Biomarkers in Bipolar Disorders

1st Edition - January 16, 2022
Editors: Rodrigo Machado-Vieira, Jair Soares
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 2 1 3 9 8 - 8
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 2 1 3 9 9 - 5

Biomarkers in Bipolar Disorders summarizes cutting-edge findings in biomarkers' research, emphasizing the most promising findings, tools and technologies relevant to drug developme… Read more

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Biomarkers in Bipolar Disorders summarizes cutting-edge findings in biomarkers' research, emphasizing the most promising findings, tools and technologies relevant to drug development and personalized medicine. Key findings cover different levels of evidence such as genes, molecules, cells, systems, brain and behavior related to diagnosis (state and trait/endophenotypes), prediction of treatment response and follow-up outcomes, along with the most promising perspectives in each area. Each section includes a comprehensive and focused overview on the state-of-the-art and perspectives. The book concludes with a section on practical applications, encompassing diagnostics development (genetic testing, biomarkers), and new drug development.

Edited by Dr. Rodrigo Machado-Vieira and Dr. Jair C. Soares, and contributed by leading experts in the field of biomarker research, this book will be become the leading tool for all researchers and clinicians in Bipolar Disorder.

Cover image
Title page
Table of Contents
Copyright
List of contributors
Preface
Chapter 1. Biomarkers in bipolar disorder: an overview
Abstract
1.1 Introduction
1.2 Biomarker definition and rationale for biomarkers in bipolar disorder
1.3 Biomarker categories and potential uses in bipolar disorder
1.4 Biomarkers in bipolar disorder: current limitations
1.5 Future directions in the field of biomarkers in bipolar disorder
1.6 Conclusion
References
Chapter 2. Neural biomarkers of suicidal behavior: from cognition and circuits to cells (and back)
Abstract
2.1 Neurocognitive studies of suicidal behavior
2.2 Postmortem brain research: exploring the cellular and molecular roots of suicide
Acknowledgment
References
Chapter 3. Metabolomics of bipolar disorder
Abstract
3.1 Metabolomics in psychiatric disorders
3.2 Biomarkers in bipolar disorder
3.3 Metabolomics in bipolar disorder
3.4 Future directions of metabolomics as a tool for biomarker discovery and clinical implications
References
Chapter 4. Behavioral models of bipolar disorder
Abstract
4.1 Background
4.2 Animal models of mania
4.3 Mania-like behavior assessment in animals
4.4 Animal models of depression
4.5 Depressive-like behavior assessment in animals
4.6 Conclusions and future directions
References
Chapter 5. Structural neuroimaging markers in bipolar disorder
Abstract
5.1 Introduction
5.2 Biomarker concepts and neuroimaging markers in psychiatry
5.3 Structural neuroimaging in psychiatry
5.4 Neuroimaging as a tool to improve the diagnostic accuracy of bipolar disorder
5.5 Neuroimaging markers in high-risk populations
5.6 Summary and conclusions
References
Chapter 6. Magnetic Resonance Spectroscopy in Bipolar Disorder
Abstract
6.1 Background
6.2 Proton magnetic resonance spectroscopy
6.3 Metabolite abnormalities in bipolar disorder
6.4 Brain regions involved in cognitive and affective regulation
6.5 Conclusion and future directions
References
Further reading
Chapter 7. Precision psychiatry in bipolar disorder
Abstract
7.1 Introduction
7.2 Diagnosis and differential diagnosis
7.3 Prognosis prediction
7.4 Suicidality prediction
7.5 Treatment selection
7.6 Supervised and unsupervised learning
7.7 Conclusion
References
Chapter 8. Genome-wide association study biomarkers in bipolar disorder
Abstract
8.1 Introduction
8.2 Generic epidemiology: heritability and family studies
8.3 Genome-wide association studies
8.4 Recent results of genome-wide association studies in bipolar disorder
8.5 Fine mapping: from loci to genes
8.6 Common variant heritability and coheritability
8.7 Polygenic risk scores
8.8 Missing heritability
8.9 Genome-wide association studies and treatment of bipolar disorder (pharmacogenetics)
8.10 Challenges and opportunities for the next era of genome-wide association studies in bipolar disorder
8.11 Conclusions
References
Chapter 9. Mitochondrial dysfunction in bipolar disorder
Abstract
9.1 Introduction
9.2 Proposal of mitochondrial hypothesis
9.3 Cellular models
9.4 Cerebrospinal fluid
9.5 Genetics
9.6 Postmortem brains
9.7 Animal models
9.8 Drug discovery research
9.9 iPS cell model
9.10 Molecular and cellular pathogenesis in the paraventricular thalamic nucleus (PVT) and action mechanisms of antibipolar drugs
9.11 Neural circuits around the paraventricular thalamic nucleus (PVT)
9.12 Conclusion
Acknowledgments
References
Chapter 10. Mechanisms of aging in bipolar disorder
Abstract
10.1 Introduction
10.2 Cellular senescence and telomere attrition in bipolar disorder
10.3 Epigenetic alterations, DNA damage, and genomic instability
10.4 Mitochondria dysfunction
10.5 Altered intercellular communication
