot phase before randomization begins. All treatments continue for 6 months. The major assessment battery is administered at intake, 3 months, 6 months, and followup 6 months later. All treatments are closely monitored via audiotapes and supervision for purposes of developing and refining the CT plus drug treatment. The audiotapes are also used for development of the adherence measure. The primary outcome measures are Hamilton Rating Scale for Depression scores, Beck Depression Inventory scores, percent of patients who achieve clinical remission of symptoms, and percent showing attrition from treatment. Compliance with the treatment regimens is also a targeted and measured outcome variable. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000376 •

Fluoxetine for Anxious Children Condition(s): Anxiety Disorders Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to see if it is safe and effective to use fluoxetine to treat children and adolescents with Generalized Anxiety Disorder (GAD). Anxiety disorders are one of the most common psychiatric disorders in children and adolescents, and can cause disturbances in the child's school, social, and family lives. Having an anxiety disorder puts a child at risk for depression and drug abuse, and appears to continue into adulthood. There is very little information on anxiety medications for children. Children will be assigned randomly (like tossing a coin) to receive either fluoxetine or an inactive placebo for 12 weeks. Each child will be monitored for symptoms and side effects throughout the study. He/she will have blood tests at Weeks 4, 8, and 12 to measure drug levels in the blood. The study will last for 12 weeks. A child is eligible for this study if he/she: Is 8 to 17 years old and has anxiety disorder. A child will not be eligible for this study if he/she: Has current major depression, panic disorder, or obsessive-compulsive disorder, or abuses alcohol or drugs. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000381

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Gabapentin For the Control of Hot Flashes in Women With Breast Cancer Condition(s): Anxiety Disorder; Breast Cancer; Depression; Hot Flashes; Quality of Life Study Status: This study is no longer recruiting patients. Sponsor(s): James P. Wilmot Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Gabapentin may be effective for the control of hot flashes. It is not yet known if gabapentin is effective in treating hot flashes. PURPOSE:

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Randomized clinical trial to study the effectiveness of gabapentin in controlling hot flashes in women who have breast cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022074 •

Treatment of Youth with ADHD and Anxiety Condition(s): Attention Deficit Hyperactivity Disorder; Anxiety, Separation; Social Phobia; Generalized Anxiety Disorder Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this NIMH-sponsored pilot study is to collect information on the efficacy and safety of drug treatments for children and adolescents who suffer from both ADHD and anxiety disorders. Specifically, the study will examine the benefits of the stimulant medication both alone and in combination with fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) that has antianxiety effects. Young people aged 6 to 17 diagnosed with these co-occurring disorders may be eligible to participate. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012584

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Combination Chemotherapy Plus Fluoxetine in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer Condition(s): Anxiety Disorder; Depression; Fatigue; Non-small cell lung cancer Study Status: This study is suspended. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more cancer cells. An antidepressant such as fluoxetine may improve the quality of life in patients undergoing chemotherapy. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus fluoxetine in treating patients who have advanced or recurrent non-small cell lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005850

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New Drugs in the Treatment of Mood Disorders Condition(s): Anxiety Disorder; Mood Disorder; Psychotic Disorder Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH)

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Purpose - Excerpt: This clinical study compares the effectiveness of two anticonvulsants Lamotrigine (Lamictal) Monotherapy and Gabapentin (Neurontin) in patients with treatment resistant affective disorders. We initially have found that the response rate to lamotrigine (51%) exceeded that of gabapentin (28%) or placebo (21%). In this study the placebo phase has been dropped so that we examine possible clinical and biological factors predictors of response. The drugs will be given in a randomized order for six weeks each and you will not know when you are on a given one. There will be a 2-4 week "washout" period between treatments. If you respond well to one of these treatments, a longer open continuation period will be offered at the end of this study. This would involve one or both drugs in combination. A variety of rating scales and brain imaging procedures will also be offered before and during each drug evaluation. Both lamotrigine and gabapentin are generally well tolerated. A serious potentially life threatening rash occurs in about 1/500 patients treated with lamotrigine, however. Common side effects are rash, dizziness, unsteadiness, double vision, blurred vision, nausea, vomiting, insomnia, sedation, and headache. These side effects are usually mild, and resolve with continued time on the drug or a decrease in dosage. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001482 •

Panic Disorder Study Condition(s): Panic Disorder Study Status: This study is not yet open for patient recruitment. Sponsor(s): Wyeth-Ayerst Research Purpose - Excerpt: The primary objective is to determine the efficacy, safety, and tolerability of venlafaxine extended release (ER) capsules in the treatment of outpatients with panic disorder (PD) in comparison to those of placebo. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044772

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Phase II Double-Blind, Placebo-Controlled Study of the Reinforcing Effects of Alprazolam in Patients with Anxiety Condition(s): Anxiety Disorder; Panic Disorder Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA); University of Texas Purpose - Excerpt: Objectives: I. Determine whether the benzodiazepine alprazolam reinforces self-medication behavior in anxious patients with varying histories of using other drugs. II. Establish outpatient methods for the study of self-medication and drug reinforcement in patients vulnerable to prescription drug abuse or dependence. III. Evaluate the influence of alcohol and other non-prescription drug use as determinants of vulnerability in these patients. IV. Identify personality, attitudinal, or other variables

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that might predict different patterns of self-medication. V. Assess the effects of cognitive-behavioral therapy on alprazolam self-medication. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004373 •

Pilot Study of Vestibular Rehabilitation Training for Panic Disorder With Vestibular Dysfunction Condition(s): Vestibular Diseases; Agoraphobia; Panic Disorder Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); University of Pittsburgh Purpose - Excerpt: Objectives: I. Evaluate whether vestibular rehabilitation training is of value in reducing anxiety symptoms in patients with panic disorder with or without agoraphobia who have vestibular dysfunction as identified by clinical vestibular tests. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004366

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Randomized Study of Cognitive-Behavioral Therapy vs Imipramine and Their Combination for Panic Disorder Condition(s): Panic Disorder Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH); Long Island Jewish Medical Center Purpose - Excerpt: Objectives: I. Determine which treatment is most effective for patients with panic disorder: cognitive-behavioral therapy (CBT) plus imipramine (IMI), CBT plus placebo, CBT alone, IMI alone, or placebo alone. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004834

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Treatment for Anxiety in Children Condition(s): Obsessive-Compulsive Disorder; Anxiety Disorders; Generalized Anxiety Disorder; Social Phobia; Separation Anxiety Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to see if it is effective to treat children with anxiety disorders with fluvoxamine. Fluvoxamine has been successfully used to treat obsessive-compulsive disorder (OCD) in adults and children. Anxiety disorders other than OCD, such as generalized anxiety disorder, social phobia, or separation anxiety, are very common in youth and are not always responsive to behavioral therapies alone. These disorders may respond to fluvoxamine. A child will be evaluated

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for 3 weeks before he/she is assigned randomly (like tossing a coin) to receive either fluvoxamine or an inactive placebo for 8 weeks. After this double-blind phase (neither the child/parents nor the doctor know which treatment is being given), the child will have the option of continuing treatment during a 4-month open-label extension period (both the child/parents and the doctor know which the child is receiving). A child may be eligible for this study if he/she: Is 6 to 17 years old and has been diagnosed with an anxiety disorder (i.e., generalized anxiety disorder, social phobia, or separation anxiety). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000389

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 “anxiety 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 ANXIETY 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 “anxiety disorders” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on anxiety disorders, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Anxiety Disorders By performing a patent search focusing on anxiety 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 anxiety disorders: •

2-benzazepines with 5- and 6-membered heterocyclic rings to treat pain and anxiety disorders Inventor(s): Bock; Mark G. (Hatfield, PA), Evans; Ben E. (Lansdale, PA), Freidinger; Roger M. (Lansdale, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,210,082 Date filed: May 16, 1991 Abstract: Pharmaceutical compositions containing aromatic 2-benzazepines with fused 5- or 6-membered heterocyclic rings are disclosed which are useful in the treatment of panic disorder or anxiety disorder. Excerpt(s): This application is related to Merck U.S. patent application Ser. No. 353,224. Cholecystokinins (CCK) and gastrin are structurally-related neuropeptides which exist in gastrointestinal tissue and in the the central nervous system (see, V. Mutt, Gastrointestinal Hormones, G. B. J. Glass, Ed., Raven Press, N.Y., p. 169 and G. Nisson, ibid, p. 127). The isolation of the 33-amino acid polypeptide, cholecystokinin (CCK-33), from porcine intestine, Mutt, V. et al., "Structure of Porcine Cholecystokininpancreozymin. 1. Cleavage with Thrombin and Trypsin", European J. Biochem. 6, 156, (1968), was followed by the discovery that it occurs in numerous molecular forms at various sites throughout the peripheral and central nervous systems, Larsson, L. et al., "Localization and Molecular Heterogeneity of Cholecystokinin in the Central and Peripheral Nervous System", Brain Res., 165, 201 (1979). In the mammalian brain the predominant fragments are the carboxy terminal octapeptide, H-AspTyr(SO.sub.3 H)-Met-Gly-Trp-Met-Asp-Phe-NH.sub.2 (CCK-8s, CCK.sub.26-33) and tetrapeptide, CCK-4 (CCK.sub.30-33). The carboxy terminal octapeptide possesses the full biological profile of CCK, Dockray, G.J. et al., "Isolation, Structure and Biological Activity of Two Cholecystokinin Octapeptides from Sheep Brain", Nature 274, 711 (1978), and meets many anatomical and biochemical criteria which characterize a neurotransmitter, Vanderhaeghen, J.J. et al., "J. Neuronal Cholecystokinin", Ann. N.Y. Acad. Sci., 448, (1985). The presence of high concentrations of CCK-8s in the mammalian CNS is complemented with findings of specific and high affinity membrane-bound CCK binding sites, Innis, R.B. et al., "Distinct Cholecystokinin Receptors in Brain and Pancreas", Proc. Natl. Acad. Sci. U.S.A., 77, 6917 (1980). Web site: http://www.delphion.com/details?pn=US05210082__

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2-hydroxymethylolanzapine compositions and methods Inventor(s): Yelle; William E. (Littleton, MA) Assignee(s): Sepracor Inc. (Marlborough, MA) Patent Number: 6,174,882 Date filed: November 22, 1999 Abstract: Methods and compositions are disclosed utilizing 2-hydroxymethylolanzapine for the treatment of psychosis in humans. 2-Hydroxymethylolanzapine exhibits a lessened liability toward drug-drug interactions than olanzapine and a more predictable

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dosing regimen than olanzapine. 2-Hydroxymethylolanzapine is also useful for the treatment of acute mania, mild anxiety states, anxiety disorders, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, autistic disorder, excessive aggression, substance abuse, depressive signs and symptoms, tic disorder, functional bowel disorder and fungal dermatitis. Excerpt(s): The invention relates to methods of treating psychosis, acute mania, mild anxiety states, schizophrenia, bipolar disorder, autistic disorder, excessive aggression, substance abuse, depressive signs and symptoms, tic disorder, functional bowel disorder and fungal dermatitis. It is commercially available as Zyprexa.RTM. from Eli Lilly Co. The antipsychotic effect of olanzapine is ascribed by the literature to blocking of the dopamine D.sub.2 receptor and to 5-HT antagonism. Formation of 2hydroxymethylolanzapine occurs in the liver through the enzymes of the P450 system. 2-Hydroxymethylolanzapine is formed by cytochrome P450 2D6 (CYP2D6). CYP2D6 is polymorphically expressed in the human population. The mutant allele constitutes the recessive trait. Homozygous carriers of the mutation completely lack CYP2D6 and are referred to as poor metabolizers; persons homozygous and heterozygous for the "normal" allele are extensive metabolizers. In addition to problems arising from variability in dosage regimens, the clinical use of CYP2D6-metabolized drugs and of CYP2D6 inhibitors, which includes a variety of antiarrhythmic agents, betaadrenoceptor blockers and tricyclic antidepressants, in conjunction with olanzapine, may inhibit olanzapine metabolism. Web site: http://www.delphion.com/details?pn=US06174882__ •

Anxiolytic composition Inventor(s): Lammintausta; Risto (Turku, FI), Virtanen; Raimo (Rusko, FI) Assignee(s): Farmos-Yhtyma Oy (Turku, FI) Patent Number: 4,783,477 Date filed: November 9, 1987 Abstract: Medetomidine is useful in the treatment of anxiety disorders. Excerpt(s): This invention relates to anxiolytic compositions, i.e. compositions useful in the therapy of anxiety. We have now found that this compound also possesses anxiolytic effects. Anxiety disorder is a rather wide concept including, e.g., general anxiety, panic disorder and various kinds of withdrawal symptoms. Web site: http://www.delphion.com/details?pn=US04783477__

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Betaxolol hydrochloride for the treatment of anxiety disorders Inventor(s): Swartz; Conrad Melton (P.O. Box 2952, Greenville, NC 27836-0952) Assignee(s): none reported Patent Number: 5,798,393 Date filed: April 2, 1996 Abstract: The compound betaxolol has the chemical formula:1-›4›2cyclopropylmethoxy)ethyl!phenoxy!-3-›1-methylethyl)amino!-2-propanol.It is administered, preferably orally, once per day in 4-12 mg. tablets for the treatment of

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symptoms of anxiety disorder in human patients. Such symptoms include those present in Generalized Anxiety Disorder (GAD), which include somatic symptoms such as panic, palpitations and pounding heart. Excerpt(s): The present invention relates to medicine and more particularly to the administration of pharmaceuticals to relieve mental disorders. Anxiety symptoms are common, and they pose risks to the person who suffers such symptoms as well as his family and co-workers. The psychiatric mental condition (diagnosis) of Generalized Anxiety Disorder (GAD) is an archetype of problematic anxiety. According to the American Psychiatric Association's Diagnostic and Treatment Manual of Psychiatry, 4th edition (DSM-4) the core symptoms of GAD include feelings of being on edge or easily upset, easily fatigued, irritability, argumentativeness or easy anger, decreased concentration or instances of mind blanking, muscle tension, and sleep disturbance consisting of difficulty in falling asleep or oversensitive awakening. GAD is considered to be present when at least several of these symptoms are present. These symptoms are commonly associated with a fluctuating mood, which can include a sense of sadness or desperation, and feelings of being overwhelmed or victimized. In some patients, anxiety is also associated with a variety of body-related (or "somatic") symptoms, which are themselves unpleasant and distressing. These somatic symptoms include panic; palpitations, pounding heart or accelerated heart rate; sweating; shaking or trembling; shortness of breath or smothering; feelings of choking; chest discomfort; tightness or pain; nausea or abdominal distress; feelings of unsteadiness, lightheadedness, faintness or similar dizziness; feeling of unreality or depersonalization (detachment from self); fears of losing control or of going crazy; fears of dying; sensations of numbness or tingling, typically in the fingers or around the lips; cold sweats, chills or hot flushes; tension headache; gas pains; intestinal spasms; restless agitation; dry mouth; and decreased tolerance for physical exertion. Web site: http://www.delphion.com/details?pn=US05798393__ •

Blood levels of CCK peptides relative to panic disorder treatment Inventor(s): Sheehan; David V. (Lutz, FL), Talbot; Janet D. (Lutz, FL), Thomas; Thomas N. (Palm Harbor, FL) Assignee(s): University of South Florida (Tampa, FL) Patent Number: 5,558,987 Date filed: November 18, 1994 Abstract: A method of treating a patient having a panic disorder, the patient having an elevated CCK peptide plasma level, by lowering the plasma CCK peptide level of the patient. A further method provides a diagnosis of panic disorder in a patient by detecting if that patient's plasma contains elevated CCK peptide levels. A further method determines the efficacy of the drug for the treatment of panic disorder by detecting the ability of the drug to lower elevated CCK peptide levels in a model for panic disorder. Additionally, a method of dosing a patient having elevated CCK peptide levels with an antipanic disorder drug is characterized by administering the drug to a patient and monitoring the lowering of the elevated plasma CCK peptide levels of the patient. Excerpt(s): The present invention relates to the relationship between cholecystokinin (CCK) and panic disorder. More specifically, the present invention provides 1) a method of treating a patient having a panic disorder, 2) a method of diagnosing panic

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disorder in a patient, 3) a method of determining the efficacy of a drug for the treatment of panic disorder, and 4) a method of predicting the vulnerability of a patient to panic disorder. The present invention relates to the relationship between panic disorder and cholecystokinin (CCK). Panic disorder affects 3.6% of the general population(1) and 1014% of patients in cardiology practices (2,3). It is a chronic relapsing illness(4,5) characterized by paroxysmal anxiety attacks that strike suddenly and for no apparent reason. Seventy-five percent of its victims are women(6). It has a unimodal age of onset (mean 23 years) rarely starting before age 12 or after age 45(7) and is 12 times more frequent in the 25-44 age group than in the 65+ age group(6). Panic disorder is more common in monozygotic than in dizygotic twins(8). Its inheritance pattern is consistent with single locus genetics (9,10,11) and preliminary evidence implicates the long arm of chromosome 16(12). It is associated with an increased risk of mitral valve prolapse(13), hypertension(14), alcohol abuse and dependence(15), and has an excess mortality from suicide and among men from cardiovascular death(16). The lack of understanding of the biochemical basis of panic disorder is hampering the development of drugs effective in the treatment of this disorder. Web site: http://www.delphion.com/details?pn=US05558987__ •

Centrally-acting beta-blockers and serotonin-enhancers for the treatment of anxiety disorders and adjustment disorders with anxiety Inventor(s): Swartz; Conrad Melton (1215 McCutcheon Ave., Richmond Heights, MO 63117) Assignee(s): none reported Patent Number: 6,218,395 Date filed: August 2, 1999 Abstract: A combination of medicines are administered daily for the relief of the symptoms of an Anxiety Disorder or an Adjustment Disorder With Anxiety. The combination comprises a centrally-acting beta-blocker which passes the brain blood barrier, preferably the beta-blocker betaxolol, and a serotonin-enhancer, for example, the serotonin agonist buspirone or the serotonin reuptake inhibitor sertraline. Excerpt(s): The present invention relates to medicine and more particularly to the administration of pharmaceuticals to relieve anxiety disorders and adjustment disorders with anxiety. Anxiety disorders are common, and they pose discomfort and health risks to the person who suffers with symptoms, his family and his co-workers. The term "anxiety disorders" refers here to the group of conditions which are longstanding and persistent. They are listed under this term in the Diagnostic and Statistical Manual of Psychiatry, Fourth Edition. The presently accepted names of such anxiety disorders are: Generalized Anxiety Disorder, Obsessive-Compulsive Disorder, PostTraumatic Stress Disorder, Acute Stress Disorder, Panic Disorder, Agoraphobia, Specific Phobia, Social Phobia, Anxiety Disorder Due to General Medical Condition, Substance-Induced Anxiety Disorder, and Anxiety Disorder Not Otherwise Specified. These "anxiety disorders" are different from ordinary "reactive anxiety" which occurs in the normal course of life, for example, due to the stress of moving from one house to another. Such reactive anxiety disorders, without medication, decrease with time, e.g., in one to four weeks. Web site: http://www.delphion.com/details?pn=US06218395__

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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: 6,169,098 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 paroxetine, in the form of its free base, or a pharmaceutically acceptable salt and/or solvate thereof 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 and a second component (b) which is paroxetine, or a pharmaceutically acceptable salt and/or solvate thereof 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 that the compound (R)-5-carbamoyl-8-fluoro-3-N,N-dicyclobutylamino-3,4dihydro-2H-1-benzopyr an, which has high affinity to 5-HT receptors and antagonizes 5-HT.sub.IA -mediated responses, induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors. Web site: http://www.delphion.com/details?pn=US06169098__

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Compositions containing sertraline and a 5-HT.sub.1D receptor agonist or antagonist Inventor(s): Chenard; Bertrand L. (New York, NY), Howard; Harry R. (New York, NY), Macor; John E. (New York, NY), Schulz; David W. (New York, NY), Sprouse; Jeffrey S. (New York, NY) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 5,597,826 Date filed: September 14, 1994 Abstract: The present invention relates to novel compositions containing the serotonin selective re-uptake inhibitor (SSRI), preferably (1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4tetrahydro-N-methyl-1-naphthalenam ine, and an agonist or antagonist of the serotonin 1 (5-HT.sub.1) receptor and to the use of such compositions for treating or preventing a condition selected from mood disorders, including depression, seasonal affective disorders and dysthmia, anxiety disorders including generalized anxiety disorder and panic disorder; agoraphobia, avoidant personality disorder; social phobia; obsessive compulsive disorder; post-traumatic stress disorder; memory disorders including dementia, amnestic disorders and age-associated memory impairment; disorders of eating behavior, including anorexia nervosa and bulimia nervosa; obesity; cluster headache; migraine; pain; Alzheimer's disease; chronic paroxysmal hemicrania; headache associated with vascular disorders; Parkinson's disease, including dementia in Parkinson's disease, neuroleptic-induced parkinsonism and tardive dyskinesias; endocrine disorders such as hyperprolactinaemia; vasospasm (particularly in the cerebral vasculature); hypertension; disorders in the gastrointestinal tract where changes in motility and secretion are involved; sexual dysfunction, including premature ejaculation; and chemical dependencies. Excerpt(s): The present invention relates to novel compositions containing the serotonin selective re-uptake inhibitor (SSRI) (1S-cis)-4-(3,4- dichlorophenyl)-1,2,3,4-tetrahydro-Nmethyl-1-naphthalenemine (hereinafter sertraline) and an agonist or antagonist of the serotonin 1 (5-HT.sub.1) receptor and to the use of such compositions for treating or preventing a condition selected from mood disorders, including depression, seasonal effective disorders and dysthmia, anxiety disorders including generalized anxiety disorder and panic disorder; agoraphobia, avoidant personality disorder; social phobia; obsessive compulsive disorder; post-traumatic stress disorder; memory disorders including dementia, amnestic disorders and age-associated memory impairment; disorders of eating behavior, including anorexia nervosa and bulimia nervosa; obesity; cluster headache; migraine; pain; Alzheimer's disease; chronic paroxysmal hemicrania; headache associated with vascular disorders; Parkinson's disease, including dementia in Parkinson's disease, neuroleptic-induced parkinsonism and tardive dyskinesias; endocrine disorders such as hyperprolactinaemia; vasospasm (particularly in the cerebral vasculature); hypertension; disorders in the gastrointestinal tract where changes in motility and secretion are involved; sexual dysfunction, including premature ejaculation; and chemical dependencies. U.S. Pat. No. 4,536,518 issued Aug. 20, 1985 refers to sertraline and derivatives thereof and states that these compounds are useful as antidepressant agents. U.S. Pat. No. 4,940,731 issued Jul. 10, 1990 refers to a method of treating premature ejaculation using sertraline. Web site: http://www.delphion.com/details?pn=US05597826__

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Duplications of human chromosome 15q24-25 and anxiety disorders, diagnostic methods for their detection Inventor(s): Estivill Palleja; Xavier (Barcelona, ES), Gratacos; Monica (Barcelona, ES), Nadal; Marga (Barcelona, ES), Pujana; Miguel Angel (Barcelona, ES), Volpini; Victor (Barcelona, ES) Assignee(s): Palleja, Zavier Estivell (Barcelona, ES) Patent Number: 6,225,057 Date filed: July 23, 1998 Abstract: A method for identifying a person at risk for developing an anxiety disorder, said anxiety disorder selected from the group consisting of agoraphobia, social phobia, panic attacks, panic disorders, simple phobia, mood disorders, major depression, schizophrenia, and hypermobility syndrome associated with duplication of a region of the genomic sequence of human chromosome 15q24-25 defined by boundaries D15S925 (proximal end) and DS15S736 (distal end). The method comprises identifying the presence of duplication in the region of the genomic sequence of human chromosome 15q24-25 defined by the boundaries D15S925 (proximal end) and DS15S736 (distal end) in said person. Excerpt(s): Panic disorder, agoraphobia, social phobia and other anxiety disorders affect 5-10% of the general population. There are no biochemical, cytological or molecular tools for the diagnosis of anxiety disorders. Moreover, the gene or genes predisposing to anxiety disorders have not yet been localised. We have studied the clinical association between panic/agoraphobia and joint hypermobility syndrome, and have identified several pedigrees in which these disorders cosegregate. We have detected a 10 centiMorgan (cM) duplication of human chromosome 15 (15q24-25) in the affected subjects of families with several members suffering from anxiety and depression disorders. The 15q24-25 duplication segregates with panic disorder, agoraphobia, social phobia, depression and joint hypermobility syndrome. The 15q24-25 duplication is strongly linked to panic disorder, agoraphobia, social phobia and joint hypermobility syndrome (lod score 4.9). Affected-only analysis for the phenotype defined only by the anxiety disorders gave a lod score of 3.36. All but one of the 45 subjects of these families with these anxiety disorders had the 15q24-25 duplication. Mosaicism was detected in 80% of the affected subjects, with 40-70% of their lymphocytes having the 15q24-25 duplication. We have also studied 50 unrelated non-familial cases of panic disorder and/or agoraphobia and all had the 15q24-25 duplication. The duplicated region contains 10 known genes of which NTRK3 and LOXL1 are likely to be involved in anxiety and joint hypermobility. We propose that this genomic mutation, which is present in 7% of the general population, is the major susceptibility mutation for panic disorder, agoraphobia, major depression and social phobia in familial and sporadic cases. We have developed cytological, cytogenetic and molecular methods for the specific diagnosis of the 15q24-25 duplication causing anxiety disorders. Anxiety disorders are neurotic alterations that include generalised anxiety disorder, phobic disorders, panic disorders (panic attacks, panic disorder and agoraphobia) and obsessive-compulsive disorders. The prevalence of this group of alterations is estimated in about 10% in the adult population and up to 5% in infantile patients. Several million people worldwide are affected by anxiety disorders, but the actual prevalence rates of these alterations are probably higher. Anxiety and panic disorders aggregate in families. The familial transmission of anxiety disorders has often been explained by common familial environmental factors. Twin studies of anxiety disorders have shown a high concordance among monozygotic twins. The mode of familial transmission of panic

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disorder is unclear, but it has been suggested that anxiety, panic attacks and agoraphobia have an autosomal dominant pattern of inheritance with incomplete penetrance. Although a major gene is supposed to be involved in panic disorder, multifactorial/polygenic inheritance has also been postulated. Web site: http://www.delphion.com/details?pn=US06225057__ •

Gepirone for alleviation of panic disorders Inventor(s): Kurtz; Neil (Weston, CT), Newton; Roger E. (Evansville, IN), Temple, Jr.; Davis L. (Wallingford, CT) Assignee(s): Bristol-Myers Company (New York, NY) Patent Number: 4,782,060 Date filed: July 29, 1987 Abstract: Gepirone and its pharmaceutically acceptable salts are useful in alleviation of panic disorders which can take the form of clinical syndromes comprising, for example, panic attacks, agoraphobia and phobic anxiety. Excerpt(s): This invention is concerned with a drug bio-affecting body-treating process which employs the pyrimidine compound 4,4-dimethyl-1-[4-[4-(2-pyrimidinyl)-1piperazinyl]butyl]-2,6-piperidinedi one or a pharmaceutically acceptable acid addition salt thereof. The synthesis of the compound and the disclosure of its anxiolytic properties are described in the following patents and publications. 1. D. L. Temple, Jr., U.S. Pat. No. 4,423,049, issued Dec. 27, 1983. Web site: http://www.delphion.com/details?pn=US04782060__

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Method for alleviation of panic disorders Inventor(s): Kurtz; Neil M. (Westport, CT), Newton; Roger E. (Evansville, IN), Temple, Jr.; Davis L. (Wallingford, CT) Assignee(s): Bristol-Myers Company (New York, NY) Patent Number: 4,634,703 Date filed: October 25, 1985 Abstract: Buspirone and its pharmaceutically acceptable salts are useful in alleviation of panic disorders which can take the form of clinical syndromes comprising, for example, panic attacks, agoraphobia and phobic anxiety. Excerpt(s): This invention is concerned with a drug bioaffecting body-treating process which employs the pyrimidine compound 8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]8-azaspiro[4.5]decane-7,9-dio ne or a pharmaceutically acceptable acid addition salt thereof. The synthesis of the compound and the disclosure of its psychotropic properties are described in the following patents and publications. 1. Y. H. Wu, et al., J. Med. Chem., 15, 477 (1972). Web site: http://www.delphion.com/details?pn=US04634703__

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Method for the treatment of panic disorder Inventor(s): Schweizer; Edward E. (Wilmington, DE) Assignee(s): Trustees of the University of Pennsylvania (Philadelphia, PA) Patent Number: 5,166,202 Date filed: December 13, 1991 Abstract: Midazolam and its pharmaceutically acceptable salts are useful in the treatment of panic disorder, panic attacks and the prevention of panic attacks. Excerpt(s): This invention relates to a method for treatment of panic disorder. More particularly, a method of treating panic disorder with intranasal midazolam is provided. Panic disorder is an illness which is estimated to afflict 1.5-2% of the adult population. The hallmark of panic disorder is the sudden, crescendo panic attack which may be as fleeting as a few minutes in duration, or may persist for over an hour before subsiding. The majority of patients suffering from panic disorder report an average attack frequency (four 4-symptom attacks) of less than one per day, which is true even for many moderate-to-severely ill patients such as those treated in the large CrossNational Collaborative Panic Study (Ballenger, J. C. et al., "Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. I. Efficacy in short-term treatment," Arch Gen Psychiatry, 45:413-422 (1988)). Current treatment strategies for panic disorder focus on attempts to control and prevent these intermittent, but severe and often disabling panic attacks, and thereby to reduce the associated inter-episode anticipatory anxiety, phobic avoidance, and somatic preoccupations. To accomplish this effectively with drug therapy requires daily doses of high potency benzodiazepines such as alprazolam, or daily doses of antidepressants such as imipramine. Web site: http://www.delphion.com/details?pn=US05166202__

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Method for treating anxiety, anxiety disorders and insomnia Inventor(s): Chouinard; Guy (4015 Chemin Trafalgar, Montreal, CA) Assignee(s): none reported Patent Number: 6,372,792 Date filed: January 29, 1998 Abstract: Treatment of the anxiety disorders and insomnia in humans may be accomplished by administering gabapentin in an effective amount. Excerpt(s): This invention relates to treatment of anxiety, including all of the anxiety disorders, and insomnia in humans by administration of gabapentin, its derivatives and pharmaceutically acceptable salts. Gabapentin is a generic term used to identify the chemical compound (1-aminomethyl)-1-cyclohexaneacetic acid. It is useful in therapy of certain cerebral disorders such as certain forms of epilepsy, faintness attacks, hypokinesia and cranial traumas. U.S. Pat. Nos. 4,024,175 and 4,087,544 cover the compound and its uses. They also disclose an acid salt, i.e. gabapentin hydrochloride hydrate in a ratio of 4:4:1 and a sodium salt of gabapentin hydrate in a ratio of 2:1. These patents are hereby incorporated by reference. Pregabalin is a long-acting form of gabapentin with the formula (S)-3-(aminomethyl)-5-methyl-hexanoic acid and CAS Registry Number: 148553-50-8, CI 1008. The compounds are described in U.S. Pat. Nos. 5,608,090 and 5,599,973, the disclosure of which are incorporated herein by reference to show additional forms of gabapentin usable in this invention. U.S. Pat. No. 5,084,479

