NEUROBIOLOGY OF MENTAL ILLNESS This page intentionally left blank NEUROBIOLOGY OF MENTAL ILLNESS FOURTH EDITION EDITED BY Dennis S. Charney, MD Pamela Sklar, MD, PhD ANNE AND JOEL EHRENKRANZ, DEAN, PROFESSOR, DEPARTMENTS OF PSYCHIATRY, ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI NEUROSCIENCE, AND GENETICS AND GENOMIC EXECUTIVE VICE PRESIDENT FOR ACADEMIC AFFAIRS, SCIENCES THE MOUNT SINAI MEDICAL CENTER CHIEF, DIVISION OF PSYCHIATRIC GENOMICS PROFESSOR, DEPARTMENTS OF PSYCHIATRY, ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI NEUROSCIENCE, AND NEW YORK, NY PHARMACOLOGY & SYSTEMS THERAPEUTICS NEW YORK, NY Joseph D. Buxbaum, PhD Eric J. Nestler, MD, PhD G. HAROLD AND LEILA Y. MATHERS PROFESSOR, NASH FAMILY PROFESSOR, DEPARTMENTS OF PSYCHIATRY, NEUROSCIENCE, AND DEPARTMENTS OF NEUROSCIENCE, PSYCHIATRY, GENETICS AND GENOMIC SCIENCES AND PHARMACOLOGY & SYSTEMS THERAPEUTICS CHIEF, DIVISION OF NEURODEVELOPMENTAL CHAIR, DEPARTMENT OF NEUROSCIENCE DISORDERS DIRECTOR, THE FRIEDMAN BRAIN INSTITUTE DIRECTOR, SEAVER AUTISM CENTER ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI NEW YORK, NY NEW YORK, NY SECTION EDITORS Eric J. Nestler, MD, PhD Antonello Bonci , MD Karl Deisseroth, MD, PhD Nora D. Volkow, MD Pamela Sklar, MD, PhD David M. Holtzman, MD Helen S. Mayberg, MD Joseph D. Buxbaum, PhD Kerry J. Ressler, MD, PhD Dennis S. Charney, MD 1 3 Oxford University Press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide. Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne Mexico City Nairobi New Delhi Shanghai Taipei Toronto With offi ces in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan Poland Portugal Singapore South Korea Switzerland Th ailand Turkey Ukraine Vietnam Oxford is a registered trademark of Oxford University Press in the UK and certain other countries. Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016 © Oxford University Press 2013 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Oxford University Press, or as expressly permitted by law, by license, or under terms agreed with the appropriate reproduction rights organization. Inquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, at the address above. You must not circulate this work in any other form and you must impose this same condition on any acquirer. Library of Congress Cataloging-in-Publication Data Neurobiology of mental illness / edited by Dennis S. Charney . . . [et al.]. — 4th ed. p. ; cm. Includes bibliographical references and index. ISBN 978–0–19–993495–9 (alk. paper) I. Charney, Dennis S. [DNLM: 1. Mental Disorders—etiology. 2. Mental Disorders—physiopathology. 3. Mental Disorders—therapy. 4. Neurobiology. WM 140] 616.8—dc23 2012538316 Th is material is not intended to be, and should not be considered, a substitute for medical or other professional advice. Treatment for the conditions described in this material is highly dependent on the individual circumstances. And, while this material is designed to off er accurate information with respect to the subject matter covered and to be current as of the time it was written, research and knowledge about medical and health issues is constantly evolving and dose schedules for medications are being revised continually, with new side eff ects recognized and accounted for regularly. Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations. Th e publisher and the authors make no representations or warranties to readers, express or implied, as to the accuracy or completeness of this material. Without limiting the foregoing, the publisher and the authors make no representations or warranties as to the accuracy or effi cacy of the drug dosages mentioned in the material. Th e authors and the publisher do not accept, and expressly disclaim, any responsibility for any liability, loss, or risk that may be claimed or incurred as a consequence of the use and/or application of any of the contents of this material. 9 8 7 6 5 4 3 2 1 Printed in the United States of America on acid-free paper CONTENTS Preface i x 10. OPTOGENETIC TECHNOLOGIES FOR PSYCHIATRIC DISEASE RESEARCH: CURRENT STATUS Contributors xi AND CHALLENGES 1 38 Lief E. Fenno and Karl Deisseroth SECTION I 11. BLOOD–BRAIN BARRIER OPENING AND DRUG DELIVERY USING FOCUSED ULTRASOUND INTRODUCTION TO BASIC AND MICROBUBBLES 1 48 NEUROSCIENCE 1 Elisa E. Konofagou Eric J. Nestler 12. GENETIC METHODOLOGIES AND APPLICATIONS 1 60 1. OVERVIEW OF BRAIN DEVELOPMENT 3 Shaun M. Purcell John L. R. Rubenstein 13. THE BRAIN AND ITS EPIGENOME 1 72 2. NEUROCHEMICAL SYSTEMS IN THE Amanda C. Mitchell, Yan Jiang, Cyril J. Peter, CENTRAL NERVOUS SYSTEM 1 2 Ki A. Goosens, and Schahram Akbarian Ariel Y. Deutch and Robert H. Roth 14. NETWORK METHODS FOR ELUCIDATING THE COMPLEXITY OF COMMON 3. PRINCIPLES OF ELECTROPHYSIOLOGY 2 7 HUMAN DISEASES 183 Evelyn K. Lambe Eric E. Schadt 4. PRINCIPLES OF SIGNAL TRANSDUCTION 3 9 15. BRAIN IMAGING METHODOLOGIES 1 99 Jean-Antoine Girault and Paul Greengard Hanzhang Lu, Yihong Yang, and Peiying Liu 5. SYNAPTIC AND NEURAL PLASTICITY 6 4 16. IMAGE-GUIDED BRAIN STIMULATION 2 12 Sa ï d Kourrich and Antonello Bonci Mark S. George, Joseph J. Taylor, and Jaimie M. Henderson 6. PRINCIPLES OF MOLECULAR BIOLOGY 7 6 Steven E. Hyman and Eric J. Nestler 7. EPIGENETICS OF PSYCHIATRIC DISEASES 8 8 SECTION III Bryan E. McGill and Huda Y. Zoghbi PSYCHOTIC DISORDERS 221 Pamela Sklar SECTION II NEW METHODS AND NEW TECHNOLOGIES 17. DIAGNOSIS OF THE PSYCHOSES 2 23 FOR PRECLINICAL AND CLINICAL Lianne Morris Smith, Julie W. Messinger, and Dolores Malaspina NEUROBIOLOGY 107 Karl Deisseroth 18. GENETICS OF SCHIZOPHRENIA AND BIPOLAR DISORDER 2 32 8. TRANSGENIC TOOLS AND ANIMAL Pamela Sklar MODELS OF MENTAL ILLNESS 1 09 19. GENOMIC SYNDROMES IN SCHIZOPHRENIA: Lisa M. Monteggia, William A. Carlezon, Jr., OVERLAPPING PHENOTYPES 2 47 and Ralph J. DiLeone George Kirov, Michael C. O’Donovan, 9. APPLICATION OF STEM CELLS TO UNDERSTANDING and Michael J. Owen PSYCHIATRIC DISORDERS 1 23 20. NEUROIMAGING OF PSYCHOTIC DISORDERS 2 56 Kimberly M. Christian, Hongjun Song, and Guo-li Ming Stephan Heckers, Neil Woodward, and Dost Öngür CONTENTS | v 21. COGNITIVE AND MOTIVATIONAL