Epigenetics in Psychiatry

2nd Edition - August 21, 2021
Imprint: Academic Press
Editors: Jacob Peedicayil, Dennis R. Grayson, Dimitri Avramopoulos
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 2 3 5 7 7 - 5
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 2 3 5 7 8 - 2

Epigenetics in Psychiatry, Second Edition covers all major areas of psychiatry in which extensive epigenetic research has been performed, fully encompassing a diverse and maturing… Read more

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Epigenetics in Psychiatry, Second Edition covers all major areas of psychiatry in which extensive epigenetic research has been performed, fully encompassing a diverse and maturing field, including drug addiction, bipolar disorder, epidemiology, cognitive disorders, and the uses of putative epigenetic-based psychotropic drugs. Uniquely, each chapter correlates epigenetics with relevant advances across genomics, transcriptomics, and proteomics. The book acts as a catalyst for further research in this growing area of psychiatry.

This new edition has been fully revised to address recent advances in epigenetic understanding of psychiatric disorders, evoking data consortia (e.g., CommonMind, ATAC-seq), single cell analysis, and epigenome-wide association studies to empower new research. The book also examines epigenetic effects of the microbiome on psychiatric disorders, and the use of neuroimaging in studying the role of epigenetic mechanisms of gene expression. Ongoing advances in epigenetic therapy are explored in-depth.

