Molecular neurobiology for the clinician

271 Pages·2003·3.616 MB·English

by  Dennis S Charney

Molecular Neurobiology
for the Clinician
Review of Psychiatry Series
John M. Oldham, M.D., M.S.
Michelle B. Riba, M.D., M.S.
Series Editors
Molecular Neurobiology
for the Clinician
EDITED BY
Dennis S. Charney, M.D.
No. 3
Washington, DC
London, England
Note: The authors have worked to ensure that all information in this book is
accurate at the time of publication and consistent with general psychiatric and
medical standards, and that information concerning drug dosages, schedules,
and routes of administration is accurate at the time of publication and consistent
with standards set by the U. S. Food and Drug Administration and the general
medical community. As medical research and practice continue to advance,
however, therapeutic standards may change. Moreover, specific situations may
require a specific therapeutic response not included in this book. For these reasons
and because human and mechanical errors sometimes occur, we recommend
that readers follow the advice of physicians directly involved in their care or the
care of a member of their family.
Books published by American Psychiatric Publishing, Inc., represent the views
and opinions of the individual authors and do not necessarily represent the
policies and opinions of APPI or the American Psychiatric Association.
Copyright © 2003 American Psychiatric Publishing, Inc.
ALL RIGHTS RESERVED
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The correct citation for this book is
Charney DS (editor): Molecular Neurobiology for the Clinician (Review of
Psychiatry Series, Volume 22, Number 3; Oldham JM and Riba MB, series
editors). Washington, DC, American Psychiatric Publishing, 2003
Library of Congress Cataloging-in-Publication Data
Molecular neurobiology for the clinician / edited by Dennis S. Charney
p. ; cm.
Includes bibliographical references and index.
ISBN 1-58562-113-7 (alk. paper)
1. Neurobehavioral disorders—Molecular aspects. 2. Molecular
neurobiology. 3. Biological psychiatry. I. Charney, Dennis S. II. Review of
psychiatry series ; v. 22, 3.
[DNLM: 1. Biological Psychiatry. 2. Mental Disorders. 3. Neurobiology.
WM 102 M718 2003]
RC455.4.B5M676 2003
616.89—dc21
2003043664
British Library Cataloguing in Publication Data
A CIP record is available from the British Library.
Contents
Contributors vii
Introduction to the Review of Psychiatry Series ix
John M. Oldham, M.D., M.S., and
Michelle B. Riba, M.D., M.S., Series Editors
Preface xiii
Dennis S. Charney, M.D.
Chapter 1
Molecular Neurobiology of Childhood- and
Adolescent-Onset Psychiatric Disorders 1
Jeremy Veenstra-VanderWeele, M.D., and
Edwin H. Cook Jr., M.D.
Chromosomal and Relatively SimpleGeneticDisorders 3
Complex Disorders 8
Complex Genetic Disorders With Variable-Onset
PsychiatricPhenotypes 34
Summary 39
References 41
Chapter 2
Molecular Genetics: A Role in Diagnosis and
Treatment of Psychiatric Disorders? 63
Francis J. McMahon, M.D.
Genetic Basis of Major Mental Illness 63
Common Alleles for Common Diseases 64
The Common Disease–Common VariantHypothesis 67
Translating Genetic Findings IntoClinicalPractice 68
Specific Applications of Genetic Findings 69
Genetic Attributable Risk 72
Conclusion: The Psychiatrist as
InterpreterofGeneticFindings 73
References 73
Chapter 3
Molecular Neurobiology and Schizophrenia:
Implications for Etiology and Treatment 75
Andrew R. Gilbert, M.D., David W. Volk, Ph.D., and
David A. Lewis, M.D.
Etiological Factors and Schizophrenia 76
Genetic Variation and Schizophrenia 81
Molecular Systems and Schizophrenia: Molecular
Alterations in the Context of Neural Circuitry 87
Implications for Understanding the
Etiopathogenesis of Schizophrenia 98
References 100
Chapter 4
Molecular Mechanisms of Drug Addiction 107
Eric J. Nestler, M.D., Ph.D.
Role of CREB in Drug Addiction 108
(cid:1)
Role of FosB in Drug Addiction 113
Conclusion 117
References 118
Chapter 5
Cellular Neurobiology of Severe Mood and
AnxietyDisorders: Implications for
Development of NovelTherapeutics 123
