Neurobiology of Mental Illness

1259 Pages·2013·26.986 MB·English

by  Dennis S. Charney, Joseph D. Buxbaum, Pamela Sklar, Eric J. Nestler

NEUROBIOLOGY OF MENTAL ILLNESS
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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

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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
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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