Neurobiology of Mental Illness

Dennis S. Charney, MD is Dean at the Icahn School of Medicine at Mount Sinai, Executive Vice President for Academic Affairs, The Mount Sinai Medical Center, and Anne and Joel Ehrenkranz Professor in the Departments of Psychiatry, Neuroscience, and Pharmacology & Systems Therapeutics at the Icahn School of Medicine at Mount Sinai in New York, NY. He is a world expert in the neurobiology and treatment of mood and anxiety disorders. He has made fundamental contributions to the understanding of neural circuits and neurochemistry related to human anxiety, fear, mood and discovery of new treatment for mood and anxiety disorders. He later expanded this area into pioneering research related to the psychobiological mechanisms of human resilience to stress. His work has been carried out over two decades at Yale University School of Medicine, and during four years at the National Institute of Mental Health (NIMH). It continues today at the Icahn School of Medicine at Mount Sinai.

Joseph D. Buxbaum, PhD, is a Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, where he is also director of the Seaver Autism Center for Research and Treatment. He is a world-renowned molecular geneticist and spearheads research into human psychiatric and neurological diseases. As Vice Chair for Research in Psychiatry, Dr. Buxbaum helps set the research direction for the Department, which is ranked among the top 20 psychiatry departments in the country in NIH funding.

Pamela Sklar, MD, received her BA from St. John's College and her MD and PhD from Johns Hopkins School of Medicine and Neuroscience. She is a neuroscientist, human geneticist and clinical psychiatrist investigating the genetic causes of psychiatric disorders, including schizophrenia and bipolar disorder. A major focus of her prior work has been to identify susceptibility genes for psychiatric diseases by applying tools developed for understanding and characterizing human sequence variation. Currently, she is Chief of the Division of Psychiatric Genomics, and Professor of Psychiatry, Neuroscience, Genetics and Genomic Sciences.

Eric J. Nestler, MD, PhD, received his BA, MD, and PhD degrees from Yale University. He then served on the Yale faculty, where he was named the Elizabeth Mears and House Jameson Professor of Psychiatry of Neurobiology and Director of the Abraham Ribicoff Research Facilities. In 2000, Dr. Nestler was named the McGinley Professor of Psychiatry and Chairman of the Department of Psychiatry at the University of Texas Southwestern Medical Center at Dallas, before accepting his current position at Mount Sinai in 2008. Dr. Nestler has been a pioneer in the field of molecular psychiatry, whose research has helped us understand the molecular mechanisms of addiction and depression based on work in animal models.

TABLE OF CONTENTS
PREFACE
CONTRIBUTORS

SECTION 1: INTRODUCTION TO BASIC NEUROSCIENCE
ERIC J. NESTLER
1. OVERVIEW OF BRAIN DEVELOPMENT
JOHN L. R. RUBENSTEIN
2. NEUROCHEMICAL SYSTEMS IN THE CENTRAL NERVOUS SYSTEM
ARIEL Y. DEUTCH AND ROBERT H. ROTH
3. PRINCIPLES OF ELECTROPHYSIOLOGY
EVELYN K. LAMBE
4. PRINCIPLES OF SIGNAL TRANSDUCTION
JEAN-ANTOINE GIRAULT AND PAUL GREENGARD
5. SYNAPTIC AND NEURAL PLASTICITY
SAID KOURRICH AND ANTONELLO BONCI
6. PRINCIPLES OF MOLECULAR BIOLOGY
STEVEN E. HYMAN AND ERIC J. NESTLER
7. EPIGENETICS OF PSYCHIATRIC DISEASES
BRYAN E. MCGILL AND HUDA Y. ZOGHBI

SECTION 2: NEW METHODS AND NEW TECHNOLOGIES FOR PRECLINICAL AND CLINICAL NEUROBIOLOGY
KARL DEISSEROTH
8. TRANSGENIC TOOLS AND ANIMAL MODELS OF MENTAL ILLNESS
LISA M. MONTEGGIA, WILLIAM CARLEZON, JR. AND RALPH J. DILEONE
9. APPLICATION OF STEM CELLS TO UNDERSTANDING PSYCHIATRIC DISORDERS
KIMBERLY M. CHRISTIAN, HONGJUN SONG AND GUO-LI MING
10. OPTOGENETIC TECHNOLOGIES FOR PSYCHIATRIC DISEASE RESEARCH: CURRENT STATUS AND CHALLENGES
LIEF E. FENNO AND KARL DEISSEROTH
11. BLOOD-BRAIN BARRIER OPENING AND DRUG DELIVERY USING FOCUSED ULTRASOUND AND MICROBUBBLES
ELISA E. KONOFAGOU
12. GENETIC METHODOLOGIES AND APPLICATIONS
SHAUN M. PURCELL
13. THE BRAIN AND ITS EPIGENOME
AMANDA C. MITCHELL, YAN JIANG, CYRIL J. PETER, KI A. GOOSENS AND SCHAHRAM AKBARIAN
14. NETWORK METHODS FOR ELUCIDATING THE COMPLEXITY OF COMMON HUMAN DISEASES
ERIC E. SCHADT
15. BRAIN IMAGING METHODOLOGIES
HANZHANG LU, YIHONG YANG AND PEIYING LIU
16. IMAGE-GUIDED BRAIN STIMULATION
MARK S. GEORGE, JOSEPH J. TAYLOR AND JAIMIE HENDERSON