NEUROSCIENCE 36. GONADAL STEROIDS AND MOOD DISORDERS 4 83 OF PSYCHOTIC DISORDERS 2 69 David R. Rubinow, Peter J. Schmidt, Alan Anticevic, Erin C. Dowd, and Deanna M. Barch and Claire D. Craft 22. MOUSE MODELS OF SCHIZOPHRENIA 37. DEPRESSION AND MEDICAL ILLNESS 4 96 AND BIPOLAR DISORDER 2 87 Tami D. Benton, Joshua Blume, Paul Crits-Christoph, Mikhail V. Pletnikov and Christopher A. Ross Benoit Dubé, and Dwight L. Evans 23. CORTICAL GABA NEURONS IN SCHIZOPHRENIA 3 01 38. TREATMENTS FOR DEPRESSION 5 08 Allison A. Curley and David A. Lewis Dan V. Iosifescu, James W. Murrough, and Dennis S. Charney 24. SYNAPTIC DISEASE IN PSYCHIATRY 3 11 Seth G. N. Grant 25. NEURODEVELOPMENT AND SCHIZOPHRENIA 3 27 SECTION V Ester J. Kwon, Takahiro Soda, and Li-Huei Tsai ANXIETY DISORDERS 527 Kerry J. Ressler 26. NEUROBIOLOGY OF MENTAL ILLNESS PSYCHOSIS PRONENESS 3 38 39. DIAGNOSIS OF ANXIETY DISORDERS 5 29 Raquel E. Gur Meghan E. Keough, Murray B. Stein, and Peter P. Roy-Byrne 27. PSYCHOTIC DISORDERS: NEUROCHEMISTRY AND PHARMACOTHERAPY 3 46 40. GENETICS OF ANXIETY DISORDERS 5 37 Carol A. Tamminga and Elena I. Ivleva Javier A. Perez, Takeshi Otowa, Roxann Roberson-Nay, and John M. Hettema 28. THE NEUROBIOLOGY OF BIPOLAR DISORDER 3 55 Katherine E. Burdick , Stephen J. Haggarty, 41. NEUROBIOLOGY OF FEAR AND ANXIETY: and Roy Perlis CONTRIBUTIONS OF ANIMAL MODELS TO CURRENT UNDERSTANDING 5 49 Christopher K. Cain, Gregory M. Sullivan, and Joseph E. LeDoux SECTION IV MOOD DISORDERS 365 42. DIFFERENTIAL ROLES OF GABA RECEPTORS IN ANXIETY 567 Helen S. Mayberg Hanns M ö hler 29. THE DIAGNOSIS OF MOOD DISORDERS 3 67 43. PREFRONTAL CORTEX REGULATION Jan Fawcett and Brant Hager OF EMOTION AND ANXIETY 5 80 Bronwyn M. Graham and Mohammed R. Milad 30. GENETICS OF DEPRESSION 3 96 Douglas F. Levinson 44. DEVELOPMENTAL COMPONENTS OF FEAR AND ANXIETY IN ANIMAL MODELS 5 93 31. ANIMAL MODELS OF MOOD DISORDERS 4 11 Siobhan S. Pattwell, Anne-Marie Mouly, Georgia E. Hodes and Scott J. Russo Regina M. Sullivan, and Francis S. Lee 32. MOLECULAR AND CELLULAR PATHOGENESIS OF 45. FUNCTIONAL NEUROCIRCUITRY AND DEPRESSION AND MECHANISMS FOR TREATMENT NEUROIMAGING STUDIES OF ANXIETY DISORDERS 6 06 RESPONSE 425 Madeleine S. Goodkind, Anett Gyurak, Ronald S. Duman and Amit Etkin 33. PATHOGENESIS OF DEPRESSION: 46. NOVEL TREATMENT APPROACHES FOR ANXIETY CLINICAL STUDIES 438 DISORDERS 621 Maura A. Furey, Daniel C. Mathews, Anita Van Zwieten, Gail A. Alvares, and Carlos A. Zarate Jr. and Adam J. Guastella 34. NEURAL CIRCUITRY OF DEPRESSION 4 55 47. PHARMACOTHERAPY OF ANXIETY DISORDERS 6 36 Joseph L. Price and Wayne C. Drevets James W. Murrough, Dan V. Iosifescu, and Dennis S. Charney 35. NEUROBIOLOGY OF DEPRESSION IN LATER LIFE: ANATOMY OF MELANCHOLIA 4 70 48. NEUROBIOLOGY AND TREATMENT OF OCD 6 46 K. Ranga Rama Krishnan Susanne E. Ahmari and H. Blair Simpson vi | CONTENTS 49. NEUROBIOLOGY AND TREATMENT OF PTSD 6 62 62. STRUCTURAL, FUNCTIONAL, AND MOLECULAR NEUROIMAGING BIOMARKERS FOR Karen E. Murray, Orion P. Keifer Jr., Kerry J. Ressler, ALZHEIMER’S DISEASE 8 21 Seth Davin Norrholm, and Tanja