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states that compounds such as gabapentin are used for treating neurodegenerative disorders, perinatal asphyxia, status epilepticus, Alzheimer's, Huntington's, Parkinson's, and Amyotrophic Lateral Sclerosis. That invention covers treating neurodegenerative disorders termed acute brain injury. These include but are not limited to: stroke, head trauma, and asphyxia. Web site: http://www.delphion.com/details?pn=US06372792__ •

Method for treating panic disorder Inventor(s): Sikter; Andras (Budapest, HU) Assignee(s): S+V Engineering Kft. (Budapest, HU) Patent Number: 5,348,749 Date filed: November 5, 1992 Abstract: A method for treating panic disorder, which comprises administering to a human suffering from panic disorder 0.03 to 1.5 mmoles of zinc and 2 to 100 mmoles of magnesium and 2 to 60 mmoles of phosphorus and 3 to 90 mmoles of potassium as a daily dose in a composition consisting essentially of zinc, magnesium, phosphorus and potassium, in a weight ratio of 1-15:25-200:50-200:100-500, respectively. Excerpt(s): This application is a continuation-in-part of co-pending international application No. PCT/HU91/00018 filed May 10, 1991, which designates the United States. The invention relates to a method for treating panic disorder in humans, by administration of a novel pharmaceutical composition comprising zinc, magnesium, phosphorus and potassium in a determined ratio. It is known that mineral substances and trace elements are of vital importance in the human (generally in living) organism(s). A great number of publications deal with the effect of the given elements (such as zinc, potassium, magnesium and phosphorus) applied separately. Web site: http://www.delphion.com/details?pn=US05348749__

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Methods and compositions for treating and preventing anxiety and anxiety disorders using optically pure (R) tofisopam Inventor(s): Klein; Donald F. (New York, NY), Landry; Donald W. (New York, NY) Assignee(s): Janus Pharmaceuticals, Inc. (New York, NY) Patent Number: 6,080,736 Date filed: October 27, 1999 Abstract: Methods are disclosed utilizing the R enantiomer of tofisopam. This compound is useful in the treatment or prevention of anxiety or anxiety disorders while substantially reducing adverse effects associated with racemic tofisopam. Excerpt(s): This invention relates to methods and pharmaceutical compositions for treating and preventing anxiety and anxiety disorders using optically pure tofisopam. The concept of chirality is basic to organic and biochemistry and has become a significant factor in determining the actions of a pharmacologic agent. An atom, particularly a carbon atom, is said to be chiral or stereogenic when it is bound to four different atoms or groups in a tetrahedral arrangement. All four atoms or groups must be different in order to make the central atom a chiral center. The importance of this is

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that such an arrangement can not be superimposed on its mirror image by any rotation of bonds or positioning of the molecule. The two molecules are isomers, that is they have the same empirical formula, but they are not identical and short of breaking and remaking bonds they can not be made identical. Molecules that differ in the spatial arrangement of their atoms but have the same points of attachments are called stereoisomers. Enantiomers are a subgroup of stereoisomers that are nonsuperimposable mirror images. All molecules that contain stereogenic or chiral centers must have enantiomers. If a molecule can be superimposed on its mirror image by rotation or any motion other than bond making and breaking then they are identical and not enantiomers. A molecule that has more than one chiral center may generate multiple stereoisomers and these are called diastereomers. Web site: http://www.delphion.com/details?pn=US06080736__ •

Peptide analogues Inventor(s): Dong; Zheng Xin (Holliston, MA) Assignee(s): Societe de Conseils de Recherches et d'Applications Scientifiques, SAS (Paris, FR) Patent Number: 6,242,563 Date filed: June 28, 1999 Abstract: The present invention is directed to novel analogues of PACAP (Pituitary Adenylate Cyclase Activating Polypeptide) as described in the specification, which are agonists of the PACAP receptor and as such are useful in treating cerebrovascular ischemia, male impotence, motor neuron disease, neuropathy, pain, depression, anxiety disorders, brain trauma, memory impairments, dementia, cognitive disorder, central nervous system diseases (such as Parkinson's disease, Alzheimer's disease), migraine, neurodegenerative diseases, ischemic heart disease, myocardial infarction, fibrosis, restenosis, diabetes mellitus, muscle disease, gastric ulcer, stroke, atherosclerosis, hypertension, septic shock, thrombosis, retina disease, cardiovascular disease, renal failure and cardiac failure and the prevention of neuronal cell death in a mammal. This invention is also directed to pharmaceutical compositions useful therefor. Excerpt(s): The present invention is directed to novel analogues of PACAP (Pituitary Adenylate Cyclase Activating Polypeptide) and the use thereof for treating the conditions and or diseases as described herein. A review of PACAP and its physiological function is summarized in Christophe, J., Biochimica et Biophysica Acta, 1154, 183-199 (1993), as follows. At least two classes of PACAP receptors have been described in mammalian tissues and cell lines: type I PACAP-preferring receptors and type II receptors which bind PACAP-27, PACAP-38 and VIP (vasoactive intestinal peptide) (Cauvin, A., et al., Peptides, 11, 773-777 (1990) and Shivers, B. D., et al., Endocrinology, 128, 3055-3065 (1991)). In addition, the first type is capable to display two subtypes, and the second type can be tentatively divided into three subtypes. Web site: http://www.delphion.com/details?pn=US06242563__

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System for treating patients with anxiety disorders Inventor(s): Hodges; Larry F. (Lithonia, GA), Rothbaum; Barbara O. (Atlanta, GA) Assignee(s): Emory University and Georgia Tech Research Corporation (Atlanta, GA) Patent Number: 5,807,114 Date filed: March 27, 1996 Abstract: A virtual reality system provides effective exposure treatment for psychiatric patients suffering from a particular anxiety disorder. The system is characterized by a video screen disposed in front of the patient to display an image of a specific graphical environment that is intended to trigger anxiety within the patient as a result of the particular patient phobia. A headset is worn by the patient, and has sensors disposed to detect movement and positioning of the patient's head. A computer program controls the operation of the system, and is designed to control the display of the graphical environment on the video screen, monitor the headset sensors and determine the position of the patient's head, and controllably manipulate the graphical environment displayed on the video screen to reflect the movement and position of the patient's head. In a preferred embodiment, a sensor is provided to automatically detect a level of patient anxiety, and the computer program is designed to monitor this sensor and controllably manipulate the graphical environment displayed on the video screen in response thereto. In other embodiments, sound and tactile feedback are provided to further enhance the graphic emulation. Excerpt(s): The present invention generally relates to psychiatric treatment of patients with phobias, and more particularly to a system for providing exposure therapy for psychiatric treatment of patients having various phobias. As is well known, people from all walks of life are known to suffer from a wide variety of phobias or related anxiety disorders. Simply defined, a phobia is an irrational fear of an object, activity, or situation that leads to a compelling desire to avoid it--e.g., fear of heights. Not only are there a wide variety of phobias, but any given type may manifest itself differently, or to a different degree, in different persons. Therefore, treatment programs are generally tailored individually to specific patients. Nevertheless, certain generalities in regard to treatment programs can be made. Namely, exposure theory espouses the view that patients suffering from a particular phobia can be treated to successfully manage that phobia by repeated exposure to the particular situation. For example, patients suffering from acrophobia (fear of heights) may be treated by exposure to high places. Elevators, balconies, building windows, bridges, and airplanes are environments where a patient being treated for acrophobia may be deployed. Although the degree of success varies from patient to patient, exposure therapy has been proven effective in many cases and controlled studies. Web site: http://www.delphion.com/details?pn=US05807114__

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Techniques for treating anxiety disorders by brain stimulation and drug infusion Inventor(s): Rise; Mark T. (Monticello, MN) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 6,263,237 Date filed: February 14, 2000

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Abstract: Techniques using one or more drugs and/or electrical stimulation for treating an anxiety disorder by means of an implantable signal generator and electrode and/or an implantable pump and catheter. A catheter is surgically implanted in the brain to infuse the drugs, and one or more electrodes may be surgically implanted in the brain to provide electrical stimulation. Excerpt(s): This invention relates to nerve tissue stimulation and infusion techniques, and more particularly relates to such techniques for treating anxiety disorders, including generalized anxiety disorder, obsessive-compulsive disorders, panic attacks and phobias. Some people suffer from chronic intractable anxiety disorders. The key feature of anxiety disorders is the frequent occurrence of the symptoms of fear; arousal, restlessness, heightened responsiveness, accelerated heart beat, elevated blood pressure, sweating, a desire to run or escape and avoidance behavior. Generally, anxiety is a normal response to certain life situations and can be beneficial to the person experiencing it. However, excessive or inappropriate anxiety can be detrimental. Anxiety disorders are the most common psychiatric disorders, affecting between 10 to 30 percent of the general population (Robins et. al., Arch Gen Psychiatry 1984; 41:949958). These disorders include generalized anxiety, phobias, panic attacks, and obsessivecompulsions. Generalized anxiety is characterized by unrealistic or excessive worry, lasting long periods of time (i.e. months). The symptoms of generalized anxiety are excessive muscle tension; overactivity in the autonomic nervous system evidenced by shortness of breath, sweating, cold hands, hyperventilation and tachycardia; and increased vigilance manifest as an increased startle response or difficulty in concentrating. Generalized anxiety is treated with oral medications from the benzodiazepine category such as chlordiazepoxide (Librium.RTM.) and diazepam (Valium.RTM.). These drugs have been shown to act by enhancing the activity of GABA.sub.A receptors leading to a hyperpolarization of neurons. The specific neurons affected are believed to be located in the amygdala which is part or the limbic system, a subset of the brain thought to be of central importance for emotional behavior. Web site: http://www.delphion.com/details?pn=US06263237__ •

Treatment of anxiety disorders Inventor(s): Amrein; Roman (31 Landhausweg, CH-4126 Bettingen, CH), Versiani; Marcio (Avda. Copacabana 1133, S. 1303, BR-22070 Rio de Janeiro, BR) Assignee(s): none reported Patent Number: 5,371,082 Date filed: September 14, 1993 Abstract: The invention relates to the use of p-chloro-N-(2-morpholinoethyl)benzamide in the treatment of anxiety disorders, such as, panic disorders, social phobia and obsessive compulsive disorder, Excerpt(s): The invention relates to the use of p-chloro-N-(2morpholinoethyl)benzamide [also known as moclobemide] in the treatment of anxiety disorders, such as, panic disorders, social phobia and obsessive disorders. Depressive and anxiety symptoms frequently overlap. Efficacy of tricyclic antidepressants (TCAs) and classical irreversible monoamine oxidase inhibitors (MAOIs) in anxiety disorders has been demonstrated in results from clinical trials and case reports. The anxiolytic effects of antidepressants are widely believed to be specific and not an epiphenomenon of antidepressant or patholytic effects. In long term treatment, tricyclic antidepressants

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(TCAs) appear to be effective. However, the poor tolerance of TCAs and the risks associated with conventional irreversible MAOIs are limitations to their usefulness. Therefore, there is a strong demand for alternative drugs particularly for chronic and long term treatment. Web site: http://www.delphion.com/details?pn=US05371082__ •

Treatment of panic disorders with estazolam Inventor(s): Coleman; James H. (Cumberland, RI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,481,208 Date filed: June 6, 1983 Abstract: Therapeutic process for treating panic disorders in humans comprising, the systemic administration of a 6-phenyl-8-chloro-4H-s-triazolo[4,3-a][1,4]benzodiazepine including the N-oxides and pharmacologically acceptable acid addition salts thereof in combination with a pharmaceutical carrier. Excerpt(s): Panic attacks, a spontaneous attack, thought to be a biochemical disorder of genetic origin, begins in the majority of subjects at ages 15 to 30 years. The attacks occur with no apparent reason to the subject and are accompanied by symptoms of hyperventilation, heart-pounding, pain in head, numbness or tingling of the limbs, hot and cold flashes, lump in throat, and the like. The attacks continue to occur and can lead the subject to become house bound. Various treatments have been prescribed, including hypnosis and behavior therapies and chemotherapy, particularly the administration of imipramine hydrochloride or phenelzine sulfate. The latter although somewhat effective have undesirable side-effects, chlordiazepoxide and diazepam have been tried but found not effective to block the panic attack. Estazolam has been indicated for the management of anxiety disorders. Web site: http://www.delphion.com/details?pn=US04481208__

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Treatment of posttraumatic stress disorder, obsessive-compulsive disorder and related neuropsychiatric disorders Inventor(s): Fogel; Barry S. (Waban, MA) Assignee(s): Synchroneuron, LLC (Waban, MA) Patent Number: 6,391,922 Date filed: March 19, 1999 Abstract: The present invention describes a novel treatment for neuropsychiatric disorders, including anxiety disorders, mood disorders, psychotic disorders, somatoform disorders, and neuropsychiatric symptoms resulting from movement disorders. The treatment of the present invention utilizes any agent that simultaneously act as NMDA-type glutamate receptor antagonists and GABA-A receptor agonists. Preferably these two activities are characteristic of a single agent, for example acamprosate (calcium N-acetylhomotaurinate). Alternatively, separate agents having these activities can be combined as a compound or mixture and thereby administered together. The invention also provides for a third agent that acts as a non-competitive

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NMDA-receptor blocking agent or ion channel blocker, that augments the effect of the primary treatment. A particularly preferred ion channel blocking agent is magnesium. Excerpt(s): The present invention relates to novel drug treatments for neuropsychiatric disorders, for example anxiety disorders, psychotic disorders, mood disorders and somatoform disorders. These treatments relieve symptoms of disorders characterized by repetitive, stereotyped, an unwanted, intrusive, or involuntary thoughts, perceptions, or behaviors. These include posttraumatic stress disorder, obsessive-compulsive disorder, somatization disorder, hypochondriasis, and body dysmorphic disorder. Contemporary drug therapy for these conditions is limited in efficacy, with many patients continuing to have symptoms despite treatment. Antidepressants, mood stabilizers, anti-anxiety drugs, and antipsychotic drugs all have been used to treat them. Even when they provide some relief, persistent intrusive, repetitive mental phenomena may remain as a distressing symptom. Thus, when a person with posttraumatic stress disorder is treated with an antidepressant, mood may improve while "flashbacks" of the traumatic event continue. Clearly, there is a need for additional medications efficacious for the treatment of these disorders, and especially for medications that suppress or eliminate the recurrent unwanted, intrusive, or involuntary thoughts, perceptions and behaviors characteristic of those disorders. Such medications might also be used to reduce such symptoms when they occur as part of another psychiatric syndrome, such as depression or schizophrenia, or when they are incidental to a neurological disorder such as Tourette's syndrome or Huntington's disease. "re-experiencing the trauma, psychic numbing or avoidance of stimuli associated with the trauma, and increased arousal. Reexperiencing phenomena include intrusive memories, flashbacks, nightmares, and psychological or physiological distress in response to trauma reminders. Intrusive memories are spontaneous, unwanted, distressing recollections of the traumatic event. Repeated nightmares contain themes of the trauma or a highly accurate and detailed recreation of the actual event(s). Flashbacks are dissociative states in which components of the event are relived, and the person feels as if he or she is experiencing the event for a few seconds for as long as days. Reactivity to trauma-related stimuli can involve intense emotional distress or physical symptoms similar to those of a panic attack, when the patient is exposed to sights, sounds, smells or events that were present during the traumatic event. Avoidance may include thoughts, feelings, situations or activities that are reminders of the trauma. Numbing may occur through amnesia, emotional detachment, restricted affect, or loss of interest in activities. Increased arousal may include insomnia, irritability, hypervigilance, increased startle response, or impaired concentration. This disorder can have pervasive effects on an individual's interpersonal behavior and all spheres of his or her life." (Charney D S et al.: Neurobiological mechanisms of human anxiety. In Fogel B S, Schiffer R B, Rao S M: Neuropsychiatry. Baltimore: Williams & Wilkins, 1996, pp. 257-286). Web site: http://www.delphion.com/details?pn=US06391922__ •

Use of 5-HT.sub.3 receptor antagonists in treating panic disorders or obsessive compulsive disorders Inventor(s): Azcona; Alberto E. (Basel, CH), Taylor; Pamela (Basel, CH) Assignee(s): Sandoz Ltd. (Basel, CH) Patent Number: 5,530,008 Date filed: January 24, 1994

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Abstract: 5-HT.sub.3 Receptor antagonists are useful in treating panic disorders or obsessive compulsive disorders. Excerpt(s): The present invention relates to a new use, in particular a new pharmaceutical use, for the compound group comprising 5HT.sub.3 receptor antagonists, said compound group being referred to hereinafter collectively as COMPOUNDS OF THE INVENTION. 5-HT.sub.3 receptor antagonists are a well known class of compounds. Spatial models for 5-HT.sub.3 receptors and 5-HT.sub.3 antagonists have been proposed recently by M. F. Hibert and S. Peroutka. They are typically compounds which act on 5-HT.sub.3 receptors on the e.g. isolated rabbit heart or vagus nerve by antagonizing the action of 5-HT thereon. They may have a pA.sub.2 greater than 6 or preferably more than 8 or 9.5-HT.sub.3 antagonists may be selective for 5-HT.sub.3 receptors as compared to other serotonin receptors or dopamine receptors. vi) a compound specifically or generically disclosed in DE 3,740,352 A, WO 8803801 A, EP 266,899 A, GB 2,192,885 A, GB 2,208,862 A, EP 219,929 A, EP 219,193 A, EP 212,398 A, EP 210,840 A, EP 191,562 A, EP 248,843 A, WO 89/09217, the contents of which are incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US05530008__

Patent Applications on Anxiety 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 anxiety disorders: •

Carbamate compounds for use in preventing or treating anxiety disorders Inventor(s): Plata-Salaman, Carlos R.; (Ambler, PA), Twyman, Roy E.; (Doylestown, PA), Zhao, Boyu; (Lansdale, PA) Correspondence: AUDLEY A. CIAMPORCERO JR.; JOHNSON & JOHNSON; ONE JOHNSON & JOHNSON PLAZA; NEW BRUNSWICK; NJ; 08933-7003; US Patent Application Number: 20020143053 Date filed: February 21, 2002 Abstract: This invention is directed to a method for preventing or treating anxiety disorders comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of Formula (I) and Formula (II): 1wherein phenyl is substituted at X with one to five halogen atoms selected from the group consisting of fluorine, chlorine, bromine and iodine; and, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.4 alkyl; wherein C.sub.1-C.sub.4 alkyl is optionally substituted with phenyl (wherein phenyl is optionally substituted with substituents independently selected from the group consisting of halogen, C.sub.1C.sub.4 alkyl, C.sub.1-C.sub.4 alkoxy, amino, nitro and cyano). Excerpt(s): This application claims benefit of provisional application Serial No. 60/271,689, filed Feb. 27, 2001, which is hereby incorporated by reference. This invention is directed to a method for use of a carbamate compound in preventing or

10

This has been a common practice outside the United States prior to December 2000.

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treating anxiety disorders. More particularly, this invention is directed to a method for use of halogenated 2-phenyl-1,2-ethanediol monocarbamate or dicarbamate compounds for preventing or treating anxiety disorders. Anxiety disorders, one of the most prevalent psychiatric illnesses in the general community, represents a group of emotional states consisting of psychophysiological responses to anticipation of unreal or imagined danger which are not a result of physical disorders, drug abuse or other psychiatric conditions (Anxiety Overview, Market Research Reports, 2001; Briley M and Moret C, Present and Future Anxiolytics, Drugs, 2000, 3 (7), 695-699; Stein M B, Neurobiological perspectives on social phobia: From affiliation to zoology, Biol. Psychiatry, 1998, 44 (12), 1277-1285; Newburn G, Psychiatric disorders associated with traumatic brain injury. Optimal treatment, CNS Drugs, 1998, 9 (6), 441-456; Lidberg L, et. al., Suicide attempts and impulse control disorder are related to low cerebrospinal fluid 5-HIAA in mentally disordered violent offenders, Acta Psychiatr. Scand., 2000, 101 (5), 395-402; Van Ameringen M, et. al., Drugs in development for social anxiety disorder: more to social anxiety than meets the SSRI, Expert Opin. Invest. Drugs, 2000, 9 (10), 2215-2231; Zhuang X, et. al., Altered emotional states in knockout mice lacking 5-HT1A or 5-HT1B receptors, Neuropsychopharmacology, 1999, 21 (2S), 52S-60S). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Certain arylaliphatic and heteroaryl-aliphatic piperazinyl pyrazines and their use in the treatment of serotonin-related diseases Inventor(s): Jonsson, Mattias; (Uppsala, SE), Nilsson, Bjorn; (Uppsala, SE), Nilsson, Jonas; (Uppsala, SE), Pelcman, Benjamin; (Stockholm, SE), Ringberg, Erik; (Uppsala, SE), Tejbrant, Jan; (Enskede, SE), Thor, Markus; (Knivsta, SE) Correspondence: JEFFREY D. HSI; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20030092694 Date filed: October 11, 2002 Abstract: The invention relates to compounds of the general formula (I): 1whereinAr is optionally substituted aryl or heteroaryl;A is (i) --O--, --S--, --SO.sub.2--, --NH--, (ii) a C.sub.1-4-alkyl- or C.sub.1-6-acyl-substituted nitrogen atom or (iii) a C.sub.1-8-alkylene chain or a heteroalkylene chain having 2 to 8 chain atoms, which optionally contains at least one unsaturation, and which may be substituted and/or contain a bridge to form a saturated or partially or fully unsaturated ring having 3-8 ring members;B is -C(R.sub.4)(R.sub.5)--, --OC(R.sub.4)(R.sub.5)--, --N(R.sub.6)C(R.sub.4)(R.sub.5)--, -N(R.sub.6)--, --O--, --S-- or --SO.sub.2--;R is optionally substituted C.sub.3-8-cycloalkyl, aryl or heteroaryl;R.sub.1 is (i) a saturated or unsaturated azacyclic or aminoazacyclic ring, or a saturated diazacyclic or aminodiazacyclic ring, which has 4 to 7 ring members, or a saturated aminoazabicyclic, azabicyclic or diazabicyclic ring which has 7 to 10 ring members, which rings optionally are substituted in one or more positions, or a group -[C(R.sub.4)(R.sub.5)].sub.xN(R.sub.2a)(R.sub.3a)];R.sub.2a, R.sub.3a, R.sub.4, R.sub.5, R.sub.6 and x are as defined in the claims, and n is 0 or 1; and pharmaceutically acceptable salts, hydrates and prodrug forms thereofThe compounds may be prepared by per se conventional methods and can be used for treating a human or animal subject suffering from a serotonin-related disorder, such as eating disorders, especially obesity, memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, sexual dysfunctions, and urinary disorders The invention also relates to such use as well as to pharmaceutical compositions comprising a compound of formula (I)

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Excerpt(s): The present application is a continuation-in-part application of app. Ser. No. 09/5/73,348, "Novel Compounds, Their Use and Preparation", Attorney Docket No. 1614-233P, filed on May 19, 2000, which claims priority to provisional App. No. 60/137,527, filed on Jun. 3, 1999; the entire contents of which are hereby incorporated by reference. The present invention relates to novel compounds, to pharmaceutical compositions comprising the compounds, to processes for their preparation, as well as to the use of the compounds for the preparation of a medicament which particularly acts on the central nervous system. Many diseases of the central nervous system are influenced by the adrenergic, the dopaminergic, and the serotonergic neurotransmitter systems. For example, serotonin has been implicated in a number of diseases and conditions which originate in the central nervous system. A number of pharmacological and genetic experiments involving receptors for serotonin strongly implicate the 5HT.sub.2c receptor subtype in the regulation of food intake (Obes. Res. 1995, 3, Suppl. 4, 449S-462S). The 5-HT.sub.2c receptor subtype is transcribed and expressed in hypothalamic structures associated with appetite regulation. It has been demonstrated that the non-specific 5-HT.sub.2c receptor agonist m-chlorophenylpiperazine (mCPP), which has some preference for the 5-HT.sub.2c receptor, causes weight loss in mice that express the normal 5-HT2c receptor while the compound lacks activity in mice expressing the mutated inactive form of the 5-HT.sub.2c receptor (Nature 1995, 374, 542546). In a recent clinical study, a slight but sustained reduction in body weight was obtained after 2 weeks of treatment with mCPP in obese subjects (Psychopharmacology 1997, 133, 309-312). Weight reduction has also been reported from clinical studies with other "serotonergic" agents (see e.g. IDrugs 1998, 1, 456-470). For example, the 5-HT reuptake inhibitor fluoxetine and the 5-HT releasing agent/reuptake inhibitor dexfenfluramine have exhibited weight reduction in controlled studies. However, currently available drugs that increase serotonergic transmission appear to have only a moderate and, in some cases, transient effects on the body weight. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cyclopropylindole derivatives as selective serotonin reuptake inhibitors Inventor(s): Catt, John D.; (Newburgh, IN), Denhart, Derek John; (Wallingford, CT), Deskus, Jeffrey A.; (Marlborough, CT), Ditta, Jonathan L.; (Middletown, CT), Epperson, James R.; (Cromwell, CT), Higgins, Mendi A.; (Middletown, CT), King, Dalton; (Hamden, CT), Marcin, Lawrence R.; (Bethany, CT), Mattson, Ronald J.; (Meriden, CT) Correspondence: STEPHEN B. DAVIS; BRISTOL-MYERS SQUIBB COMPANY; PATENT DEPARTMENT; P O BOX 4000; PRINCETON; NJ; 08543-4000; US Patent Application Number: 20030073849 Date filed: March 5, 2002 Abstract: The present invention relates to compounds of Formula (I) and pharmaceutically acceptable salts or solvates thereof and pharmaceutically acceptable formulations comprising said compounds 1useful for the treatment of depression, anxiety disorders, premature ejaculation, chronic pain, obsessive-compulsive disorder, feeding disorders, premenstrual dysphoric disorder, panic disorders and psychotic disorders including bipolar disorder and schizophrenia. Excerpt(s): This non-provisional application claims priority from provisional application U.S. Ser. No. 60/279,888 filed Mar. 29, 2001, from provisional application U.S. Ser. No. 60/293,122 filed May 23, 2001 and from provisional application U.S. Ser. No. 60/327,804 filed Oct. 9, 2001. The present invention relates to cyclopropylindole derivatives and

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pharmaceutical compositions comprising said derivatives useful for the treatment of various psychiatric disorders and premature ejaculation. Selective serotonin reuptake inhibitors (SSRIs) are effective for the treatment of mental depression and have been reported to be useful for treating chronic pain. See R. W. Fuller, Pharmacologic Modification of Serotonergic Function: Drugs for the Study and Treatment of Psychiatric and Other Disorders," J. Clin. Psychiatry, 47:4 (Suppl.) April 1986, pp. 4-8 and Selective Serotonin Reuptake Inhibitors. Edited by J P Feighner and W F Boyer, Chichester, England. John Wiley & Sons, 1991, pp 89-108. SSRI's have also demonstrated efficacy for the treatment of anxiety disorders. More recently, SSRI's have demonstrated efficacy in the treatment of premature ejaculation. See Kim and Paick, Short-term Analysis of the Effects of As Needed Use of Sertraline at 5 pm for the Treatment of Premature Ejaculation, Urology 54:544-547 (1999); Kim and Paick, Self Therapy with Sertraline given PRN at 5 pm in treatment of Premature Ejaculation, Journal of Urology 54:544-547 (1998); McMahon and Touma, Treatment of Premature Ejaculation with Paroxetine Hydrochloride As Needed: 2 Single-Blind Placebo Controlled Crossover Studies Journal of Urology 161:1826-1830 (1999); Haensal et al., Clomipramine and sexual function in men with premature ejaculation and controls Journal of Urology 158:1310-1315 (1998); and McMahon and Touma, Treatment of Premature Ejaculation with Paraoxetine Hydrochloride International Journal Impotence Research 11:241-246 (1999). Thus novel SSRI's effective for the treatment of these and other disorders would be greatly advantageous. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Fused heterocyclic compounds Inventor(s): Chen, Xiaoqi; (San Mateo, CA), Dai, Kang; (Albany, CA), Fan, Pingchen; (Fremont, CA), Huang, Shugui; (San Bruno, CA), Li, Leping; (Burlingame, CA), Mihalic, Jeffrey Thomas; (San Francisco, CA) Correspondence: Tularik Inc.; Two Corporate Drive; So. San Francisco; CA; 94080; US Patent Application Number: 20030023085 Date filed: May 3, 2002 Abstract: Compounds, compositions and methods are provided that are useful in the treatment and/or prevention of a condition or disorder mediated by a G-protein coupled receptor. In particular, the compounds of the invention are useful in the treatment and/or prevention of eating disorders, obesity, anxiety disorders and mood disorders. Excerpt(s): The present invention relates to compounds and compositions useful in the treatment of conditions and disorders associated with eating behavior, energy homeostasis and anxiety. G-protein coupled receptors play important roles in diverse signaling processes, including those involved with sensory and hormonal signal transduction. Eating disorders, which represent a major health concern throughout the world, have been linked to GPCR regulation. On the one hand, disorders such as obesity, the excess deposition of fat in the subcutaneous tissues, manifest themselves by an increase in body weight. Individuals who are obese often have, or are susceptible to, medical abnormalities including respiratory difficulties, cardiovascular disease, diabetes and hypertension. On the other hand, disorders like cachexia, the general lack of nutrition and wasting associated with chronic disease and/or emotional disturbance, are associated with a decrease in body weight. The neuropeptide melanin-concentrating hormone (MCH), a cyclic hypothalamic peptide involved in the regulation of several