SECTION 3: PSYCHOTIC DISORDERS
PAMELA SKLAR
17. DIAGNOSIS OF THE PSYCHOSES
LIANNE MORRIS SMITH, JULIE W. MESSINGER AND DOLORES MALASPINA
18. GENETICS OF SCHIZOPHRENIA AND BIPOLAR DISORDER
PAMELA SKLAR
19. GENOMIC SYNDROMES IN SCHIZOPHRENIA: OVERLAPPING PHENOTYPES
GEORGE KIROV, MICHAEL O'DONOVAN AND MICHAEL J. OWEN
20. NEUROIMAGING OF PSYCHOTIC DISORDERS
STEPHAN HECKERS, NEIL WOODWARD AND DOST ONGUR
21. COGNITIVE AND MOTIVATIONAL NEUROSCIENCE OF PSYCHOTIC DISORDERS
ALAN ANTICEVIC, ERIN C. DOWD AND DEANNA M. BARCH
22. MOUSE MODELS OF SCHIZOPHRENIA AND BIPOLAR DISORDER
MIKHAIL V. PLETNIKOV AND CHRISTOPHER A. ROSS
23. CORTICAL GABA NEURONS IN SCHIZOPHRENIA
ALLISON A. CURLEY AND DAVID A. LEWIS
24. SYNAPTIC DISEASE IN PSYCHIATRY
SETH G. N. GRANT
25. NEURODEVELOPMENT AND SCHIZOPHRENIA
ESTER J. KWON, TAKAHIRO SODA AND LI-HUEI TSAI
26. NEUROBIOLOGY OF MENTAL ILLNESS PSYCHOSIS PRONENESS
RAQUEL E. GUR
27. PSYCHOTIC DISORDERS: NEUROCHEMISTRY AND PHARMACOTHERAPY
CAROL A. TAMMINGA AND ELENA I. IVLEVA
28. NEUROBIOLOGY OF BIPOLAR DISORDER
KATE BURDICK, STEPHEN HAGGARTY AND ROY PERLIS

SECTION 4: MOOD DISORDERS
HELEN S. MAYBERG
29. THE DIAGNOSIS OF MOOD DISORDERS
JAN FAWCETT AND BRANT HAGER
30. GENETICS OF DEPRESSION
DOUGLAS F. LEVINSON
31. ANIMAL MODELS OF MOOD DISORDERS
GEORGIA E. HODES AND SCOTT J. RUSSO
32. MOLECULAR AND CELLULAR PATHOGENESIS OF DEPRESSION AND MECHANISMS FOR TREATMENT RESPONSE
RONALD S. DUMAN
33. PATHOGENESIS OF DEPRESSION: CLINICAL STUDIES
MAURA A. FUREY, DANIEL C. MATHEWS AND CARLOS A. ZARATE JR.
34. NEURAL CIRCUITRY OF DEPRESSION
JOSEPH L. PRICE AND WAYNE C. DREVETS
35. NEUROBIOLOGY OF DEPRESSION IN LATER LIFE: ANATOMY OF MELANCHOLIA
K. RANGA RAMA KRISHNAN
36. GONADAL STEROIDS AND MOOD DISORDERS
DAVID R. RUBINOW, PETER J. SCHMIDT AND CLAIRE D. CRAFT
37. DEPRESSION AND MEDICAL ILLNESS
TAMI D. BENTON, JOSHUA BLUME, PAUL CRITS-CHRISTOPH, BENOIT DUBE AND DWIGHT L. EVANS
38. TREATMENTS FOR DEPRESSION
DAN V. IOSIFESCU, JAMES W. MURROUGH AND DENNIS S. CHARNEY

SECTION 5: ANXIETY DISORDERS
KERRY J. RESSLER
39. DIAGNOSIS OF ANXIETY DISORDERS
MEGHAN E. KEOUGH, MURRAY B. STEIN AND PETER P. ROY-BYRNE
40. GENETICS OF ANXIETY DISORDERS
JAVIER A. PEREZ, TAKESHI OTOWA, ROXANN ROBERSON-NAY AND JOHN M. HETTEMA
41. THE NEUROBIOLOGY OF FEAR AND ANXIETY: CONTRIBUTIONS OF ANIMAL MODELS TO CURRENT UNDERSTANDING
CHRISTOPHER K. CAIN, GREGORY SULLIVAN AND JOSEPH E. LEDOUX
42. DIFFERENTIAL ROLES OF GABA RECEPTORS IN ANXIETY
HANNS MOHLER
43. PREFRONTAL CORTEX REGULATION OF EMOTION AND ANXIETY
BRONWYN M. GRAHAM AND MOHAMMED R. MILAD
44. DEVELOPMENTAL COMPONENTS OF FEAR AND ANXIETY IN ANIMAL MODELS
SIOBHAN S. PATTWELL, ANNE-MARIE MOULY, REGINA M. SULLIVAN AND FRANCIS S. LEE
45. FUNCTIONAL NEUROCIRCUITRY AND NEUROIMAGING STUDIES OF ANXIETY DISORDERS
MADELEINE S. GOODKIND, ANETT GYURAK AND AMIT ETKIN
46. NOVEL TREATMENT APPROACHES FOR ANXIETY DISORDERS
ANITA VAN ZWIETEN, GAIL A. ALVARES & ADAM J. GUASTELLA
47. PHARMACOTHERAPY OF ANXIETY DISORDERS
DAN V. IOSIFESCU, JAMES W. MURROUGH AND DENNIS S. CHARNEY
48. NEUROBIOLOGY AND TREATMENT OF OCD
SUSANNE E. AHMARI AND H. BLAIR SIMPSON
49. NEUROBIOLOGY AND TREATMENT OF PTSD
KAREN E. MURRAY, ORION P. KEIFER, JR., KERRY J. RESSLER, SETH DAVIN NORRHOLM AND TANJA JOVANOVIC

SECTION 6: SUBSTANCE USE DISORDERS
ANTONELLO BONCI AND NORA VOLKOW
50. ANIMAL MODELS OF ADDICTION
CHRISTOPHER J. EVANS, RAFAEL MALDONADO LOPEZ, YVETTE F. TACHE, AND J. DAVID JENTSCH
51. CELLULAR AND MOLECULAR MECHANISMS OF ADDICTION
KATHRYN J. REISSNER AND PETER W. KALIVAS
52. THE GENETIC BASIS OF ADDICTIVE DISORDERS
DAVID GOLDMAN
53. BRAIN DEVELOPMENT AND THE RISK FOR SUBSTANCE ABUSE
KRISTINA CAUDLE AND BJ CASEY
54. MOLECULAR IMAGING IN ADDICTIVE DISORDERS
CHELSEA L. ROBERTSON, STEVEN M. BERMAN AND EDYTHE D. LONDON
55. BRAIN, REWARD, AND DRUG ADDICTION
VANI PARIYADATH, MARTIN P. PAULUS AND ELLIOT A. STEIN
56. MAGNETIC RESONANCE SPECTROSCOPY STUDIES IN SUBSTANCE ABUSERS
LINDA CHANG, CHRISTINE C. CLOAK AND JOHN L. HOLT
57. PHARMACOTHERAPY OF SUBSTANCE USE DISORDERS
JANE B. ACRI AND PHILIP SKOLNICK
58. EPIDEMIOLOGY OF SUBSTANCE USE DISORDERS
DENISE B. KANDEL, MEI-CHEN HU AND PAMELA C. GRIESLER

SECTION 7: DEMENTIA
DAVID M. HOLTZMAN
59. CLINICAL AND NEUROPSYCHOLOGICAL FEATURES OF ALZHEIMER'S DISEASE
JASON HASSENSTAB, JEFFREY BURNS AND JOHN C. MORRIS
60. THE GENETICS OF ALZHEIMER'S DISEASE
RUDOLPH E. TANZI
61. EXPERIMENTAL ANIMAL MODELS OF ALZHEIMER'S DISEASE
DAVE MORGAN
62. STRUCTURAL, FUNCTIONAL AND MOLECULAR NEUROIMAGING BIOMARKERS FOR ALZHEIMER'S DISEASE
JAMES B. BREWER, JORGE SEPULCRE AND KEITH A. JOHNSON
63. FLUID BIOMARKERS FOR ALZHEIMER'S DISEASE
ANNE M. FAGAN
64. CURRENT THERAPIES FOR ALZHEIMER'S DISEASE
MARY SANO AND JUDITH A. NEUGROSCHL
65. DISEASE-MODIFYING THERAPIES FOR ALZHEIMER'S DISEASE
JOSHUA D. GRILL AND JEFFREY CUMMINGS/
66. LEWY BODY DEMENTIAS
STELLA KARANTZOULIS AND JAMES E. GALVIN
67. CLINICAL FEATURES AND PATHOGENESIS OF FTD
GEORGES NAASAN AND BRUCE MILLER
68. PATHOGENESIS, DIAGNOSIS AND TREATMENT OF VASCULAR AND MIXED DEMENTIAS
HELENA CHANG CHUI
69. CLINICAL FEATURES AND PATHOGENESIS OF PRION DISEASE
JOEL WATTS AND MICHAEL D. GESCHWIND

SECTION 8: PSYCHIATRIC DISORDERS OF CHILDHOOD ONSET
JOSEPH D. BUXBAUM
70. EPIDEMIOLOGY OF NEUROPSYCHIATRIC AND DEVELOPMENTAL DISORDERS OF CHILDHOOD
ELISE ROBINSON, BENJAMIN NEALE AND MARK J. DALY
71. RARE VARIANTS OF SUBSTANTIAL EFFECT IN PSYCHIATRIC DISORDERS OF CHILDHOOD ONSET
HEATHER C. MEFFORD
72. EPIGENETICS IN EARLY LIFE PROGRAMMING
TRACY L. BALE
73. ANIMAL MODELS IN PSYCHIATRIC DISORDERS OF CHILDHOOD ONSET
RICHARD PAYLOR, ALEXIA M. THOMAS, SURABI VEERARAGAVAN AND SHANNON M. HAMILTON
74. NEUROPATHOLOGY AND SYNAPTIC ALTERATIONS IN NEURODEVELOPMENTAL DISORDERS
MARA DIERSSEN AND SALVADOR MARTINEZ
75. FUNCTIONAL CONNECTIVITY: APPLICATION TO DEVELOPMENTAL DISORDERS
LUKE BLOY, RAGINI VERMA AND TIMOTHY P.L. ROBERTS
76. INTELLECTUAL DISABILITY SYNDROMES
CHARLES E. SCHWARTZ, FIORELLA GURRIERI AND GIOVANNI NERI
77. AUTISM SPECTRUM DISORDERS
ALEXANDER KOLEVZON, A. TING WANG, DAVID GRODBERG AND JOSEPH D. BUXBAUM
78. NEUROBIOLOGY OF ATTENTION DEFICIT HYPERACTIVITY DISORDER
STEPHEN V. FARAONE AND JOSEPH BIEDERMAN
79. TOURETTE SYNDROME AND TIC DISORDERS
KYLE WILLIAMS, MICHAEL H. BLOCH, MATTHEW W. STATE AND CHRISTOPHER PITTENGER
80. NOVEL THERAPEUTICS IN CHILDHOOD ONSET PSYCHIATRIC DISORDERS
DOROTHY E. GRICE, ALEXANDER KOLEVZON, WALTER E. KAUFMANN AND JOSEPH D. BUXBAUM

SECTION 9: SPECIAL TOPIC AREAS
DENNIS S. CHARNEY
81. DSM-5 OVERVIEW AND GOALS
DAVID J. KUPFER AND SUSAN K. SCHULTZ
82. THE INFIRMITIES OF PSYCHIATRIC DIAGNOSIS
STEVEN E. HYMAN
83. TOWARD PRECISION MEDICINE IN PSYCHIATRY: THE NIMH RESEARCH DOMAIN CRITERIA PROJECT
BRUCE N. CUTHBERT AND THOMAS R. INSEL
84. NEUROBIOLOGY OF PERSONALITY DISORDERS: THE SHIFT IN DSM-5
M. MERCEDES PEREZ-RODRIGUEZ, ANTONIA S. NEW AND LARRY J. SIEVER
85. THE NEUROBIOLOGY OF AGGRESSION
R. JAMES R. BLAIR
86. NEUROBIOLOGY OF SOCIAL ATTACHMENT
ADAM S. SMITH, KELLY LEI AND ZUOXIN WANG
87. THE NEUROBIOLOGY OF SLEEP
GIULIO TONONI AND CHIARA CIRELLI
88. THE NEUROBIOLOGY OF RESILIENCE
ADRIANA FEDER, MARGARET HAGLUND, GANG WU, STEVEN M. SOUTHWICK AND DENNIS S. CHARNEY
89. NEUROBIOLOGY OF EATING DISORDERS
THOMAS B. HILDEBRANDT AND AMANDA DOWNEY
INDEX