Epigenetics in psychiatry (San Diego, 2014). - ОГЛАВЛЕНИЕ / CONTENTS

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ОбложкаEpigenetics in psychiatry / ed. by J.Peedicayil, D.R.Grayson, D.Avramopoulos. - San Diego: Academic Press, 2014. - xxviii, 635 p.: ill. - Bibliogr. at the end of the chapters. - Ind.: p.621-635. - ISBN 978-0-12-417114-5
 

Место хранения: 02 | Отделение ГПНТБ СО РАН | Новосибирск

Оглавление / Contents
 
Preface ....................................................... xxi
About the Editors ........................................... xxiii
List of Contributors .......................................... xxv

PART 1  GENERAL ASPECTS OF EPIGENETICS IN PSYCHIATRY
CHAPTER 1  Introduction to Epigenetics in Psychiatry ............ 3
Richard Lee and Dimitrios Avramopoulos
Introduction .................................................... 4
Genetics of psychiatric disorders ............................... 4
   Schizophrenia ................................................ 6
   Autism spectrum disorder ..................................... 8
   Bipolar disorder ............................................. 9
   Major depressive disorder .................................... 9
   Attention deficit hyperactivity disorder .................... 10
Genotype versus phenotype ...................................... 10
Missing heritability ........................................... 10
Epigenetics in psychiatric disorders ........................... 12
   Nutrition ................................................... 13
   Prenatal infection .......................................... 14
   Stress ...................................................... 14
Epigenetic versus genetic approaches to psychiatric disorders .. 16
Moving epigenetics forward ..................................... 18
Conclusion ..................................................... 19
References ..................................................... 20
Glossary ....................................................... 24

CHAPTER 2 Outline of Epigenetics ............................... 27
Bidisha Paul and Trygve O. Tollefsbol
Introduction ................................................... 28
Molecular mechanisms of epigenetics ............................ 29
   DNA methylation ............................................. 29
   DNA methylation, development, and disease ................... 31
   Chromatin remodeling and histone modifications .............. 32
Histone acetylation ............................................ 32
Histone methylation ............................................ 34
Other histone modifications .................................... 34
   Non-Coding RNA .............................................. 34
   microRNA .................................................... 35
Correlation of epigenetics with genetics, transcriptomics,
and proteomics ................................................. 36
Clinical and medical implication of epigenetics ................ 37
Conclusion ..................................................... 38
Acknowledgments ................................................ 39
References ..................................................... 39
Glossary ....................................................... 43

CHAPTER 3  A Brief History of Epigenetics in Psychiatry ........ 45
Jacob Peedicayil
Introduction ................................................... 45
Erikson's epigenetic principle ................................. 46
Schizophrenia: the epigenetic puzzle ........................... 47
Later theoretical developments ................................. 47
Experimental (laboratory) studies on epigenetics in
   psychiatry .................................................. 48
The social environment and epigenetics in psychiatry ........... 49
Conclusions .................................................... 49
References ..................................................... 49
Glossary ....................................................... 50

CHAPTER 4  Roles of Epigenetics in the Neural Stem Cell and
Neuron ......................................................... 51
Naoki Yamamoto, Masahiro Uesaka, Takuya Imamura, and Kinichi
Nakashima
Outline of neural cell production during cortical
development .................................................... 53
Epigenetic regulation of exit from cell proliferation cycle
toward postmitotic neurons during early cortical development ... 54
Epigenetic regulation underlying properties of multipotent
neural stem cells and their differentiation into upper layer
cortical neurons and astrocytes ................................ 55
Epigenetic regulation of postnatal oligodendrocyte
differentiation and adult neurogenesis ......................... 58
Combination of taws-acting epigenetic modifiers involved in
epigenome formation ............................................ 59
Importance of focusing on epigenetics in neuronal functions .... 62
Impact of epigenetic regulation on synaptic plasticity,
learning, and memory ........................................... 63
Plasticity of epigenetic profile in neurons in response to
extrinsic stimuli .............................................. 65
The robust identity of neurons defined by the epigenetic
status ......................................................... 69
Concluding remarks ............................................. 72
Acknowledgments ................................................ 73
References ..................................................... 73
Glossary ....................................................... 77