Jovanovic James B. Brewer, Jorge Sepulcre, and Keith A. Johnson 63. FLUID BIOMARKERS FOR ALZHEIMER’S DISEASE 8 34 SECTION VI Anne M. Fagan SUBSTANCE USE DISORDERS 673 64. CURRENT THERAPIES FOR ALZHEIMER’S DISEASE 8 44 Antonello Bonci and Nora D. Volkow Mary Sano and Judith Neugroschl 50. ANIMAL MODELS OF ADDICTION 6 75 65. DISEASE-MODIFYING THERAPIES Rafael Maldonado, J. David Jentsch, FOR ALZHEIMER’S DISEASE 8 54 Brigitte L. Kieffer, and Christopher J. Evans Joshua D. Grill and Jeffrey Cummings 51. CELLULAR AND MOLECULAR MECHANISMS 66. LEWY BODY DEMENTIAS 8 72 OF ADDICTION 6 83 Stella Karantzoulis and James E. Galvin Kathryn J. Reissner and Peter W. Kalivas 67. CLINICAL FEATURES AND PATHOGENESIS 52. THE GENETIC BASIS OF ADDICTIVE DISORDERS 6 96 OF FRONTOTEMPORAL DEMENTIA 8 87 David Goldman Georges Naasan and Bruce Miller 53. BRAIN DEVELOPMENT AND THE RISK 68. PATHOGENESIS, DIAGNOSIS, AND TREATMENT FOR SUBSTANCE ABUSE 7 06 OF VASCULAR AND MIXED DEMENTIAS 9 00 Kristina Caudle and B.J. Casey Helena Chang Chui 54. MOLECULAR IMAGING IN ADDICTIVE DISORDERS 7 16 69. CLINICAL FEATURES AND PATHOGENESIS Chelsea L. Robertson, Steven M. Berman, OF PRION DISEASE 9 15 and Edythe D. London Joel C. Watts and Michael D. Geschwind 55. BRAIN, REWARD, AND DRUG ADDICTION 7 32 Vani Pariyadath, Martin P. Paulus, and Elliot A. Stein SECTION VIII 56. MAGNETIC RESONANCE SPECTROSCOPY STUDIES IN SUBSTANCE ABUSERS 7 42 PSYCHIATRIC DISORDERS OF Linda Chang, Christine C. Cloak, and John L. Holt CHILDHOOD ONSET 931 Joseph D. Buxbaum 57. PHARMACOTHERAPY OF SUBSTANCE USE DISORDERS 761 70. EPIDEMIOLOGY OF NEUROPSYCHIATRIC AND Jane B. Acri and Phil Skolnick DEVELOPMENTAL DISORDERS OF CHILDHOOD 9 33 Elise B. Robinson, Benjamin M. Neale, and Mark J. Daly 58. EPIDEMIOLOGY OF SUBSTANCE USE DISORDERS 7 72 Denise B. Kandel, Mei-Chen Hu, 71. RARE VARIANTS OF SUBSTANTIAL EFFECT IN and Pamela C. Griesler PSYCHIATRIC DISORDERS OF CHILDHOOD ONSET 9 44 Heather C. Mefford 72. EPIGENETICS IN EARLY LIFE PROGRAMMING 9 55 SECTION VII Tracy L. Bale DEMENTIA 789 David M. Holtzman 73. ANIMAL MODELS IN PSYCHIATRIC DISORDERS OF CHILDHOOD ONSET 9 67 59. CLINICAL AND NEUROPSYCHOLOGICAL FEATURES Richard Paylor, Alexia M. Thomas, OF ALZHEIMER’S DISEASE 7 91 Surabi Veeraragavan, and Shannon M. Hamilton Jason Hassenstab, Jeffrey Burns, and John C. Morris 74. NEUROPATHOLOGY AND SYNAPTIC ALTERATIONS 60. THE GENETICS OF ALZHEIMER’S DISEASE 8 05 IN NEURODEVELOPMENTAL DISORDERS 9 80 Rudolph E. Tanzi Mara Dierssen and Salvador Mart í nez 61. EXPERIMENTAL ANIMAL MODELS 75. FUNCTIONAL CONNECTIVITY: APPLICATION OF ALZHEIMER’S DISEASE 8 10 TO DEVELOPMENTAL DISORDERS 9 95 Dave Morgan Luke Bloy, Ragini Verma, and Timothy P. L. Roberts CONTENTS | vii 76. INTELLECTUAL DISABILITY SYNDROMES 1 010 82. THE INFIRMITIES OF PSYCHIATRIC DIAGNOSIS 1 072 Charles E. Schwartz, Fiorella Gurrieri, Steven E. Hyman and Giovanni Neri 83. TOWARD PRECISION MEDICINE IN PSYCHIATRY: 77. AUTISM SPECTRUM DISORDERS 1 022 THE NIMH RESEARCH DOMAIN CRITERIA PROJECT 1 076 Alexander Kolevzon, A. Ting Wang, Bruce N. Cuthbert and Thomas R. Insel David Grodberg, and Joseph D. Buxbaum 84. THE NEUROBIOLOGY OF PERSONALITY 78. NEUROBIOLOGY OF ATTENTION DISORDERS: THE SHIFT TO DSM-5 1 089 DEFICIT/HYPERACTIVITY DISORDER 1 034 M. Mercedes Perez-Rodriguez, Stephen V. Faraone and Joseph Biederman Antonia S. New, and Larry J. Siever 79. TOURETTE SYNDROME AND TIC DISORDERS 1 048 85. THE NEUROBIOLOGY OF AGGRESSION 1 103 Kyle Williams, Michael H. Bloch, R. James R. Blair Matthew W. State, and Christopher Pittenger 86. THE NEUROBIOLOGY OF SOCIAL ATTACHMENT 1 112 80. NOVEL THERAPEUTICS IN CHILDHOOD Adam S. Smith, Kelly Lei, and Zuoxin Wang ONSET PSYCHIATRIC DISORDERS 1 061 Dorothy E. Grice, Alexander Kolevzon, 87. THE NEUROBIOLOGY OF SLEEP 1 127 Walter E. Kaufmann, and Joseph D. Buxbaum Giulio Tononi and Chiara Cirelli 88. THE NEUROBIOLOGY OF RESILIENCE 1 144 Adriana Feder, Margaret Haglund, Gang Wu, SECTION IX Steven M. Southwick, and Dennis S. Charney SPECIAL TOPIC AREAS 1065 Dennis S. Charney 89. THE NEUROBIOLOGY OF EATING DISORDERS 1 171 Thomas B. Hildebrandt and Amanda Downey 81. DSM-5 OVERVIEW AND GOALS 1 067 David J. Kupfer and Susan K. Schultz Index 1 187 viii | CONTENTS PREFACE Th ese are exciting yet frustrating times for psychiatry. Our and plasticity, with an eye on their contribution to complex knowledge of basic brain function continues to increase at an behaviors. accelerating pace as the tools of biology—from genetics and Section II reviews the methods used to examine the bio- epigenetics to detailed exploration of brain circuits in animals logical basis of mental illness in animal models and in humans. and humans—become ever more powerful and penetrating. Th is part has been expanded to refl ect critically important Yet this explosion of knowledge of the brain has not been technical advances in complex genetics (including powerful translated into fundamental advances in our understanding sequencing technologies and related bioinformatics), epige- of the pathophysiology of most major psychiatric syndromes, netics, stem cell biology, optogenetics, cognitive neuroscience, the diagnosis of these syndromes based on their underlying and brain imaging. We believe that this range of exciting meth- biological mechanisms, or the treatment and prevention of odologies off er unique opportunities for the translation of pre- mental illness. clinical and clinical research into badly needed breakthroughs Why has there been such a divide between our basic knowl- in our therapeutic toolkit. edge and clinical advances? First and foremost, the brain has Th e remaining parts of the book cover the neurobiology proved to be far more complicated than ever imagined a gen- and genetics of major psychiatric disorders: psychoses (includ- eration ago, and the disorders of the brain that manifest pri- ing bipolar disorder), mood disorders, anxiety disorders, sub- marily in behavioral abnormalities (i.e., mental illness) are far stance abuse disorders, dementias, disorders of childhood more complicated too in terms of their genetic causes and the onset, and special topic areas. Each of these