Cover image
Title page
Table of Contents
Copyright
List of contributors
About the editors
Preface
Section 1: General aspects of epigenetics in psychiatry
Chapter 1. Introduction to epigenetics in psychiatry
Abstract
Introduction
Genetics of psychiatric disorders
Schizophrenia
Autism spectrum disorder
Bipolar disorder
Major depressive disorder
Attention deficit hyperactivity disorder
Genetic overlaps and phenotypic continuum
Overview of genetics and connections to epigenetics
Epigenetics in psychiatric disorders
Nutrition
Prenatal infection
Stress
Epigenetic versus genetic approaches to psychiatric disorders
Moving epigenetics forward
Conclusion
References
Chapter 2. Outline of epigenetics
Abstract
Introduction
Epigenetics throughout the mammalian lifetime
Classification of protein molecules of epigenetic changes
Molecular mechanisms of epigenetics
Clinical significance of DNA methylation
Histone methylation
Clinical significance of histone methylation
Histone acetylation
Clinical significance of histone acetylation
Other histone modifications
Clinical significance of other histone modifications
Chromatin remodelers
Clinical significance of chromatin remodeling
MicroRNAs and small-interfering RNAs (RNAi)
Clinical significance of micro RNAs and small interfering RNAs (RNAi)
Non-coding RNAs and transposons
Clinical significance of non-coding RNAs and transposons
Other epigenetic proteins
Clinical significance of other epigenetic proteins
Epigenetics in therapy
Conclusion
References
Chapter 3. A brief history of epigenetics in psychiatry
Abstract
Introduction
Erikson’s epigenetic principle
Schizophrenia: the epigenetic puzzle
Later theoretical developments
Experimental (laboratory) studies on epigenetics in psychiatry
The social environment and epigenetics in psychiatry
Recent developments
Conclusions
References
Chapter 4. Roles of epigenetics in the neural stem cell and neuron
Abstract
Outline of neural cell production during cortical development
Epigenetic regulation of exit from cell proliferation cycle toward post-mitotic neurons during early cortical development
Epigenetic regulation underlying properties of multipotent neural stem cells and their differentiation into upper layer cortical neurons and astrocytes
Epigenetic regulation of postnatal oligodendrocyte differentiation and adult neurogenesis
Combination of trans-acting epigenetic modifiers involved in epigenome formation
Importance of focusing on epigenetics in neuronal functions
Impact of epigenetic regulation on synaptic plasticity, learning, and memory
Plasticity of epigenetic profile in neurons in response to extrinsic stimuli
The robust identity of neurons defined by the epigenetic status
Therapeutic approaches utilizing artificial neurogenesis
Concluding remarks
Acknowledgments
References
Chapter 5. Role of epigenetics in the brain
Abstract
Introduction
Role of epigenetics in evolution
Role of epigenetics in brain development
Brain development
Epigenetics in early brain development
Epigenetics in adult neurogenesis and later brain maturation
Epigenetics and extrinsic factors regulating brain development
Role of epigenetic mechanisms in brain function
Epigenetics and memory
Epigenetics and stress
Epigenetics and cognitive dysfunction
Concluding remarks
Acknowledgments
References
Chapter 6. Epigenetic epidemiology of psychiatric disorders
Abstract
Introduction
Causal inference in epigenetic epidemiology
Study designs in epigenetic epidemiology
Methodologic issues to consider in epigenetic epidemiology
Emerging literature and future directions
Conclusions
Acknowledgments
References
Chapter 7. ATAC-seq and psychiatric disorders
Abstract
Introduction
The assay for transposase accessible chromatin followed by sequencing (ATAC-seq)
ATAC-seq in the study of brain development/homeostasis
ATAC-seq in the study of disease models
ATAC-seq in the study of human brain tissue
Fundamentals of analyzing ATAC-seq data
Future perspectives
References
Chapter 8. Single cell RNA sequencing in psychiatric disorders
Abstract
Introduction
Neurodevelopment
Major depressive disorder
Autism spectrum disorder
Conclusions
References
Chapter 9. Single cell transcriptomics and epigenomics methods provide high resolution genomics profiling of brain disorders
Abstract
Introduction
Transcriptomics in single cells
Epigenetics in single cells
Conclusion
Acknowledgments
References
Chapter 10. Laboratory techniques in psychiatric epigenetics
Abstract
Introduction
DNA methylation
Chromatin
Non-coding RNA
Conclusion
References
Chapter 11. Laboratory epigenetic models of schizophrenia
Abstract
Introduction
Mimicking schizophrenia: chronic D-lysergic acid diethylamide administration to simulate psychosis
Laboratory
In Vivo epigenetic models of schizophrenia
In vitro epigenetic models of schizophrenia
Conclusions
References
Chapter 12. Animal models of environmental manipulations causing epigenetic modifications that increase risk for major depressive disorder and anxiety disorders
Abstract
Introduction
Rationale for the use of rodent models
Depression and anxiety-like phenotypes in rodents
Prenatal exposures
Other prenatal exposures
Postnatal exposures
Adulthood exposures
Future directions
Conclusions