CHAPTER 5  Role of Epigenetics in the Brain .................... 79
Stephanie Matt, Eric D. Roth, and Tania L. Roth
Introduction ................................................... 80
Role of epigenetics in evolution ............................... 81
Role of epigenetics in brain development ....................... 83
   Brain development ........................................... 83
   Epigenetics in early brain development ...................... 85
   Epigenetics in adult neurogenesis and later brain
   maturation .................................................. 88
   Epigenetics and extrinsic factors regulating brain
   development ................................................. 89
Role of epigenetic mechanisms in brain function ................ 90
   Epigenetics and memory ...................................... 90
   Epigenetics and stress ...................................... 91
   Epigenetics and cognitive dysfunction ....................... 93
Concluding remarks ............................................. 94
Acknowledgments ................................................ 95
References ..................................................... 95
Glossary ....................................................... 99

CHAPTER 6  Epigenetic Epidemiology of Psychiatric Disorders ... 101
Monica Uddin, Angela Bustamante, and Satoshi Toyokawa
Introduction .................................................. 103
Causal inference in epigenetic epidemiology ................... 103
Study designs in epigenetic epidemiology ...................... 105
Methodologie issues to consider in epigenetic epidemiology .... 114
   Tissue and cell specificity of epigenetic marks ............ 114
   Defining mechanistic relationships among DNA sequence,
   epigenetic, and gene expression variation .................. 116
   Unknown effect sizes in disease-associated epigenetic
   variation .................................................. 118
Importance of a life course perspective ....................... 118
Conclusions ................................................... 122
References .................................................... 122
Glossary ...................................................... 127

CHAPTER 7  Laboratory Techniques in Psychiatric Epigenetics ... 111
Chris Murgatroyd
Introduction .................................................. 131
DNA methylation ............................................... 131
Global quantification of DNA methylation ...................... 132
Higher resolution analyses of DNA methylation ................. 133
   Sodium bisulfite treatment ................................. 133
   Restriction enzyme digestion ............................... 134
   Affinity capture ........................................... 136
Gene-specific quantification of DNA methylation ............... 137
   Methylation-specific PCR methods ........................... 137
   Bisulfite sequencing approaches ............................ 138
   Methylated DNA affinity enrichment approaches .............. 141
Genome-wide DNA methylation analysis .......................... 142
   Microarray-based methylation approaches .................... 142
   Next-generation sequencing-based methylation analysis ...... 143
   Roche/454 sequencing of converted-converted DNA ............ 144
   SOLiD™ sequencing of converted-converted DNA ............... 144
   Illumina sequencing of converted-converted DNA ............. 145
   Ion torrent ................................................ 145
Genome approaches ............................................. 145
5hmC approaches ............................................... 146
Chromatin ..................................................... 148
Global histone analyses ....................................... 149
Sequence-specific and genome-wide histone analyses ............ 149
   Chromatin immunoprecipitation (ChIP) ....................... 149
   Analyzing multiple binding events .......................... 152
   Gene-specific ChIP ......................................... 152
   Genome-wide ChIP ........................................... 152
   Open chromatin ............................................. 153
   Mapping chromatin interactions ............................. 154
Conclusion .................................................... 156
References .................................................... 156
Glossary ...................................................... 161

CHAPTER 8 Laboratory Epigenetic Models of Schizophrenia
Jacob Peedicayil, Erbo Dong, and Dennis R. Grayson
Introduction .................................................. 164
Laboratory non-epigenetic models of schizophrenia ............. 164
   In vitro non-epigenetic models of schizophrenia ............ 165
   In vivo rodent non-epigenetic models of schizophrenia ...... 165
Mimicking schizophrenia: chronic d-lysergic acid
diethylamide administration to simulate psychosis ............. 165
In vivo epigenetic models of schizophrenia .................... 166
   L-methionine-induced hypermethylation (MIH) model of
   schizophrenia .............................................. 166
Assessment of L-methionine-induced hypermethylation model of
schizophrenia ................................................. 167
Prenatal restraint stress model for schizophrenia ............. 168
Prenatal restraint stress model in mice ....................... 168
Prenatal restraint stress model in rats ....................... 169
Assessment of prenatal restraint stress as an epigenetic
model of schizophrenia ........................................ 170
Prenatal infection models ..................................... 171
In vitro epigenetic cell-based models of schizophrenia ........ 171
   Epigenetic models of schizophrenia based on cell culture ... 171
   NT2 neuronal precursor cells ............................... 172
   Primary neuronal cultures .................................. 172
   Induced human pluripotent stem cells ....................... 174
   Assessment of epigenetic cell-based models of
   schizophrenia .............................................. 175
Conclusions ................................................... 175
References .................................................... 176
Glossary ...................................................... 179