Patents 165

functions in the brain, has previously been found to be a major regulator of eating behavior and energy homeostasis. It has previously been determined that MCH is the natural ligand for the 353-amino acid orphan G-protein-coupled-receptor (GPCR) termed SLC-1 (also known as GPR24). Subsequent to this determination, SLC-1, which is sequentially homologous to the somatostatin receptors, is frequently referred to as melanin-concentrating hormone receptor (MCH receptor, MCHR or MCHR1) (see Chambers et al., Nature 400:261-65 (1999); Saito et al., Nature 400:265-69 (1999); and Saito et al., TEM 11(8):299-303 (2000)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Human kcnq5 potassium channel, methods and compositions thereof Inventor(s): Boissard, Christopher G.; (Northford, CT), Dworetzky, Steven I.; (Middlefield, CT), Gribkoff, Valentin K.; (Wallingford, CT), Ramanathan, Chandra S.; (Wallingford, CT), Trojnacki, Joanne T.; (Guilford, CT) Correspondence: MARLA J MATHIAS; BRISTOL-MYERS SQUIBB COMPANY; PATENT DEPARTMENT; P O BOX 4000; PRINCETON; NJ; 08543-4000; US Patent Application Number: 20020040000 Date filed: May 24, 2001 Abstract: An isolated polynucleotide encoding a novel potassium channel polypeptide, KCNQ5, that is expressed primarily in brain and skeletal muscle is described. The new polypeptide has been cloned and isolated from a human brain cDNA library and is a member the KCNQ family of potassium channels. The provided human KCNQ5 nucleic acid sequence and encoded polypeptide can be employed for diagnostic, screening and therapeutic uses. Moreover, the hKCNQ5 polypeptide can be used to assay for KCNQ5 potassium channel modulators, which can be utilized in the treatment of neurological, neurophysiological, neuropsychological and neuroaffective diseases, conditions and disorders, including, but not limited to, acute and chronic pain, migraine, acute stroke, dementia, vascular dementia, trauma, epilepsy, amyelotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's Disease, learning and cognitive disorders, and neurophysiological disorders including anxiety disorders, depression, bipolar disorders, sleep disorders, addiction, and eating disorders. Excerpt(s): This application claims benefit of provisional patent application U.S. Ser. No. 60/207,389, filed May 26, 2000. The present invention relates generally to the KCNQ family of potassium channels. More specifically, the present invention provides a new potassium channel polypeptide, KCNQ5, which was cloned and isolated from human tissue. Human KCNQ5 is found to be expressed primarily in brain and skeletal muscle. The present invention further provides methods for modulating the KCNQ5 potassium channel and assays for detecting channel modulators, which have use in the treatment of a variety of neurological, neurophysiological and neuropsychological conditions, disorders and diseases. Potassium channels are membrane-spanning proteins that generally act to hyperpolarize neurons. Physiological studies indicate that potassium currents are found in most cells and are associated with a wide range of functions, including the regulation of the electrical properties of excitable cells. Depending on the type of potassium channel, its functional activity can be controlled by transmembrane voltage, different ligands, protein phosphorylation, or other second messengers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Isoforms of mouse serotonin 5-HT2c receptor Inventor(s): Fong, Tong M.; (Somerset, NJ), Liu, Jie; (Dayton, NJ), Van Der Ploeg, Leonardus H.T.; (Scotch Plains, NJ) Correspondence: MERCK AND CO INC; P O BOX 2000; RAHWAY; NJ; 070650907 Patent Application Number: 20030109685 Date filed: December 17, 2002 Abstract: The invention includes mouse serotonin 5-HT2c receptor isoforms having amino acid replacements at one or more positions of the natural mouse serotonin 5HT2c receptor polypeptide sequence, specifically at one or more of positions 157, 159 and 161. The polypeptides are useful for identifying ligands which bind with the serotonin 5-HT2c receptor and modulators of the serotonin 5-HT2c, and for identifying drugs with affinity for 5-HT2 receptors which are used to treat schizophrenia, Parkinsonism, and anxiety disorders. Excerpt(s): The present application claims priority of U.S. provisional application Serial No. 60/124,439, filed Mar. 15, 1999. Serotonin is a neuromodulator capable of inducing and modulating a wide variety of behavioral functions such as sleep, appetite, locomotion, sexual activity and vascular contraction. It is accepted that serotonin activity is mediated by its interaction with receptors, designated serotoninergic receptors of 5-HT (for 5-hydroxytryptamine) receptors. Molecular biology studies as well as pharmacological studies have revealed the existence of a large number of subtypes of 5-HT receptors. The 5-HT receptors which have been described to date belong either to the family of receptors associated with ion channels (5-HT3 receptors), or to the family of receptors which interact with G proteins and which possess seven transmembrane domains. Moreover, analysis of the amino acid sequences has shown that the 5-HT receptors which interact with G proteins may be subdivided into six distinct groups: 5-HT1 receptors, comprising the mammalian subtypes 5-HT1a, 5-HT1b, 5-HT1d, 5-HT1e and 5-HT1f, as well as three Drosophila 5-HT receptors; 5-HT2 receptors comprising three subtypes, 5-HT2a, 5-HT2b and 5-HT2c; 5-HT4 receptor; 5HT5 receptor; 5-HT6 receptor; and 5-HT7 receptor. Drugs with affinity for 5-HT2 receptors are used to treat schizophrenia, Parkinsonism, and anxiety disorders. The 5HT2c receptor subtype has been particularly interesting to investigators searching for the molecular bases of neuropsychiatric disorders. The 5-HT2c receptor is widely expressed in the brain where it is involved in regulating endocrine responses. Particular responses include the production and secretion of adrenocorticotropic hormone, oxytocin and prolactin. Genes for mouse, rat and human (Saltzman et al., Biochem. Biophys. Res. Commun. 181:1469, 1991) 5-HT2c receptors have been cloned. Burns et al., Nature vol. 387 15 May 1997 pp. 303-308 describes rat 5-HT2c receptor isoforms resulting from RNA editing events involving transcripts encodong the serotonin receptor. The functional state of 5-HT2c receptors in normal controls and various patient groups has been studied in vivo by administering 1-(3-chlorophenyl)piperazine (mCPP), a non-selective 5-HT2c agonist, and measuring hormonal and psychological responses. In alcoholism, panic disorder, seasonal affective disorder and obsessive-compulsive disorder, mCPP has been shown to induce different hormonal and psychological responses in patients and controls. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 167

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Method of collecting data on anxiety disorders and related research Inventor(s): Farvolden, Peter Gordon; (Toronto, CA), Godmaire, Jean-Paul Maurice; (Toronto, CA), van Mierlo, Trevor David Vernon; (Toronto, CA) Correspondence: Piasetzki & Nenniger; Attn.: Gregory A. Piasetzki; 2308-120 Adelaide Street West; Toronto; ON; M5H 1T1; CA Patent Application Number: 20030139946 Date filed: January 21, 2003 Abstract: Diagnostic information relating to anxiety disorders is obtained by a method comprising the steps of (1) asking subjects questions relating to anxiety disorder symptoms; (2) receiving answers to the questions; (3) generating an original final report; (4) summarizing in the final report endorsed anxiety disorder symptoms; (5) indicating in the final report unendorsed anxiety disorder symptoms. Data relating to anxiety disorders is collected by keeping statistics on the answers given by the subjects and making the statistics available to researchers. Researchers are then provided access to the data from the population of subjects to conduct research on anxiety disorders. Also, the data collected is assessed to determine whether the questioning process should be modified in response to the data, so as to provide better information for researchers to use in their research. Excerpt(s): This invention relates to the field of data and information collection, and in particular, data and information collection relating to anxiety disorders. In North America, anxiety disorders are among the most common of psychiatric conditions. According to one estimate, at any one time, as much as 10% of the population is afflicted with one or more anxiety disorders. Anxiety disorders typically interfere significantly with the life of the sufferer. For example, this interference can take the form of compulsive behaviour, intense feelings of anxiety, fear or helplessness, or avoidance of situations which make the person anxious. Furthermore, individual anxiety disorders have high rates of co-morbidity with other psychiatric conditions, including other anxiety disorders, depression, and substance abuse. Thus, anxiety disorders take a substantial personal toll on those afflicted with them. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods of treating anxiety disorders Inventor(s): Bowlby, Mark R.; (Richboro, PA), Rosenzweig-Lipson, Sharon J.; (East Brunswick, NJ) Correspondence: WYETH; FIVE GIRALDA FARMS; MADISON; NJ; 07940; US Patent Application Number: 20020111379 Date filed: December 17, 2001 Abstract: This invention provides methods for treating, preventing or inhibiting anxiety, anxiety-related conditions and phobias in a mammal using compounds of the formula: 1wherein: R.sub.1 is H, alkyl, alkanoyl or the radical Ar; R.sub.2 is H or alkyl; R.sub.3 is alkoxy, NH.sub.2, alkylamino, dialkylamino, amino substituted by the radical Ar, alkyl, alkenyl, alkynyl, or the radicals Ar or ArO--; R.sub.4 is H, alkyl or the radical Ar; R.sub.5 is H or alkyl or the radical Ar; or a pharmaceutically acceptable salt or ester form thereof; Ar is an optionally substituted phenyl radical; and n is 0 or 1, or a pharmaceutically acceptable salt or ester form thereof, with the methods particularly

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including the use of N-[2-amino-4-(4-fluorobenzylami- no)-phenyl]carbamic acid ethyl ester, also known as retigabine. Excerpt(s): This application claims priority from copending provisional application Serial No. 60/256,834, filed Dec. 20, 2000, the entire disclosure of which is hereby incorporated by reference. This invention relates to novel methods for treating, preventing or inhibiting anxiety and anxiety-related conditions in a mammal, preferably in a human. The methods of this invention include the treatment, prevention, inhibition and amelioration of conditions including anxiety, generalized anxiety disorder, panic anxiety, obsessive compulsive disorder, social phobia, post-traumatic stress disorder, agoraphobia and specific phobias. and their properties as anti-epileptic, muscle relaxing, fever-reducing and peripheral analgesic agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Modulation of memory, learning and/or anxiety states Inventor(s): Crosier, Kathryn E.; (Auckland, NZ), Crosier, Philip S.; (Auckland, NZ) Correspondence: NIXON & VANDERHYE P.C.; 8th Floor; 1100 North Glebe Rd.; Arlington; VA; 22201-4714; US Patent Application Number: 20020111293 Date filed: April 15, 2002 Abstract: This invention relates to the modification of long-term potentiation (LTP), learning, memory and/or anxiety states. More particularly, it relates to methods of prophylactically or therapeutically treating LTP, leating, memory and/or anxiety disorders in a patient and to medicaments for use in such methods. Excerpt(s): This invention relates to the modification of long-term potentiation (LTP), learning; memory and/or anxiety states. More particularly, it relates to methods of prophylactically or therapeutically treating LTP, learning, memory and/or anxiety disorders in a patient and to medicaments for use in such methods. Long-term potentiation (LTP) is a long-sting increase in synaptic efficacy which is induced typically by high-frequency stimulation of afferent fibers (Bliss and Loma 1973). LTP, together with its converse, long-term depression (LTD), is considered an attractive candidate memory storage mechanism. Consistent with this is an observed association between a severe impairment of LTP and impaired learning and retention of spatial task induced by a selective knockout of functional NMDA receptors in area CA1 of the hippocampus, McHugh et al (1996); Tsien et al (1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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New drug combinations Inventor(s): Taylor, Duncan Paul; (Kalamazoo, MI) Correspondence: Stephen L. Nesbitt; Pharmacia & Upjohn Company; Global Intellectual Property; 301 Henrietta Street; Kalamazoo; MI; 49001; US Patent Application Number: 20030078262 Date filed: November 5, 2002

Patents 169

Abstract: This patent application describes, a new combination treatment of selective, noradrenaline-reuptake inhibitors (NARI) and specifically, reboxetine, and pindolol to provide rapid relief to patients suffering from depression, general anxiety, attention deficit hyperactivity disorder (ADHD), anxiety disorders such as obsessive compulsive disorders (OCD), panic disorders (PD), social phobia (SD) and the like. Excerpt(s): This invention describes new treatments that should provide for a fast acting rapid onset of relief from several nervous system disorders, and it involves the administration of the drug reboxetine in combination with the drug pindolol. The introduction of tricyclic antidepressants in the early 1960s has provided a major advance in the treatment of neuropsychiatric disorders. Reactive and endogenous depressions, diagnoses formerly carrying grave prognostic implications, have become, with the introduction of the tricyclics, manageable disorders with a much smaller toll on the patient and the society as a whole. The early tricyclic compounds were reuptake inhibitors of all the catecholamines released in the synaptic cleft, thus resulting in prolongation and enhancement of the dopamine (DA), noradrenaline (NA) and serotonin (5-hydroxytryptamine=5-HT) action. Lack of selectivity also causes undesired side effects particularly on the acetylcholine (especially the muscarinic component), and histamine mediated neurotransmission. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Olanzapine-N-oxide compositions and methods Inventor(s): Yelle, William E.; (Littleton, MA) Correspondence: Mary Louise Gioeni; HESLIN ROTHENBERG FARLEY & MESITI P.C.; 5 Columbia Circle; Albany; NY; 12203; US Patent Application Number: 20020065272 Date filed: October 30, 2001 Abstract: Methods and compositions are disclosed utilizing olanzapine-N-oxide for the treatment of psychosis in humans. Olanzapine-N-oxide exhibits a lessened liability toward drug-drug interactions than olanzapine and a more predictable dosing regimen than olanzapine. Olanzapine-N-oxide is also useful for the treatment of acute mania, mild anxiety states, anxiety disorders, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, autistic disorder, excessive aggression, substance abuse, depressive signs and symptoms, tic disorder, functional bowel disorder and fungal dermatitis. Excerpt(s): The invention relates to methods of treating psychosis, acute mania, mild anxiety states, schizophrenia, bipolar disorder, autistic disorder, excessive aggression, substance abuse, depressive signs and symptoms, tic disorder, functional bowel disorder and fungal dermatitis. It is commercially available as Zyprexa.RTM. from Eli Lilly Co. The antipsychotic effect of olanzapine is ascribed by the literature to blocking of the dopamine D.sub.2 receptor and to 5-HT antagonism. Because olanzapine is oxidized to olanzapine-N-oxide in the liver by P450 enzymes, drug-drug interactions arise from the concomitant administration of other drugs that stimulate or inhibit P450 or rely on P450 enzymes for their disposition. The human liver flavin-containing monooxygenase (FMO3) is involved in the metabolism of olanzapine-N-oxide. Exemplary drugs metabolized by the FMO3 enzyme include cimetidine and tamoxifen. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pharmaceutical compositions and methods for treating anxiety, anxiety disorders and memory impairment using NAALADase inhibitors Inventor(s): Slusher, Barbara S.; (Kingsville, MD) Correspondence: Rouget F. Henschel; Lyon & Lyon, LLP; Suite 1040; 1701 Pennsylvania Ave. NW; Washington; DC; 22202; US Patent Application Number: 20030013687 Date filed: February 20, 2002 Abstract: The present invention relates to pharmaceutical compositions and methods of using NAALADase inhibitors for treating glutamate-mediated diseases, disorders and conditions selected from the group consisting of anxiety, anxiety disorders and memory impairment. Excerpt(s): The present invention relates to pharmaceutical compositions and methods for treating glutamate-mediated diseases, disorders and conditions, particularly anxiety, anxiety disorders and memory impairment, using NAALADase inhibitors. Anxiety disorders afflict over 23 million Americans. These people are tormented by panic attacks, obsessive thoughts, flashbacks, nightmares or countless frightening physical symptoms. Classes of drugs which are prescribed for the treatment of anxiety disorders include the benzodiazepines (such as diazepam) and buspirone hydrochloride. Although the benzodiazepines have achieved widespread acceptance since their introduction in the 1960's, their use is restricted due to their adverse side effects, in particular their tendency to induce dependence. While lacking the dependence-inducing side effects of the benzodiazepines, buspirone hydrochloride has a slow onset of action (about 4 weeks). Thus, there is a need for new pharmaceutical compositions and methods for treating anxiety and anxiety disorders. Excessive activation of glutamate receptors has been implicated in anxiety and anxiety disorders. Significantly higher glutamate plasma levels have been detected in patients with mood disorders than in comparison subjects. In social interaction tests on rats, the blocking of basal glutamate excitation elicited anxiolytic-like effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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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

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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 •

Polymorphic DNAs and their use for diagnosis of susceptibility to panic disorder Inventor(s): Hattori, Eiji; (Saitama, JP), Yoshikawa, Takeo; (Saitama, JP) Correspondence: MORRISON & FOERSTER LLP; 3811 VALLEY CENTRE DRIVE; SUITE 500; SAN DIEGO; CA; 92130-2332; US Patent Application Number: 20020160390 Date filed: December 7, 2001 Abstract: The present invention relates to a method for diagnosing panic disorder, said method being based on the determination of the class of polymorphism of the short tandem repeat (STR) complex in the upstream region of human cholecystokinin gene. The polymorphic DNA comprises a DNA sequence, having a general formula (1):5'(GGAA).sub.n1X(GGAG).sub.n2(GGAA).sub.n3(GGGA).sub.n4GAG(AGAC).sub.n 5Y(G- GAA).sub.n63' (1)wherein X denotes a DNA sequence of SEQ ID NO: 1, Y denotes a DNA sequence of SEQ ID NO:2 and each of n1, n2, n3, n4, n5 and n6 denotes independently 0 or a positive integral number, whereby said DNA ranging from 363 to 399 base pairs in length. The invention also relates to an assay kit used for implementing said method. Excerpt(s): This application claims priority to Japanese Patent Application No. 2000375090, filed on Dec. 8, 2000. The present invention relates to novel polymorphisms, and more specifically, to polymorphisms of the short tandem repeat type in the 5'-upstream region of human cholecystokinin gene, and their use, i.e. a method and a kit for diagnosis of susceptibility to panic disorder. Panic disorder is a common and genetically complex mental illness, characterized by recurrent and unexpected panic attacks. It exhibits a lifetime prevalence rate of between 1.2/100 to 2.4/100 in the general population (Weissman, M. M. et al., Arch. Gen. Psychiatry, 1997; 54, 305-309). Family studies have consistently shown a higher prevalence ranging from between 7.7% to

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20.5% in the first-degree relatives of probands. Twin studies have shown concordance rates of 25% for MZ twins and 10% for DZ twins (Skre, I. et al., Acta Psychiatr Scand. 1993; 88, 85-92). These epidemiological studies suggest involvement of genetic factors in the development of this disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Regulation of human serotonin-like g protein-coupled receptor Inventor(s): Ramakrishnan, Shyam; (Brighton, MA) Correspondence: BANNER & WITCOFF; 1001 G STREET N W; SUITE 1100; WASHINGTON; DC; 20001; US Patent Application Number: 20030114643 Date filed: September 18, 2002 Abstract: Reagents which regulate human serotonin-like G protein-coupled receptor (5HT-GPCR) and reagents which bind to human 5-HT-GPCR gene products can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to disorders of both the central and the peripheral nervous system, for example in primary and secondary disorders after brain injury, disorders of mood, anxiety disorders, disorders of thought and volition, disorders of sleep and wakefulness, diseases of the motor unit like neurogenic and myopathic disorders, neurodegenerative disorders like Alzheimer's and Parkinson's disease, disorders leading to peripheral and chronic pain. Excerpt(s): The invention relates to the area of G-protein coupled receptors. More particularly, it relates to the area of human serotonin-like G protein-coupled receptor and its regulation. Many medically significant biological processes are mediated by signal transduction pathways that involve G-proteins (Lefkowitz, Nature 351, 353-354, 1991). The family of G-protein coupled receptors (GPCR) includes receptors for hormones, neurotransmitters, growth factors, and viruses. Specific examples of GPCRs include receptors for such diverse agents as dopamine, calcitonin, adrenergic hormones, endothelin, cAMP, adenosine, acetylcholine, serotonin, histamine, thrombin, kinin, follicle stimulating hormone, opsins, endothelial differentiation gene-1, rhodopsins, odorants, cytomegalovirus, G-proteins themselves, effector proteins such as phospholipase C, adenyl cyclase, and phosphodiesterase, and actuator proteins such as protein kinase A and protein kinase C. GPCRs possess seven conserved membranespanning domains connecting at least eight divergent hydrophilic loops. GPCRs (also known as 7TM receptors) have been characterized as including these seven conserved hydrophobic stretches of about 20 to 30 amino acids, connecting at least eight divergent hydrophilic loops. Most GPCRs have single conserved cysteine residues in each of the first two extracellular loops, which form disulfide bonds that are believed to stabilize functional protein structure. The seven transmembrane regions are designated as TM1, TM2, TM3, TM4, TM5, TM6, and TM7. TM3 has been implicated in signal transduction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Substituted imidazoles as cannabinoid receptor modulators Inventor(s): Finke, Paul E.; (Milltown, NJ), Mills, Sander G.; (Scotch Plains, NJ), Plummer, Christopher W.; (Keasbey, NJ), Shah, Shrenik K.; (Metuchen, NJ), Truong, Quang T.; (Edison, NJ) Correspondence: MERCK AND CO INC; P O BOX 2000; RAHWAY; NJ; 070650907 Patent Application Number: 20030114495 Date filed: July 17, 2002 Abstract: The use of compounds of the present invention as antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor particularly in the treatment, prevention and suppression of diseases mediated by the Cannabinoid-1 (CB1) receptor. The invention is concerned with the use of these novel compounds to selectively antagonize the Cannabinoid-1 (CB1) receptor. As such, compounds of the present invention are useful as psychotropic drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, particularly to opiates, alcohol, and nicotine. The compounds are also useful for the treatment of obesity or eating disorders associated with excessive food intake and complications associated therewith. Novel compounds of structural formula (I) are also claimed. Excerpt(s): The present application claims priority of U.S. provisional application Serial No. 60/307,224, filed Jul. 20, 2001. and pharmaceutically acceptable salts thereof which are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the Cannabinoid-1 (CB1) receptor. The invention is concerned with the use of these novel compounds to selectively antagonize the Cannabinoid-1 (CB1) receptor. As such, compounds of the present invention are useful as psychotropic drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuroinflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, particularly to opiates, alcohol, and nicotine. The compounds are also useful for the treatment of obesity or eating disorders associated with excessive food intake and complications associated therewith. The present invention is also concerned with treatment of these conditions, and the use of compounds of the present invention for manufacture of a medicament useful in treating these conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Substituted pyrimidinones and pyrimidinthiones Inventor(s): Corbett, Jeffrey W.; (Portage, MI), Ennis, Michael Dalton; (Mattawan, MI), Frank, Kristine E.; (Portage, MI), Fu, Jian-Min; (Kalamazoo, MI), Hoffman, Robert Louis; (Kalamazoo, MI), Verhoest, Patrick R.; (Augusta, MI) Correspondence: PHARMACIA & UPJOHN; 301 HENRIETTA ST; 0228-32-LAW; KALAMAZOO; MI; 49007; US Patent Application Number: 20030195222 Date filed: February 20, 2003 Abstract: This invention relates to substituted pyrimidinone and pyrimidithione derivatives that bind with high affifnity to CRF1 receptors, including human CRF1 receptors. This invention also relates to methods of using the compounds of the invention to treat a disorder or condition, the treatment of which can be effected or facilitated by antagonizing a CRF receptor, such as CNS disorders or diseases, particularly anxiety disorders, and depression and stress related disorders. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/359164 filed on Feb. 22, 2002. The present invention relates generally to compounds that bind to CRF receptors and particularly to substituted pyrimidinone and pyrimidithione derivatives that are CRF1 receptor antagonists, and to the use thereof as treatment for disorders that are associated with CRF or CRF1 receptors. Corticotropin releasing factor (CRF) is a 41 amino acid peptide that is the primary physiological regulator of proopiomelanocortin (POMC) derived peptide secretion from the anterior pituitary gland [J. Rivier et al., Proc. Natl. 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 the 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 that CRF plays a significant role in integrating the response in 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)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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System and method for treatment of mood and/or anxiety disorders by electrical brain stimulation and/or drug infusion Inventor(s): Whitehurst, Todd K.; (Sherman Oaks, CA) Correspondence: ADVANCED BIONICS CORPORATION; 12740 SAN FERNANDO ROAD; SYLMAR; CA; 91342; US Patent Application Number: 20020013612 Date filed: June 15, 2001 Abstract: A system and method for introducing one or more stimulating drugs and/or applying electrical stimulation to the brain to treat mood and/or anxiety disorders uses an implantable system control unit (SCU), specifically an implantable signal/pulse generator (IPG) or microstimulator with two or more electrodes in the case of electrical

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stimulation, and an implantable pump with one or more catheters in the case of drug infusion. In cases requiring both electrical and drug stimulation, one or more SCUs are used. Alternatively and preferably, when needed, an SCU provides both electrical stimulation and one or more stimulating drugs. In a preferred embodiment, the system is capable of open- and closed-loop operation. In closed-loop operation, at least one SCU includes a sensor, and the sensed condition is used to adjust stimulation parameters. Excerpt(s): The present application claims the benefit of U.S. Provisional Application Serial No. 60/212,871, filed Jun. 20, 2000, which application is incorporated herein by reference in its entirety. The present invention generally relates to implantable drug delivery and electrical stimulation systems and methods, and more particularly relates to utilizing one or more implantable devices to deliver electrical stimulation and/or one or more stimulating drugs as a treatment for mood and/or anxiety disorders. Recent estimates indicate that more than 19 million Americans over the age of 18 years experience a depressive illness each year. The American Psychiatric Association recognizes several types of clinical depression, including Mild Depression (Dysthymia), Major Depression, and Bipolar Disorder (Manic-Depression). Major Depression is defined by a constellation of chronic symptoms that include sleep problems, appetite problems, anhedonia or lack of energy, feelings of worthlessness or hopelessness, difficulty concentrating, and suicidal thoughts. Approximately 9.2 million Americans suffer from Major Depression, and approximately 15 percent of all people who suffer from Major Depression take their own lives. Bipolar Disorder involves major depressive episodes alternating with high-energy periods of rash behavior, poor judgment, and grand delusions. An estimated one percent of the American population experiences Bipolar Disorder annually. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Therapeutic or preventive medicines for mood disorders or anxiety disorders Inventor(s): Nagase, Hiroshi; (Kamakura, JP), Saitoh, Akiyoshi; (Kamakura, JP), Tanaka, Toshiaki; (Zushi, JP) Correspondence: SCHNADER HARRISON SEGAL & LEWIS, LLP; 1600 MARKET STREET; SUITE 3600; PHILADELPHIA; PA; 19103 Patent Application Number: 20030166656 Date filed: January 3, 2003 Abstract: A drug for curing or preventing mood disorder or anxiety disorder that has fewer and milder side effects comprising, as an effective component, an isoquinoline derivative or a physiologically acceptable acid addition salt thereof, the representative example of the isoquinoline derivative being (4aS, 12aS)-2-methyl-4a-(3hydroxyphenyl)-1,2,3,4,4a,5,12,12a-octah- ydroquinolino [2,3-g]isoquinoline; a method for curing or preventing mood disorder or anxiety disorder using the same; and a use of the isoquinoline derivative or the physiologically acceptable acid addition salt thereof for the manufacture of a medicament for curing or preventing mood disorder and anxiety disorder. Excerpt(s): The present invention relates to a drug for curing or preventing mood disorder or anxiety disorder comprising an isoquinoline derivative or a physiologically acceptable acid addition salt thereof, to a method for curing or preventing mood disorder or anxiety disorder using the same, and to a use of the isoquinoline derivative or the physiologically acceptable acid addition salt thereof for the manufacture of a

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medicament for curing or preventing mood disorder or anxiety disorder. In modern aging societies and high stress societies, psychiatric disorders have shown an increase. Particularly, mood disorder and anxiety disorder have shown a sharp increase. Tricyclic antidepressants are used as the therapeutic drug for curing mood disorder. Representative examples thereof are imipramine and desipramine. However, tricyclic antidepressants have many side effects and thus there is a problem of tolerance. For example, tricyclic antidepressants require several weeks before their therapeutic effects appear, are cardiotoxic if overdosed, and have various side effects such as dry mouth, constipation, and difficulty urinating. These side effects cause a decrease in tolerance. Recently, selective serotonin reuptake inhibitors (SSRIs), such as fluvoxamine and fluoxetine, have been developed as mood disorder therapeutic drugs that have fewer and milder side effects than tricyclic antidepressants. SSRIs are safer than the existing drugs and are superior in that SSRIs are effective against newer adaptive disorders such as obsessive compulsive disorder and panic disorder. However, the side effects including digestive disorders such as nausea, vomiting, and diarrhea, sexual dysfunction, headache, and insomnia are still reported. Moreover, SSRIs require several weeks before their therapeutic effects appear and have a low effectiveness against patients of severe depression. Development of therapeutic drugs for mood disorder that have fewer and milder side effects and can reliably achieve the effect is strongly desired. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Therapeutic use of selective PDE10 inhibitors Inventor(s): Lebel, Lorraine A.; (North Stonington, CT), Menniti, Frank S.; (Mystic, CT), Schmidt, Christopher J.; (Old Lyme, CT) Correspondence: PFIZER INC; 150 EAST 42ND STREET; 5TH FLOOR - STOP 49; NEW YORK; NY; 10017-5612; US Patent Application Number: 20030008806 Date filed: April 19, 2002 Abstract: The invention provides a method for treating certain neurologic and psychiatric disorders in mammals, including humans, comprising administration of a selective PDE10 inhbitor. In particular, the invention relates to treatment of mood, movement, and anxiety disorders; psychosis; drug, for example alcohol, addiction; and disorders having as a symptom deficient cognition. The invention furthermore provides the use of papaverine as a selective inhibitor of PDE10. Excerpt(s): This application claims priority under 35 U.S.C. 119(e) of U.S. Application No. 60/285,148, filed Apr. 20, 2001. The subject invention relates to the treatment of disorders of the central nervous system. More particularly, the invention relates to treatment of neurologic and psychiatric disorders, for example psychosis and disorders comprising deficient cognition as a symptom. This invention also relates to PDE10 inhibition. The cyclic nucleotides, cyclic-adenosine monophosphate (cAMP) and cyclicguanosine monophosphate (cGMP), function as intracellular second messengers regulating a vast array of intracellular processes including in neurons in the central nervous system. cAMP is synthesized by a family of membrane bound enzymes, the adenylyl cyclases. A broad range of serpin family receptors regulates these enzymes through a coupling mechanism mediated by heterotrimeric G-proteins. Increases in intracellular cAMP leads to activation of cAMP-dependent protein kinases, which regulate the activity of other signaling kinases, transcription factors, and enzymes via their phosphorylation. Cyclic-AMP may also directly affect the activity of cyclic

