Biomarkers in Bipolar Disorders

Biomarkers in Bipolar Disorders

1st Edition - January 16, 2022

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  • Editors: Rodrigo Machado-Vieira, Jair Soares
  • Paperback ISBN: 9780128213988
  • eBook ISBN: 9780128213995

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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.

Key Features

  • Describes strategies for the biomarker discovery of relevant proteins differentially expressed in Bipolar Disorder
  • Presents techniques and main findings in transcriptome research related to CNS synaptic function
  • Provides an overview on current behavioral strategies and their validity in drug development in Bipolar Disorder
  • Discusses current genetic findings, integrating tests for treatments leading to personalized treatments


Advanced students and researchers in neuroscience, psychology, medicine, health sciences, and pharmacology. Clinicians treating patients with bipolar disorder

Table of Contents

  • 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

Product details

  • No. of pages: 528
  • Language: English
  • Copyright: © Academic Press 2022
  • Published: January 16, 2022
  • Imprint: Academic Press
  • Paperback ISBN: 9780128213988
  • eBook ISBN: 9780128213995

About the Editors

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

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