References
Section 2: Epigenetics of psychiatric disorders
Chapter 13. 5-Methylcytosine and 5-hydroxymethylcytosine in psychiatric epigenetics
Abstract
Introduction to the epigenome
Clinical relevance of epigenetic mechanisms
CpG islands and DNA methylation
DNA methylating enzymes
DNMT1 overexpression in psychosis
DNA methylation biomarkers
Genome-wide methylation studies
Genome-wide array-based methods
Methylation of BDNF in psychiatric disorders
Array-based studies for SZ
Second generation methylation arrays and SZ
Enrichment sequencing for studies of SZ
Methylome-wide association studies of SZ
Genome-wide studies of methylation in ASD
Hydroxymethylcytosine, historical perspective
5hmC in psychiatric disorders
Summary and conclusions
References
Chapter 14. Pathogenic histone modifications in schizophrenia are targets for therapy
Abstract
A short introduction to histone modifications
Histone methylation and schizophrenia pathogenesis
Aberrant histone acetylation in schizophrenia
Other types of histone modifications associated with SCZ pathogenesis
Current therapeutic targets modulating histone codes
Methodological challenges of histone modification analyses
Conclusion and perspectives
References
Chapter 15. Non-coding RNAs and psychiatric disorders
Abstract
Introduction
Types and functions of non-coding RNAs
Role of non-coding RNAs in the brain
Role of non-coding RNAs in schizophrenia
Studies on postmortem brain
Studies on peripheral tissues
Role of non-coding RNAs in bipolar disorder
Role of non-coding RNAs in major depressive disorder
Polymorphisms of genes encoding miRNAs associated with psychiatric disorders
Conclusions and future directions
References
Chapter 16. Epigenetics of bipolar disorder
Abstract
Introduction
Bipolar disorder (BD)
Epigenetic mechanisms
Epigenetic alterations in BD
Evidence of epigenetic modifications in the treatment of the BD
Future directions and perspectives
References
Chapter 17. Epigenetics of major depressive disorder
Abstract
Major depressive disorder
Stress and the HPA axis
Stress consequences
Epigenetics
Brain vs. peripheral tissues for epigenetic studies
Stress and DNA methylation
Major depressive disorder and DNA methylation
Depression and histone modifications
Summary and future directions
References
Chapter 18. The epigenetics of suicide: The critical impact of environment on epigenetic regulation in suicide
Abstract
Introduction
The molecular consequences of early-life adversity: transcriptional regulation by epigenetic mechanisms
Neurotrophic factors
Alterations affecting other neurotransmitters and molecular substrates in the suicide brain
Investigating genome wide DNA methylation patterns
New epigenetic substrates and mechanisms
Concluding remarks
References
Chapter 19. Epigenetics in posttraumatic stress disorder
Abstract
Introduction
HPA axis in PTSD and stress-related disorders
Epigenetic effects of stress
Implications of epigenetics for the treatment of PTSD and related disorders
Conclusions
Acknowledgments
References
Chapter 20. Epigenetics and cognitive disorders
Abstract
Introduction: role of epigenetics in memory and neurodegeneration
DNA methylation
Histone modifications
DNA methylation changes and histone modifications in Alzheimer’s disease
DNA methylation changes and histone modifications in Huntington’s disease
DNA methylation changes and histone modifications in Parkinson’s disease
Conclusions
References
Chapter 21. Epigenetics in intellectual disability
Abstract
Introduction
Definition of epigenetics
Types of epigenetic disruption in ID
Abnormal epigenetic silencing in ID
Mutations in genes encoding epigenetic regulators
Summary and conclusions
References
Chapter 22. Epigenetics and pervasive developmental disorders
Abstract
Introduction
Common pathways and mechanisms in NDDs
Epigenetics as an explanation of variability in developmental disorders
Control of transcription is key in the process of gene expression and is the first line of epigenetic control
Epigenetic mechanisms and intellectual and neurodevelopmental disabilities
How do epigenetic modifications contribute to diversity?
Examples of human neurodevelopmental disorders with autistic features linking epigenetics and phenotype variation
What is the function of MeCP2?
Epigenetics and imprinting disorders
Epigenetic interactions between ASD and NDD conditions
X-Linked disorders associated with ID
Copy number variations
Can drugs be developed for NDDs based on epigenetics?
Conclusions
References
Chapter 23. Epigenetics in child psychiatry
Abstract
Introduction
Epigenetics and pediatric neuropsychiatric disorders
Prenatal human neurodevelopment
Postnatal DNA methylation
Attention deficit hyperactivity disorder
ADHD medications and gene expression
Epigenetic mechanism and treatment
Conclusion
References
Chapter 24. Epigenetic mechanisms of drug addiction vulnerability
Abstract
Introduction
Epigenetic response to drugs of abuse
Vulnerability to drug addiction
Epigenetic inheritance of addiction
Future directions
Conclusions
References
Chapter 25. Alcohol use disorder and associated alterations in brain epigenetic marks
Abstract
Introduction
Histone modifications in alcohol use disorder
Non-coding RNAs and RNA modifications in alcohol use disorder
DNA methylation: a novel biomarker for alcohol use disorder
Conclusion
Acknowledgments
References
Section 3: Epigenetic effects of currently used psychotropic drugs
Chapter 26. Epigenetic effects of currently used psychotropic drugs
Abstract
Introduction
Epigenetic effects of antipsychotics
Epigenetic effects of anxiolytics
Epigenetic effects of antidepressants
Monoamine oxidase inhibitors
Epigenetic effects of mood stabilizers
Epigenetic effects of valproic acid
Epigenetic effects of lithium salts
Epigenetic effects of lamotrigine
Conclusions
Acknowledgments
References
Chapter 27. DNA methyltransferase inhibitors and psychiatric disorders
Abstract
Introduction
DNA methylation and DNMTs
DNA methylation and DNMTs in the developing and adult brain
DNMT inhibitors: currently available drugs and their mechanisms of action
Experimental use of DNMT inhibitors in neuroscience research: relevance for learning and memory
Therapeutic potential of DNMT inhibitors in schizophrenia
Therapeutic potential of DNMT inhibitors in depression
Therapeutic potential of DNMT inhibitors in bipolar disorders
Therapeutic potential of DNMT inhibitors in posttraumatic stress disorder
Conclusions, future directions, and challenges
References
Chapter 28. Histone Deacetylase Inhibitors and Psychiatric Disorders
Abstract
Introduction
HATs and HDACs maintain transcription homeostasis
HDACs
HDAC types
HDACs in normal brain, behavior and in psychopathology
HDAC class IIa
HDAC class IIb
HDAC class III
HDAC class IV
HDAC inhibitors
Clinical trials of HDACi
HDACi tested in animal models of neuropsychiatric disorders
HDACi in psychotic disorders (e.g., schizophrenia, bipolar disorder)
HDACi in MDD
HDACi in drug addiction
HDACi in neurological disorders
HDACi classes
Short-chain fatty acids (COOH group)
Hydroxamates (NHOH group)
Linear cap hydroxamates
Branched hydroxamates
Hydroxamates with variable linker/linkerless regions
Benzamides (PhNH2)
Cyclic tetrapeptides
Ketone group
Constraints in the development of HDACi as therapeutics for CNS disorders
Recent efforts to develop selective HDACi
Design of future HDACi for psychiatric disorders
Acknowledgments
References
Chapter 29. Epigenetics in psychotherapy
Abstract
Introduction
Findings linking psychotherapy with epigenetic changes
Conclusion/future directions
References
Chapter 30. Functional genomics of psychiatric disease risk using genome engineering
Abstract
Introduction
Identification of putative causal risk variants in neuropsychiatry
Introduction to human induced pluripotent stem cells
Genome engineering in neuropsychiatry
Large-scale and high-throughput applications of CRISPR engineering
Future advances towards large-scale functional validation of non-coding elements in brain cells
Conclusions
Acknowledgments
Conflict of interest
References
Section 4: Nutritional effects on epigenetics in psychiatry
Chapter 31. Nutritional effects on epigenetics in psychiatry
Abstract
Introduction
Nutritional epigenetics: the link between nutrition and epigenetics
Effects of nutrition on DNA methylation
Effect of nutrition on histone modifications
Effects of nutrition on RNA-mediated regulation of gene expression
Nutritional effects on epigenetics in psychiatry
Effects of prenatal nutrition on epigenetics in psychiatry
Effects of postnatal nutrition on epigenetics in psychiatry
Transgenerational (heritable) effects of nutrition on epigenetics in psychiatry
Clinical applications of nutritional effects on epigenetics in psychiatry
Use of methyl donors in major depressive disorder
Use of methyl donors in the treatment of major psychoses
Use of methyl donors in cognitive disorders
Concluding remarks
References
Chapter 32. Systems biology and the epigenetics of psychiatric disorders
Abstract
Introduction
Relevance of systems biology in elucidating the pathogenesis of psychiatric disorders
Relevance of systems biology in identifying epigenetic biomarkers in psychiatric disorders
Relevance of systems biology in identifying drugs for psychiatric disorders
Current consortia and projects in psychiatric disorders involving systems biology
Concluding remarks
References
Chapter 33. Transgenerational epigenetics and psychiatric disorders
Abstract
A novel non-Mendelian mechanism of inheritance
Evidence for transgenerational transmission of disease risk
Molecular mechanisms for epigenetic inheritance
Epigenetic inheritance of psychiatric disease-related behaviors in animal models
Evidence for transgenerational transmission from human studies
Conclusion
References
Chapter 34. Epigenetic aspects of the microbiota and psychiatric disorders
Abstract
Introduction
Effects of the host on the microbiota
Non-epigenetic effects of the microbiota on the host
Epigenetic effects of the microbiota on the host
Effects on DNA methylation
Effects on histone modifications
Effects on non-coding RNAs
Epigenetic aspects of the microbiota and psychiatric disorders
Epigenetic effects of the microbiota on brain development
Epigenetic effects of the microbiota on normal behavior
Non-epigenetic effects of the microbiota on psychiatric disorders
Epigenetic effects of the microbiota on psychiatric disorders
Concluding remarks
References
Index