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nucleotide regulated ion channels, phosphodiesterases, or guanine nucleotide exchange factors. Recent studies also suggest that intracellular cAMP may function as a precursor for the neuromodulator, adenosine, following its transport out of the cell. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment of posttraumatic strees disorder, obsessive-compulsive disorder and related neuropsychiatric disorders Inventor(s): Fogel, Barry S.; (Waban, MA) Correspondence: Choate, Hall & Stewart; Exchange Place; 53 State Street; Boston; MA; 02109; US Patent Application Number: 20020119912 Date filed: March 1, 2002 Abstract: The present invention describes a novel treatment for neuropsychiatric disorders, including anxiety disorders, mood disorders, psychotic disorders, somatoform disorders, and neuropsychiatric symptoms resulting from movement disorders. The treatment of the present invention utilizes any agent that simultaneously act as NMDA-type glutamate receptor antagonists and GABA-A receptor agonists. Preferably these two activities are characteristic of a single agent, for example acamprosate (calcium N-acetylhomotaurinate). Alternatively, separate agents having these activities can be combined as a compound or mixture and thereby administered together. The invention also provides for a third agent that acts as a non-competitive NMDA-receptor blocking agent or ion channel blocker, that augments the effect of the primary treatment. A particularly preferred ion channel blocking agent is magnesium. Excerpt(s): The present application is a Continuation application of co-pending U.S. patent application Ser. No. 09/273,036 filed Mar. 19, 1999, which is a Continuation-inpart application of co-pending U.S. patent application Ser. No. 09/006,641 filed Jan. 13, 1998, the entire contents of which are incorporated herein by reference. The present invention relates to novel drug treatments for neuropsychiatric disorders, for example anxiety disorders, psychotic disorders, mood disorders and somatoform disorders. These treatments relieve symptoms of disorders characterized by repetitive, stereotyped, an unwanted, intrusive, or involuntary thoughts, perceptions, or behaviors. These include posttraumatic stress disorder, obsessive-compulsive disorder, somatization disorder, hypochondriasis, and body dysmorphic disorder. Contemporary drug therapy for these conditions is limited in efficacy, with many patients continuing to have symptoms despite treatment. Antidepressants, mood stabilizers, anti-anxiety drugs, and antipsychotic drugs all have been used to treat them. Even when they provide some relief, persistent intrusive, repetitive mental phenomena may remain as a distressing symptom. Thus, when a person with posttraumatic stress disorder is treated with an antidepressant, mood may improve while "flashbacks" of the traumatic event continue. Clearly, there is a need for additional medications efficacious for the treatment of these disorders, and especially for medications that suppress or eliminate the recurrent unwanted, intrusive, or involuntary thoughts, perceptions and behaviors characteristic of those disorders. Such medications might also be used to reduce such symptoms when they occur as part of another psychiatric syndrome, such as depression or schizophrenia, or when they are incidental to a neurological disorder such as Tourette's syndrome or Huntington's disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with anxiety 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 “anxiety 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 anxiety disorders. You can also use this procedure to view pending patent applications concerning anxiety 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 ANXIETY DISORDERS Overview This chapter provides bibliographic book references relating to anxiety disorders. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on anxiety 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 “anxiety 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 anxiety disorders: •

Learning Disabilities and ADHD: A Family Guide to Living and Learning Together Source: New York, NY: John Wiley and Sons, Inc. 1997. 228 p. Contact: Available from John Wiley and Sons, Inc. Distribution Center, 1 Wiley Drive, Somerset, NJ 08875-1272. (800) 225-5945 or (732) 469-4400. Fax (732) 302-2300. E-mail: [email protected]. Website: www.wiley.com. PRICE: $14.95 plus shipping and handling. ISBN: 0471155101. Summary: In this book, parents are offered expert guidance and insight to help cope with learning disabilities in their children and to learn to serve as their child's advocate. Topics covered in the ten chapters include the early signs and symptoms of learning disabilities and attention deficit hyperactivity disorder (ADHD), the latest advances in educational, medical and psychological treatments (including drug and behavior therapies), how learning problems affect the whole family, social problems and social

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skills, the homework issue, strategies to help the child succeed both in and out of school, the transition to adult life, emotional issues (learned helplessness, anxiety disorders, depression, behavior disorders), and resources and treatment approaches. Practical strategies and checklists are offered throughout the book; case scenarios help to illustrate the concepts under discussion. The book includes five appendices: the evaluation process, the legal rights of children with disabilities, diagnostic criteria for ADHD, diagnostic tests and instruments, and resources. A glossary of terms, a list of recommended reading, and a subject index conclude the volume. •

Mental Health and the Elderly: Service Delivery Issues Source: Cleveland, OH: Western Reserve Geriatric Education Center, Case Western Reserve University School of Medicine. 1989. 66 p. Contact: Western Reserve Geriatric Education Center, Case Western Reserve University School of Medicine. 12200 Fairhill Road, Cleveland, OH 44120. (216) 368-5433. PRICE: $5.00. Summary: This book discusses issues in the delivery of mental health services to elderly persons. The issues are approached from a systemic and policy making perspective. The first chapter reviews research findings on four types of mental disorders commonly seen in the elderly: Alzheimer's disease and other dementias, depression, schizophrenia and anxiety disorders, and substance abuse. The second chapter explores barriers to the delivery of mental health services for the elderly. The barriers include system issues that impede the planning and delivery of services, attitudes toward mental health programs held by elderly persons and their families, and the attitudes and levels of knowledge and skills among mental health and aging professionals who work with the elderly. The third chapter presents case studies of state level initiatives in Michigan and Pennsylvania that demonstrate a variety of strategies used to address barriers to mental health care for the elderly. The fourth chapter discusses lessons from these cases concerning collaboration between the aging and mental health systems that are relevant to agencies in other states. 93 references.

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Mental Illness: A Homecare Guide Source: New York, NY: John Wiley and Sons, Inc. 1989. 274 p. Contact: Available from John Wiley and Sons, Inc. 605 Third Avenue, New York, NY 10158. (212) 850-6000. PRICE: $12.95. ISBN: 0471611573. Summary: This book is a step-by-step guide for caregivers of people with mental illness, including those with Alzheimer's disease. Based on the authors' belief that a familycentered, loving environment is ultimately a more healing situation than a hospital or other facility, the book provides information that family members need in order to plan home care, ease the transition from hospital to home, and deal with the problems that arise from caring for a mentally ill relative. In nontechnical language, the authors explore various issues such as different types of mental illness, from the schizophrenia to mood and anxiety disorders; diagnosing the problem through differential diagnosis and specialized tests; practical details of basic planning such as consultations with the doctor and the precautions involved in dispensing medications; and what to do when family relationships invariably become strained. In addition, the book provides a comprehensive list of organizations throughout the country that furnish family and individual support including the National Alliance for the Mentally Ill (NAMI), the National Mental Health Association (NMHA), and the National Mental Health Consumer Self-Help Clearinghouse. The chapters discuss: choosing a primary care

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physician and his or her role, medication, sexuality, behavior in public places, crisis intervention, and community support. •

Concise Guide to Psychiatry for Primary Care Practitioners Source: Washington, DC: American Psychiatric Press. 1999. 236 p. Contact: American Psychiatric Press, Inc. 1400 K Street, N.W. Washington, DC 20005. (800) 368-5777. E-mail: [email protected]. Website: www.appi.org. PRICE: $27.95. ISBN: 0880483458. APPI item number: 8345. Summary: This book is designed to be a practical, user-friendly guide for primary care physicians to use when dealing with psychiatric disorders in their ambulatory care patients. It includes chapters on mood disorders, anxiety disorders, substance abuse disorders, cognitive disorders, somatoform and related disorders, psychotic disorders, difficult doctor-patient relationships, sexual disorders, sleep disorders, eating and weight disorders, and suicide and violence. The chapter on cognitive disorders discusses Alzheimer's disease, vascular dementia, subcortical dementia, dementia secondary to alcoholism, and irreversible dementias; the evaluation of dementia; and the treatment of cognitive, behavioral, and psychiatric symptoms.

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Handbook of Geriatric Assessment. 3rd ed Source: Gaithersburg, MD: Aspen Publishers. 2000. 361 p. Contact: Available from Aspen Publishers. 200 Orchard Ridge Drive, Suite 200, Gaithersburg, MD 20878. Orders: 1-800-638-8437. ISBN: 0-8342-1248- X. PRICE: $55. Summary: This book presents a multidimensional approach to the assessment of older adults, including those with dementia. Thirteen chapters address the following topics: (1) the context of geriatric care, (2) ethnicity and geriatric assessment, (3) mental status assessment, (4) functional assessment, (5) the older driver, (6) social assessment, (7) advance directives, (8) the physical examination, (9) pain assessment, (10) health promotion and disease prevention, (11) assessment in special settings (nursing home, home care, hospice), (12) the University of Cincinnati's Geriatric Evaluation Center, and (13) putting geriatric assessment into practice. The chapter on mental status examination discusses the differential diagnosis of dementia, mental status assessment instruments, assessment of mood, substance abuse, and anxiety disorders. Other chapters, such as those on physical examination and pain assessment, include sections specifically addressing the care of patients with cognitive impairment.

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Geriatric Psychopharmacology Source: New York, NY: Marcel Dekker, Inc. 1998. 469 p. Contact: Available from Marcel Dekker, Inc., Cimarron Road, P. O. Box 5005, Monticello, NY 12701-5185. (800)228-1160 or FAX (914)796-1772. Internet access: http://www.dekker.com. PRICE: $175.00. ISBN: 0824798511. Summary: This book presents information to doctors in the fields of gerontology, geriatric medicine, and geriatric psychiatry. Clinicians who deal with elderly patients need to learn the difference in the coping skills of the elderly, how their metabolic functions are altered, and the differences in elderly patients' presentation of illness and responses to treatment compared to the nonelderly. This book details the experiences and knowledge of modern geriatric psychiatrists and discusses gaps in current knowledge. In geriatric pharmacology it is necessary for doctors dealing with the elderly

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to have a sophisticated understanding of the available medicines and how they are influenced by factors that affect the elderly so that outcomes are enhanced and adverse complications are avoided. The contributors provide information on general principles of geriatric psychopharmacology, treatment of depression, treatment of depression with associated conditions, bipolar disorder, late-life psychosis, anxiety disorders, and dementia. 17 figures, 25 tables, numerous references, index. •

Over-50 Guide to Psychiatric Medications Source: Washington, DC: American Psychiatric Association, Council on Aging. 1989. 148 p. Contact: American Psychiatric Association. 1400 K Street, NW, Washington, DC 20005. (202) 682-6000 or FAX (202) 682-6114. PRICE: $10.00. ISBN: 0890421277. Summary: This guide describes general considerations for the use of medications in treating mental illness in older adults. The guide details the use of medications in treating mood disorders, anxiety disorders, insomnia and other sleep disorders, disturbed thinking and behavior, and Alzheimer's disease (AD) and other forms of dementia. AD is the most common case of dementia. Dementia affects the function of many parts of the brain, including the areas involved in emotions and control over behavior. Thus, patients may experience not only intellectual decline but also disturbances of mood and behavior. Physicians may use some of the various psychoactive medicines to help relieve the emotional and behavioral disturbances that may occur in patients with dementia.

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Concise Guide to Geriatric Psychiatry. 2nd ed Source: Washington, DC: American Psychiatric Press, Inc. 1997. 326 p. Contact: American Psychiatric Press, Inc. 1400 K Street, NW, Washington, DC 20005. (800) 368-5777; (202) 682-6262. Internet access: http://www.appi.org. PRICE: $21.00. ISBN: 0880487968. Order Number: INET8796. Summary: This handbook is intended to assist geriatric psychiatrists in the diagnosis and treatment of mental disorders that often are seen in later life. The book provides background information about contemporary issues in aging and health care, barriers to geriatric mental health care, and strategies for working effectively with older patients. It includes an overview of the process of normal aging and the cognitive, personality, and physical changes that occur as people age. It discusses the diagnosis and treatment of major depression and bipolar mood disorder, Alzheimer's disease (AD) and other dementias, delirium, anxiety disorders, late-onset psychosis, sleep disorders, substance abuse, sexual dysfunction, and other psychiatric illnesses. The chapter on AD discusses the diagnosis, epidemiology, clinical presentation, pathogenesis, diagnostic criteria, clinical evaluation, and treatment. An appendix includes various clinical assessment instruments with scoring instructions or ordering information.

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Mental Health Care for People With HIV Infection Contact: New York Department of Health, AIDS Institute, Room 359, Corning Tower, Albany, NY, 12237, (518) 486-1383. Summary: This monograph presents guidelines about providing mental health care to persons with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). It includes the following chapters: (1) The Role of the Primary Care Practitioner in Assessing and Treating Mental Health in Persons with HIV, (2)

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Psychiatric/Mental Status Evaluations in Primary Care Settings, (3) Working with Patients' Personalities and Styles, (4) Family Issues for Patients with HIV/AIDS, (5) Cognitive Disorders and HIV/AIDS, (6) Depression and Mania in Patients with HIV/AIDS, (7) Suicidality in Patients with HIV/AIDS, (8) Anxiety Disorders in Patients with HIV/AIDS, and (9) Trauma and Post-Traumatic Stress Disorder in Patients with HIV/AIDS. The appendices include information on the relation between HIV-related and psychotropic medications, HIV-related causes of psychiatric symptoms, and mental health care resources in New York State.

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 “anxiety disorders” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “anxiety disorders” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “anxiety disorders” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

A Cognitive-Behavioral Approach to Generalized Anxiety Disorder (Comprehensive Summaries of Uppsala Dissertations, 838) by Elisabeth Breitholtz (1999); ISBN: 915544444X; http://www.amazon.com/exec/obidos/ASIN/915544444X/icongroupinterna

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Advances in the Neurobiology of Anxiety Disorders by Herman Gerrit Marinus Westenberg (Editor), et al; ISBN: 0471961248; http://www.amazon.com/exec/obidos/ASIN/0471961248/icongroupinterna

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An End to Panic: Breakthrough Techniques for Overcoming Panic Disorder by Elke Zuercher-White (1998); ISBN: 1572241136; http://www.amazon.com/exec/obidos/ASIN/1572241136/icongroupinterna

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Anxiety and the Anxiety Disorders by A. Hussain Tuma (Editor), Jack D. Maser (1985); ISBN: 0898595320; http://www.amazon.com/exec/obidos/ASIN/0898595320/icongroupinterna

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Anxiety Disorder Workbook by Mary Ellen Popkin; ISBN: 1587492873; http://www.amazon.com/exec/obidos/ASIN/1587492873/icongroupinterna

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Anxiety Disorders by Paul Caldwell (2004); ISBN: 1552978745; http://www.amazon.com/exec/obidos/ASIN/1552978745/icongroupinterna

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Anxiety Disorders by David J. Nutt (Editor), J. C. Ballenger (Editor) (2003); ISBN: 0632059389; http://www.amazon.com/exec/obidos/ASIN/0632059389/icongroupinterna

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Anxiety Disorders by Vimala Veeraraghavan (Author), Shalini Singh (Author); ISBN: 076199615X; http://www.amazon.com/exec/obidos/ASIN/076199615X/icongroupinterna

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Anxiety Disorders; ISBN: 0943158303; http://www.amazon.com/exec/obidos/ASIN/0943158303/icongroupinterna

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Anxiety Disorders : An Introduction to Clinical Management and Research by Eric J. L. Griez (Editor), et al (2002); ISBN: 0471978736; http://www.amazon.com/exec/obidos/ASIN/0471978736/icongroupinterna

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Anxiety Disorders and Phobias: A Cognitive Perspective by Aaron T., M.D. Beck, et al (1990); ISBN: 0465003850; http://www.amazon.com/exec/obidos/ASIN/0465003850/icongroupinterna

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Anxiety Disorders Comorbid with Depression - Volume 2: Social Phobia, Generalized Anxiety Disorder, Obsessive Compulsive Disorder and Post Traumatic Stress Disorder - Pocketbook by Dan J. Stein, Eric Hollander; ISBN: 1841840505; http://www.amazon.com/exec/obidos/ASIN/1841840505/icongroupinterna

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Anxiety Disorders Comorbid with Depression: Panic Disorder and Agoraphobia by Spilios Argyropolous, et al; ISBN: 1841840491; http://www.amazon.com/exec/obidos/ASIN/1841840491/icongroupinterna

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Anxiety Disorders in Adults: An Evidence-Based Approach to Psychological Treatment by Peter D. McLean, Sheila R. Woody; ISBN: 0195116259; http://www.amazon.com/exec/obidos/ASIN/0195116259/icongroupinterna

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Anxiety Disorders in African Americans by Steven Friedman (Editor) (1994); ISBN: 0826185401; http://www.amazon.com/exec/obidos/ASIN/0826185401/icongroupinterna

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Anxiety Disorders in Children (Developmental Clinical Psychology and Psychiatry Series, 20) by Rachel G. Klein, Cynthia G. Last; ISBN: 0803932200; http://www.amazon.com/exec/obidos/ASIN/0803932200/icongroupinterna

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Anxiety Disorders in Children and Adolescents by John S. March (Editor); ISBN: 0898628342; http://www.amazon.com/exec/obidos/ASIN/0898628342/icongroupinterna

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Anxiety Disorders in Children and Adolescents (Clinical Practice, No 22) by Syed Arshad Husain, Javad H. Kashani; ISBN: 0880484675; http://www.amazon.com/exec/obidos/ASIN/0880484675/icongroupinterna

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Anxiety Disorders in Children and Adolescents: Epidemiology, Risk Factors and Treatment (Biobehavioural Perspectives on Health and Disease Prevention, V. 4) by Cecilia A. Essau (Editor), Franz Petermann (Editor) (2003); ISBN: 1583912320; http://www.amazon.com/exec/obidos/ASIN/1583912320/icongroupinterna

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Anxiety Disorders in Children and Adolescents: Research, Assessment and Intervention by Wendy K. Silverman (Editor), Philip D. A. Treffers (Editor); ISBN: 0521789664; http://www.amazon.com/exec/obidos/ASIN/0521789664/icongroupinterna

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Anxiety Disorders in Youth: Cognitive-Behavioral Interventions (Psychology Practitioner Guidebooks Series) by Philip C. Kendall; ISBN: 0205145892; http://www.amazon.com/exec/obidos/ASIN/0205145892/icongroupinterna

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Anxiety Disorders Interview Schedule for DSM IV: Complete Kit Interview Schedule for Children by Anne Alano (1997); ISBN: 0158131509; http://www.amazon.com/exec/obidos/ASIN/0158131509/icongroupinterna

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Anxiety Disorders Interview Schedule: Adis-R by David H. Barlow, Peter A. Di Nardo (1989); ISBN: 1880659034; http://www.amazon.com/exec/obidos/ASIN/1880659034/icongroupinterna

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Anxiety Disorders of Childhood by Rachel Gittleman (Editor), et al; ISBN: 0898626587; http://www.amazon.com/exec/obidos/ASIN/0898626587/icongroupinterna

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Anxiety Disorders: A Practitioner's Guide by Theo K. Bouman (Contributor), et al; ISBN: 0471931128; http://www.amazon.com/exec/obidos/ASIN/0471931128/icongroupinterna

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Anxiety Disorders: A Scientific Approach for Selecting the Most Effective Treatment (Practitioner's Resource Series) by Samuel Knapp, Leon Vandecreek (1994); ISBN: 1568870000; http://www.amazon.com/exec/obidos/ASIN/1568870000/icongroupinterna

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Anxiety Disorders: Medical Subject Analysis and Bibliography by Alexander D. Farrell (1987); ISBN: 088164613X; http://www.amazon.com/exec/obidos/ASIN/088164613X/icongroupinterna

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Anxiety Disorders: Psychological and Biological Perspectives by Brian F. Shaw (1987); ISBN: 0306424851; http://www.amazon.com/exec/obidos/ASIN/0306424851/icongroupinterna

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Anxiety Disorders: Psychological Approaches to Theory and Treatment by Michelle Genevieve Craske (1998); ISBN: 0813332508; http://www.amazon.com/exec/obidos/ASIN/0813332508/icongroupinterna

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Anxiety Disorders: The Caregivers, Third Edition by Ken Strong (2003); ISBN: 1590790561; http://www.amazon.com/exec/obidos/ASIN/1590790561/icongroupinterna

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Anxiety, Phobias & Panic Disorders - a clinical guideline [DOWNLOAD: PDF] by Apollo Managed Care Consultants (Author); ISBN: B00007CIEU; http://www.amazon.com/exec/obidos/ASIN/B00007CIEU/icongroupinterna

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Biology of Anxiety Disorders (Progress in Psychiatry Series, No 36) by Rudolf, M.D. Hoehn-Saric, Daniel, Ph.D. McLeod (Editor) (1993); ISBN: 0880484764; http://www.amazon.com/exec/obidos/ASIN/0880484764/icongroupinterna

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Chronic Anxiety: Generalized Anxiety Disorder and Mixed Anxiety-Depression by Ronald M. Rapee (Editor), David H. Barlow (Editor); ISBN: 0898627710; http://www.amazon.com/exec/obidos/ASIN/0898627710/icongroupinterna

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Clients Manual for the Cognitive-Behavioral Treatment of Anxiety Disorders (2nd Edition) by Larry D. Smyth; ISBN: 1889287962; http://www.amazon.com/exec/obidos/ASIN/1889287962/icongroupinterna

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Clinical Aspects of Panic Disorder by James C. Ballenger (Editor); ISBN: 0471566942; http://www.amazon.com/exec/obidos/ASIN/0471566942/icongroupinterna

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Clinical Handbook of Anxiety Disorders in Children and Adolescents by Andrew R. Eisen (Editor), et al (1995); ISBN: 1568212941; http://www.amazon.com/exec/obidos/ASIN/1568212941/icongroupinterna

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Clinical Manual of Anxiety Disorders by Dan J. Stein (Editor) (2004); ISBN: 1585620769; http://www.amazon.com/exec/obidos/ASIN/1585620769/icongroupinterna

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Clinician's Manual for the Cognitive-Behavioral Treatment of Post Traumatic Stress Disorder and the other Anxiety Disorders (2nd Edition) by Larry D. Smyth (1999); ISBN: 1889287997; http://www.amazon.com/exec/obidos/ASIN/1889287997/icongroupinterna

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Clinician's Manual on Anxiety Disorders and Comorbid Depression by Nutt, et al; ISBN: 1858733979; http://www.amazon.com/exec/obidos/ASIN/1858733979/icongroupinterna

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Cognitive Therapy of Anxiety and Panic Disorder: First Interview Techniques (Cassette) by Aaron Beck; ISBN: 9990058547; http://www.amazon.com/exec/obidos/ASIN/9990058547/icongroupinterna

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Cognitive Therapy of Anxiety and Panic Disorders: First Interview by Aaron T. Beck (Author); ISBN: 0898628741; http://www.amazon.com/exec/obidos/ASIN/0898628741/icongroupinterna

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Cognitive Therapy of Anxiety Disorders : A Practice Manual and Conceptual Guide by Adrian Wells (Author); ISBN: 047196476X; http://www.amazon.com/exec/obidos/ASIN/047196476X/icongroupinterna

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Cognitive-Affective Neuroscience of Depression and Anxiety Disorders by Dan J Stein; ISBN: 1841841005; http://www.amazon.com/exec/obidos/ASIN/1841841005/icongroupinterna

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Comorbidity of Mood and Anxiety Disorders by Jack D. Maser, C. Robert Cloninger (Editor) (1990); ISBN: 0880483245; http://www.amazon.com/exec/obidos/ASIN/0880483245/icongroupinterna

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Comparative Treatments of Anxiety Disorders by Robert A. Ditomasso (Editor), Elizabeth A. Gosch (Editor) (2002); ISBN: 0826148328; http://www.amazon.com/exec/obidos/ASIN/0826148328/icongroupinterna

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Concise Guide to Anxiety Disorders (Concise Guides) by Eric Hollander, Daphne Simeon (2002); ISBN: 1585620807; http://www.amazon.com/exec/obidos/ASIN/1585620807/icongroupinterna

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Conquering Panic and Anxiety Disorders: Success Stories, Strategies, and Other Good News by Jenna Glatzer (Editor), Paul Foxman (Commentary) (2002); ISBN: 0897933818; http://www.amazon.com/exec/obidos/ASIN/0897933818/icongroupinterna

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Contemporary Issues and Prospects for Research in Anxiety Disorders (Handbook of Anxiety, Vol 5) by Graham D. Burrows, et al; ISBN: 0444896023; http://www.amazon.com/exec/obidos/ASIN/0444896023/icongroupinterna

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Current Controversies in the Anxiety Disorders by Ronald M. Rapee (Editor); ISBN: 157230023X; http://www.amazon.com/exec/obidos/ASIN/157230023X/icongroupinterna

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Current Therapeutic Approaches to Panic and Other Anxiety Disorders: Collegium Internationale Neuro-Psychopharmacologicum Regional Workshop, Monte C by G. Darcourt, et al (1994); ISBN: 3805559895; http://www.amazon.com/exec/obidos/ASIN/3805559895/icongroupinterna

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Diagnosis and Treatment of Anxiety Disorders (1991); ISBN: 0880483210; http://www.amazon.com/exec/obidos/ASIN/0880483210/icongroupinterna

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Diagnosis and Treatment of Anxiety Disorders: A Physician's Handbook by Thomas J. McGlynn (Editor), Harry L. Metcalf (Editor) (1991); ISBN: 088048523X; http://www.amazon.com/exec/obidos/ASIN/088048523X/icongroupinterna

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Diagnosis Anxiety Disorders by Pasnau (Author) (1987); ISBN: 052134493X; http://www.amazon.com/exec/obidos/ASIN/052134493X/icongroupinterna

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Drug Therapy and Anxiety Disorders (Psychiatric Disorders: Drugs & Psychology for the Mind and Body) by Shirley Brinkerhoff; ISBN: 1590845617; http://www.amazon.com/exec/obidos/ASIN/1590845617/icongroupinterna

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Fresh Perspectives on Anxiety Disorders (Annual Series of European Research in Behavior Therapy, 4) by P.M.G. Emmelkamp (Editor) (1989); ISBN: 9026510160; http://www.amazon.com/exec/obidos/ASIN/9026510160/icongroupinterna

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Gender Differences in Mood & Anxiety Disorders: From Bench to Bedside by Ellen Leibenluft (Editor) (1999); ISBN: 0880489588; http://www.amazon.com/exec/obidos/ASIN/0880489588/icongroupinterna

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Generalised Anxiety Disorder: Symptomatology, Pathogenesis and Management by David Nutt (Editor), et al (2002); ISBN: 1841841315; http://www.amazon.com/exec/obidos/ASIN/1841841315/icongroupinterna

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Generalized Anxiety Disorder : Advances in Research and Practice by Richard G. Heimberg (Editor), et al (2004); ISBN: 1572309725; http://www.amazon.com/exec/obidos/ASIN/1572309725/icongroupinterna

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Generalized Anxiety Disorder: diagnosis, treatment and its relationship to other anxiety disorders - pocketbook by David Nutt, et al (1998); ISBN: 1853176591; http://www.amazon.com/exec/obidos/ASIN/1853176591/icongroupinterna

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Growing Up With Anxiety Disorder by Mark Arthur Pagel (2003); ISBN: 1403384436; http://www.amazon.com/exec/obidos/ASIN/1403384436/icongroupinterna

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Handbook of Anxiety Disorders by Cynthia G. Last; ISBN: 0080327664; http://www.amazon.com/exec/obidos/ASIN/0080327664/icongroupinterna

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Handbook of the Treatment of the Anxiety Disorders by Carol Lindemann (Editor) (1996); ISBN: 1568218052; http://www.amazon.com/exec/obidos/ASIN/1568218052/icongroupinterna

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Integrative Treatment of Anxiety Disorders by James M. Ellison (Editor) (1996); ISBN: 0880487151; http://www.amazon.com/exec/obidos/ASIN/0880487151/icongroupinterna

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International Handbook of Phobic and Anxiety Disorders in Children and Adolescents (Issues in Clinical Child Psychology) by Thomas H. Ollendick, et al (1994); ISBN: 0306447592; http://www.amazon.com/exec/obidos/ASIN/0306447592/icongroupinterna

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Let's Talk Facts About Anxiety Disorders: Prepack of 50 by The American Psychiatric Association Division of Public Affairs (1999); ISBN: 0890423601; http://www.amazon.com/exec/obidos/ASIN/0890423601/icongroupinterna

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Long-Term Treatments of Anxiety Disorders by Matig R. Mavissakalian (Editor), Robert F. Prien (Editor) (1996); ISBN: 0880486562; http://www.amazon.com/exec/obidos/ASIN/0880486562/icongroupinterna

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Mental Health Disorders Sourcebook: Basic Information About Schizophrenia, Depression, Bipolar Disorder, Panic Disorder, Obsessive-Compulsive Disorder, Phobias and Other Anxiety disorder (Health Reference Series, Vol 9) by Karen Bellenir (Editor) (1997); ISBN: 0780800400; http://www.amazon.com/exec/obidos/ASIN/0780800400/icongroupinterna

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Mood & Anxiety Disorders by John A. Rush (Editor), A. John Rush (Editor); ISBN: 0683305166; http://www.amazon.com/exec/obidos/ASIN/0683305166/icongroupinterna

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Mood and Anxiety Disorders in Children and Adolescent: a psychopharmacological approach by David Nutt, et al; ISBN: 1853179248; http://www.amazon.com/exec/obidos/ASIN/1853179248/icongroupinterna

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Neuropsychological Perspectives On Affective And Anxiety Disorders: A Special Issue of the Journal Cognition and Emotion by Richard J. Davidson (Editor); ISBN: 0863779719; http://www.amazon.com/exec/obidos/ASIN/0863779719/icongroupinterna

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Origins of Phobias and Anxiety Disorders: Why More Women Than Men (The First Volume in the New Brat Series on Clinical Psychology) by Michelle Craske (Editor) (2003); ISBN: 0080440320; http://www.amazon.com/exec/obidos/ASIN/0080440320/icongroupinterna

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Overcoming Anxiety: Panic Attacks and Anxiety Disorders (Health Body, Healthy Soul Series) by David Hazard (2003); ISBN: 0736911944; http://www.amazon.com/exec/obidos/ASIN/0736911944/icongroupinterna

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Overcoming Generalized Anxiety Disorder - Client Manual: A Relaxation, Cognitive Restructuring, and Exposure-Based Protocol for the Treatment of Gad by John R. White (1999); ISBN: 1572241454; http://www.amazon.com/exec/obidos/ASIN/1572241454/icongroupinterna

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Overcoming Generalized Anxiety Disorder: Therapist Protocol (Best Practices for Therapy Series) by John R. White, White John (1999); ISBN: 1572241446; http://www.amazon.com/exec/obidos/ASIN/1572241446/icongroupinterna

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Panic and Anxiety Disorder: 121 Tips, Real-life Advice, Resources & More, Second Edition by Linda Manassee Buell; ISBN: 1928607055; http://www.amazon.com/exec/obidos/ASIN/1928607055/icongroupinterna