CHAPTER 9  Animal Models of Environmental Manipulations
Resulting in Epigenetic Modifications That Increase Risk for
Affective Disorders ........................................... 181
Sarah Adams Schoenrock and Lisa M. Tarantino
Mood disorders ................................................ 182
Rationale for the use of animal models ........................ 183
Mood and anxiety-like phenotypes in rodents ................... 184
Prenatal exposures ............................................ 184
   Maternal mood and stress ................................... 185
   Exposure to toxins ......................................... 186
   Nutritional deficiencies ................................... 187
Postnatal exposures ........................................... 188
   Maternal care and bonding .................................. 188
   Maternal abuse and neglect ................................. 190
Adulthood exposures ........................................... 191
   Social stress .............................................. 192
   Stressful life events ...................................... 192
   Reproductive hormones ...................................... 193
Future directions ............................................. 194
   Sex differences in epigenetic modifications ................ 194
   New experimental populations ............................... 194
   Measure gene-specific modifications ........................ 195
Conclusions ................................................... 196
References .................................................... 197
Glossary ...................................................... 205

PART 2  EPIGENETICS OF PSYCHIATRIC DISORDERS 

CHAPTER 10 5-Methycytosine and 5-Hydroxymethylcytosine in
Psychiatric Epigenetics ....................................... 209
Dennis R. Grayson and Alessandro Guidotti
Introduction to the epigenome ................................. 210
CpG islands and DNA methylation ............................... 213
DNA methylating enzymes ....................................... 214
DNMT1 overexpression in psychosis ............................. 217
DNA methylation biomarkers .................................... 217
Genome-wide methylation studies ............................... 219
Genome-wide array-based methods ............................... 219
Methylation of BDNF in psychiatric disorders .................. 221
Array-based studies for SZ .................................... 224
Second-generation methylation arrays and SZ ................... 226
Enrichment sequencing for studies of SZ ....................... 226
Genome-wide studies of methylation in ASD ..................... 227
Hydroxymethylcytosine historical perspective .................. 229
5-hmC in psychiatric disorders ................................ 231
Summary and conclusions ....................................... 231
References .................................................... 232
Glossary ...................................................... 239

CHAPTER 11 Pathogenic Histone Modifications in Schizophrenia
are Targets for Therapy ....................................... 241
Hamid Mostafavi Abdolmaleky and Sam Thiagalingam
A brief introduction to histone modifications ................. 242
Histone methylation and schizophrenia pathogenesis ............ 243
Aberrant histone acetylation in schizophrenia ................. 244
Other types of histone modifications associated with SZ
pathogenesis .................................................. 245
Current therapeutic targets modulating histone codes .......... 246
Methodological challenges of histone modification analyses .... 247
Conclusion and perspectives ................................... 248
References .................................................... 248
Glossary ...................................................... 251

CHAPTER 12 Non-Coding RNAs and Psychiatric Disorders .......... 253
Jacob Peedicayil and Natalie J. Beveridge
Introduction .................................................. 254
Types and functions of non-coding RNAs ........................ 254
Role of non-coding RNAs in the brain .......................... 256
Role of non-coding RNAs in schizophrenia ...................... 257
   Studies on postmortem brain ................................ 258
   Studies on peripheral tissues .............................. 259
Role of non-coding RNAs in bipolar disorder ................... 260
   Studies on postmortem brain ................................ 260
   Studies on peripheral tissues .............................. 260
   Role of non-coding RNAs in major depressive disorder ....... 260
   Studies on postmortem brain ................................ 260
   Studies on peripheral tissues .............................. 261
Polymorphisms of genes encoding miRNAs associated with
psychiatric disorders ......................................... 261
Conclusions and future directions ............................. 261
References .................................................... 262
Glossary ...................................................... 264

CHAPTER 13 Epigenetics of Bipolar Disorder .................... 265
Gen Shinozaki, Benjamin Hing, and James B. Potash
The epigenetic hypothesis in bipolar disorder ................. 266
Epigenetic mechanisms ......................................... 267
Direct examination of epigenetic impact from the study of
bipolar disorder .............................................. 268
Single-gene DNA methylation studies and bipolar disorder ...... 270
Genome-wide methylation studies and bipolar disorder .......... 271
Histone modifications studies and bipolar disorder ............ 272
Epigenetics of stress as an entry point ....................... 273
Epigenetics of neuroplasticity ................................ 274
Future directions ............................................. 274
Conclusions ................................................... 275
References .................................................... 276
Glossary ...................................................... 278