10.6 Concluding remarks
References
Chapter 11. Neuroprogression in bipolar disorder
Abstract
11.1 Introduction
11.2 Clinical evidence of neuroprogression
11.3 Biological basis of neuroprogression
11.4 Future perspectives of the field
11.5 Conclusions
References
Chapter 12. Neuroimmune pathways in bipolar disorder
Abstract
12.1 On the search for the “black bile”
12.2 Immune system: an overview
12.3 Evidence of immune dysfunction in bipolar disorder
12.4 Immune (cerebrospinal fluid and blood) markers of diagnosis in other psychiatric conditions (major depressive disorder and schizophrenia)
12.5 Integrating immune dysfunction with the pathogenesis, physiopathology, and prognosis of bipolar disorder
12.6 Immune-based strategies for bipolar disorder
12.7 Immune markers as predictors of treatment mood response
12.8 Conclusion
References
Chapter 13. Glutamate-based preclinical and clinical dysfunction and treatment in bipolar disorder
Abstract
13.1 Preclinical
13.2 Clinical
13.3 Treatment
13.4 Conclusion
References
Chapter 14. Neurocognitive endophenotypes in bipolar disorders
Abstract
14.1 Cognitive dysfunctions in bipolar disorders
14.2 Impact of cognitive dysfunctions in bipolar disorders
14.3 Concept of endophenotypes
14.4 Neurocognitive endophenotypes in bipolar disorders
14.5 Conclusion
References
Chapter 15. DNA methylation in bipolar disorder
Abstract
15.1 Introduction
15.2 DNA methylation and bipolar disorder diagnosis
15.3 DNA methylation and treatment response in bipolar disorder
15.4 DNA methylation and animal and preclinical model studies of bipolar disorder
15.5 Summary
References
Chapter 16. Biomarkers of lithium efficacy in bipolar disorders
Abstract
16.1 Lithium’s efficacy
16.2 Biomarkers of lithium prophylaxis efficacy
16.3 Biomarkers for lithium efficacy in acute mood episodes
16.4 Conclusions
References
Chapter 17. Neuroendocrine and stress pathways in bipolar disorders
Abstract
17.1 Introduction
17.2 The hypothalamus–pituitary–adrenal axis
17.3 Steroid hormones
17.4 Mineralocorticoid receptors and glucocorticoid receptors
17.5 Neuroendocrine function test
17.6 Impact of stress on bipolar disorders
17.7 Conclusion
References
Chapter 18. Intracellular signaling cascades in bipolar disorder
Abstract
18.1 Introduction
18.2 Calcium signaling
18.3 Diacylglycerol and protein kinase C pathways
18.4 GSK3-β and Wnt pathways
18.5 Brain-derived neurotrophic factor
18.6 Mitochondrial dysfunction
18.7 Conclusion
References
Chapter 19. Circadian biomarkers of bipolar disorder
Abstract
19.1 Biomarkers of bipolar disorder
19.2 Objectively measured sleep, activity, and circadian rhythms
19.3 Endophenotypes for bipolar disorder
19.4 Summary, challenges, and opportunities for future research
Acknowledgments
References
Chapter 20. DNA damage and repair mechanisms in bipolar disorder
Abstract
20.1 Introduction
20.2 Oxidative stress and its relevance to bipolar disorder
20.3 DNA damage and repair mechanisms
20.4 DNA damage markers in bipolar disorder
20.5 Quantification of 8-oxo-dG in bipolar disorder
20.6 DNA damage and affective states of bipolar disorder
20.7 DNA repair markers in bipolar disorder
20.8 Future directions
References
Chapter 21. Microbiome and bipolar disorder
Abstract
21.1 The microbiota-gut-brain axis: a new approach in bipolar disorder biomarkers
21.2 The microbiota-gut-brain axis
21.3 Microbiota-gut-brain axis and bipolar disorder: gut microbiota as a potential biomarker for bipolar disorder
21.4 Main limitations of current research on microbiota-gut-brain axis and bipolar disorder
21.5 Conclusions and future directions
References
Chapter 22. Inflammation, stress, and gut-brain axis as therapeutic targets in bipolar disorder
Abstract
22.1 Introduction
22.2 Gastrointestinal dysfunction and inflammation
22.3 Gastrointestinal dysfunction in psychiatric disorders
22.4 What is the human gut microbiota?
22.5 The microbiome-gut-brain axis
22.6 Microbiome-gut-brain-axis findings in neuropsychiatric disorders
22.7 Human studies
22.8 Bipolar disorder
22.9 Treatment
22.10 Conclusion and future directions
References
Chapter 23. Bipolar disorder and plasticity: a key target for new treatment
Abstract
23.1 Introduction
23.2 Concepts of plasticity and implications in bipolar disorder
23.3 Cellular studies
23.4 Neuroimaging studies
23.5 Drugs development targeting GSK-3β
23.6 Summary
References
Chapter 24. Proteomic biomarkers for bipolar disorder
Abstract
24.1 Introduction
24.2 The development of proteomic techniques
24.3 Proteome characterization of the peripheral blood
24.4 Current status
24.5 Differentially abundant proteins
24.6 Biological processes and pathways
24.7 The future of “OMICS”
24.8 Future directions
References
Further reading
Chapter 25. Pharmacogenomics in bipolar disorder: towards precision psychiatry and personalized treatment
Abstract
25.1 Background
25.2 Pharmacogenomics and genetic variation
25.3 Pharmacokinetic: drug metabolism
25.4 Pharmacogenomics of drugs commonly used in bipolar disorder
25.5 Future directions for the field
References
Index

Rodrigo Machado-Vieira

Rodrigo Machado-Vieira, MD, PhD, MSc, is a Professor of Psychiatry and Director of the Experimental Therapeutics and Molecular Pathophysiology Program at the University of Texas, UTHealth, Houston. He was previously at the Intramural National Institute of Mental Health (NIMH), where he was the Director of the Translational Research Clinic in Mood Disorders at the Experimental Therapeutics and Pathophysiology Branch. Machado-Vieira received his MD from PUC-RS in Porto Alegre, Brazil and his PhD in Psychiatry at the University of Sao Paulo, following his Residency Training in Psychiatry. After a postdoctoral fellowship at the Laboratory of Molecular Pathophysiology and Experimental Therapeutics at NIMH, he led the Mood Disorders Program, LIM-27 at the Institute of Psychiatry, University of Sao Paulo, Brazil. Dr. Machado-Vieira has received several grants and Awards for his research on Mood Disorders including the National Institutes of Health Fellows Award for Research Excellence, the Brazilian Psychiatric Association Award, the Gerald Klerman Young Investigator Award, Depression and Bipolar Support Alliance (DBSA), Sao Paulo Young Investigator Research Award, and the Stanley Medical Research Institute Research Award. He was Chair of the Nominating Committee of the International Society for Bipolar Disorders (ISBD). Dr. Machado-Vieira published more than 200 articles published and over 12,500 citations.

Affiliations and expertise

Department of Psychiatry and Behavioral Sciences, University of Texas, UTHealth, McGovern Medical School

Jair Soares

Dr. Jair C. Soares joined UTHealth in 2009 as Professor and Chair of the department of Psychiatry and Behavioral Sciences, and the Pat R. Rutherford, Jr. Chair in Psychiatry at the McGovern Medical School, as well as the Executive Director of UTHealth Harris County Psychiatric Center. A Board-certified psychiatrist, he also serves as Chief of Psychiatry Services at Memorial Hermann Hospital and LBJ Hospital. The sites provide patient care and are clinical training and research facilities for UTHealth medical students, psychiatry residents and psychiatry fellows. Dr. Soares directs the UTHealth Center of Excellence on Mood Disorders, which focuses on the search for causes and the development of new treatments for mood disorders. The Center is comprised of an active research team that specializes in clinical neurosciences (neuroimaging, neurophysiology, cognitive neurosciences, and genetics) and clinical psychopharmacology and interventions research. Dr. Soares received his medical degree from the University of Sao Paulo (Brazil) and completed a general psychiatry residency at the Western Psychiatric Institute and Clinic at the University of Pittsburgh. Subsequently, Dr. Soares completed a brain imaging fellowship at the Yale University School of Medicine Department of Psychiatry. He obtained a PhD in medical sciences at the Federal University of Rio Grande do Sul (Brazil). Prior to joining UTHealth, Dr. Soares served as the Distinguished Professor of Psychiatry and Director of the Center of Excellence for Research and Treatment of Bipolar Disorders at the University of North Carolina at Chapel Hill, and as Deputy Chair for Research and Division Chief for Mood and Anxiety Disorders with the Department of Psychiatry at The University of Texas Health Science Center at San Antonio. Dr. Soares has published more than 350 peer-reviewed articles and book chapters in the psychiatric literature and has held editorial positions on a number of national and international medical journals. His research has been funded over the years by multiple grants from NIH, VA, private foundations and the pharmaceutical industry. Since April 2015, he has been the co-editor in chief for the Journal of Affective Disorders. Since 2018, he has served as president of the International Society on Affective Disorders. He also is co-editor in chief for a new spin-off publication, Journal of Affective Disorders Reports, which was launched in 2020. Currently he serves as president-elect for the American Association for Chairs of Academic Departments of Psychiatry. He also serves in the finance committee and in the travel award committee for the International Society for Clinical Trials Methodology (ISCTM).

Affiliations and expertise

Professor, Chair and Pat R. Rutherford Chair in Psychiatry McGovern Medical School Department of Psychiatry and Behavioral Sciences Chief Executive Officer, UTHealth Harris County Psychiatric Center

Life Sciences

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Biomarkers in Bipolar Disorders

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Rodrigo Machado-Vieira

Jair Soares