parts has been associated abnormalities at the epigenetic, cellular, and circuit augmented in several diff erent areas as a refl ection of research levels. We have also learned that eff ective translation will not progress. Th e last section, on special topics, includes chap- occur automatically or organically and will require a far more ters that address diagnostic schemes for mental illness. Th e concerted eff ort than mounted thus far to link fi ndings in basic release of our new edition coincides with the publication of neurobiology and genetics to the human syndromes. Th e good DSM-5 ( Diagnostic and Statistical Manual-5) by the American news is that leaders at the National Institutes of Health, aca- Psychiatric Association. Unfortunately, the diagnostic classifi - demia, and industry recognize the need for such collabora- cation system utilized by DSM-5 remains limited by necessity, tions, with many exciting ventures now underway or planned because it is still based primarily on phenomenology rather to meet the challenges ahead. than etiology and pathophysiology. Alternative perspectives on W e have completely revamped the fourth edition of diagnosis, for example, RDoC (research domain criteria), are Neurobiology of Mental Illness to address these challenging yet therefore also presented. We predict that the research advances promising times. We have recruited two new book editors to reviewed in our textbook will ultimately lead to diagnostic sys- add depth and breadth of expertise, and have engaged a team tems in which genetic and neurobiological abnormalities have of all new section editors, each of whom represents a leader in a primary role. his or her fi elds. Accordingly, new authors have been enlisted Th is edition of N eurobiology of Mental Illness refl ects the for a majority of the chapters that now comprise this book, continuing reintegration of psychiatry into the mainstream with many new chapters added and old ones removed to refl ect of biomedical science. Th e research tools that are transform- progress in the fi eld. Th e result is a thoroughly updated view of ing other branches of medicine—epidemiology, genetics, epi- the state of psychiatry, both its basic underpinnings and clini- genetics, molecular and cell biology, imaging, and medicinal cal evidence, with a view toward advances that can be expected chemistry—will also one day transform psychiatry. It is our in the coming years and the methodology that will bring us hope that, like us, the reader is optimistic that the progress in there. genetics and in molecular, cellular, and systems neuroscience A s before, Section I provides an overview of basic neu- described in this textbook will eventually break new ground in roscience that is relevant to clinical psychiatry and expand- the diagnosis, treatment, and prevention of disabling psychi- ing its foundations. Molecular neurobiology and molecular atric disorders. genetics are emphasized in the context of brain development, neuropharmacology, neuronal function, and neural networks Th e Editors PREFACE | ix