CHAPTER 14 Epigenetics in Major Depressive Disorder ........... 279
Zachary A. Kaminsky
Introduction .................................................. 280
What is major depression? ..................................... 281
Brain imaging endophenotypes in MDD ........................... 281
Two genetically driven hypotheses of depression ............... 282
Nature and nurture in MDD ..................................... 283
GWAS and the missing heritability ............................. 284
Environmental influence, epigenetics, and the missing
heritability .................................................. 284
Maternal diet and epigenetically mediated effects on
neurodevelopment outcomes ..................................... 285
Gestational consequences of maternal stress ................... 286
Early-life adversity-mediated epigenetic reprogramming ........ 287
The epigenetic intersect of gonadal hormonal fluctuation and
mood .......................................................... 288
Inflammation .................................................. 290
The effects of glucocorticoid system disruption in MDD ........ 290
Epigenetic etiology and brain imaging endophenotype ........... 292
DNA methylome scans in MDD .................................... 293
Conclusion .................................................... 294
References .................................................... 295
Glossary ...................................................... 302

CHAPTER 15 The Epigenetics of Suicide: The Critical Impact
of the Environment on Epigenetic Regulation in Suicide ....... 303
Benoit Labonté, Pierre-Eric Lutz, and Gustavo Turecki
Suicide perspectives .......................................... 304
The molecular consequences of early-life adversity:
Transcriptional regulation by epigenetic mechanisms ........... 306
   Glucocorticoid receptor .................................... 306
   Corticotropin-releasing hormone ............................ 308
   Arginine vasopressin ....................................... 309
   Neurotrophic factors ....................................... 309
Other epigenetic alterations in suicide brains ................ 311
   Ribosomal RNA gene ......................................... 311
   Polyamine system ........................................... 311
   GABAergic system ........................................... 311
   Serotonergic system ........................................ 312
Investigating genome-wide DNA methylation patterns ............ 313
Toward an integrative model of stress-induced
psychopathology ............................................... 314
Concluding remarks ............................................ 316
References .................................................... 316
Glossary ...................................................... 324

CHAPTER 16 Epigenetics in Posttraumatic Stress Disorder ....... 325
Richard G. Hunter
Introduction .................................................. 326
The lasting impact of early adversity ......................... 327
HPA axis in PTSD and stress-related disorders ................. 328
Epigenetic effects of stress .................................. 330
   Stress and trauma in development ........................... 330
   Stress and trauma in adult life ............................ 332
Implications of epigenetics for the treatment of PTSD and
related disorders ............................................. 334
Conclusions ................................................... 335
Acknowledgments ............................................... 335
References .................................................... 336
Glossary ...................................................... 341

CHAPTER 17 Epigenetics and Cognitive Disorders ................ 343
Fabio Coppedè
Introduction: role of epigenetics in memory and
neurodegeneration ............................................. 345
   DNA methylation ............................................ 345
   Histone modifications ...................................... 347
DNA methylation changes and histone modifications in
Alzheimer's disease ........................................... 348
   DNA methylation changes in Alzheimer's disease: cell
   cultures and animal models ................................. 349
   DNA methylation changes in Alzheimer's disease:
   postmortem brains .......................................... 352
   DNA methylation changes in Alzheimer's disease:
   peripheral blood cells ..................................... 353
   Histone modifications in Alzheimer's disease ............... 354
DNA methylation changes and histone modifications in
Huntington's disease .......................................... 355
   DNA methylation changes in Huntington's disease ............ 356
   Histone modifications in Huntington's disease .............. 357
DNA methylation changes and histone modifications in
Parkinson's disease ........................................... 358
   DNA methylation changes in Parkinson's disease: cell
   cultures and animal models ................................. 359
   DNA methylation changes in Parkinson's disease:
   individuals ................................................ 359
   Histone modifications in Parkinson's disease ............... 360
Conclusions ................................................... 362
References .................................................... 362
Glossary ...................................................... 367