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Panic Disorder (Perspectives on Mental Health) by Nancy M. Campbell; ISBN: 0736810307; http://www.amazon.com/exec/obidos/ASIN/0736810307/icongroupinterna

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Panic Disorder and Agoraphobia : A Guide by John H., M.D. Greist, James W., M.D. Jefferson (1998); ISBN: 1890802158; http://www.amazon.com/exec/obidos/ASIN/1890802158/icongroupinterna

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Panic Disorder and Anxiety in Adolescence by Sara Golden Mattis, et al; ISBN: 1854333526; http://www.amazon.com/exec/obidos/ASIN/1854333526/icongroupinterna

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Panic Disorder: Assessment and Treatment Through a Wide-Angle Lens by Frank M. Dattilio, Jesus A. Salas-Auvert (2000); ISBN: 1891944355; http://www.amazon.com/exec/obidos/ASIN/1891944355/icongroupinterna

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Panic Disorder: The Great Pretender by H. Michael Zal, Michael H. Zal (1990); ISBN: 0306432978; http://www.amazon.com/exec/obidos/ASIN/0306432978/icongroupinterna

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Pharmacotherapy of Anxiety Disorders by Katharine J. Palmer, Katherine J. Palmer (2000); ISBN: 0864710712; http://www.amazon.com/exec/obidos/ASIN/0864710712/icongroupinterna

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Phobic and Anxiety Disorders in Children and Adolescents: A Clinician's Guide to Effective Psychosocial and Pharmacological Interventions by Thomas H. Ollendick (Editor), John S. March (Editor) (2003); ISBN: 0195135946; http://www.amazon.com/exec/obidos/ASIN/0195135946/icongroupinterna

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Psychological Assessment and Treatment of Anxiety Disorders by Vimala Veeraraghavan, Shalini Singh; ISBN: 0761995587; http://www.amazon.com/exec/obidos/ASIN/0761995587/icongroupinterna

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Separation Anxiety Disorder: Psychodynamics and Psychotherapy by Richard A. Gardner (1984); ISBN: 0933812108; http://www.amazon.com/exec/obidos/ASIN/0933812108/icongroupinterna

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Sexual Aversion And Sexual Phobias And Panic Disorders by Helen Singer Kaplan, Donald F., M.D. Klein (Contributor); ISBN: 0876304501; http://www.amazon.com/exec/obidos/ASIN/0876304501/icongroupinterna

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Stress Strategies: The Treatment of Anxiety Disorders by C. B. Scrignar; ISBN: 3805536054; http://www.amazon.com/exec/obidos/ASIN/3805536054/icongroupinterna

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Textbook of Anxiety Disorders by Dan J. Stein (Editor), Eric Hollander (Editor); ISBN: 0880488298; http://www.amazon.com/exec/obidos/ASIN/0880488298/icongroupinterna

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The Anxiety Disorders by Russell Jr Noyes (Author), Rudolf Hoehn-Saric (Author); ISBN: 0521552079; http://www.amazon.com/exec/obidos/ASIN/0521552079/icongroupinterna

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The Clinical Management of Anxiety Disorders by William Coryell (Editor), George Winokur (Editor) (1991); ISBN: 0195059530; http://www.amazon.com/exec/obidos/ASIN/0195059530/icongroupinterna

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The Handbook of Phobia Therapy: Rapid Symptom Relief in Anxiety Disorders by Carol Lindemann (Editor) (1989); ISBN: 0876688660; http://www.amazon.com/exec/obidos/ASIN/0876688660/icongroupinterna

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The Nature and Treatment of Anxiety Disorders by C. Barr Taylor, Bruce Arnow (Contributor); ISBN: 0029329817; http://www.amazon.com/exec/obidos/ASIN/0029329817/icongroupinterna

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The TAB-P Protocol : The Complete Home-Study Course in Cognitive-Behavioral Exposure-Based Psychotherapy for the Treatment of PTSD and the other Anxiety Disorders (6 Manuals + 5 Video Tapes) by Larry D. Smyth; ISBN: 1889287989; http://www.amazon.com/exec/obidos/ASIN/1889287989/icongroupinterna

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The Treatment of Anxiety Disorders : Clinician Guides and Patient Manuals by Gavin Andrews (Author), et al (2002); ISBN: 0521788773; http://www.amazon.com/exec/obidos/ASIN/0521788773/icongroupinterna

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Treating Anxiety Disorders by Walton T. Roth (Editor) (1996); ISBN: 0787903167; http://www.amazon.com/exec/obidos/ASIN/0787903167/icongroupinterna

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Treating Anxiety Disorders by Rodrigo A. Munoz (Editor); ISBN: 1555429890; http://www.amazon.com/exec/obidos/ASIN/1555429890/icongroupinterna

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Treating Anxiety Disorders: A Guide for Human Service Professionals (Sage Human Services Guides, Vol 45) by Bruce A. Thyer; ISBN: 0803927924; http://www.amazon.com/exec/obidos/ASIN/0803927924/icongroupinterna

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Treatment Plans and Interventions for Depression and Anxiety Disorders by Robert L. Leahy (Author), Stephen J. Holland (Author); ISBN: 1572305142; http://www.amazon.com/exec/obidos/ASIN/1572305142/icongroupinterna

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Understanding Major Anxiety Disorders and Addiction (No 5418) by Katie Evans, J. Michael Evans (1991); ISBN: 9993163503; http://www.amazon.com/exec/obidos/ASIN/9993163503/icongroupinterna

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Understanding Panic and Other Anxiety Disorders (Understanding Health and Sickness Series) by Benjamin A. Root (2000); ISBN: 1578062454; http://www.amazon.com/exec/obidos/ASIN/1578062454/icongroupinterna

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Uneasy Lives: Understanding Anxiety Disorders (Encyclopedia of Psychological Disorders) by Linda N. Bayer (2000); ISBN: 0791053164; http://www.amazon.com/exec/obidos/ASIN/0791053164/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “anxiety disorders” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Diagnosis and treatment of anxiety disorders Author: Pasnau, Robert O.,; Year: 1969; Washington, D.C.: American Psychiatric Press, c1984; ISBN: 088048022X http://www.amazon.com/exec/obidos/ASIN/088048022X/icongroupinterna

Chapters on Anxiety Disorders In order to find chapters that specifically relate to anxiety disorders, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and anxiety 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 “anxiety disorders” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on anxiety disorders: •

Behavioral and Psychiatric Disorders Source: in Little, J.W., et al. Dental Management of the Medically Compromised Patient. 5th ed. St. Louis, MO: Mosby, Inc. 1997. p. 546-575. Contact: Available from Harcourt Health Sciences. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177. Fax (800) 874-6418. Website: www.harcourthealth.com. PRICE: $48.00 plus shipping and handling. ISBN: 0815156340.

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Summary: A working knowledge of the multitude of compromised health states is essential for dental professionals, as the majority of medically compromised patients need or want oral health care. This chapter on behavioral and psychiatric disorders is from a text that provides the dental practitioner with an up to date reference work describing the dental management of patients with selected medical problems. In this chapter, the authors discuss problems encountered in dental practice that stem from a patient's behavioral patterns rather than from physical conditions. The authors stress that both patients with emotional factors that contribute to oral or systemic problems and patients with more serious mental disorders can be managed in an understanding, safe, and empathetic manner. The authors discuss incidence and prevalence of anxiety disorders, mood disorders, and somatoform disorders; psychologic factors affecting physical conditions, including substance abuse, schizophrenia, and organic mental syndromes (dementia, Alzheimer's disease, delirium); etiology; pathophysiology and complications; signs and symptoms (clinical presentation and laboratory findings); drugs used to treat psychiatric disorders; and the dental management of this population, including patient attitude toward the dentist, the psychologic significance of the oral cavity, and behavior toward illness; and management of specific patients, including those with depression bipolar disorder, somatoform disorder, psychophysiologic disorder, a cocaine habit, schizophrenia, Alzheimer's disease, and suicidal patients. The chapter concludes with a section on drug interactions and side effects in patients with mental disorders, including tricyclic antidepressants, monoamine oxidase inhibitors, antianxiety drugs, and antipsychotic drugs. 3 figures. 25 tables. 40 references. •

Psychological Disorders Source: in Franz, M.J., et al, eds. Core Curriculum for Diabetes Education. 4th ed.: (Volume 3) Diabetes Education and Program Management. Chicago, IL: American Association of Diabetes Educators (AADE). 2001. p. 145-176. Contact: Available from American Association of Diabetes Educators. AADE Member Service Center, 100 W. Monroe Street, Suite 400, Chicago, IL 60603. (800) 338-3633. Fax (312) 424-2427. Website: www.diabeteseducator.org. PRICE: Individual volume $45.00 for members and $60.00 for nonmembers; complete 4-volume set $149.95 for members and $199.95 for nonmembers; plus shipping and handling. ISBN: 1881876071 (Volume 3); 1881876098 (4-volume set). Summary: Persons with diabetes may disproportionately exhibit certain psychological disorders, and the course and consequences of some of these disorders may be more severe for persons with diabetes. This chapter on psychological disorders is from a book in a series of four texts that make up a Core Curriculum, designed primarily to help educators prepare for the Certified Diabetes Educator (CDE) exam. Topics include the relationship between diabetes and mental disorders common to people with diabetes, including depressive disorders, anxiety disorders (including specific phobia), eating disorders, and adjustment disorders; the various psychological disorders that can affect diabetes management; subclinical syndromes that might impair diabetes self care; current counseling and psychotherapeutic treatments for the psychological problems that are common among people with diabetes; current pharmacological (drug) treatments for the psychological problems that are common among people with diabetes; and the indications for referring a patient to a mental health specialist for consultation or treatment. The chapter lists the learning objectives for that chapter, presents information in outline and bulleted format, summarizes the key educational considerations, offers self review questions and questions for discussion, presents

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illustrative case reports, and concludes with a list of references. A post-test and the answers to the post-test questions are appended to the chapter. 6 tables. 91 references. •

Psychiatric Profile of Tinnitus Patients Referred to an Audiological Clinic Source: in Hazell, J., ed. Proceedings of the Sixth International Tinnitus Seminar. London, England: Tinnitus and Hyperacusis Centre. 1999. p. 283-285. Contact: Available from Tinnitus and Hyperacusis Centre. 32 Devonshire Place, London, W1N 1PE, United Kingdom. Fax 44 + (0) 207 486 2218. E-mail: [email protected]. Website: www.tinnitus.org. PRICE: Contact publisher for price. ISBN: 0953695700. Also available on CD-ROM. Summary: This article is from a lengthy document that reprints the proceedings of the Sixth International Tinnitus Seminar, held in Cambridge, United Kingdom, in September 1999 and hosted by the British Society of Audiology. In this article, the authors report on a study undertaken to investigate psychiatric parameters in consecutive tinnitus patients without severe hearing impairments. A total of 98 patients were included in the study group (33 women and 65 men); 82 patients (30 women and 52 men) fulfilled the assessment. The assessment included a standardized diagnostic interview for multiaxial psychiatric diagnostics and the Hospital Anxiety and Depression Scale, which is a self administered scale with subscales for anxiety and depression. The patients described the present symptoms of tinnitus (24 months after the first tinnitus consultation) as follows: 17 percent did not perceive tinnitus any more; 4 percent said that they seldom think of their tinnitus; 39 percent did not experience tinnitus, unless they felt lonely or depressed, unless it was quiet, or when someone talked about tinnitus; 33 percent said that tinnitus is always severe; and 5 percent told that it was difficult to think about anything other than tinnitus (the remaining 2 percent did not give any conclusive answer). The authors note that the occurrence of depressive and anxiety related syndromes in tinnitus patients were remarkably high (62 out of 80 patients) in this study. These symptoms also covaried with tinnitus. In 90 percent of the tinnitus patients with depression or anxiety disorders, the psychiatric disorder had started before or at the same time as the onset of tinnitus. It is often claimed that depression is secondary to tinnitus (i.e., the patient is depressed because of the tinnitus), but these results indicate that tinnitus is secondary or parallel in time to depression or anxiety orders. The authors conclude that since psychological factors are known to enhance tinnitus suffering, early identification and treatment of these symptoms can be of crucial importance to avoid the process from emergence of tinnitus to tinnitus that has severe impact on the daily activity and quality of life. 2 figures. 27 references.

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Early Identification of Therapy Resistant Tinnitus Source: in Hazell, J., ed. Proceedings of the Sixth International Tinnitus Seminar. London, England: Tinnitus and Hyperacusis Centre. 1999. p. 268-270. Contact: Available from Tinnitus and Hyperacusis Centre. 32 Devonshire Place, London, W1N 1PE, United Kingdom. Fax 44 + (0) 207 486 2218. E-mail: [email protected]. Website: www.tinnitus.org. PRICE: Contact publisher for price. ISBN: 0953695700. Also available on CD-ROM. Summary: This article on therapy resistant tinnitus is from a lengthy document that reprints the proceedings of the Sixth International Tinnitus Seminar, held in Cambridge, United Kingdom, in September 1999 and hosted by the British Society of Audiology. In this article, the authors report on their research study which investigated risk factors for therapy resistant tinnitus (as measured by absence from work, related to tinnitus,

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abbreviated at AWT). The study included 172 consecutive tinnitus patients consulting an audiological physician during a 6 month period at a university hospital in Goteborg, Sweden (54 women and 118 men). The patients were reassessed 18 months later in order to identify and investigate the therapy resistant patients. In the study, 18 out of the 79 patients who completed the study were absent from work due to tinnitus. There were significant correlations between the tinnitus severity questionnaire (TSQ) and AWT, including questions concerning how much tinnitus reduces the overall quality of life, how often tinnitus is noticed during the waking hours or impairs concentration, and how often tinnitus makes the patients feel anxious or worried, tense or irritable, or depressed and miserable. The main predictors influencing AWT were the questions concerning depression and reduced mobility, but also physical exercise on a regular basis and hearing thresholds over both ears for the low and mid frequencies. The authors conclude that it is of great importance to identify and treat depression and anxiety disorders initially, so the risks for the progression of tinnitus are minimized. 1 figure. 2 tables. 11 references. •

Other Dementias and Mental Disorders Due to General Medical Conditions Source: in Sadavoy, J.; et al., eds. Comprehensive Review of Geriatric Psychiatry-II. 2nd ed. Washington, DC: American Psychiatric Press, Inc. 1996. p. 497-528. Contact: American Psychiatric Press, Inc. 1400 K Street, NW, Washington, DC 20005. (202) 682-6262; FAX (202) 789-2648. PRICE: $95.00 plus $7.50 shipping. Internet access: http://www.appi.org. ISBN: 0880487232. Summary: This chapter discusses forms of dementia other than Alzheimer's disease and vascular dementia. The first half of the chapter discusses forms of dementia considered in the differential diagnosis of progressive cognitive impairment. The second part of the chapter describes the secondary mental disorders referred to as 'organic mental disorders' in the 'Diagnostic and Statistical Manual of Mental Disorders, III, Revised' (DSM). The author explains that the term 'organic' was deleted from the DSM IV; thus, experts should specify the actual physical disorder or responsible substance. The dementias discussed include: focal cortical dementias (Pick's disease and others); subcortical dementias (Huntington's disease, dementia in Parkinson's disease, and progressive supranuclear palsy); normal pressure hydrocephalus; dementias caused by an infectious disease (Creutzfeldt-Jakob disease and HIV encephalopathy); dementia associated with metabolic disorders; dementia after head injury; dementia associated with toxic substances; dementia associated with brain tumors; mental disorders due to general medical conditions; amnestic disorders; mood disorders due to a general medical condition; anxiety disorders due to a general medical condition; psychotic disorders due to a general medical condition, with delusions; psychotic disorders due to a general medical condition, with hallucinations; and personality changes due to a general medical condition. 4 tables, 94 references.

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Psychiatric Issues in Rheumatology Source: in Maddison, P.J.; et al., Eds. Oxford Textbook of Rheumatology. Volume 1. New York, NY: Oxford University Press, Inc. 1993. p. 188-196. Contact: Available from Oxford University Press, Inc., New York, NY. Summary: This chapter for health professionals focuses on the recognition and treatment of psychiatric disorders that occur among individuals with rheumatic diseases. The topic of psycho neuroimmunology is discussed. The psychiatric manifestations of various rheumatic diseases are described, including those of systemic

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lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, systemic vasculitides, Lyme disease, and juvenile chronic arthritis. The psychiatric side effects of corticosteriods, cyclosporin A, antimalarials, and nonsteroidal anti-inflammatory drugs are highlighted. Strategies for managing depression with antidepressant medications and for managing anxiety disorders and sleep disturbances are also presented. 59 references and 8 tables. •

Emotional Issues Source: in Osman, B.B. Learning Disabilities and ADHD: A Family Guide to Living and Learning Together. New York, NY: John Wiley and Sons, Inc. 1997. p. 166-180. Contact: Available from John Wiley and Sons, Inc. Distribution Center, 1 Wiley Drive, Somerset, NJ 08875-1272. (800) 225-5945 or (732) 469-4400. Fax (732) 302-2300. E-mail: [email protected]. Website: www.wiley.com. PRICE: $14.95 plus shipping and handling. ISBN: 0471155101. Summary: This chapter on emotional issues is from a book to help parents cope with learning disabilities in their children and to learn to serve as their child's advocate. The author discusses four emotional difficulties to which children and adolescents with learning differences seem particularly vulnerable: learned helplessness, anxiety disorders, depression, and behavior disorders. Although these problems are not necessarily life threatening, they can affect the entire family and may even persist beyond adolescence unless they are addressed. Specific topics include learning to take responsibility (to combat learned helplessness); separation anxiety; obsessive compulsive symptoms; the criteria for a diagnosis of depression; the interrelationship of learning disabilities, attention deficit hyperactivity disorder (ADHD) and depression; the evaluation process to differentiate depression; and the role of prevention as the treatment of choice. The author calls for the prevention of emotional and behavioral disturbances in childhood to become the priority in mental health, rather than treatment for children after problems emerge (the present approach). Practical strategies and checklists are offered throughout the chapter; case scenarios help to illustrate the concepts under discussion.

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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. 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

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barriers remain to comprehensive oral care for elderly psychiatric patients. 49 references. (AA-M). •

Psychological Benefits of Exercise Source: in Devlin, J.T. and Schneider, S.H., eds. Handbook of Exercise in Diabetes. Alexandria, VA: American Diabetes Association. 2002. p. 125-134. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $69.95 plus shipping and handling. ISBN: 1580400191. Summary: This chapter on the psychological benefits of exercise is from a book that provides a practical, comprehensive guide to diabetes and exercise for health care professionals involved in patient care. In this chapter, the authors emphasize that exercise can have important effects on mental health for individuals with and without psychiatric disorders. Regular exercise can have an antidepressant effect in patients with mild to moderate depressive disorders. Aerobic exercise can reduce anxiety levels acutely, and regular exercise may have a role in reducing chronic anxiety in individuals with anxiety disorders. Emotionally healthy individuals who exercise regularly report improved mood, sense of well-being, and self-esteem. Rarely, exercise may have negative psychological effects, such as exercise addiction. It is not known how often or for how long individuals should exercise to achieve optimal psychological benefit. Adherence to exercise regimens is problematic; 50 percent of those beginning an exercise program will drop out yet little is known about predicting adherence to exercise programs. The authors conclude that patients with diabetes, like healthy individuals, can benefit emotionally as well as physically from regular exercise. 2 tables. 30 references.

•

Psychosocial Aspects of Diabetes in Adult Populations Source: in Harris, M.I., et al., eds., for the National Diabetes Data Group (NDDG). Diabetes in America. 2nd ed. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. 1995. p. 507-517. Contact: Available from National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747 or (301) 654-3327. Fax (301) 634-0716. E-mail: [email protected]. Also available at http://www.niddk.nih.gov/. PRICE: Full-text book and chapter available online at no charge; book may be purchased for $20.00. Order number: DM-96 (book). Summary: This chapter on the psychosocial aspects of diabetes in the adult population is from a compilation and assessment of data on diabetes and its complications in the United States. It is a prevalent clinical belief that depression in diabetes is secondary to psychosocial hardship brought on by increasing severity of the diabetes. However, studies that examined this relationship did not find statistically significant associations between depression and severity of diabetes. The authors postulate that the presence of diabetes complications alone may not result in depression unless severe functional limitations such as blindness, impotence, and cognitive impairment are present. The nature of depression in diabetes is complex, and adverse life events, severity of the medical illness, genetic and personality factors, and psychiatric history are all likely contributors to its occurrence. The prevalence of psychiatric disorders other than depression in diabetes has not been extensively studied. There is evidence that anxiety disorders are significantly more common in this group, particularly generalized anxiety

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disorder and simple phobia. The prevalence of anorexia nervosa and bulimia nervosa in diabetes is unknown, but interest in these disorders remains high because of their potential for adverse effects on glycemic control. The relationship between stress and glucose regulation in diabetes has been the subject of considerable study, but findings have been inconsistent. Stress has been reported to increase, decrease, or have no significant effect on diabetes glycemic control. The threshold for the reporting of diabetes symptoms may be lowered by psychological factors, particularly depression and anxiety, and both psychological and physiological factors may contribute to diabetes symptoms. Also, the efficacy of psychotropic medication for psychiatric disorders in patients with diabetes is largely unknown. However, these pharmaceuticals may have side effects that limit their use in persons with diabetes. Thus, psychotherapy may have a prominent place in diabetes treatment options. 9 tables. 71 references. •

Vestibular Rehabilitation Source: in Canalis, R.F. and Lambert, P.R., eds. Ear: Comprehensive Otology. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 681-692. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 223-2300. Website: www.lww.com. PRICE: $179.00 plus shipping and handling. ISBN: 078171558X. Summary: This chapter on vestibular rehabilitation is from a textbook that offers complete coverage of the field of clinical otology (study of the ear). The book is oriented to serve both the otolaryngology resident as a practical learning tool and the practicing otolaryngologist as an updated reference source of clinical and basic information. Vertigo (a spinning sensation) or disequilibrium may persist because of poor central nervous system compensation, even after the acute injury has healed. Some patients develop poor postural control strategies that are destabilizing in certain settings; these patients often benefit from a program of vestibular rehabilitation therapy. Topics include the physiologic rationale for vestibular rehabilitation, including acute compensation for vestibular lesions, chronic compensation, neuropharmacology of vestibular compensation, and decompensation; the clinical assessment of vestibular compensation, including the clinical history and vestibular testing; the efficacy of and patient selection criteria for vestibular rehabilitation, including controlled studies of efficacy, uncompensated unilateral peripheral lesions, positional vertigo, disequilibrium of aging, use after vestibular surgery, head injury, malingering, panic disorder and other anxiety disorders, Meniere's disease, the use of a diagnostic trial, and inappropriate candidates; and common techniques of vestibular rehabilitation, including habituation of pathologic responses, postural control exercises, visual vestibular interaction, conditioning activities, maintenance of initial results, the role of the therapist in patient education, and the role of the physician. 3 appendices. 33 references.

•

Emotional Responses to Diagnosis Source: in Anderson, B.J. and Rubin, R.R., eds. Practical Psychology for Diabetes Clinicians: How to Deal with the Key Behavioral Issues Faced by Patients and Health Care Teams. Alexandria, VA: American Diabetes Association. 1996. p. 155-162. Contact: Available from American Diabetes Association. Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (404) 442-9742. PRICE: $19.95 (members); $24.95 (nonmembers). ISBN: 0945448732. Summary: This chapter, from a guidebook on behavioral issues for diabetes clinicians, covers emotional responses to diagnosis and the potentially negative impact of these

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responses on self care. The authors offer information and guidelines for treating emotional problems and disorders in individuals with newly diagnosed diabetes. Many of the issues addressed here may also apply to patients with diabetes of longer duration. Topics include denial at diagnosis and how to address it; screening for other emotional problems, including depression and anxiety disorders; the role of family and medical staff in treating emotional problems; balancing effective self care with good quality of life; and the need to refer to mental health professionals. 3 references. •

Psychologic Factors and Orofacial Pain: Axis II Source: in Okeson, J.P. Bell's Orofacial Pains. 5th ed. Carol Stream, IL: Quintessence Publishing Company, Inc. 1995. p. 457-479. Contact: Available from Quintessence Publishing Company, Inc. 551 North Kimberly Drive, Carol Stream, IL 60188-1881. (800) 621-0387 or (630) 682-3223; Fax (630) 682-3288; E-mail: [email protected]; http://www.quintpub.com. PRICE: $68.00 plus shipping and handling. ISBN: 0867152931. Summary: This chapter, from a text on orofacial pains, discusses psychological factors and orofacial pain. After an introductory section describing the role of psychologic factors in all experiences of pain, the author discusses acute pain versus chronic pain and the biopsychosocial model; symptoms of chronicity; the psychologic significance of orofacial pains; the classification of mental disorders; mood disorders; anxiety disorders; somatoform disorders; other conditions that may be a focus of clinical attention, including malingering and psychologic factors affecting a medical condition; and general therapeutic considerations. 6 figures. 24 references.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to anxiety disorders have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:12 •

Georgia Mental Health Sourcebook Source: Atlanta, GA: Care Solutions, Inc. 1994. 177 p. Contact: Available from Care Solutions, Inc. 8302 Dunwoody Place, Suite 352, Atlanta, GA 30350. (404) 642-6722; (800) 227-3410; FAX (404) 640-6073. PRICE: $24.95 plus $3.00 shipping and handling. ISBN: 0963193961. Summary: This guide for consumers and professionals provides basic definitions of mental illness, information about the types of mental health services available, and where to call for help within Georgia. Resources are organized by category and geographic area. Some of the more common mental difficulties and disorders are briefly described and include mood and anxiety disorders; schizophrenia; dementia, including Alzheimer's disease; substance abuse; and eating, sleeping, and sexual disorders. Topics

12 You will need to limit your search to “Directory” and “anxiety disorders” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “anxiety disorders” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.

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include information about where to start in seeking help; mental health issues involving children; special issues such as older adults and mental health, family relationship, homelessness, suicide, and AIDS; violence, aggression, and emotional crises; health insurance and financial options; and legal and ethical issues. Among the community resources listed are residential and day treatment services, counseling and outpatient services, supportive living programs, advocacy and support groups, multicultural programs, substance abuse programs, psychiatric hospitals, and children and adolescent programs. Over 1,700 providers are listed.

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CHAPTER 8. MULTIMEDIA ON ANXIETY DISORDERS Overview In this chapter, we show you how to keep current on multimedia sources of information on anxiety disorders. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Bibliography: Multimedia on Anxiety Disorders The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in anxiety disorders (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on anxiety disorders: •

Anxiety disorder [electronic resource] Source: Nu-Vision, Inc; Year: 1989; Format: Electronic resource; [Philadelphia, Pa.]: Lippincott, [1989]

•

Anxiety disorders [videorecording]: generalized anxiety, agoraphobia, and obsessive compulsive anxiety Source: [presented by] Medical Sciences Teaching Laboratories, Television Section and Department of Psychiatry, School of Medicine, University of North Carol; Year: 1988; Format: Videorecording; [Chapel Hill, N.C.]: The Labs, c1988

•

Anxiety disorders workshop [sound recording] Source: [Menninger, Division of Continuing Education]; Year: 1992; Format: Sound recording; [Topeka, Kan.]: Menninger, [1992]

•

Managing anxiety disorders [videorecording] Source: produced by Gardiner-Caldwell SynerMed; Year: 1990; Format: Videorecording; [Kansas City, Mo.]: American Academy of Family Physicians, c1990

•

Office diagnosis and management of anxiety disorders [videorecording] Source: a production of the Office of Health Extension, Public Service, and Research for the University of Alabama School of Medicine, UAB; Year: 1985; Format: Videorecording; Carrboro, NC: Health Sciences Consortium, c1985

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•

Patients with anxiety disorders [electronic resource] Source: written by Susan Chaney; Year: 1985; Format: Electronic resource; Edwardsville, KS: Medi-Sim, c1985

•

Phobias and panic disorders [videorecording] Source: presented by the Warren Magnuson Clinical Center, National Institutes of Health, Office of Clinical Reports & Inquiries; a production of AVP Inc; Year: 1985; Format: Videorecording; [Los Angeles, Calif.]: Hospital Satellite Network, c1985

•

The Anxiety disorders [videorecording] Source: a production of Alvin H. Perlmutter, Inc., in association with Toby Levine Communications, Inc; Year: 1991; Format: Videorecording; [New York, N.Y.]: A.H. Perlmutter: T. Levine Communications, c1991

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CHAPTER 9. PERIODICALS AND NEWS ON ANXIETY DISORDERS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover anxiety disorders.

News Services and Press Releases One of the simplest ways of tracking press releases on anxiety 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 “anxiety 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 anxiety 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 “anxiety disorders” (or synonyms). The following was recently listed in this archive for anxiety disorders: •

Forest seeks to market new SSRI for panic disorder Source: Reuters Industry Breifing Date: May 01, 2003

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•

Generalized anxiety disorder linked with ulcers Source: Reuters Health eLine Date: December 30, 2002

•

Cognitive behavioral therapy may prevent anxiety disorders in at-risk children Source: Reuters Medical News Date: October 28, 2002

•

Lundbeck antidepressant appears effective against anxiety disorders Source: Reuters Industry Breifing Date: March 20, 2002

•

Sertraline is safe, efficacious for treatment of pediatric anxiety disorder Source: Reuters Industry Breifing Date: January 01, 2002

•

Miscarriage may cause anxiety disorder to recur Source: Reuters Health eLine Date: July 27, 2001

•

Wyeth UK markets venlafaxine for generalized anxiety disorder Source: Reuters Medical News Date: July 16, 2001

•

Sexual dysfunction often accompanies anxiety disorders Source: Reuters Medical News Date: July 16, 2001

•

Sex problems linked to anxiety disorders Source: Reuters Health eLine Date: July 13, 2001

•

Treatment with fluvoxamine an option for children with anxiety disorders Source: Reuters Industry Breifing Date: April 25, 2001

•

Antidepressant approved to treat anxiety disorder Source: Reuters Health eLine Date: April 17, 2001

•

FDA approves Paxil for generalized anxiety disorder Source: Reuters Medical News Date: April 16, 2001

•

Once-daily venlafaxine effective for generalized anxiety disorder Source: Reuters Medical News Date: April 02, 2001

•

Anxiety disorders associated with lower risk of CAD in women with chest pain Source: Reuters Medical News Date: February 28, 2001

•

Cyberonics cleared to start pilot study of vagus nerve stimulation for anxiety disorders Source: Reuters Industry Breifing Date: January 29, 2001

•

Primary care physicians in US not managing depressive, anxiety disorders well Source: Reuters Medical News Date: January 15, 2001

Periodicals and News

•

Young, heavy smokers at risk of anxiety disorders Source: Reuters Health eLine Date: November 07, 2000

•

Smoking tobacco may raise risk of anxiety disorders during early adulthood Source: Reuters Medical News Date: November 07, 2000

•

Once-a-day medication effective in anxiety disorder Source: Reuters Health eLine Date: June 21, 2000

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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 “anxiety 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 “anxiety disorders” (or synonyms). If you know the name of a company that is relevant to anxiety 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/.