Jacob Peedicayil

Dr Jacob Peedicayil completed MBBS in 1984 and MD in pharmacology in 1991, both at the Christian Medical College, Vellore, India. From 1993 to 1995 he did a Post-Doctoral Fellowship at the Centre for Cellular and Molecular Biology, Hyderabad, India. From 1995 to 1998 he worked as a Research Fellow in the Department of Neurological Sciences, Christian Medical College, Vellore. Since 1998 he has been on the faculty of the Department of Pharmacology and Clinical Pharmacology, Christian Medical College, Vellore, becoming a professor in 2007. He does theoretical research on epigenetics, focusing on epigenetics in psychiatry. In addition, he is involved in experimental research in smooth muscle pharmacology.

Affiliations and expertise

Professor, Department of Pharmacology and Clinical Pharmacology, Christian Medical College, Vellore, India

Dennis R. Grayson

Dr Dennis R. Grayson received his PhD from the Department of Biochemistry at Wayne State University School of Medicine in 1984. He has been interested in mechanisms associated with gene expression for over 35 years. He joined the laboratory of Dr James E. Darnell at the Rockefeller University as a Post-Doctoral Fellow in 1984 to study cell-type specific transcription factors and their interaction with promoters and enhancers. In 1988, Dr Grayson joined the Fidia-Georgetown Institute for the Neurosciences at Georgetown University to study gene expression programs in neurons and continued this research program at Allegheny Singer Research Institute in Pittsburgh from 1995 to 1998. He continued his interests in psychiatry and joined the Psychiatric Institute at the University of Illinois in 1998. This represented a unique opportunity to pursue the molecular underpinnings of schizophrenia. Dr Grayson has received NRSA post-doctoral support, and R01 and K04 funding from the National Institutes of Health to support his work. He has published over 140 papers in peer-reviewed journals and is regularly invited to speak at numerous national and international meetings. He is currently Director of the Epigenetic Core of the Center for Alcohol Research in Epigenetics.

Affiliations and expertise

Professor of Molecular Neuroscience, University of Illinois at Chicago, IL, USA

Dimitri Avramopoulos

Dr. Dimitrios Avramopoulos received his MD from the University of Athens, Greece in 1990 and his PhD from the University of Crete in 1995 for his work on mapping human genes on chromosome 21 and deciphering the origin of chromosomal non-disjunction in trisomy 21, mentored by Dr Stylianos Antonarakis. He undertook his post-doctoral work at Johns Hopkins University where he became a faculty member in the Department of Psychiatry in 2002. He is currently on the faculty of the Department of Genetic Medicine and the Department of Psychiatry at Johns Hopkins University where he works on the genetics of psychiatric disorders. He is interested in the identification and functional follow up of disease-causing variants in the genome. He uses cellular models and genome editing to decipher the mechanisms through which disease - associated variants affect the brain, individually or in combinations, through the disruption of functional networks and the regulation of the corresponding genes.

Affiliations and expertise

Associate Professor of Genetic Medicine, Johns Hopkins, Medicine, Baltimore, MD, USA

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Epigenetics in Psychiatry

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Jacob Peedicayil

Dennis R. Grayson

Dimitri Avramopoulos

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