CHAPTER 18 Epigenetics in intellectual Disability ............. 369
Nathalie G. Bérubé and Jamie M. Kramer
Introduction .................................................. 371
   Definition of epigenetics .................................. 372
   Types of epigenetic disruption in ID ....................... 372
Abnormal epigenetic silencing in ID ........................... 372
   Fragile X syndrome is caused by trinucleotide repeat
   expansion and abnormal epigenetic silencing of FMR1 ........ 372
Genomic imprinting of the chromosome 15q11q13 region in
Prader-Willi and Angelman syndromes ........................... 373
Mutations in genes encoding epigenetic regulators ............. 376
DNA methylation in ID ......................................... 376
   Disruption of DNA methyltransferases in ID ................. 376
   Methyl-CpG-binding protein, MeCP2, and Rett syndrome ....... 377
Disruption of ATP-dependent chromatin remodeling in ID ........ 379
   Alpha thalassemia mental retardation syndrome and the
   ATRX protein ............................................... 379
   Mutations in core members of the BAF chromatin remodeling
   complex cause ID ........................................... 380
   Mutations in the CHD chromatin remodeling family cause
   ID, autism, and epilepsy ................................... 381
   SRCAP mutations cause Floating-Harbor syndrome ............. 382
Histone methylation in ID ..................................... 382
   Disruption of COMPASS-like complexes causes III ............ 382
   Kleefstra syndrome is caused by mutations in EHMT1 ......... 384
   Disruption of the histone methyltransferases NSD1 and
   EZH2 causes ID-associated overgrowth disorders ............. 384
   Disruption of histone demethylases causes ID ............... 385
Histone acetylation in ID ..................................... 385
   Histone acetyltransferases in ID ........................... 385
   Histone deacetylases in ID ................................. 386
Histone ubiquitination in ID .................................. 386
Summary and conclusions ....................................... 387
References .................................................... 387
Glossary ...................................................... 393

CHAPTER 19 Epigenetics and Pervasive Developmental Disorders .. 395
Andrea L. Gropman
Introduction .................................................. 397
   Autism spectrum disorders and neurodevelopmental
   disabilities ............................................... 397
   Common pathways and mechanisms in NDDs ..................... 399
   Epigenetics as an explanation of variability in
   developmental disorders .................................... 399
   Control of transcription is key in the process of gene
   expression and is the first line of epigenetic control ..... 400
Epigenetic mechanisms and intellectual and neurodevelopmental
disabilities .................................................. 400
How do epigenetic modifications contribute to diversity? ...... 402
   Examples of human neurodevelopmental disorders with
   autistic features linking epigenetics and phenotype
   variation .................................................. 403
   Epigenetics and imprinting disorders ....................... 406
   Epigenetic interactions between ASD and NDD conditions ..... 408
   X-linked disorders associated with ID ...................... 408
   Copy number variations ..................................... 410
Can drugs be developed for NDDs based on epigenetics? ......... 415
Conclusions ................................................... 417
References .................................................... 417
Glossary ...................................................... 423

CHAPTER 20 Epigenetics in Child Psychiatry .................... 425
Josephine Elia, Richard Kingsley, Oliver Yost, Charles
Bongiorno, Carolyn Bernacki, Alexander Ambmsini, Makiko
Okuyama, and Hakon Hakonarson
Introduction .................................................. 426
Epigenetic mechanisms ......................................... 427
   DNA methylation ............................................ 427
   Chromosome organization .................................... 427
   Transcription factors ...................................... 427
   Posttranslational regulation ............................... 429
Epigenetic processes and child psychiatric disorders .......... 429
   Attention deficit hyperactivity disorder ................... 429
   Autism ..................................................... 430
Psychotropic drugs and gene expression ........................ 431
Psychotropic drugs and epigenetics ............................ 431
   Histone modifications ...................................... 431
   DNA methylation ............................................ 434
   miRNAs ..................................................... 434
Adverse effects of psychotropic drugs ......................... 434
   Immediate early genes ...................................... 435
Conclusion .................................................... 436
References .................................................... 436
Glossary ...................................................... 440