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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “anxiety disorders” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “anxiety disorders” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on anxiety disorders: •

Tourette Syndrome: The Neurology of a Tic (From the Point of View of the Scientist.) Source: American Speech-Language-Hearing Association. The ASHA Leader, Vol. 7 No. 14, August 6, 2002. Contact: American Speech-Language-Hearing Association. Available from the American Speech-Language-Hearing Association. 10801 Rockville Pike, Rockville, MD 20852. Voice/TTY (800) 498-2071, available 8:30 a.m.-5:00 p.m. ET. E-mail: [email protected]. Web site: http://professional.asha.org/. Summary: The article looks at the pathology of Tourette syndrome (TS) including comorbidities: anxiety disorders, language and learning disorders, mood disorders, attention deficit disorder (ADD), and obsessive compulsive disorders (OCD), vocal and phonic tics, and coprolalia (blurting out obscenities or socially inappropriate words or phrases). The writers also discuss the negative impact that these symptoms can have on an individual with TS, in childhood and adult life, and appropriate speech treatment for TS. Selected references are included at the end of the article. This is a two-part article. (See also The Anatomy of a Tic--From the Point of View of a Person With TS.) Selected references.

•

Dry Mouth Source: Mayo Clinic Health Letter. 19(7): 6. July 2001. Contact: Available from Mayo Clinic Health Letter. 200 First Street, SW, Rochester, MN 55905. (800) 333-9037 or (303) 604-1465. E-mail: [email protected]. Summary: This newsletter article provides people who have persistent dry mouth, or xerostomia, with information on this condition. Lack of saliva is a common problem that may seem little more than a nuisance, but it should not be ignored. Saliva is important because it makes it easier to talk, helps prevent tooth decay, washes away food and plaque from the teeth, limits bacterial growth, neutralizes damaging acids, enhances the ability to taste food, and makes swallowing easier. Most cases of dry mouth are related to common nonprescription and prescription medications taken by older people. Other causes include chemotherapy drugs, radiation treatments to the head and neck, and nerve damage in the head and neck. In addition, conditions such as Sjogren's syndrome,

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endocrine disorders, Alzheimer's disease, stroke, anxiety disorders, and depression can lead to dry mouth. Diagnosis is based on the medical history, a physical examination, and tests. When the cause of dry mouth cannot be changed, saliva flow may be improved by sucking on sugar free candy, chewing sugar free gum, and taking the drug pilocarpine.

Academic Periodicals covering Anxiety Disorders Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to anxiety disorders. In addition to these sources, you can search for articles covering anxiety 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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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for anxiety disorders. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with anxiety disorders. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).

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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to anxiety disorders: Antidepressants, Monoamine Oxidase (Mao) Inhibitor •

Systemic - U.S. Brands: Marplan; Nardil; Parnate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202054.html

Antidepressants, Tricyclic •

Systemic - U.S. Brands: Anafranil; Asendin; Aventyl; Elavil; Endep; Norfranil; Norpramin; Pamelor; Sinequan; Surmontil; Tipramine; Tofranil; Tofranil-PM; Vivactil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202055.html

Benzodiazepines •

Systemic - U.S. Brands: Alprazolam Intensol; Ativan; Dalmane; Diastat; Diazepam Intensol; Dizac; Doral; Halcion; Klonopin; Librium; Lorazepam Intensol; Paxipam; ProSom; Restoril; Serax; Tranxene T-Tab; Tranxene-SD; Tranxene-SD Half Strength; Valium; Xanax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202084.html

Buspirone •

Systemic - U.S. Brands: BuSpar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202100.html

Paroxetine •

Systemic - U.S. Brands: Paxil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202717.html

Sertraline •

Systemic - U.S. Brands: Zoloft http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202651.html

Venlafaxine •

Systemic - U.S. Brands: Effexor http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202764.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

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PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute13: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

13

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

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

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

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

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

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

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.14 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:15 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

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

14

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 15 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “anxiety disorders” using the “Detailed Search” option. Go directly to the following hyperlink: 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 the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “anxiety disorders” (or synonyms) into the “For these words:” box. The following is a sample result: •

Clinical Management of the HIV - Infected Adult: A Manual for Mid - Level Clinicians Contact: University of Illinois at Chicago, Midwest AIDS Education and Training Center, 808 S Wood St M/C 779, Chicago, IL, 60612-7303, (312) 996-1373. Summary: This manual contains the protocol for the management of the HIV-infected patient. It begins with health maintenance protocols, which allow the clinician to provide a standardized database for the assessment and treatment of HIV-related problems, including acute intervention and ongoing supportive care. The HIV-specific laboratory protocols provide a guideline for monitoring patients with HIV infection which identifies other co-infections and assists in tracking disease progression. The HIVspecific assessment tool is used to help clinicians and caretakers measure the patient's ability to carry out activities of daily living. Complaint-specific protocols cover the ears, nose and sinuses, mouth and throat, fever, headache, shortness of breath, and seizures. The disease-specific protocols include cervical disease, histoplasmosis, HIV-related cardiomyopathy, oral candidiasis, kaposi's sarcoma, and many other specific diseases. Neuropsychiatric protocols offer guidelines for the treatment of major depression, generalized anxiety disorders, panic disorder, suicide, and AIDS dementia complex. The manual concludes with a comprehensive drug protocol--this includes antiretroviral therapy and common HIV medications.

•

Adolescent mental health: Summary and recommended action proposals Source: Sacramento, CA: California Commission on the Status of Women. 1994. 234 pp. Contact: Available from California Commission on the Status of Women, 1303 J Street, Suite 400, Sacramento, CA 95814-2900. Telephone: (916) 445- 3173. Available at no charge. Summary: This report provides a compilation of testimony at two hearings on adolescent mental health held by the commission in 1993, additional information provided by noted authorities in the field of adolescent medicine and mental health, and recommendations for action. Topics include an overview of women's mental health, depressing and anxiety disorders, eating disorders, emotional effects of physical and

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sexual abuse, self esteem, teen pregnancies, homelessness and runaway kids, substance abuse. Appendices include examples of programs that work, resource lists, and a bibliography.

The NLM Gateway16 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “anxiety 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 32363 455 933 94 28 33873

HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.20 Simply search by “anxiety disorders” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

16

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

17

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 18 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 19 20

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists21 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.22 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Anxiety Disorders In the following section, we will discuss databases and references which relate to the Genome Project and anxiety 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).24 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information.

21 Adapted 22

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 23 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 24 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “anxiety 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 anxiety disorders: •

Panic Disorder Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?167870

•

Panic Disorder 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607853 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

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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

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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

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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

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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

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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

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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

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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

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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 “anxiety disorders” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database25 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database26 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “anxiety 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).

25 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 26 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 anxiety 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 Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to anxiety 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 anxiety 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 “anxiety disorders”:

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Other guides Bipolar Disorder http://www.nlm.nih.gov/medlineplus/bipolardisorder.html Children's Health http://www.nlm.nih.gov/medlineplus/childrenshealth.html Epilepsy http://www.nlm.nih.gov/medlineplus/epilepsy.html Mental Health http://www.nlm.nih.gov/medlineplus/mentalhealth.html Neuromuscular Disorders http://www.nlm.nih.gov/medlineplus/neuromusculardisorders.html Obsessive-Compulsive Disorder http://www.nlm.nih.gov/medlineplus/obsessivecompulsivedisorder.html Panic Disorder http://www.nlm.nih.gov/medlineplus/panicdisorder.html Post-Traumatic Stress Disorder http://www.nlm.nih.gov/medlineplus/posttraumaticstressdisorder.html Respiratory Diseases http://www.nlm.nih.gov/medlineplus/respiratorydiseases.html

Within the health topic page dedicated to anxiety disorders, the following was listed: •

General/Overviews Answers to Your Questions About Panic Disorder Source: American Psychological Association http://www.apa.org/pubinfo/panic.html Closer Look at Panic Disorder Source: American Psychiatric Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZXHSH3DM C&sub_cat=47 Panic Attack Source: Anxiety Disorders Association of America http://www.adaa.org/AnxietyDisorderInfor/PanicDisAgor.cfm

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Treatment Anxiety Disorders Information: Guide to Treatment Source: Anxiety Disorders Association of America http://www.adaa.org/AnxietyDisorderInfor/GuidetoTre.cfm Getting Treatment for Panic Disorder Source: National Institute of Mental Health http://www.nimh.nih.gov/anxiety/getpd.cfm

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Medications Source: National Institute of Mental Health http://www.nimh.nih.gov/publicat/medicate.cfm Psychosocial Treatments Source: National Alliance for the Mentally Ill http://www.nami.org/Content/ContentGroups/Helpline1/Psychosocial_Treatme nts.htm •

Children Bedtime Panic Attacks: 'My Child Gets Hysterical Before Bedtime' Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00430 Panic Disorder in Children and Adolescents Source: American Academy of Child and Adolescent Psychiatry http://www.aacap.org/publications/factsfam/panic.htm

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From the National Institutes of Health Understanding Panic Disorder Source: National Institute of Mental Health http://www.nimh.nih.gov/anxiety/upd.cfm

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Organizations Anxiety Disorders Association of America http://www.adaa.org/ National Institute of Mental Health http://www.nimh.nih.gov/ National Mental Health Association http://www.nmha.org/

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Research Anxiety Disorders Research at the National Institute of Mental Health Source: National Institute of Mental Health http://www.nimh.nih.gov/publicat/anxresfact.cfm Panic Disorder and Depression in Parents Linked to Mental Disorders in Children Source: American Psychiatric Association http://www.medem.com/search/article_display.cfm?path=n:&mstr=/ZZZXJC3KJ HC.html&soc=APA&srch_typ=NAV_SERCH

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Statistics Numbers Count: Mental Disorders in America Source: National Institute of Mental Health http://www.nimh.nih.gov/publicat/numbers.cfm

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Teenagers All About Anxiety Source: Nemours Foundation http://kidshealth.org/teen/your_mind/mental_health/anxiety.html

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 Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on anxiety disorders. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

IBS Anxiety Profile Source: Milwaukee, WI: International Foundation for Functional Gastrointestinal Disorders. 1996. 2 p. Contact: Available from International Foundation for Functional Gastrointestinal Disorders (IFFGD). P.O. Box 170864, Milwaukee, WI 53217. (888) 964-2001 or (414) 9641799. Fax (414) 964-7176. E-mail: [email protected]. Website: www.iffgd.org. PRICE: $0.50. Summary: This fact sheet describes the impact of anxiety on people with irritable bowel syndrome (IBS). The author notes that chronic anxiety can disrupt performance and trigger a broad range of psychophysiological complaints, including IBS. Apart from depression, four types of anxiety disorders are commonly found among people with IBS (an individual may have more than one): panic disorder, phobias, obsessive-compulsive disorder, and generalized anxiety disorder (GAD). Among these disorders, GAD is the most common diagnosis for patients with IBS. The author notes the specific symptoms in the categories of motor tension, autonomic hyperactivity, and vigilance and scanning; from these symptoms, six are required for a diagnosis. Also, self-defeating patterns of thought are often found to be associated with GAD and the other anxiety disorders. These patterns of thought usually have five associated features which are especially common in people with IBS: intrusive, anticipatory, catastrophic, perfectionistic, and hidden thoughts. The fact sheet concludes with a brief discussion of treatments for IBSrelated anxiety, notably cognitive-behavioral therapy (CBT). (AA-M).

•

Fatigue Contact: National AIDS Treatment Information Project, Beth Israel Deaconess Medical Center, Beth Israel Hospital, 330 Brookline Ave Libby Bldg 317, Boston, MA, 02215, (617) 667-5520, http://www.natip.org.

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Summary: This fact sheet, for individuals with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), discusses fatigue. Fatigue is common in persons with HIV/AIDS and can be long lasting or brief, causing HIVpositive individuals to be unable to perform usual activities because of a lack of muscle strength. Medical, psychiatric, or lifestyle factors and side effects from medicines can cause fatigue. Medical causes of fatigue include viral illnesses and opportunistic diseases. Psychiatric causes of fatigue include depression and anxiety disorders. Some of the lifestyle-related causes of fatigue include overwork, insufficient sleep, excessive or inadequate exercise, poor dietary habits, and substance abuse. Drugs that may cause side effects include efavirenz, interferon, central nervous system medications, and betablocker drugs. Fatigue is evaluated through a physical examination, medical history, and laboratory testing. Fatigue is managed by identifying and addressing its underlying causes. A table is provided that identifies the common causes of fatigue in HIV-positive individuals. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “anxiety disorders” (or synonyms). The following was recently posted: •

Major depression, panic disorder and generalized anxiety disorder in adults in primary care Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 January (revised 2002 May); 55 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3350&nbr=2576&a mp;string=anxiety+AND+disorders

•

Practice guideline for the treatment of patients with panic disorder. Source: American Psychiatric Association - Medical Specialty Society; 1998 May; 86 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1429&nbr=669&am p;string=anxiety+AND+disorders Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Anxiety Disorders Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=48

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Anxiety Disorders in Children and Adolescents Summary: This is one of a series of fact sheets on the mental, emotional, and behavior disorders that can appear in childhood or adolescence. Source: SAMHSA's National Mental Health Information Center, Center for Mental Health Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5165

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Anxiety Disorders: Medication Summary: This online consumer information booklet, describes the four categories of psychotherapeutic medications based on the symptoms for which they are primarily used (antipsychotic, antimanic, Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2239

•

Anxiety Disorders: Phobias Summary: This online fact sheet provides basic information for the lay person. It discusses specific phobias and treatment options, and includes referrals for additional resources. Source: National Mental Health Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2206

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Facts About Anxiety Disorders Summary: Covers the prevalence and kinds of anxiety disorders and includes a quiz. Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6625

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Facts About Generalized Anxiety Disorders Summary: A brief fact sheet about the prevalence, causes, and treatments for generalized anxiety disorders. Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6626

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Facts About Panic Disorder Summary: This 4-page fact sheet covers the prevalence, causes, and treatments for panic disorder. Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6628

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Find a Professional Therapist Summary: The Anxiety Disorders Association of America provides a list of its members who have identified themselves as mental health providers. For ease of use, these providers are listed geographically. Source: Anxiety Disorders Association of America http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6815

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Generalized Anxiety Disorder (GAD): A Real Illness Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6563

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Mental Health Publications & Education Programs Summary: Conference proceedings, consumer publications, and public education program materials on anxiety, attention deficit hyperactivity disorder, depression, panic disorder, learning disabilities, bipolar Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=358

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Panic Disorder: A Real Illness Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6565

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When Fear Holds Sway: Panic Disorder Summary: This 2-page fact sheet describes panic disorder, research about the disorder, and treatment of the disorder. Source: National Institute of Mental Health, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6633 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 anxiety 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.

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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Associations and Anxiety Disorders The following is a list of associations that provide information on and resources relating to anxiety disorders: •

Anxiety Disorders Association of America Telephone: (240) 485-1001 Fax: (240) 485-1035 Email: [email protected] Web Site: http://www.adaa.org Background: The mission of the Anxiety Disorders Association of America (ADAA) is to promote the prevention and cure of anxiety disorders and to improve the lives of all affected individuals. ADAA offers several materials concerning anxiety disorders including a quarterly newsletter that contains clinical information and updates, news on the latest events that ADAA is sponsoring, and personal accounts from affected individuals and members who share their experiences. ADAA also sponsors a variety of events each year including 'National Anxiety Disorders Screening Day' and an annual national conference. Relevant area(s) of interest: Anxiety Disorders, Panic Disorders

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to anxiety disorders. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with anxiety disorders.

Patient Resources

231

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 anxiety 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/. Simply type in “anxiety 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 “anxiety 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 “anxiety 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 “anxiety disorders” (or a synonym) into the search box, and click “Submit Query.”

233

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.27

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

27

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

234 Anxiety Disorders

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)28: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

28

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

235

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

236 Anxiety Disorders

•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

237

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

238 Anxiety Disorders

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

239

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on anxiety disorders: •

Basic Guidelines for Anxiety Disorders Panic disorder Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000924.htm Panic disorder with agoraphobia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000923.htm

•

Signs & Symptoms for Anxiety Disorders Agitation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Blushing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003241.htm

240 Anxiety Disorders

Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Dizziness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003093.htm Facial paralysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003028.htm Faintness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Flushing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003241.htm Heartburn Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003114.htm Nausea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Numbness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003206.htm Palpitations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Shortness of breath Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Skin, clammy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003216.htm Sleep disturbances Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Sweating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003218.htm Tingling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003206.htm Trembling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003192.htm

Online Glossaries 241

•

Diagnostics and Tests for Anxiety Disorders Cocaine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003578.htm

•

Nutrition for Anxiety Disorders Caffeine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002445.htm

•

Background Topics for Anxiety Disorders Alcohol use Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001944.htm Cardiovascular Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002310.htm Central nervous system Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002311.htm Choking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000047.htm Endocrine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002351.htm Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Stimulants Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002308.htm Substance abuse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001945.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

242 Anxiety Disorders

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

243

ANXIETY 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] Aberrant: Wandering or deviating from the usual or normal course. [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] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [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]

244 Anxiety Disorders

Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [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] Adenosine Monophosphate: Adenylic acid. Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjustment Disorders: Maladaptive reactions to identifiable psychosocial stressors occurring within a short time after onset of the stressor. They are manifested by either impairment in social or occupational functioning or by symptoms (depression, anxiety, etc.) that are in excess of a normal and expected reaction to the stressor. [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 Medicine: A branch of medicine pertaining to the diagnosis and treatment of diseases occurring during the period beginning with puberty until the cessation of somatic growth. [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 Uptake Inhibitors: Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (antidepressive agents, tricyclic) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aetiology: Study of the causes of disease. [EU] 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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium

Dictionary 245

cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] 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] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] 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 Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alprostadil: A potent vasodilator agent that increases peripheral blood flow. It inhibits platelet aggregation and has many other biological effects such as bronchodilation, mediation of inflammation, etc. [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] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]

Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and

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tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid 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] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [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] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] 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] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] 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] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory

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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] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]

Anthropology: The science devoted to the comparative study of man. [NIH] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidepressive Agents: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several monoamine oxidase inhibitors are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents also appear to act through brain catecholamine systems. A third group (antidepressive agents, secondgeneration) is a diverse group of drugs including some that act specifically on serotonergic systems. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [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.

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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] 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] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Apathy: Lack of feeling or emotion; indifference. [EU] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [NIH] Appetite Regulation: Physiologic mechanisms which regulate or control the appetite and food intake. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH]

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Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] 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] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [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] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH]

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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] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; 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] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Behavioral Medicine: The interdisciplinary field concerned with the development and integration of behavioral and biomedical science, knowledge, and techniques relevant to health and illness and the application of this knowledge and these techniques to prevention, diagnosis, treatment, and rehabilitation. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Betaxolol: A cardioselective beta-1-adrenergic antagonist with no partial agonist activity. [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] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Factors: Compounds made by living organisms that contribute to or influence a phenomenon or process. They have biological or physiological activities. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH]

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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 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] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [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] Body Fluids: Liquid components of living organisms. [NIH] Body Image: Individuals' personal concept of their bodies as objects in and bound by space, independently and apart from all other objects. [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.

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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] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Brain Injuries: Acute and chronic injuries to the brain, including the cerebral hemispheres, cerebellum, and brain stem. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with diffuse axonal injury or coma, posttraumatic. Localized injuries may be associated with neurobehavioral manifestations; hemiparesis, or other focal neurologic deficits. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [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] 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] Bronchial: Pertaining to one or more bronchi. [EU] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] 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] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [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

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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 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] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotoxic: Having a poisonous or deleterious effect upon the heart. [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] 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

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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] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] 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 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 proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [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] 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]

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Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and 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] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Child Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders in children. [NIH] Chlordiazepoxide: An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawl. [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] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing

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acetylcholine or a related compound. [EU] 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] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronobiology: The study of biological systems as affected by time. Aging, biological rhythms, and cyclic phenomena are included. Statistical, computer-aided mathematical procedures are used to describe, in mathematical terminology, various biological functions over time. [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] 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]

Claudication: Limping or lameness. [EU] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [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] Clomipramine: A tricyclic antidepressant similar to imipramine that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine. [NIH]

Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gaba receptor responses. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU]

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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] 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] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive 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] Cognitive Therapy: A direct form of psychotherapy based on the interpretation of situations (cognitive structure of experiences) that determine how an individual feels and behaves. It is based on the premise that cognition, the process of acquiring knowledge and forming beliefs, is a primary determinant of mood and behavior. The therapy uses behavioral and verbal techniques to identify and correct negative thinking that is at the root of the aberrant behavior. [NIH] Colitis: Inflammation of the colon. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] 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

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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] Compulsion: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Compulsive Behavior: The behavior of performing an act persistently and repetitively without it leading to reward or pleasure. The act is usually a small, circumscribed behavior, almost ritualistic, yet not pathologically disturbing. Examples of compulsive behavior include twirling of hair, checking something constantly, not wanting pennies in change, straightening tilted pictures, etc. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken

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from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] 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] Conditioned stimulus: A situation in which one signal, or stimulus, is given just before another signal. After this happens several times, the first signal alone can cause the response that would usually need the second signal. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] 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] Constrict: Tighten; narrow. [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] Consumer Advocacy: The promotion and support of consumers' rights and interests. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

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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 by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [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] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] 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] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be

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classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Criterion: A standard by which something may be judged. [EU] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [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] 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] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] 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] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide,

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from a chemical compound. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] 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] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] 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] 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] 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.

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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] Dermatitis: Any inflammation of the skin. [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] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Dexfenfluramine: The S-isomer of fenfluramine. It is a serotonin agonist and is used as an anorectic. Unlike fenfluramine, it does not possess any catecholamine agonist activity. [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] Diagnostic trial: A research study that evaluates methods of detecting 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] Diffuse Axonal Injury: A relatively common sequela of blunt head injury, characterized by a global disruption of axons throughout the brain. Associated clinical features may include neurobehavioral manifestations; persistent vegetative state; dementia; and other disorders. [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

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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] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dipyridamole: A drug that prevents blood cell clumping and enhances the effectiveness of fluorouracil and other chemotherapeutic agents. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] 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;

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superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Double-Blind Method: A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment. [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 Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Evaluation: Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duke: A lamp which produces ultraviolet radiations for certain ophthalmologic therapy. [NIH]

Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] 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] Ego: The conscious portion of the personality structure which serves to mediate between the demands of the primitive instinctual drives, (the id), of internalized parental and social

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prohibitions or the conscience, (the superego), and of reality. [NIH] Ejaculation: The release of semen through the penis during orgasm. [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] Electroacupuncture: A form of acupuncture using low frequency electrically stimulated needles to produce analgesia and anesthesia and to treat disease. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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] 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] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emetic: An agent that causes vomiting. [EU] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] 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] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH]

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Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [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] Enhancer: Transcriptional element in the virus genome. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [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] 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] 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] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

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Estazolam: A benzodiazepine with anticonvulsant, hypnotic, and muscle relaxant properties. It has been shown in some cases to be more potent than diazepam or nitrazepam. [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] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [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] 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] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Practice: A medical specialty concerned with the provision of continuing, comprehensive primary health care for the entire family. [NIH] Family Relations: Behavioral, psychological, and social relations among various members of the nuclear family and the extended family. [NIH] 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]

Feasibility Studies: Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project. [NIH]

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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] Fenfluramine: A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] 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] 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] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [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] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above,

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and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]

Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Frostbite: Damage to tissues as the result of low environmental temperatures. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] 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] 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]

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Gene Pool: The total genetic information possessed by the reproductive members of a population of sexually reproducing organisms. [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 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 Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] 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 Assessment: Evaluation of the level of physical, physiological, or mental functioning in the older population group. [NIH] Geriatric Psychiatry: A subspecialty of psychiatry concerned with the mental health of the aged. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH]

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Glutamate: Excitatory neurotransmitter of the brain. [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] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [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] Guanine Nucleotide Exchange Factors: Protein factors that promote the exchange of GTP for GDP bound to GTP-binding proteins. [NIH] Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of the limbic system. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Habituate: Eventual cessation of response to a repeated sound. [NIH] Habituation: Decline in response of an organism to environmental or other stimuli with repeated or maintained exposure. [NIH] Hallucinogens: Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise. [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 Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts

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may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [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] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemicrania: An ache or a pain in one side of the head, as in migraine. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [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] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU]

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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] Hospice: Institution dedicated to caring for the terminally ill. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] 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] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [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] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [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

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an increase in the number of cells. [NIH] Hyperventilation: A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] 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] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] 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] Idiopathic myelofibrosis: A progressive disease in which the bone marrow is replaced by fibrous tissue and is unable to produce red blood cells; the cause is unknown. [NIH] Illusion: A false interpretation of a genuine percept. [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]

Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization

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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] 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] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantable pump: A small device installed under the skin to administer a steady dose of drugs. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] Impulse Control Disorders: Disorders whose essential features are the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the individual or to others. Individuals experience an increased sense of tension prior to the act and pleasure, gratification, or release of tension at the time of committing the act. [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] Infantile: Pertaining to an infant or to infancy. [EU] 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

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clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infuse: To pour (a liquid) into something. [EU] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [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] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [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] 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] 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] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU]

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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] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intrinsic Factor: A glycoprotein secreted by the cells of the gastric glands that is required for the absorption of vitamin B 12. Deficiency of intrinsic factor results in pernicious anemia. [NIH]

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] 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] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH]

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Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kaposi: A tumor characterized by development, essentially in men, of violet red patches and nodules on the skin. This disease also affects deeper organs. [NIH] Kava: Dried rhizome and roots of Piper methysticum, a shrub native to Oceania and known for its anti-anxiety and sedative properties. Heavy usage results in some adverse effects. It contains alkaloids, lactones, kawain, methysticin, mucilage, starch, and yangonin. Kava is also the name of the pungent beverage prepared from the plant's roots. [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] 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] 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] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laterality: Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot. [NIH] Learning Disorders: Conditions characterized by a significant discrepancy between an individual's perceived level of intellect and their ability to acquire new language and other cognitive skills. These disorders may result from organic or psychological conditions. Relatively common subtypes include dyslexia, dyscalculia, and dysgraphia. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [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] Lipid: Fat. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] 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] Locus Coeruleus: Bluish region in the superior angle of the fourth ventricle floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the pontomesencephalic central gray (griseum centrale). It is also known as nucleus pigmentosus pontis. [NIH] Lod: The lowest analyte content which, if actually present, will be detected with reasonable statistical certainty and can be identified according to the identification criteria of the method. If both accuracy and precision are constant over a concentration range. [NIH] Lod Score: The total relative probability, expressed on a logarithmic scale, that a linkage relationship exists among selected loci. Lod is an acronym for "logarithmic odds." [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH]

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Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lorazepam: An anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] 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] 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] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malingering: Simulation of symptoms of illness or injury with intent to deceive in order to obtain a goal, e.g., a claim of physical illness to avoid jury duty. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] 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] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive

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material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [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] 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]

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Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] 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] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabolization: The chemical process by which matter is broken down into simpler substances, said especially of food processed by the human body. [EU] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat, especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]

Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Miotic: 1. Pertaining to, characterized by, or producing miosis : contraction of the pupil. 2. An agent that causes the pupil to contract. 3. Meiotic: characterized by cell division. [EU] Mitral Valve: The valve between the left atrium and left ventricle of the heart. [NIH] Mitral Valve Prolapse: Abnormal protrusion of one or both of the leaflets of the mitral valve into the left atrium during systole. This may be accompanied by mitral regurgitation, systolic murmur, nonejection click, or cardiac arrhythmia. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [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

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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] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] 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] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion 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] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH]

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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 relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mutism: Inability or refusal to speak. [EU] Mycosis: Any disease caused by a fungus. [EU] Mycosis Fungoides: A chronic malignant T-cell lymphoma of the skin. In the late stages the lymph nodes and viscera are affected. [NIH] Mydriasis: Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in Adie syndrome. [NIH]

Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [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] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] 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]

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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] 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] 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] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Nervousness: Excessive excitability and irritability, with mental and physical unrest. [EU] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]

Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]

Neurobehavioral Manifestations: Signs and symptoms of higher cortical dysfunction caused by organic conditions. These include certain behavioral alterations and impairments of skills involved in the acquisition, processing, and utilization of knowledge or information. [NIH]

Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord.

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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] Neurosciences: The scientific disciplines concerned with the embryology, anatomy, physiology, biochemistry, pharmacology, etc., of the nervous sytem. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]

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] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [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] Nitrazepam: A benzodiazepine derivative used as an anticonvulsant and hypnotic. [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] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Family: A family composed of spouses and their children. [NIH]

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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] 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] Obsession: A recurrent, persistent thought, image, or impulse that is unwanted and distressing (ego-dystonic) and comes involuntarily to mind despite attempts to ignore or suppress it. Common obsessions involve thoughts of violence, contamination, and selfdoubt. [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] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] 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] 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

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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] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Orthostatic: Pertaining to or caused by standing erect. [EU] Otolaryngologist: A doctor who specializes in treating diseases of the ear, nose, and throat. Also called an ENT doctor. [NIH] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Otolith: A complex calcareous concretion in the inner ear which controls man's sense of balance and reactions to acceleration. [NIH] Otology: The branch of medicine which deals with the diagnosis and treatment of the disorders and diseases of the ear. [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] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overwork: Work strain that exceeds a person's natural physical or mental capabilities. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by

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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] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paraventricular Hypothalamic Nucleus: Nucleus in the anterior part of the hypothalamus. [NIH]

Parent-Child Relations: The interactions between parent and child. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [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] 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] 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] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penile Implantation: Surgical insertion of cylindric hydraulic devices for the treatment of

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organic impotence. [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] Pentagastrin: A synthetic polypeptide that has effects like gastrin when given parenterally. It stimulates the secretion of gastric acid, pepsin, and intrinsic factor, and has been used as a diagnostic aid. [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] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [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] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Personality Assessment: The determination and evaluation of personality attributes by interviews, observations, tests, or scales. Articles concerning personality measurement are considered to be within scope of this term. [NIH] Personality Disorders: A major deviation from normal patterns of behavior. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative

292 Anxiety Disorders

logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phentolamine: A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of Raynaud's disease and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease. [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] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously

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concentrated light rays or specific wavelengths. [NIH] Phylogeny: The relationships of groups of organisms as reflected by their evolutionary history. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [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] Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [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] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [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] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH]

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Policy Making: The decision process by which individuals, groups or institutions establish policies pertaining to plans, programs or procedures. [NIH] Polygenic Inheritance: A phenotypic outcome that is determined by more than one gene, such as a variety of physical characteristics or diseases. [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] 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] Population Control: Includes mechanisms or programs which control the numbers of individuals in a population of humans or animals. [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] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [NIH] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] 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] 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] Precipitation: The act or process of precipitating. [EU] 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

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fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] 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] Prescription drug abuse: Using two or more drugs interchangeably in an attempt to counteract the adverse effects of one with the other or to potentiate the effects of one with the other, so that an interdependent habit requiring both is formed. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Preventive Medicine: A medical specialty primarily concerned with prevention of disease and the promotion and preservation of health in the individual. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [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] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Profusion: Profusion is the number of small rounded opacities per unit area, that is, per zone. [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] 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] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Prone: Having the front portion of the body downwards. [NIH]

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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] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] 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] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [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 Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] 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]

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Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychological Theory: Principles applied to the analysis and explanation of psychological or behavioral phenomena. [NIH] 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]

Psychosexual: Pertaining to the mental aspects of sex. [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] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] 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]

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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] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [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]

Punishment: The application of an unpleasant stimulus or penalty for the purpose of eliminating or correcting undesirable behavior. [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] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of

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an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [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 Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [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] 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 blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [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] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH]

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Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] 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] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] 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] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after 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] Retrospective: Looking back at events that have already taken place. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH]

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Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] 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] 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] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [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] Sediment: A precipitate, especially one that is formed spontaneously. [EU]

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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] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] 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] 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] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [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] Serotonin Uptake Inhibitors: Compounds that specifically inhibit the reuptake of serotonin in the brain. This increases the serotonin concentration in the synaptic cleft which then activates serotonin receptors to a greater extent. These agents have been used in treatment of depression, panic disorder, obsessive-compulsive behavior, and alcoholism, as analgesics, and to treat obesity and bulimia. Many of the adrenergic uptake inhibitors also inhibit serotonin uptake; they are not included here. [NIH]

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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] 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] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

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] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [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 Problems: Situations affecting a significant number of people, that are believed to be sources of difficulty or threaten the stability of the community, and that require programs of amelioration. [NIH]

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Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [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] 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] 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 bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU]

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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] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [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]

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Strained: A stretched condition of a ligament. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [NIH] 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] 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] 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] Subcutaneous: Beneath the skin. [NIH] 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]

Substrate: A substance upon which an enzyme acts. [EU] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [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]

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Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of 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 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] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systole: Period of contraction of the heart, especially of the ventricles. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU]

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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] Terminalis: A groove on the lateral surface of the right atrium. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [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] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] 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] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] 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] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness.

Dictionary 309

[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] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tobacco Use Disorder: Tobacco used to the detriment of a person's health or social functioning. Tobacco dependence is included. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonal: Based on special tests used for a topographic diagnosis of perceptive deafness (damage of the Corti organ, peripheral or central damage, i. e. the auditive cortex). [NIH] 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] Topical: On the surface of the body. [NIH] Torture: The intentional infliction of physical or mental suffering upon an individual or individuals, including the torture of animals. [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] Tranquilizing Agents: A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the anti-anxiety agents (minor tranquilizers), antimanic agents, and the antipsychotic agents (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. [NIH]

310 Anxiety Disorders

Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [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]

Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] 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] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tryptophan Hydroxylase: An enzyme that catalyzes the hydroxylation of tryptophan to 5hydroxytryptophan in the presence of NADPH and molecular oxygen. It is important in the biosynthesis of serotonin. EC 1.14.16.4 [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [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 release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH]

Dictionary 311

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] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [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] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [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] 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] Vagal: Pertaining to the vagus nerve. [EU] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vagotomy: The interruption or removal of any part of the vagus (10th cranial) nerve. Vagotomy may be performed for research or for therapeutic purposes. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valerian: Valeriana officinale, an ancient, sedative herb of the large family Valerianaceae. The roots were formerly used to treat hysterias and other neurotic states and are presently used to treat sleep disorders. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoactive Intestinal Peptide: A highly basic, single-chain polypeptide isolated from the intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems. It is also found in several parts of the central and peripheral nervous systems and is a neurotransmitter. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is

312 Anxiety Disorders

used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] 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] 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] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] 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] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [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]

Dictionary 313

Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called 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] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] War: Hostile conflict between organized groups of people. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. [NIH]

Zygote: The fertilized ovum. [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]

315

INDEX 2 2-Propanol, 147, 243 A Abdomen, 243, 251, 278, 280, 305, 308, 311, 312 Abdominal, 63, 101, 135, 148, 243, 270, 278, 289, 290, 295 Abdominal Pain, 63, 101, 243, 270, 278 Aberrant, 243, 257 Acculturation, 14, 243 Acetone, 243 Acetylcholine, 169, 172, 243, 255 Activities of Daily Living, 216, 243 Acute myelogenous leukemia, 243 Acute myeloid leukemia, 133, 243 Acute nonlymphocytic leukemia, 243 Acyl, 162, 243 Adaptability, 243, 254 Adaptation, 243, 293 Adenine, 243, 244 Adenocarcinoma, 244, 287 Adenosine, 92, 172, 176, 244, 252, 292 Adenosine Monophosphate, 176, 244 Adjustment, 149, 191, 243, 244 Adjustment Disorders, 149, 191, 244 Adolescence, 10, 18, 19, 27, 31, 49, 51, 89, 92, 188, 194, 228, 244 Adolescent Medicine, 216, 244 Adrenal Cortex, 244, 260, 295 Adrenal Medulla, 244, 254, 267, 287 Adrenergic, 53, 163, 172, 244, 247, 248, 250, 264, 267, 292, 302, 306, 310, 313 Adrenergic Uptake Inhibitors, 244, 302 Adverse Effect, 4, 155, 196, 244, 248, 279, 295, 303 Aetiology, 106, 244 Afferent, 66, 168, 244, 295, 302 Affinity, 7, 48, 146, 150, 166, 244, 245, 249, 263, 280, 304 Agar, 244, 293 Age of Onset, 149, 245, 252, 310 Agonist, 11, 21, 52, 56, 149, 151, 163, 166, 245, 248, 250, 252, 263, 264, 287, 293, 307 Akathisia, 245, 248 Alertness, 134, 245, 252 Algorithms, 43, 245, 251 Alkaline, 245, 252, 289 Alkaloid, 245, 257, 284, 287, 290, 313

Alleles, 45, 245, 273 Allergen, 245, 263, 302 Alpha Particles, 245, 298 Alprostadil, 6, 245 Alternative medicine, 203, 245 Ambulatory Care, 181, 245 Ameliorating, 172, 245 Amenorrhea, 245, 247 Amine, 245, 273 Amino Acid Sequence, 166, 246, 247, 271 Amino Acids, 172, 246, 271, 287, 291, 294, 296 Amnesia, 160, 246 Amnestic, 151, 193, 246, 269, 282, 283 Amphetamines, 244, 246, 257 Amygdala, 8, 11, 13, 16, 36, 50, 56, 73, 97, 158, 246, 250, 280, 302 Anaesthesia, 246, 276 Anal, 54, 62, 126, 246, 269, 280 Analgesic, 168, 246, 284, 288 Analog, 112, 246, 269 Analogous, 246, 265, 310 Anaphylatoxins, 246, 258 Anatomical, 38, 66, 68, 146, 246, 249, 276, 286, 301 Anemia, 246, 278, 284 Anesthesia, 246, 247, 261, 266, 283 Animal model, 8, 11, 21, 36, 39, 46, 54, 246 Anorexia, 122, 151, 196, 246, 247, 270 Anorexia Nervosa, 122, 151, 196, 247 Antagonism, 147, 169, 247, 252 Antecedent, 79, 247 Anthropology, 28, 247 Anti-Anxiety Agents, 247, 297, 309 Antiarrhythmic, 147, 247 Antibacterial, 247, 304 Antibiotic, 247, 290, 304, 308 Antibodies, 119, 247, 272, 293 Antibody, 244, 247, 248, 257, 261, 272, 274, 276, 282, 284, 298, 302, 304 Anticoagulant, 247, 296 Anticonvulsant, 56, 247, 255, 256, 268, 281, 287 Antidepressive Agents, 244, 247, 297 Antiemetic, 247, 248 Antigen, 244, 247, 248, 258, 274, 276, 282, 302 Antigen-Antibody Complex, 248, 258

316 Anxiety Disorders

Anti-infective, 248, 278 Anti-inflammatory, 194, 248, 271 Antipsychotic, 5, 46, 147, 160, 169, 177, 191, 228, 248, 286, 309 Antiseptic, 243, 248, 254 Antiviral, 248, 277, 291 Anus, 246, 248, 252 Anxiolytic, 147, 248 Apathy, 248, 286 Aphasia, 246, 248 Apomorphine, 6, 248 Appetite Regulation, 163, 248 Applicability, 29, 248 Aqueous, 248, 250, 266 Aromatic, 146, 248, 292 Arrhythmia, 28, 247, 248, 283 Arterial, 249, 255, 260, 274, 296, 307 Arteries, 249, 251, 260, 278, 283, 285, 298 Asphyxia, 155, 249 Assay, 35, 165, 171, 249 Astringent, 249, 254 Astrocytes, 249, 284 Ataxia, 249, 274 Atrial, 249, 260, 310 Atrioventricular, 249, 260 Atrium, 249, 260, 283, 308, 310, 312 Atrophy, 249, 286 Auditory, 57, 60, 249, 282, 295, 311 Autoimmune disease, 249, 285 Autonomic, 6, 28, 44, 53, 55, 63, 66, 158, 174, 226, 243, 248, 249, 287, 291, 304, 306 Autonomic Nervous System, 28, 158, 249, 291, 304, 306 Autoradiography, 8, 249 B Bacteria, 243, 247, 249, 250, 262, 269, 283, 304, 310, 311 Bactericidal, 249, 268 Bacteriophage, 250, 293, 310 Bacteriuria, 250, 311 Basal Ganglia, 248, 249, 250, 252, 256, 275, 280 Basal Ganglia Diseases, 249, 250, 256, 275 Base, 11, 22, 34, 59, 150, 171, 243, 250, 262, 271, 279, 308 Behavior Therapy, 61, 75, 106, 136, 187, 250 Behavioral Medicine, 54, 250 Benign, 250, 252, 272, 286, 298 Benzene, 250 Benzodiazepines, 56, 72, 89, 90, 107, 154, 170, 208, 250, 252

Betaxolol, 72, 147, 149, 250 Bile, 250, 270, 280, 305 Binding Sites, 146, 250 Biochemical, 58, 134, 146, 149, 152, 159, 245, 250, 279, 302 Biological Factors, 41, 140, 250 Biological response modifier, 250, 251, 277 Biological therapy, 251, 272 Biosynthesis, 12, 38, 251, 268, 310 Biotechnology, 66, 67, 190, 203, 215, 251 Biotransformation, 251 Bipolar Disorder, 37, 46, 76, 100, 131, 147, 163, 165, 169, 175, 182, 187, 191, 224, 251 Bladder, 251, 276, 285, 286, 311 Blastocyst, 251, 259, 293 Bloating, 251, 278 Blood Coagulation, 251, 253, 308 Blood Glucose, 4, 251, 277 Blood Platelets, 251, 302 Blood pressure, 158, 251, 253, 255, 274, 275, 284, 291, 298, 304 Blood vessel, 251, 253, 255, 260, 278, 281, 291, 303, 306, 308, 311, 312 Body Fluids, 251, 304 Body Image, 37, 251, 262 Bone Marrow, 243, 250, 251, 275, 276, 281, 284, 285, 304, 305 Bowel, 63, 147, 169, 246, 251, 252, 263, 275, 278, 305 Bowel Movement, 252, 264, 275, 305 Brachytherapy, 252, 277, 298 Brain Injuries, 69, 252 Brain Neoplasms, 252, 274 Brain Stem, 252, 254 Branch, 237, 244, 252, 266, 281, 282, 287, 288, 289, 290, 297, 304, 307, 308 Breakdown, 252, 263, 270 Bromine, 161, 252 Bronchial, 252, 273 Bulimia, 58, 92, 151, 196, 252, 302 Bupropion, 11, 51, 252 Buspirone, 73, 119, 149, 153, 170, 208, 252 C Cachexia, 164, 252 Caffeine, 71, 112, 241, 252 Calcium, 17, 159, 177, 252, 253, 257, 290, 296, 303 Calcium Channels, 253, 290 Candidiasis, 216, 253 Candidosis, 253 Capsules, 134, 140, 253 Carbohydrate, 253, 301

Index 317

Carbon Dioxide, 37, 53, 78, 120, 253, 261, 269, 275, 293, 300 Carboxy, 146, 253 Carcinogenic, 250, 253, 277, 305 Carcinoma, 253, 287, 305 Cardiac, 17, 28, 44, 53, 117, 156, 247, 252, 253, 260, 262, 266, 267, 268, 283, 285, 305, 306 Cardiology, 17, 87, 149, 253 Cardiomyopathy, 216, 253 Cardiorespiratory, 253, 283 Cardioselective, 250, 253 Cardiotoxic, 176, 253 Cardiovascular, 17, 47, 53, 81, 149, 156, 164, 194, 241, 253, 302, 304, 311 Cardiovascular disease, 54, 156, 164, 253 Case report, 4, 121, 158, 192, 253, 256 Case series, 253, 256 Catechol, 98, 254 Catecholamine, 247, 254, 263, 264, 292 Catheters, 175, 254, 276, 277 Caudal, 66, 254, 263, 275, 294 Causal, 10, 40, 47, 254, 278 Cell Death, 156, 254, 285 Cell Differentiation, 254, 303 Cell Division, 249, 254, 272, 282, 283, 293, 296 Cell proliferation, 254, 303 Cell Respiration, 254, 300 Cell Survival, 254, 272 Cell Transplantation, 133, 254 Central Nervous System Diseases, 156, 254 Central Nervous System Infections, 254, 272, 274 Cerebellum, 252, 254, 269 Cerebral hemispheres, 250, 252, 254, 255 Cerebral Infarction, 255, 274 Cerebrospinal, 41, 67, 162, 255, 274 Cerebrospinal fluid, 41, 162, 255, 274 Cerebrovascular, 71, 85, 156, 250, 253, 255 Cerebrum, 254, 255 Cervical, 216, 255 Cervix, 255 Character, 71, 255, 262 Chemoreceptor, 248, 255 Chemotactic Factors, 255, 258 Chemotherapy, 139, 159, 204, 255 Chest Pain, 87, 202, 255 Child Psychiatry, 31, 55, 255 Chlordiazepoxide, 80, 88, 158, 159, 255 Chlorine, 161, 255

Cholecystokinin, 146, 148, 171, 255 Cholesterol, 250, 255, 260, 305, 307 Cholinergic, 53, 248, 255, 287, 302 Chorea, 248, 256 Choroid, 256, 300 Chromosome, 47, 149, 152, 256, 280 Chronic Disease, 37, 164, 252, 256 Chronobiology, 54, 256 Cimetidine, 169, 256 CIS, 151, 256 Citalopram, 171, 256 Claudication, 6, 256 Clinical Medicine, 256, 294 Clinical study, 140, 163, 256, 259 Clomipramine, 80, 112, 164, 256 Clonazepam, 131, 256 Clonic, 256 Cloning, 47, 251, 257 Coca, 257 Cocaine, 191, 241, 257 Cochlea, 257, 277 Cochlear, 137, 257, 309, 312 Cochlear Diseases, 257, 309 Cofactor, 257, 296, 308 Cognition, 5, 56, 176, 188, 257, 286 Cognitive behavior therapy, 61, 74, 136, 257 Cognitive restructuring, 257, 306 Cognitive Therapy, 23, 116, 137, 186, 257 Colitis, 257, 278 Combination chemotherapy, 139, 257 Comorbidity, 5, 15, 17, 27, 32, 34, 40, 58, 62, 65, 73, 75, 78, 80, 84, 92, 93, 94, 100, 101, 105, 186, 257 Complement, 27, 50, 59, 246, 257, 258, 271, 302 Complementary and alternative medicine, 115, 124, 258 Complementary medicine, 115, 258 Complete remission, 258, 300 Compulsion, 258, 313 Compulsive Behavior, 258, 302 Computational Biology, 215, 258 Computed tomography, 258, 259 Computerized axial tomography, 258, 259 Computerized tomography, 53, 258 Conception, 46, 259 Concomitant, 3, 92, 150, 169, 259 Concretion, 259, 289 Conditioned stimulus, 50, 259 Confounding, 12, 259 Confusion, 259, 264, 275, 286, 311

318 Anxiety Disorders

Congestion, 248, 259 Conjugated, 259, 261 Connective Tissue, 251, 259, 269, 270, 281, 300, 301, 307 Consciousness, 246, 247, 259, 262, 264, 305 Constipation, 176, 248, 259, 278 Constrict, 259, 285 Constriction, 6, 259, 278, 288 Consultation, 28, 34, 191, 192, 259 Consumer Advocacy, 108, 259 Consumption, 14, 20, 259, 263, 270, 289 Contamination, 259, 288 Continuum, 59, 259 Contraindications, ii, 259 Control group, 5, 17, 21, 45, 50, 55, 259, 298 Controlled clinical trial, 6, 61, 64, 259, 299 Controlled study, 51, 70, 79, 112, 116, 259 Convulsions, 56, 247, 260, 275 Coordination, 254, 260, 285 Cor, 11, 54, 67, 112, 174, 260 Coronary, 17, 51, 87, 92, 253, 260, 283, 285 Coronary heart disease, 17, 51, 92, 253, 260 Coronary Thrombosis, 260, 283, 285 Corpus, 260, 281, 291, 295, 308 Corpus Luteum, 260, 281, 295 Cortex, 16, 249, 260, 267, 268, 269, 286, 295, 309 Cortical, 12, 50, 53, 60, 118, 193, 260, 286, 295, 302 Corticosteroids, 260, 271 Corticotropin-Releasing Hormone, 11, 260 Cortisol, 25, 33, 260 Cranial, 154, 254, 260, 272, 278, 288, 291, 311, 312 Craniocerebral Trauma, 250, 260, 272, 274, 309 Criterion, 43, 261 Cues, 11, 34, 261 Curare, 261, 285 Curative, 261, 287, 308 Cutaneous, 133, 253, 261, 281 Cyclic, 164, 176, 252, 256, 261, 292, 301 Cysteine, 172, 261 Cystine, 261 Cytochrome, 147, 256, 261 Cytokines, 47, 261 Cytomegalovirus, 172, 261 Cytotoxic, 261, 298, 303 D Data Collection, 25, 34, 261

Databases, Bibliographic, 215, 261 Deamination, 261, 284 Decarboxylation, 261, 273 Decision Making, 102, 262 Decompensation, 4, 196, 262 Degenerative, 262, 284 Delirium, 6, 182, 191, 194, 248, 262 Delivery of Health Care, 262, 272 Delusions, 101, 175, 193, 262, 272, 297 Dementia, 5, 6, 29, 151, 156, 165, 181, 182, 191, 193, 194, 197, 216, 248, 262, 263, 282 Dendrites, 262, 286 Density, 8, 48, 262, 288 Dental Care, 194, 262 Dental Caries, 262, 269 Dentate Gyrus, 262, 273 Depersonalization, 148, 262, 290, 301 Depolarization, 263, 303 Derealization, 263, 290 Dermatitis, 147, 169, 263 Desensitization, 58, 118, 126, 263 Desipramine, 137, 176, 263 Detoxification, 15, 263 Deuterium, 263, 274 Developing Countries, 28, 263 Dexfenfluramine, 163, 263 Diabetes Mellitus, 3, 156, 263, 271 Diagnostic procedure, 145, 203, 263 Diagnostic trial, 4, 196, 263 Diarrhea, 176, 263, 278 Diastolic, 263, 274 Diathesis, 26, 263 Diencephalon, 254, 263, 267, 275, 295, 308 Diffuse Axonal Injury, 252, 263 Digestion, 250, 251, 263, 278, 280, 305 Digestive system, 143, 263 Dilatation, 264, 295, 311 Dilation, 264, 274, 285, 311 Dimethyl, 153, 264 Dipyridamole, 92, 264 Direct, iii, 26, 36, 43, 45, 47, 207, 256, 257, 264, 290, 299, 307 Disease Progression, 216, 264 Disinfectant, 243, 264, 268 Disorientation, 259, 262, 264 Disposition, 169, 264 Dissection, 39, 73, 264 Dissociation, 126, 244, 264 Dissociative Disorders, 12, 264 Distal, 152, 264, 266, 296 Diuresis, 252, 264 Dizziness, 69, 140, 148, 240, 264, 290, 312

Index 319

Dominance, 264, 279 Dopamine, 41, 147, 161, 169, 172, 248, 252, 257, 264, 284, 292 Dorsal, 57, 66, 264, 267, 294, 302, 305 Dorsum, 264, 265 Double-Blind Method, 6, 265 Drive, ii, vi, 8, 111, 164, 179, 181, 190, 194, 197, 265, 276 Drug Design, 48, 265 Drug Evaluation, 140, 265 Drug Interactions, 146, 169, 191, 208, 209, 265 Drug Tolerance, 265, 309 Duke, 18, 31, 36, 112, 265 Dyskinesia, 248, 256, 265 Dyslexia, 265, 279 Dysphoric, 88, 103, 163, 263, 265 Dyspnea, 262, 265, 290 Dystonia, 248, 265 E Eating Disorders, 3, 37, 48, 70, 75, 162, 164, 165, 171, 173, 191, 216, 265 Edema, 262, 265, 278 Effector, 39, 172, 243, 257, 265, 287, 292 Effector cell, 265, 287 Ego, 265, 288, 299 Ejaculation, 151, 163, 164, 266, 302 Elective, 266, 294 Electroacupuncture, 60, 266 Electrode, 158, 266 Electrolyte, 262, 266, 294, 304 Electrons, 250, 266, 278, 289, 298 Electrophysiological, 9, 36, 66, 174, 266 Electroplating, 254, 266 Embryo, 251, 254, 266, 276 Embryology, 266, 287 Emetic, 248, 266 Empiric, 46, 266 Empirical, 10, 12, 14, 23, 58, 61, 125, 156, 266 Emulsion, 249, 266, 269 Encephalitis, 173, 266, 282 Encephalitis, Viral, 266 Encephalopathy, 193, 266 Endemic, 267, 305 Endocarditis, 253, 267 Endocrine System, 267, 286 Endoscopic, 267, 283 Endotoxins, 258, 267 Enhancer, 149, 267 Entorhinal Cortex, 267, 273 Environmental Health, 121, 214, 216, 267

Enzymatic, 253, 258, 262, 267, 273 Enzyme, 12, 169, 265, 267, 283, 284, 291, 292, 296, 303, 306, 308, 310, 313 Epidemic, 267, 305 Epidemiological, 17, 37, 172, 267 Epinephrine, 244, 264, 267, 287, 311 Epithalamus, 263, 267, 280 Erectile, 6, 267, 291 Erection, 267 Erythrocytes, 246, 251, 267, 299, 302 Esophagus, 264, 267, 292, 299, 305 Estazolam, 159, 268 Estrogen, 35, 58, 268, 295, 302, 307 Estrogen Antagonists, 35, 268 Estrogen receptor, 58, 268 Ethanol, 36, 256, 268 Ethnic Groups, 37, 268 Evacuation, 259, 268 Evoke, 129, 268, 305 Excitability, 268, 286 Excitation, 170, 246, 255, 268 Exhaustion, 247, 268 Exocrine, 255, 268, 289 Exogenous, 251, 268, 296, 310 Expiration, 268, 300 External-beam radiation, 268, 298 Extracellular, 7, 172, 249, 259, 268, 304 Extraction, 21, 268 Extrapyramidal, 245, 248, 264, 268 F Facial, 44, 59, 82, 240, 268, 282, 304 Family Planning, 215, 268 Family Practice, 70, 90, 121, 268 Family Relations, 180, 198, 268 Fat, 164, 251, 260, 268, 280, 285, 300 Fatigue, 139, 226, 227, 268 Feasibility Studies, 60, 268 Feces, 259, 269, 305 Fenfluramine, 263, 269 Fibrin, 251, 269, 308 Fibrinogen, 269, 308 Fibrosis, 156, 269, 301 Fissure, 262, 269, 295 Fixation, 269, 302 Flatus, 269, 270 Fluorine, 161, 269 Fluorouracil, 264, 269 Fluoxetine, 58, 83, 98, 130, 138, 139, 163, 171, 176, 269 Fluvoxamine, 18, 19, 60, 73, 80, 83, 84, 90, 104, 139, 141, 171, 176, 202, 269 Fold, 29, 38, 56, 269

320 Anxiety Disorders

Forearm, 251, 269 Fourth Ventricle, 269, 280, 308 Frontal Lobe, 255, 270, 294 Frostbite, 270, 292 Functional magnetic resonance imaging, 53, 64, 130, 270 Fungus, 253, 270, 285 G GABA, 105, 158, 159, 177, 256, 270, 303 Gallbladder, 243, 255, 264, 270 Gamma Rays, 270, 298 Ganglia, 243, 250, 270, 286, 291, 306 Gap Junctions, 270, 307 Gas, 148, 253, 255, 269, 270, 274, 278, 287, 298, 300 Gastric, 156, 256, 270, 273, 278, 291 Gastric Acid, 256, 270, 291 Gastrin, 146, 256, 270, 274, 291 Gastroenteritis, 252, 270 Gastrointestinal, 63, 146, 151, 226, 255, 256, 267, 268, 270, 302, 304, 306, 311 Gastrointestinal tract, 151, 256, 268, 270, 302, 304 Gene, 8, 10, 38, 39, 41, 152, 171, 172, 190, 245, 251, 264, 270, 271, 293, 294, 310 Gene Expression, 8, 38, 39, 41, 270 Gene Pool, 39, 271 Generator, 158, 174, 271 Genetic Code, 271, 288 Genetic Engineering, 12, 251, 257, 271 Genetic Markers, 22, 271 Genetic Screening, 38, 271 Genetics, 8, 31, 36, 40, 41, 45, 49, 59, 82, 86, 103, 131, 149, 264, 271 Genomics, 31, 271 Genotype, 32, 271, 292 Geriatric, 30, 42, 53, 77, 84, 180, 181, 182, 193, 194, 271 Geriatric Assessment, 181, 271 Geriatric Psychiatry, 30, 42, 77, 84, 181, 182, 193, 194, 271 Gestation, 271, 291, 293 Gland, 174, 244, 271, 281, 289, 293, 301, 305, 308 Glomerular, 271, 300 Glucocorticoid, 35, 271 Glucose, 37, 196, 251, 263, 271, 275, 277, 301 Glucose Intolerance, 263, 271 Glutamate, 159, 170, 177, 272 Gonadal, 272, 305 Governing Board, 272, 294

Gp120, 272, 291 Granulocytes, 272, 303, 313 Growth factors, 172, 272 Guanine Nucleotide Exchange Factors, 177, 272 Gyrus Cinguli, 272, 280 H Habitual, 255, 272 Habituate, 60, 272 Habituation, 4, 196, 272 Hallucinogens, 272, 297 Haptens, 244, 272 Headache, 77, 140, 148, 151, 176, 216, 252, 272, 274, 275, 295 Headache Disorders, 272 Health Care Costs, 50, 272, 273 Health Expenditures, 272 Health Promotion, 181, 273 Health Services, 43, 44, 50, 107, 180, 262, 273 Health Status, 14, 273 Heart attack, 253, 273 Heartbeat, 273, 306 Heme, 261, 273 Hemicrania, 151, 272, 273 Hemiparesis, 252, 273 Hemorrhage, 261, 272, 273, 306 Hemostasis, 273, 302 Hepatic, 262, 273, 284 Hereditary, 49, 273, 284, 286 Heredity, 270, 271, 273 Heritability, 21, 40, 273 Heterogeneity, 32, 38, 146, 244, 273 Heterozygotes, 8, 264, 273 Hippocampus, 16, 48, 168, 262, 273, 280, 302, 306 Histamine, 169, 172, 246, 248, 256, 273 Histidine, 273 Homeostasis, 164, 273, 304 Homogeneous, 259, 273 Homologous, 165, 245, 273, 274, 302, 307 Hormonal, 13, 57, 164, 166, 249, 274 Hospice, 181, 274 Human Development, 27, 214, 274 Hybrid, 274 Hybridization, 55, 274 Hydrocephalus, 193, 274, 278 Hydrogen, 150, 161, 245, 250, 253, 263, 274, 284, 287, 288, 289, 291, 296 Hydrolysis, 251, 274, 292, 294, 296 Hydrophilic, 172, 274 Hydrophobic, 172, 274

Index 321

Hydroxylation, 274, 310 Hyperalgesia, 63, 274 Hypersensitivity, 245, 263, 274, 300, 302 Hypertension, 6, 149, 151, 156, 164, 253, 274, 278, 292 Hyperthermia, 47, 274 Hyperthyroidism, 88, 274 Hypertrophy, 260, 274, 310 Hyperventilation, 89, 107, 158, 159, 275 Hypnotic, 5, 56, 268, 275, 281, 283, 287 Hypochondriasis, 88, 160, 177, 275 Hypoglycaemia, 262, 275 Hypokinesia, 154, 275, 290 Hypotension, 248, 260, 275 Hypothalamic, 55, 58, 163, 164, 275 Hypothalamus, 47, 58, 249, 252, 260, 263, 275, 280, 290, 293, 302, 304, 308 Hypoxia, 262, 275 I Id, 113, 122, 225, 227, 230, 236, 238, 265, 275 Idiopathic, 120, 133, 275 Idiopathic myelofibrosis, 133, 275 Illusion, 275, 312 Imaging procedures, 140, 275, 309 Imipramine, 80, 88, 141, 154, 159, 176, 256, 275 Immune function, 57, 275 Immune response, 247, 249, 272, 275, 302, 306, 312 Immune system, 174, 251, 265, 275, 276, 285, 311, 313 Immunization, 275, 276, 295, 302 Immunodeficiency, 182, 227, 276 Immunology, 244, 276 Immunosuppressive, 271, 276 Immunotherapy, 251, 263, 276 Immunotoxin, 53, 276 Implant radiation, 276, 277, 298 Implantable pump, 158, 175, 276 Implantation, 259, 276 Impotence, 156, 164, 195, 267, 276, 290, 291, 292, 313 Impulse Control Disorders, 58, 276 In vitro, 56, 276 In vivo, 8, 48, 166, 276 Incision, 276, 278 Incontinence, 69, 274, 276 Indicative, 137, 183, 276, 290, 311 Induction, 120, 248, 276, 295 Infancy, 276 Infantile, 152, 276

