Psychiatric Genomics

1st Edition - March 17, 2022
Editors: Evangelia Eirini Tsermpini, Martin Alda, George P. Patrinos
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 1 9 6 0 2 - 1
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 2 1 4 0 0 - 8

Psychiatric Genomics presents and synthesizes available knowledge in the field of psychiatric genomics, offering methodologies to advance new research and aid clinical translati… Read more

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Psychiatric Genomics presents and synthesizes available knowledge in the field of psychiatric genomics, offering methodologies to advance new research and aid clinical translation. After providing an introduction to genomics and psychiatry, international experts discuss the genomic basis of schizophrenia, bipolar disorder, depression, personality disorders, anxiety disorders, addictions, eating disorders, and sleep disorders, among other disorders. In addition, recommendations for next steps in clinical implementation and drug discovery are discussed in-depth, with chapters dedicated to pharmacogenomics and antipsychotics, antidepressants and mood stabilizers, adverse drug reactions, implementation of pharmacogenomics in psychiatric clinics, and ethical issues.

Finally, methods sections provide a solid grounding in research approaches and computational analytics, from using animal models in psychiatric genomics and accessing biobanks, to employing computational analysis, genome-wide association studies (GWAS), brain pathophysiology, and endophenotypes in psychiatric research.

Cover image
Title page
Table of Contents
Copyright
Dedication
List of contributors
About the editors
Preface
Chapter 1. Genomics and psychiatry: a historical overview
Abstract
Introduction
The Middle Ages
The 18th century
Era of enlightenment
The 19th century
The 20th century
Twin studies
Adoption studies
Modern family studies
DNA sequencing
21st century
Human genome project
Genome-wide association studies
Consortia
Lessons learned from history
References
Chapter 2. Schizophrenia genomics
Abstract
Introduction
Schizophrenia heritability
Molecular genetics before genomics
Defining the phenotype
Genome-wide association studies
Rare structural risk variants
Genome sequencing studies
Lessons learned from schizophrenia genomics
Conclusion
References
Chapter 3. Genetics of bipolar disorder
Abstract
Introduction
Family and adoption studies
Genome-wide association studies
GWAS in BD
Genetic architecture of BD
From genetic loci to disease mechanisms
Rare genetic variants in BD
Potential clinical implications of BD genetics
Conclusion
Acknowledgments
Competing financial interests
References
Chapter 4. Genetics of depression
Abstract
Genetic factors affecting the onset of depression
Conclusions
References
Chapter 5. Genetics of personality disorders
Abstract
Introduction
First evidence of genetic predisposition in personality disorders
Genome-wide associations studies in personality disorders
Conclusions
References
Chapter 6. Genomics and epigenomics of anxiety and obsessive-compulsive disorders
Abstract
Clinical genetics, molecular genetics, gene-environment interactions and epigenetics of anxiety disorders
Molecular genetics
Gene–environment interactions and epigenetics
Molecular genetics
Gene–environment interactions and epigenetics
Therapy (epi)genetics of anxiety and OCDs
Conclusion
References
Chapter 7. Neurogenetics of alcohol use disorder a subset of reward deficiency syndrome: candidate genes to be or not to be?
Abstract
Introduction—a historical overview
Finding the first alcohol gene
Understanding polygenic inheritance of alcoholism and links to opioids
GARS case–controls and targeted endophenotypes for alcohol abuse and alcoholism
Importance of genome wide association studies: convergence to candidates
Conclusion
Acknowledgments
Author contribution
Funding
Conflict of interest
References
Chapter 8. Pharmacogenomics and antipsychotics: efficacy and adverse drug reactions
Abstract
Introduction
Pharmacogenetics of antipsychotics metabolizing enzymes and drug targets
Pharmacogenes involved in antipsychotic metabolism and transport
Pharmacogenomics of antipsychotic efficacy
Candidate gene studies of treatment response
Genomic studies of antipsychotic efficacy
Epigenetics of treatment response
Pharmacogenetics of antipsychotic-induced adverse drug reactions
Tardive dyskinesia
Clozapine-induced agranulocytosis and neutropenia
Antipsychotic-induced weight gain
Pharmacogenetic-based treatment guidelines for antipsychotics
Pharmacogenomic testing
Clinical implementation studies
Conclusions
References
Chapter 9. Pharmacogenomics and antidepressants: efficacy and adverse drug reactions
Abstract
Financial disclosures (last 3 years)
Cautionary statements
Safety versus efficacy, and pharmacokinetics versus pharmacodynamics
Pharmacokinetic pharmacogenomics and efficacy
Pharmacodynamic pharmacogenomics and efficacy
Antidepressant efficacy trials using combinatorial pharmacogenomic panels
Clinical implications and future directions
Conclusions
References
Chapter 10. Pharmacogenomics and mood stabilizers: efficacy and adverse drug reactions
Abstract
Introduction
Pharmacogenomics of lithium
Pharmacogenomics of other mood stabilizers
Discussion
References
Chapter 11. Balancing prevention and respect: the ethical stakes of a psychiatric genomics lens for mental disorder and intellectual disability
Abstract
Introduction
Conceptual framing and ethical orientation: points of divergence
Challenging projections of suffering
Responding to the ethical stakes
Conclusion
Acknowledgment
References
Chapter 12. Genetic animal models for psychiatric disorders
Abstract
Genetic evidence, epidemiology, and genetic animal models
Schizophrenia
Bipolar disorder
Major depressive disorder
Conclusion
References
Chapter 13. Psychiatric genomics: brain pathophysiology and genetic factors
Abstract
Introduction
Autism spectrum disorders
Schizophrenia
Major depressive disorder
Panic disorder
Conclusions
References
Chapter 14. Integration with systems biology approaches and -omics data to characterize risk variation
Abstract
Introduction
Functional annotation of noncoding regions
Context-specific genetic regulation
Mapping GWAS to QTLs
Multi-QTL methods
Annotation of variants to gene pathways
Conclusion/Future Directions
References
Chapter 15. Usage of biobank data for psychiatric genomics and promotion of precision psychiatry
Abstract
Introduction to biobanks
Psychiatric genomics in a biobank setting
Contextualizing the limitations of biobanks for psychiatric genomics
Algorithmic phenotyping
Evaluation of algorithmic phenotyping
Chart review
Automated phenotyping
Major impact of biobanks on psychiatric genomics research
Applications to genome-wide association studies
Phenome-wide and lab-wide association studies
Practicing the implementation of precision psychiatry
Ethical considerations
Future directions
References
Chapter 16. Shared heritability among psychiatric disorders and traits
Abstract
Heritability
Shared heritability, genetic overlap, and pleiotropy
Evaluating genetic overlap
Rare variant genetic overlap
Implications for psychiatry
Conclusion
Acknowledgments
Competing financial interests
References
Chapter 17. Endophenotypes in psychiatric genomics: a selective review of their status and a call to action
Abstract
Introduction and context: The endophenotype construct
Progress in identifying genomic endophenotypes
Questioning the clinical utility of endophenotypes
Advancing a dimensional understanding of psychopathology
Clinical translation of endophenotypes
Race and racism in psychiatric genomics
Conclusions
Acknowledgment
References
Index