CHAPTER 21 Epigenetic Mechanisms of Drug Addiction
Vulnerability ................................................. 441
Wendy Wenderski and Ian Maze
Introduction .................................................. 443
Epigenetic regulation of gene expression ...................... 443
Epigenetic mechanisms in addiction ............................ 444
Acute drug exposure: rapid and specific epigenetic responses .. 445
   Histone acetylation ........................................ 445
   Histone phosphorylation .................................... 446
   Histone methylation ........................................ 447
   Chromatin remodeling ....................................... 447
   DNA methylation ............................................ 447
   Non-coding RNAs ............................................ 448
Chronic drug use .............................................. 448
   Histone acetylation ........................................ 448
   Histone methylation ........................................ 449
   Chromatin remodeling ....................................... 450
   DNA methylation ............................................ 450
   Non-coding RNAs ............................................ 451
Vulnerability to drug addiction ............................... 452
Early-life stress ............................................. 452
Mood disorders ................................................ 453
Environmental enrichment ...................................... 455
Prior drug exposure ........................................... 455
Gestational drug exposure ..................................... 456
Epigenetic inheritance of addiction ........................... 456
Future directions ............................................. 457
Conclusions ................................................... 457
References .................................................... 458
Glossary ...................................................... 461

CHAPTER 22 Mitoepigenetics and Neuropsychiatrie Disorders ..... 463
Hari Manev
Mitoepigenetics overview and relevance for brain disorders .... 464
Mitochondrial epigenetics ..................................... 466
   mtDNA methylation .......................................... 467
   mtDNA hydroxymethylation ................................... 469
   mitosRNAs .................................................. 470
Mitochondria and nDNA epigenetics ............................. 470
Epigenetics of nDNA-encoded mitochondrial genes ............... 471
Future directions ............................................. 472
   Methodological issues ...................................... 472
   Mechanistic issues ......................................... 473
   Mitoepigenetic biomarkers .................................. 473
Conclusion .................................................... 473
References .................................................... 474
Glossary ...................................................... 477

PART 3  EPIGENETIC THERAPY OF PSYCHIATRIC DISORDERS

CHAPTER 23  Epigenetic Effects of Currently Used
Psychotropic Drugs ............................................ 481
Marco P.M. Boks
Epigenetic effects of valproic acid ........................... 482
   Valproic acid and chromatin marks .......................... 483
   Valproic acid and DNA methylation .......................... 484
Epigenetic effects of antidepressants ......................... 484
   Imipramine ................................................. 485
   Amitriptyline .............................................. 486
   Clomipramine ............................................... 486
   Duloxetine ................................................. 486
   Fluoxetine ................................................. 486
   Escitalopram ............................................... 487
   Monoamine Oxidase Inhibitors ............................... 487
Epigenetic effects of antipsychotics .......................... 487
   Haloperidol ................................................ 488
   Pimozide ................................................... 488
   Clozapine .................................................. 488
   Olanzapine ................................................. 489
   Sulpiride and amisulpiride ................................. 489
   Risperidone ................................................ 489
   Antipsychotics and microRNAs ............................... 489
Epigenetic effects of Lithium salts ........................... 489
Conclusion .................................................... 490
References .................................................... 492
Glossary ...................................................... 496

CHAPTER 24 DNA Methyltransferase Inhibitors and Psychiatric
Disorders ..................................................... 497
Marija Kundakovic
Introduction .................................................. 498
DNA methylation and DNMTs ..................................... 499
DNA methylation and DNMTs in the developing and adult brain ... 501
DNMT inhibitors: currently available drugs and their
mechanisms of action .......................................... 502
Experimental use of DNMT inhibitors in neuroscience research:
relevance for learning and memory ............................. 504
Therapeutic potential of DNMT inhibitors in schizophrenia ..... 504
Therapeutic potential of DNMT inhibitors in depression ........ 506
Therapeutic potential of DNMT inhibitors in bipolar 
disorders ..................................................... 508
Therapeutic potential of DNMT inhibitors in posttraumatic
stress disorder ............................................... 508
Conclusions, future directions, and challenges ................ 509
References .................................................... 509
Glossary ...................................................... 514

CHAPTER 25 Histone Deacetylase Inhibitors and Psychiatric
Disorders ..................................................... 515
Sumana Chakravarty, Unis Ahmad Bhat, R. Gajendra Reddy,
Praveer Gupta, and Arvind Kumar
Introduction .................................................. 516
HATs and HDACs maintain transcription homeostasis ............. 517
HDACs ......................................................... 518
HDAC types .................................................... 518
HDACs in normal brain, behavior and in psychopathology ........ 518
   HDAC class 1 ............................................... 518
   HDAC class IIa ............................................. 520
   HDAC class IIb ............................................. 521
   HDAC class III ............................................. 521
   HDAC class IV .............................................. 521
HDAC inhibitors ............................................... 522
Clinical trials of HDACi ...................................... 523
HDACi tested in animal models of neuropsychiatrie disorders ... 523
HDACi in psychotic disorders (e.g., schizophrenia, bipolar
disorder) ..................................................... 523
HDACi in MDD .................................................. 529
HDACi in drug addiction ....................................... 530
HDACi in neurological disorders ............................... 530
HDACi classes ................................................. 531
   Short-chain fatty acids (COOH group) ....................... 531
   Hydroxamates (NHOH group) .................................. 531
   Benzamides (PhNH2) ......................................... 533
   Cyclic tetrapeptides ....................................... 533
   Ketone group ............................................... 534
Constraints in the development of HDACi as therapeutics for
CNS disorders ................................................. 535
Recent efforts to develop selective HDACi ..................... 535
Design of future HDACi for psychiatric disorders .............. 535
Acknowledgments ............................................... 538
References .................................................... 538
Glossary ...................................................... 544

PART 4  OTHER TOPICS IN EPIGENETICS IN PSYCHIATRY 

CHAPTER 26 The Social Environment and Epigenetics in
Psychiatry .................................................... 547
Patrick O. McGowan, Aya Sasaki, and Tania L. Roth
Introduction: social factors, genes, and gene expression
programming ................................................... 548
How mechanisms of gene regulation "above the genome"
contribute to interindividual differences in behavior ......... 549
Overview of epigenetic mechanisms ............................. 549
Targeting of epigenetic modifications to specific genes ....... 550
Epigenetic mechanisms and mental health ....................... 550
The response of epigenetic machinery to environmental signals . 551
Social factors associated with epigenetic modifications
during sensitive periods of development ....................... 552
Maternal care, epigenetics, and the HPA axis: laboratory
animal studies ................................................ 553
Parental care, epigenetics, and the HPA axis: human studies ... 554
Social factors associated with epigenetic modifications
outside of sensitive periods of development ................... 555
   Social stress, epigenetics, and the HPA axis: laboratory
   animal studies ............................................. 555
   Social stress, epigenetics, and the HPA axis: human
   studies .................................................... 557
Conclusion .................................................... 557
Acknowledgment ................................................ 558
References .................................................... 558
Glossary ...................................................... 562

CHAPTER 27 Nutritional Effects on Epigenetics in Psychiatry ... 563
Jacob Peedicayil
Introduction .................................................. 564
Nutritional epigenetics: the link between nutrition and
epigenetics ................................................... 564
Effect of nutrition on DNA methylation ........................ 564
Effect of nutrition on histone modifications .................. 566
Effect of nutrition on RNA-mediated regulation of gene
expression .................................................... 566
Nutritional effects on epigenetics in psychiatry .............. 567
Effect of prenatal nutrition on epigenetics in psychiatry ..... 567
Effect of postnatal nutrition on epigenetics in psychiatry .... 568
Transgenerational (heritable) effects of nutrition on
epigenetics in psychiatry ..................................... 569
Clinical applications of nutritional effects on epigenetics
in psychiatry ................................................. 569
Use of methyl donors in major depressive disorder ............. 570
Use of methyl donors in major psychosis ....................... 571
Use of methyl donors in cognitive disorders ................... 571
Conclusions ................................................... 571
References .................................................... 572
Glossary ...................................................... 575

CHAPTER 28 Transgenerational (Heritable) Epigenetics and
Psychiatric Disorders ......................................... 577
Tamara Brook Franklin
A novel non-Mendelian mechanism of inheritance ................ 578
   Non-Mendelian patterns of expression of endogenous genes ... 578
   Agouti viable yellow (Aνy) and axin-fused (AxinFu) ......... 578
   Exposure to environmental toxicants ........................ 579
   Metabolic influences ....................................... 581
Molecular mechanisms for epigenetic inheritance ............... 581
   DNA methylation ............................................ 582
   Posttranslational modifications on chromatin ............... 583
   RNAs (RNA, miRNA, piRNA) ................................... 584
   Paternal genome ............................................ 585
Epigenetic inheritance of psychiatric disorder-related
behavior in animal models ..................................... 585
   Stress-induced behavior .................................... 585
   Adult drug use ............................................. 588
Conclusion .................................................... 588
References .................................................... 589

Glossary ...................................................... 591
Abbreviations ................................................. 593
Glossary ...................................................... 609
Index ......................................................... 621


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Документ изменен: Wed Feb 27 14:27:40 2019. Размер: 46,070 bytes.
Посещение N 764 c 16.06.2015