Infarction, 255, 276 Inflammation, 245, 248, 257, 263, 266, 269, 270, 277, 300, 307, 311 Infuse, 158, 277 Infusion, 157, 158, 174, 175, 277 Inhalation, 37, 277, 293 Initiation, 51, 277, 310 Inner ear, 257, 277, 289 Innervation, 48, 53, 277 Inositol, 112, 124, 277, 301 Inotropic, 264, 277 Insight, 8, 89, 179, 277 Insomnia, 52, 100, 140, 154, 160, 176, 182, 277, 295 Insulator, 277, 285 Insulin, 3, 277, 310 Insulin-dependent diabetes mellitus, 3, 277 Interferon, 227, 277 Interferon-alpha, 277 Intermittent, 154, 277, 280 Internal radiation, 277, 298 Interstitial, 252, 277, 300 Intervention Studies, 49, 55, 278 Intestinal, 148, 255, 278, 311 Intestine, 146, 252, 278, 279 Intoxication, 262, 278, 313 Intracellular, 176, 252, 276, 278, 282, 294, 299, 301, 303 Intracellular Membranes, 278, 282 Intracranial Hemorrhages, 274, 278 Intracranial Hypertension, 272, 274, 278, 309 Intravenous, 277, 278 Intrinsic, 244, 278, 291 Intrinsic Factor, 278, 291 Invasive, 60, 278, 281 Involuntary, 160, 177, 250, 256, 278, 285, 299, 308 Iodine, 161, 278 Ion Channels, 36, 166, 177, 249, 278, 287, 307 Ions, 250, 253, 264, 266, 274, 278, 284, 294, 296 Irritable Bowel Syndrome, 63, 226, 278 Ischemia, 87, 156, 249, 278 Ischemic stroke, 85, 278 J Joint, 40, 60, 91, 152, 279, 307 K Kaposi, 216, 279 Kava, 91, 112, 116, 117, 119, 121, 124, 279

322 Anxiety Disorders

Kb, 214, 279 Kinetic, 279 L Labile, 257, 279 Lactation, 46, 97, 279, 289, 295 Language Disorders, 5, 279 Large Intestine, 264, 278, 279, 299, 303 Larynx, 279, 311 Latent, 10, 37, 59, 65, 279, 294 Laterality, 87, 279 Learning Disorders, 204, 279 Lectin, 279, 282 Lesion, 279, 280, 307, 311 Lethargy, 274, 279 Leukemia, 139, 279 Leukocytes, 251, 255, 261, 272, 277, 279 Library Services, 236, 279 Ligament, 279, 306 Ligands, 35, 56, 91, 165, 166, 280 Limbic, 13, 56, 66, 158, 246, 272, 280, 295 Limbic System, 56, 158, 246, 272, 280, 295 Linkage, 37, 41, 66, 271, 280 Lipid, 17, 97, 277, 280, 283, 285 Lipophilic, 56, 280 Lithium, 248, 280 Liver, 92, 147, 169, 243, 250, 256, 261, 264, 266, 269, 270, 273, 280, 284 Localization, 38, 146, 174, 280 Localized, 48, 252, 262, 269, 276, 280, 284, 293, 311 Locomotion, 166, 280, 293 Locus Coeruleus, 13, 280 Lod, 152, 280 Lod Score, 152, 280 Longitudinal study, 25, 40, 49, 280 Long-Term Care, 11, 12, 17, 47, 280 Long-Term Potentiation, 168, 280 Loop, 175, 281 Lorazepam, 133, 208, 281 Lupus, 281, 307 Lutein Cells, 281, 295 Lymph, 255, 275, 281, 285 Lymph node, 255, 275, 281, 285 Lymphatic, 277, 281, 304, 305 Lymphatic system, 281, 304, 305 Lymphoid, 247, 260, 281 Lymphoma, 133, 281, 285 M Magnetic Resonance Imaging, 133, 135, 281 Maintenance therapy, 137, 281

Malignant, 244, 252, 281, 284, 285, 286, 298, 301 Malignant tumor, 281, 284 Malingering, 4, 196, 197, 281 Malnutrition, 249, 252, 281 Mammary, 281, 307 Mania, 6, 94, 147, 169, 183, 281 Manic, 175, 248, 251, 280, 281, 297 Manic-depressive psychosis, 281, 297 Manifest, 157, 158, 164, 281 Man-made, 254, 281 Meatus, 282, 311 Medial, 16, 35, 50, 272, 282, 288, 302 Mediate, 46, 51, 55, 58, 61, 66, 264, 265, 282 Mediator, 255, 282, 302 Medical Staff, 197, 282 Medicament, 163, 173, 175, 176, 282 MEDLINE, 215, 282 Meiosis, 282, 307 Melanin, 164, 280, 282, 292, 311 Membrane, 58, 146, 165, 172, 176, 249, 253, 256, 258, 263, 268, 272, 278, 279, 282, 284, 292, 294, 300, 303, 307, 310, 313 Membrane Glycoproteins, 253, 282, 294 Membrane Proteins, 58, 282 Memory, 12, 25, 81, 87, 94, 126, 130, 134, 151, 156, 162, 168, 170, 173, 246, 262, 280, 282 Memory Disorders, 151, 162, 282 Meninges, 254, 260, 282 Menstrual Cycle, 282, 295 Menstruation, 245, 282, 295 Mental Health Services, iv, 7, 44, 72, 180, 197, 217, 228, 282 Mental Processes, 264, 283, 297 Mentors, 17, 34, 44, 54, 64, 283 Mesencephalic, 280, 283 Mesolimbic, 248, 283 Meta-Analysis, 105, 283 Metabolic disorder, 193, 283 Metabolite, 41, 251, 256, 264, 283, 295 Metabolization, 78, 283 Methionine, 264, 283 Methyltransferase, 98, 283 MI, 150, 159, 168, 174, 242, 283 Microbe, 283, 309 Microwaves, 283, 298 Midazolam, 154, 283 Migration, 14, 283 Miotic, 283, 293 Mitral Valve, 149, 283 Mitral Valve Prolapse, 149, 283

Index 323

Mobility, 193, 283 Modeling, 10, 23, 26, 56, 59, 62, 265, 283 Modification, 24, 104, 105, 117, 120, 164, 168, 194, 271, 283, 298 Molecular Structure, 284, 310 Molecule, 156, 247, 250, 258, 264, 265, 268, 272, 274, 279, 284, 288, 289, 298, 299, 303, 312 Monitor, 132, 135, 157, 284, 287 Monoamine, 41, 158, 191, 208, 247, 284, 310 Monoamine Oxidase, 158, 191, 208, 247, 284, 310 Monoclonal, 284, 298 Monophosphate, 176, 284 Morphine, 248, 284, 288 Morphology, 16, 284 Motility, 151, 284, 302 Motion Sickness, 284, 285 Motor Activity, 260, 284 Motor nerve, 284, 285, 288 Movement Disorders, 159, 177, 248, 284 Mucins, 284, 301 Mucosa, 255, 281, 284, 295, 311 Multicenter study, 42, 284 Multiple Myeloma, 133, 284 Multiple sclerosis, 165, 173, 285 Muscle relaxant, 56, 247, 268, 285 Muscle Relaxation, 16, 135, 285 Muscle tension, 148, 158, 285 Musculature, 275, 285 Mutism, 67, 285 Mycosis, 133, 285 Mycosis Fungoides, 133, 285 Mydriasis, 112, 285 Mydriatic, 264, 285, 313 Myelin, 285 Myelofibrosis, 285 Myeloma, 133, 285 Myocardial infarction, 156, 260, 283, 285 Myocardium, 283, 285 N Narcolepsy, 60, 285 Nausea, 140, 148, 176, 240, 247, 248, 270, 285, 290, 295, 311 NCI, 1, 133, 135, 138, 139, 142, 213, 256, 285 Necrosis, 255, 276, 283, 285 Neocortex, 48, 286 Neonatal, 46, 286 Neoplasm, 133, 286, 301 Neoplastic, 281, 286

Nervousness, 132, 286 Networks, 66, 286 Neural, 8, 16, 35, 45, 46, 47, 50, 51, 53, 54, 55, 60, 95, 244, 263, 284, 286, 302 Neural Pathways, 16, 286 Neuroanatomy, 52, 280, 286 Neurobehavioral Manifestations, 252, 263, 286 Neurodegenerative Diseases, 156, 250, 286 Neuroendocrine, 13, 21, 35, 43, 58, 96, 97, 286 Neuroendocrinology, 35, 286 Neurogenic, 172, 286 Neuroleptic, 151, 245, 248, 286 Neurologic, 6, 97, 176, 247, 252, 274, 286 Neuromuscular, 224, 243, 286 Neuromuscular Junction, 243, 286 Neuronal, 36, 146, 156, 253, 256, 286 Neurons, 47, 48, 50, 66, 158, 165, 176, 257, 262, 270, 285, 286, 287, 306, 307, 312 Neuropathy, 6, 156, 173, 286 Neuropeptide, 91, 164, 260, 287 Neuropharmacology, 88, 196, 287 Neurosciences, 95, 109, 118, 287 Neurosis, 275, 287, 292 Neurotic, 152, 247, 287, 311 Neurotransmitters, 36, 41, 172, 284, 287, 304 Neutrons, 245, 287, 298 Niacin, 287, 310 Nicotine, 34, 39, 51, 173, 287 Nitrazepam, 268, 287 Nitrogen, 162, 245, 269, 287, 310 Non-small cell lung cancer, 139, 287 Nonverbal Communication, 287, 297 Norepinephrine, 13, 41, 87, 244, 263, 264, 287 Nuclear, 66, 250, 266, 268, 270, 280, 282, 285, 287, 308 Nuclear Family, 268, 287 Nuclei, 66, 245, 246, 266, 267, 271, 281, 287, 288, 289, 296, 302, 312 Nucleic acid, 165, 271, 274, 287, 288 Nucleic Acid Hybridization, 274, 288 O Observational study, 91, 99, 288 Obsession, 76, 258, 288 Oculomotor, 283, 285, 288 Oculomotor Nerve, 285, 288 Odour, 248, 288 Office Visits, 100, 288 Opacity, 262, 288

324 Anxiety Disorders

Ophthalmologic, 265, 288 Opium, 284, 288, 290 Optic Chiasm, 275, 288 Optic Nerve, 288, 300 Oral Health, 191, 194, 289 Orgasm, 266, 289 Orofacial, 197, 289 Orthostatic, 87, 248, 289 Otolaryngologist, 196, 289 Otolaryngology, 66, 196, 289 Otolith, 66, 289 Otology, 196, 289 Outpatient, 15, 22, 42, 91, 102, 137, 140, 198, 289 Overdose, 7, 289 Overwork, 227, 289 Ovum, 260, 271, 289, 295, 313 Oxidation, 251, 261, 289 Oxides, 159, 289 Oxygen Consumption, 289, 300 Oxytocin, 166, 289 P Paediatric, 81, 84, 289 Palliative, 289, 308 Palsy, 193, 289, 304 Pancreas, 146, 243, 264, 277, 289, 304 Pancreatic, 255, 289 Papaverine, 6, 176, 288, 290 Paralysis, 240, 261, 273, 283, 290, 304 Paraventricular Hypothalamic Nucleus, 47, 290 Parent-Child Relations, 61, 99, 290 Paresthesias, 290 Parkinsonism, 151, 166, 248, 290 Paroxetine, 67, 106, 108, 131, 137, 150, 164, 171, 208, 290 Paroxysmal, 57, 149, 151, 272, 290 Partial remission, 290, 300 Particle, 282, 290, 310 Parturition, 290, 295 Patch, 34, 290, 310 Pathogenesis, 53, 59, 81, 182, 187, 290 Pathologic, 4, 16, 196, 253, 260, 274, 290, 300, 311 Pathophysiology, 20, 27, 36, 48, 67, 103, 112, 117, 191, 290 Patient Education, 4, 196, 226, 234, 236, 242, 290 Patient Selection, 4, 196, 290 Penicillin, 247, 290 Penile Implantation, 6, 290 Penis, 266, 291

Pentagastrin, 43, 291 Pepsin, 256, 291 Pepsin A, 256, 291 Peptide, 148, 156, 164, 174, 255, 291, 294, 296 Peptide T, 174, 291 Perception, 59, 106, 126, 262, 272, 291, 301 Pericardium, 291, 307 Perinatal, 54, 155, 291 Peripheral blood, 245, 277, 291 Peripheral Nervous System, 146, 172, 286, 289, 291, 304, 306, 311 Peripheral Vascular Disease, 291, 292 Personality Assessment, 98, 291 Personality Disorders, 12, 20, 22, 24, 25, 100, 137, 291 PH, 12, 53, 73, 291 Pharmacokinetic, 292 Pharmacologic, 8, 100, 155, 164, 246, 292, 309 Pharmacotherapy, 15, 22, 52, 76, 84, 89, 90, 100, 188, 292 Pharynx, 292, 311 Phenotype, 39, 152, 292 Phentolamine, 6, 292 Phenyl, 159, 161, 162, 167, 292 Phenylalanine, 291, 292, 311 Phobic Disorders, 5, 152, 292 Phosphodiesterase, 11, 21, 172, 292 Phospholipases, 292, 303 Phospholipids, 268, 277, 292 Phosphorus, 155, 253, 292 Phosphorylation, 165, 176, 292 Phototherapy, 292, 301 Phylogeny, 45, 293 Physical Examination, 6, 135, 181, 205, 227, 293 Physiologic, 4, 196, 245, 248, 251, 275, 282, 293, 299, 300, 310 Physiology, 16, 36, 50, 54, 57, 66, 108, 243, 253, 266, 287, 293 Pilocarpine, 205, 293 Pilot study, 26, 30, 31, 117, 139, 202, 293 Pituitary Gland, 174, 260, 293 Placenta, 293, 295 Plants, 245, 253, 257, 271, 279, 284, 287, 293, 301, 309 Plaque, 204, 293 Plasma, 13, 87, 119, 133, 148, 170, 247, 269, 271, 273, 284, 285, 293, 296, 302 Plasma cells, 247, 284, 285, 293 Plasticity, 4, 35, 36, 60, 293

Index 325

Platelet Activation, 293, 303 Platelet Aggregation, 245, 246, 293 Platinum, 281, 293 Poisoning, 248, 262, 270, 278, 285, 293 Policy Making, 180, 294 Polygenic Inheritance, 153, 294 Polymorphic, 171, 262, 294 Polymorphism, 98, 171, 294 Polypeptide, 146, 156, 165, 166, 246, 269, 274, 291, 294, 295, 296, 304, 311, 313 Population Control, 21, 294 Posterior, 246, 249, 254, 256, 264, 265, 267, 289, 294 Postsynaptic, 294, 303, 307 Post-traumatic, 26, 55, 57, 73, 151, 168, 252, 272, 284, 294 Post-traumatic stress disorder, 26, 55, 57, 73, 151, 168, 294 Postural, 4, 196, 294 Potassium, 155, 165, 294 Potassium Channels, 165, 294 Potentiate, 49, 294, 295 Potentiation, 44, 168, 280, 294, 303 Practicability, 268, 294, 310 Practice Guidelines, 217, 227, 294 Precipitation, 47, 294 Preclinical, 21, 35, 53, 294 Precursor, 80, 112, 177, 264, 265, 267, 287, 292, 294, 295, 296, 310, 311 Predisposition, 13, 40, 53, 294, 308 Prefrontal Cortex, 35, 41, 50, 294 Premenstrual, 58, 88, 103, 163, 295 Premenstrual Syndrome, 58, 295 Prenatal, 266, 271, 295 Prescription drug abuse, 140, 295 Presynaptic, 295, 307 Prevalence, 3, 14, 17, 18, 19, 22, 29, 37, 49, 53, 68, 69, 93, 99, 101, 105, 137, 152, 171, 191, 194, 195, 228, 295 Preventive Medicine, 175, 235, 295 Primary Prevention, 9, 295 Probe, 48, 295 Prodrug, 162, 295 Profusion, 6, 295 Progesterone, 58, 295, 305 Progression, 25, 38, 193, 246, 295 Progressive, 16, 193, 254, 262, 265, 272, 275, 285, 286, 293, 295, 300 Progressive disease, 275, 295 Projection, 53, 287, 288, 295 Prolactin, 166, 295 Prone, 17, 68, 295

Prophase, 296, 307 Proportional, 10, 296 Prospective study, 96, 280, 296 Protein Binding, 46, 296 Protein C, 22, 164, 172, 246, 250, 296 Protein Conformation, 246, 296 Protein Kinases, 176, 296 Protein S, 172, 190, 251, 271, 296, 308 Proteinuria, 284, 296 Proteolytic, 258, 269, 296 Prothrombin, 296, 308 Protocol, 18, 19, 25, 31, 51, 55, 65, 68, 135, 188, 189, 216, 296 Protons, 245, 274, 296, 298 Proximal, 152, 264, 295, 296, 302 Psychic, 160, 287, 296, 297, 302 Psychogenic, 6, 47, 297 Psychological Theory, 57, 297 Psychomotor, 262, 286, 297 Psychopathology, 9, 10, 12, 13, 17, 20, 22, 27, 31, 44, 49, 61, 64, 65, 102, 105, 297 Psychophysiology, 37, 40, 121, 297 Psychosexual, 54, 297 Psychosis, 16, 46, 146, 147, 169, 171, 173, 176, 182, 248, 297 Psychosomatic, 89, 103, 108, 137, 297 Psychotherapy, 4, 22, 84, 98, 116, 118, 120, 189, 196, 257, 297, 299 Psychotropic, 5, 8, 153, 173, 183, 196, 297 Psychotropic Drugs, 5, 8, 173, 297 Puberty, 244, 297 Public Health, 26, 28, 30, 35, 36, 39, 45, 55, 217, 297 Public Policy, 84, 215, 297 Public Sector, 63, 297 Publishing, 4, 6, 67, 197, 297 Pulmonary, 251, 255, 259, 260, 275, 297, 298, 300, 312 Pulmonary Artery, 251, 297, 312 Pulmonary Edema, 255, 298 Pulmonary hypertension, 260, 298 Pulmonary Ventilation, 275, 298, 300 Pulse, 174, 284, 298 Punishment, 28, 298 Q Quality of Life, 37, 43, 87, 135, 138, 139, 192, 193, 197, 298, 306 R Race, 12, 155, 283, 298 Radiation, 135, 204, 249, 268, 270, 274, 277, 281, 298, 313 Radiation therapy, 135, 268, 277, 298

326 Anxiety Disorders

Radio Waves, 135, 283, 298 Radioactive, 249, 274, 276, 277, 281, 287, 298 Radioisotope, 298, 309 Radiolabeled, 48, 298 Radiopharmaceutical, 271, 298 Radiotherapy, 252, 298 Random Allocation, 298 Randomization, 43, 138, 298 Randomized Controlled Trials, 18, 19, 299 Rape, 294, 299 Reagent, 255, 299 Reality Testing, 297, 299 Reassurance, 275, 299 Receptors, Serotonin, 299, 302 Recombinant, 12, 299, 312 Recombination, 271, 299 Rectum, 248, 252, 264, 269, 270, 276, 279, 299 Recur, 202, 299, 301 Recurrence, 251, 281, 299, 301 Red blood cells, 267, 275, 299, 301 Refer, 1, 197, 257, 264, 269, 280, 286, 287, 297, 299, 312 Reflex, 299, 311 Reflux, 92, 299 Refraction, 299, 304 Refractory, 22, 73, 133, 137, 299 Regimen, 137, 147, 169, 265, 292, 299 Regurgitation, 283, 300 Relapse, 14, 15, 34, 46, 300 Relaxant, 290, 300 Reliability, 29, 40, 58, 125, 300 Remission, 33, 138, 251, 281, 299, 300 Renal failure, 156, 262, 300 Research Design, 22, 23, 39, 50, 54, 300 Resorption, 274, 300 Respiration, 57, 253, 255, 261, 284, 300 Respiratory Physiology, 53, 107, 300 Respiratory System, 300, 311 Response rate, 140, 300 Reticular, 60, 300 Retina, 156, 256, 288, 300, 313 Retrospective, 20, 103, 300 Rheumatic Diseases, 193, 300 Rheumatism, 300 Rheumatoid, 194, 300 Rheumatoid arthritis, 194, 300 Ribose, 244, 300 Rigidity, 290, 293, 301

Risk factor, 5, 6, 17, 20, 25, 31, 33, 37, 40, 41, 44, 48, 49, 54, 59, 66, 71, 85, 192, 296, 301 Risk patient, 3, 301 S Saliva, 204, 301 Salivary, 261, 264, 301, 313 Salivary glands, 261, 264, 301 Saponins, 301, 305 Sarcoma, 216, 301 Schizoid, 301, 313 Schizotypal Personality Disorder, 262, 301, 313 Sclerosis, 155, 165, 285, 301 Screening, 12, 30, 43, 49, 59, 68, 104, 125, 132, 165, 197, 230, 256, 271, 301, 311 Seasonal Affective Disorder, 151, 166, 301 Second Messenger Systems, 287, 301 Secretion, 151, 166, 174, 256, 273, 277, 279, 284, 291, 301, 302 Secretory, 301, 307 Sedative, 56, 255, 275, 279, 281, 283, 301, 311 Sediment, 301, 311 Seizures, 95, 134, 216, 256, 262, 290, 302, 305 Selective estrogen receptor modulator, 302, 307 Self Care, 191, 197, 243, 302 Sella, 265, 293, 302 Semen, 266, 302 Sensibility, 246, 274, 302 Sensitization, 13, 302 Sensor, 157, 175, 302 Septal, 280, 302 Septal Nuclei, 280, 302 Septic, 156, 302 Sequence Homology, 291, 302 Sequencing, 23, 302 Serotonin Uptake Inhibitors, 80, 302 Sertraline, 65, 149, 151, 164, 171, 202, 208, 303 Serum, 46, 97, 246, 257, 303 Sex Characteristics, 244, 297, 303 Shock, 11, 156, 303, 310 Signal Transduction, 9, 35, 58, 164, 172, 277, 303 Signs and Symptoms, 147, 169, 179, 191, 300, 303 Skeletal, 165, 261, 284, 303 Skeleton, 279, 303 Skull, 261, 303, 308

Index 327

Small cell lung cancer, 303 Small intestine, 274, 278, 303, 312 Smooth muscle, 246, 252, 273, 284, 290, 303, 306 Social Environment, 298, 303 Social Problems, 179, 303 Social Support, 304, 306 Sodium, 154, 304 Solid tumor, 135, 304 Solitary Nucleus, 249, 304 Solvent, 243, 250, 268, 304 Soma, 304 Somatic, 42, 112, 121, 148, 154, 244, 280, 282, 291, 295, 304, 311 Somatostatin, 165, 304 Spastic, 278, 304 Spatial disorientation, 264, 304 Specialist, 36, 191, 231, 264, 304 Species, 8, 11, 254, 261, 267, 270, 274, 282, 283, 284, 298, 302, 304, 306, 310, 311, 312, 313 Specificity, 23, 36, 48, 62, 74, 104, 244, 253, 304 Spectrum, 8, 52, 174, 283, 298, 304 Sperm, 256, 305 Spinal cord, 249, 252, 254, 255, 282, 286, 291, 299, 305, 306 Spinal Nerves, 291, 305 Spleen, 261, 281, 305 Sporadic, 152, 286, 305 Squamous, 287, 305 Squamous cell carcinoma, 287, 305 Stabilization, 15, 305 Stabilizer, 69, 305 Statistically significant, 60, 195, 305 Status Epilepticus, 155, 305 Stem cell transplantation, 133, 305 Stem Cells, 305 Steroid, 46, 260, 301, 305 Stimulant, 139, 252, 273, 305 Stimulus, 13, 50, 60, 259, 265, 266, 268, 277, 278, 290, 292, 298, 299, 305, 308 Stomach, 243, 264, 267, 270, 274, 285, 291, 292, 299, 303, 305 Stool, 276, 278, 279, 305 Strained, 180, 306 Stress management, 135, 306 Stria, 11, 13, 35, 302, 306 Striatum, 48, 306 Stroke, 143, 155, 156, 165, 205, 214, 253, 278, 306 Subacute, 276, 306

Subarachnoid, 270, 272, 278, 306 Subclinical, 191, 276, 302, 306 Subcutaneous, 164, 265, 306 Subiculum, 273, 306 Subspecies, 304, 306 Substance P, 283, 301, 306 Substrate, 21, 306, 310 Sudden cardiac death, 54, 306 Support group, 108, 198, 306 Supportive care, 216, 306 Suppression, 50, 57, 173, 306 Sympathetic Nervous System, 249, 306 Sympathomimetic, 264, 267, 287, 306, 310 Symptomatic, 18, 19, 247, 255, 307 Symptomatic treatment, 247, 255, 307 Symptomatology, 43, 187, 307 Synapses, 38, 280, 287, 307 Synapsis, 307 Synaptic, 35, 36, 168, 169, 280, 287, 302, 303, 307 Synaptic Transmission, 36, 287, 307 Synaptic Vesicles, 307 Synergistic, 295, 307, 308 Systemic, 159, 180, 191, 193, 208, 251, 253, 262, 267, 277, 278, 298, 307, 310 Systemic lupus erythematosus, 194, 307 Systole, 283, 307 Systolic, 274, 283, 307 T Tachycardia, 158, 307 Tamoxifen, 169, 302, 307 Tardive, 151, 248, 256, 307 Temperament, 9, 41, 59, 135, 136, 308 Temporal, 12, 57, 95, 246, 272, 273, 282, 308 Temporal Lobe, 95, 246, 308 Terminalis, 11, 13, 35, 302, 308 Tetracycline, 12, 308 Thalamus, 48, 252, 263, 267, 280, 295, 308 Therapeutics, 58, 72, 91, 209, 284, 308 Third Ventricle, 267, 275, 308 Thorax, 243, 308, 311 Threonine, 291, 308 Threshold, 196, 268, 274, 308 Thrombin, 146, 172, 269, 293, 296, 308 Thrombomodulin, 296, 308 Thrombosis, 156, 296, 306, 308 Thrombus, 260, 276, 278, 293, 308 Thyroid, 274, 278, 308, 311 Thyroid Gland, 274, 308 Tic, 147, 169, 204, 308 Tidal Volume, 57, 275, 308

328 Anxiety Disorders

Time Management, 306, 308 Tin, 148, 159, 240, 293, 309 Tinnitus, 192, 309, 312 Tobacco Use Disorder, 34, 309 Tolerance, 148, 159, 176, 243, 256, 271, 309 Tomography, 17, 52, 53, 73, 309 Tonal, 75, 309 Tonic, 256, 309 Topical, 249, 268, 309 Torture, 14, 309 Toxic, iv, 193, 194, 250, 261, 276, 287, 309 Toxicity, 133, 136, 265, 309 Toxicokinetics, 309 Toxicology, 38, 216, 309 Toxins, 247, 253, 266, 267, 276, 309 Trace element, 155, 269, 309 Tracer, 48, 309 Tranquilizing Agents, 297, 309 Transcription Factors, 176, 310 Transdermal, 34, 310 Transduction, 172, 303, 310 Transfection, 251, 310 Transgenes, 9, 310 Translational, 45, 63, 310 Transmitter, 243, 249, 264, 278, 282, 287, 307, 310 Trauma, 14, 57, 103, 126, 155, 156, 160, 165, 173, 183, 252, 262, 285, 310 Treatment Outcome, 15, 16, 22, 75, 82, 105, 136, 310 Tremor, 283, 290, 310 Tricuspid Atresia, 260, 310 Tricyclic, 4, 20, 147, 158, 169, 176, 191, 208, 244, 247, 256, 263, 275, 310 Trigger zone, 248, 310 Tryptophan, 12, 302, 310 Tryptophan Hydroxylase, 12, 310 Tuberculosis, 259, 281, 310 Type 2 diabetes, 68, 310 Tyramine, 284, 310 Tyrosine, 13, 264, 311 U Ulcer, 156, 311 Unconditioned, 50, 311 Unconscious, 275, 311 Uremia, 300, 311 Urethra, 291, 311 Urinalysis, 132, 311 Urinary, 69, 162, 250, 274, 276, 311 Urine, 135, 250, 251, 264, 276, 296, 311 Uterine Contraction, 289, 311 Uterus, 255, 260, 282, 295, 311

V Vaccine, 296, 311 Vagal, 44, 117, 311 Vagina, 253, 255, 282, 311 Vaginitis, 253, 311 Vagotomy, 53, 311 Vagus Nerve, 161, 202, 304, 311 Valerian, 117, 311 Vascular, 6, 151, 165, 166, 173, 181, 193, 256, 272, 276, 277, 293, 308, 311 Vasoactive, 156, 311 Vasoactive Intestinal Peptide, 156, 311 Vasodilation, 290, 311 Vasodilator, 245, 264, 273, 290, 312 Vector, 310, 312 Vein, 278, 287, 312 Venlafaxine, 15, 134, 140, 202, 208, 312 Venous, 255, 262, 296, 310, 312 Ventricle, 246, 249, 260, 273, 283, 297, 298, 307, 310, 312 Ventricular, 260, 274, 310, 312 Vertigo, 4, 196, 312 Vestibular, 4, 66, 137, 141, 196, 312 Vestibule, 257, 277, 312 Vestibulocochlear Nerve, 309, 312 Vestibulocochlear Nerve Diseases, 309, 312 Veterinary Medicine, 215, 312 Villi, 274, 312 Viral, 173, 227, 266, 310, 312 Virulence, 309, 312 Virus, 182, 227, 250, 254, 267, 271, 272, 277, 293, 310, 312 Viscera, 285, 304, 312, 313 Visceral, 53, 63, 249, 280, 311, 312, 313 Visceral Afferents, 249, 311, 313 Vitamin A, 277, 313 Vitreous Body, 300, 313 Vitro, 313 Vivo, 8, 35, 48, 313 Volition, 172, 278, 313 W Wakefulness, 52, 172, 262, 313 War, 294, 313 Weight Gain, 106, 301, 313 White blood cell, 247, 279, 281, 285, 293, 313 Withdrawal, 26, 147, 262, 292, 313 X Xenograft, 246, 313 Xerostomia, 194, 204, 313 X-ray, 258, 259, 270, 282, 287, 298, 305, 313

Index 329

Y Yeasts, 253, 270, 292, 313 Yohimbine, 6, 110, 313

Z Zygote, 259, 313 Zymogen, 296, 313

330 Anxiety Disorders

Index 331

332 Anxiety Disorders