Evangelia Eirini Tsermpini

Dr. Evangelia Eirini Tsermpini is a postdoctoral researcher at the Laboratory of Pharmacogenetics, Faculty of Medicine, University of Ljubljana in Slovenia, since September 2021. She obtained her Ph.D. in 2016 from the Department of Pharmacy of the University of Patras, where she worked in the Laboratory of Pharmacogenomics and Personalized Therapy under the supervision of Professor George Patrinos. After her Ph.D., she worked as an academic scholar at the Departments of Medicine and Pharmacy of the University of Patras, and a senior research scientist and group leader at the Laboratory of Pharmacogenomics and Personalized Therapy at the Department of Pharmacy of the University of Patras, until July 2021. She was a visiting scholar at the Division of Pharmacotherapy and Experimental Therapeutics of the UNC Eshelman School of Pharmacy at the University of North Carolina, a research associate at RIKEN, Genomic Research Center for Integrative Medical Sciences in Japan, as well as at the Department of Neuroscience and Clinical Pharmacology, University of Cagliari, in Italy. Her field of expertise is psychiatric genomics, pharmacogenomics, transcriptomics and epigenomics. Her research is related to identifying genetic biomarkers associated with the development of schizophrenia, bipolar disorder, depression, alcohol use disorder and psychiatric drugs response. Other research interests include discovering and assessing miRNAs biomarkers for early diagnosis of schizophrenia and antipsychotic response and investigating leukocyte telomere length in mental disorders. Furthermore, from 2016 and until 2021 she was actively involved in the First European Implementation study, funded by the European Commission. Dr. Tsermpini has received twice the first prize for the high quality of research during her Ph.D. She has published 28 scientific articles, six chapters in international peer-reviewed journals and textbooks, and many abstracts in international conference proceedings. She is a reviewer for several scientific journals and an evaluator in grant evaluation committees.