Todd D. Gould, M.D., Neil A. Gray, B.A., and
Husseini K. Manji, M.D., F.R.C.P.C.
Signaling Networks: 126
Neurobiology of Mood Disorders 127
Neurobiology of Anxiety Disorders 160
Conclusion 175
References 178
Appendix 1: Knockout Mouse Studies That Have
Been Used to Test Anxiety-Like Behaviors 201
Appendix 2: Potential Targets for the Development of
New Treatments for Mood and Anxiety Disorders 211
Index 229
Contributors
Dennis S. Charney, M.D.
Chief, Mood and Anxiety Disorders Program; Chief, Experimental
Therapeutics and Pathophysiology Branch, National Institute of Mental
Health, Rockville, Maryland
Edwin H. Cook Jr., M.D.
Professor, Departments of Psychiatry, Pediatrics, and Human Genetics,
University of Chicago, Chicago, Illinois
Andrew R. Gilbert, M.D.
Resident in Psychiatry, Department of Psychiatry, University of Pitts-
burgh School of Medicine, Pittsburgh, Pennsylvania
Todd D. Gould, M.D.
Postdoctoral Fellow, Laboratory of Molecular Pathophysiology, Mood
and Anxiety Disorders Program, National Institute of Mental Health,
Bethesda, Maryland
Neil A. Gray, B.A.
Predoctoral Fellow, Laboratory of Molecular Pathophysiology, Mood
and Anxiety Disorders Program, National Institute of Mental Health,
Bethesda, Maryland
David A. Lewis, M.D.
Professor, Departments of Psychiatry and Neuroscience, University of
Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Husseini K. Manji, M.D., F.R.C.P.C.
Chief, Laboratory of Molecular Pathophysiology, Mood and Anxiety
Disorders Program, National Institute of Mental Health, Bethesda,
Maryland
Francis J. McMahon, M.D.
Chief, Genetic Basis of Mood and Anxiety Disorders, Mood and Anxi-
ety Disorders Program, National Institute of Mental Health, Bethesda,
Maryland
Contributors vii
Eric J. Nestler, M.D., Ph.D.
Professor and Chairman, Department of Psychiatry and Center for
Basic Neuroscience, The University of Texas Southwestern Medical
Center, Dallas, Texas
John M. Oldham, M.D., M.S.
Professor and Chair, Department of Psychiatry and Behavioral Sciences,
Medical University of South Carolina, Charleston, South Carolina
Michelle B. Riba, M.D., M.S.
Clinical Professor and Associate Chair for Education and Academic
Affairs, Department of Psychiatry, University of Michigan Medical
School, Ann Arbor, Michigan
Jeremy Veenstra-VanderWeele, M.D.
Department of Psychiatry, University of Chicago, Chicago, Illinois
David W. Volk, Ph.D.
Department of Neuroscience, University of Pittsburgh School of Medi-
cine, Pittsburgh, Pennsylvania
viii MOLECULAR NEUROBIOLOGYFORTHE CLINICIAN
Introduction to the Review
of Psychiatry Series
John M. Oldham, M.D., M.S.
Michelle B. Riba, M.D., M.S., Series Editors
2003 REVIEWOF PSYCHIATRY SERIES TITLES
• Molecular Neurobiology for the Clinician
EDITEDBY DENNIS S. CHARNEY, M.D.
• Standardized Evaluation in Clinical Practice
EDITEDBY MICHAEL B. FIRST, M.D.
• Trauma and Disaster Responses and Management
EDITEDBY ROBERT J. URSANO, M.D., AND
ANN E. NORWOOD, M.D.
• Geriatric Psychiatry
EDITEDBY ALAN M. MELLOW, M.D., PH.D.
A
s our world becomes increasingly complex, we are learning
more and living longer, yet we are presented with ever more com-
plicated biological and psychosocial challenges. Packing into our
heads all of the new things to know is a daunting task indeed.
Keeping up with our children, all of whom learn to use computers
and how to surf the Internet almost before they learn English, is
even more challenging, but there is an excitement that accompa-
nies these new languages that is sometimes almost breathtaking.
The explosion of knowledge in the field of molecular neuro-
biology charges ahead at breakneck speed, so that we have truly
arrived at the technological doorway that is beginning to reveal
the basic molecular and genetic fault lines of complex psychiatric
diseases. In Molecular Neurobiology for the Clinician, edited by Dr.
Charney, Dr. McMahon (Chapter 2) outlines a number of genetic
discoveries that have the potential to affect our clinical practice
inimportant ways, such as validating diagnostic systems and
Introduction to the Review of Psychiatry Series ix