Affiliations and expertise

Laboratory of Pharmacogenetics, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

Martin Alda

Martin Alda, MD, FRCPC is a Professor of Psychiatry and Killam Chair in Mood Disorders at Dalhousie University in Halifax, Canada. An active clinician, Dr. Alda works as the head of the Mood Disorders Program at the QEII Health Sciences Centre in Halifax. After graduating from the medical school at Charles University in Prague, he trained in psychiatry at Charles University and at the University of Ottawa. Dr. Alda’s work has been at the junction of clinical and basic research, investigating genetic and neurobiological markers of mood disorders and response to treatment. His clinical, genetic, pharmacogenetic, and brain imaging studies are based on carefully characterized prospective clinical samples and their aim is to develop methods of personalized treatment in psychiatry.

Affiliations and expertise

Professor and Killam Chair in Mood Disorders, Department of Psychiatry, Dalhousie University; Head, Mood Disorders Program NS Health Authority, Halifax, Nova Scotia, Canada

George P. Patrinos

George P. Patrinos is Professor of Pharmacogenomics and Pharmaceutical Biotechnology in the University of Patras (Greece), Department of Pharmacy, Head of Division of Pharmacology and Biosciences of the same Department and holds adjunct Full Professorships at Erasmus MC, Faculty of Medicine, Rotterdam (the Netherlands) and the United Arab Emirates University, College of Medicine, Department of Genetics and Genomics, Al-Ain (UAE). Also, since March 2018, he is Chair of the Global Genomic Medicine Collaborative (G2MC) and since May 2023 Chairman of the Scientific Advisory Board of the ASPIRE Abu Dhabi Precision Medicine Research Institute. He has ample regulatory experience, as he served for 12.5 years as Full Member and Greece’s National representative in the CHMP Pharmacogenomics Working Party of the European Medicines Agency (EMA) and he is still an active member of the European Medicines Agency participating in expert panels to provide scientific advice where needed. George is currently Director of the Laboratory of Pharmacogenomics and Individualized Therapy, the first officially established academic pharmacogenomics laboratory in Greece. His group has keen interest in research covering disciplines from wet and dry lab and public health genomics projects, all focusing on pharmacogenomics and personalized medicine. In particular, his research interests involve discovery work and clinical implementation of pharmacogenomics, focusing in particular in psychiatry but also cardiology and oncology, genomics of rare disorders and transcriptional regulation of human fetal globin genes. Moreover, George’s group is internationally recognized for its involvement in developing National/Ethnic Genetic databases to document the genetic heterogeneity in different populations worldwide and of genome informatics tools to translate genomic information into a clinically meaningful format. Also, George’s group has a keen interest in public health genomics to critically assess the impact of genomics to society and public health. George has more than 330 publications in peer-reviewed scientific journals, some of them in leading scientific journals, such as The Lancet and Lancet EBioMedicine. Also, he has co-authored and co-edited more than 15 textbooks, among which the renowned textbook “Molecular Diagnostics”, published by Academic Press, now in its 3^rd edition, while he is the editor of “Translational and Applied Genomics” book series, published by Elsevier. Furthermore, since September 2020, he serves as Editor-In-Chief of the prestigious Pharmacogenomics Journal (TPJ), published by Nature Publishing Group, Associate Editor and member of the editorial board of several scientific journals and has been a member of several international boards and advisory and evaluation committees. Apart from that, George is the main co-organizer of the Golden Helix Conferences, an international meeting series on Pharmacogenomics and Genomic Medicine with more than 50 conferences organized in more than 25 countries worldwide.

Affiliations and expertise

Department of Pharmacy, School of Health Sciences, University of Patras, Patras, Greece; Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates; Zayed Center of Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates