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Genomics, Circuits, and Pathways in Clinical Neuropsychiatry
- 1st Edition - June 7, 2016
- Editors: Thomas Lehner, Bruce L. Miller, Matthew W. State
- Language: English
- Hardback ISBN:9 7 8 - 0 - 1 2 - 8 0 0 1 0 5 - 9
- eBook ISBN:9 7 8 - 0 - 1 2 - 8 0 0 5 3 0 - 9
This foundational work comprehensively examines the current state of the genetics, genomics and brain circuitry of psychiatric and neurological disorders. It consolidates di… Read more
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Request a sales quoteThis foundational work comprehensively examines the current state of the genetics, genomics and brain circuitry of psychiatric and neurological disorders. It consolidates discoveries of specific genes and genomic regions associated with these conditions, the genetic and anatomic architecture of these syndromes, and addresses how recent advances in genomics are leading to a reappraisal of the biology underlying clinical neuroscience. In doing so, it critically examines the promise and limitations of these discoveries toward treatment, and to the interdisciplinary nature of understanding brain and behavior. Coverage includes new discoveries regarding autism, epilepsy, intellectual disability, dementias, movement disorders, language impairment, disorders of attention, schizophrenia, and bipolar disorder. Genomics, Circuits, and Pathways in Clinical Neuropsychiatry focuses on key concepts, challenges, findings, and methods in genetics, genomics, molecular pathways, brain circuitry, and related neurobiology of neurologic and psychiatric disorders.
- Provides interdisciplinary appeal in psychiatry, neurology, neuroscience, and genetics
- Identifies key concepts, methods, and findings
- Includes coverage of multiple disorders from autism to schizophrenia
- Reviews specific genes associated with disorders
- Discusses the genetic architecture of these syndromes
- Explains how recent findings are influencing the understanding of biology
- Clarifies the promise of these findings for future treatment
- List of Contributors
- Preface
- Section I. The Genome Tools and Methods
- Chapter 1. The Newly Emerging View of the Genome
- Introduction
- Conceptualizing DNA
- Information Flow in Biological Systems
- Key Definitions
- The Genome (DNA)
- Visualizing the Genome
- Large-Scale Structures in the Genome
- Small-Scale Structures in the Genome
- Multiple Roles
- Variation in the Genome
- Ethnicity and Population Frequency of Variants in the Genome
- Variation in Complex and Mendelian Disorders
- Chromatin (DNA, RNA, and Protein) and Epigenetics
- Regulatory Complexes
- Transcription (RNA)
- Posttranscriptional mRNA Modifications
- Translation
- Posttranslational Modifications
- Summary
- Chapter 2. Contribution of Genetic Epidemiology to Our Understanding of Psychiatric Disorders
- Introduction
- Background: Epidemiology
- Genetic Epidemiology of Psychiatric Disorders
- Applications of Genetic Epidemiology in Molecular Era
- Chapter 3. Natural Selection and Neuropsychiatric Disease: Theory, Observation, and Emerging Genetic Findings
- Introduction
- Epidemiology of Neuropsychiatric Disease
- Theoretical Considerations
- Hypothesis Testing: Epidemiology and Emerging Genetic Data
- Mendelian Randomization and Polygenic Risk
- De Novo Mutation and Mutation–Selection Balance
- Conclusions
- Chapter 4. Genome Tools and Methods: Rare Genetic Variation
- Rare Variants in Psychiatric Disease
- Genetic Variation
- Modern Technologies for Discovery of Rare Variants
- Microarray Technology and Large-Scale Copy Number Variants in Neurodevelopmental and Neuropsychiatric Disease
- Copy Number Variant Studies of Disease
- Studies of De Novo Mutation in Trio Families
- Case–Control Studies
- Analysis Strategies
- Detection of Rare Genetic Variation by High-Throughput Sequencing
- Rare Genetic Variation in Noncoding DNA: A New Frontier
- Rare Genetic Variants and the Potential to Affect Clinical Care
- Chapter 5. Neuroepigenomics and Human Disease
- Epigenetics
- Epigenetics in Neurobiological Research
- The Genomic Context of Transcriptional and Epigenetic Mechanisms
- Transcriptional and Epigenetic Regulatory Mechanisms
- Epigenetic Perturbation and Epigenome-Wide Assays
- Cell Type Choices in Neuroepigenomic Studies
- Interaction of the Genome With the Epigenome
- Epigenetics Mechanisms of Brain Diseases: General Principles and Future Directions
- Chapter 6. Bioinformatics in Neuropsychiatric Genomics
- What is Bioinformatics?
- Databases
- Methods
- Tools
- Standards
- Summary
- List of URLs
- Chapter 7. Imaging Genomics and ENIGMA
- Introduction
- Power of MRI
- What Is Imaging Genomics?
- Mapping Brain Diseases in Neurology
- MRI Versus Cellular Measures
- Mapping Brain Disorders: Psychiatry
- Psychiatric Neuroimaging Expands Worldwide
- ENIGMA Studies of Brain Disease
- Defusing Controversy With Meta-Analysis
- Imaging Genomics and Genome-Wide Association Studies
- Genetic Influences on the Brain
- Genes and Disease Risk
- Manhattan Plots
- Candidate Genes and Genome-Wide Association Studies
- Genome-Wide Significance
- Formation of ENIGMA in 2009
- Surprises From Imaging Genomics Consortia
- Other Neuroimaging Methods
- Multivariate Imaging Genomics and Big Data
- Searching the Brain for Gene Effects
- Conclusions
- Chapter 8. Brain in a Dish: Stem Cell Technologies to Study Disorders of the Central Nervous System
- Generating Induced Pluripotent Stem Cells
- Progress in Modeling Human Central Nervous System Pathology: Neurodevelopmental Disorders
- Rett Syndrome
- Fragile X Syndrome
- Angelman Syndrome
- Timothy Syndrome
- Contribution of Different Cell Types to Neurodevelopmental Disorders
- The Next Step of Induced Pluripotent Stem Cells: Three-Dimensional Cultures and Mini-Brains
- Limitations of Induced Pluripotent Stem Cell Model
- Genome Editing: Creating Diseased Embryonic Stem Cells
- Drug Discovery With Induced Pluripotent Stem Cells
- Conclusions
- Chapter 9. Association Strategies
- Common Variants
- Rare Variants
- Conclusions
- Chapter 10. Reconstructing Causal Network Models of Human Disease
- Introduction
- Modeling Biological Data
- Causality as a Statistical Inference
- From Assessing Causal Relationships Among Trait Pairs to Predictive Gene Networks
- Application of Predictive Network Models to High-Throughput Screening
- Conclusion and Future Directions
- Chapter 11. Gene Networks in Neuropsychiatric Disease
- Introduction
- RNA, Protein, and Epigenetic Molecular Levels in Neurobiology
- The Challenge of Spatial and Temporal Heterogeneity in the Central Nervous System
- Gene Networks Provide a Framework for Neurobiological Interpretation
- Gene Networks in Neuropsychiatric Disorders
- Conclusions and Future Directions
- Chapter 12. Somatic Mosaicism and Neurological Diseases
- Introduction
- Cortical Clonal Architecture and Somatic Mutations
- Somatic Mutations in Normal Brain
- Somatic Mutation in Neurological Disease
- Types of Somatic Variants
- Tissue Type Considerations
- Tools to Study Somatic Variation in the Brain
- Conclusion
- Chapter 1. The Newly Emerging View of the Genome
- Section II. A New Neuroanatomy
- Chapter 13. The Molecular Landscape of the Developing Human Central Nervous System
- Introduction
- The Cellular and Structural Complexity of the Human Brain
- General Principles of Human Neocortical Development
- Transcriptional Landscape of the Developing Human Brain
- Epigenomic and Regulatory Landscapes of the Developing Human Brain
- Insights Into Psychiatric and Neurological Disorders
- Conclusions and Future Directions
- Chapter 14. Optogenetic Approaches to Neural Circuit Analysis in the Mammalian Brain
- Introduction
- Tools for Functional Neural Circuit Dissection
- Functional Circuit Analysis
- Translational Medicine
- Conclusions
- Chapter 15. Brain Imaging With Magnetoencephalography During Rest and During Speech and Language Processing
- Brain Imaging With Magnetoencephalography (MEG)
- Sensing the Brain's Magnetic Fields
- From Sensing to Imaging
- Magnetoencephalography Studies in Aging and Dementia
- Summary and Conclusions
- Chapter 16. Resting-State Functional MRI: A Novel Tool for Understanding Brain Networks in Neuropsychiatric Disorders
- A Brief History of Resting-State Functional MRI
- Healthy Skepticism Drives Deeper Explorations
- Attributes of Resting-State Networks
- Default-Mode and Salience Networks
- Applications to Brain Disease
- Future Directions
- Chapter 17. Neuroimaging Advances in Alzheimer's Disease
- Introduction
- Alzheimer's Disease Defined
- Imaging Characteristics of Alzheimer's Disease
- Progression of Neuroimaging Abnormalities: An Amyloid Cascade?
- Underlying Mechanisms of Alzheimer's Disease Pathology
- Conclusions
- Chapter 18. Progressive Supranuclear Palsy and Related Parkinsonian Disorders
- Introduction
- Each Neurodegenerative Syndrome Reflects a Network
- Parkinsonian Syndromes: Parkinson Disease and Others
- Network Architecture of Neurodegenerative Parkinsonian Syndromes
- Clinicopathological Correlation in Progressive Supranuclear Palsy and Corticobasal Degeneration
- Genetic Factors in Progressive Supranuclear Palsy and Corticobasal Degeneration
- Conclusion
- Chapter 19. A New Neuroanatomy of Basal Ganglia Circuitry
- Anatomic Overview of Basal Ganglia
- Clinical Basal Ganglia Disorders
- Classical Basal Ganglia Microanatomy
- Probing Basal Ganglia Circuitry in Animal Models
- Emerging Techniques to Study Basal Ganglia Circuitry in Animals
- Probing Basal Ganglia Circuitry in Humans: Invasive Physiology
- Noninvasive Studies of Basal Ganglia Circuitry in Humans
- Conclusions
- Chapter 20. Brainstem Circuitry and Emotions
- The Structural Organization of the Brainstem
- Reticular Formation
- Reticular Formation Modulates Behavior
- Conclusion
- Chapter 21. Apathy: Frontal and Basal Ganglia Circuits
- Introduction
- Definition and Diagnosis of Apathy
- Clinical Variants, Diagnosis, and Measurement of Apathy
- Measurement and Rating Scale
- Molecular and Neuroanatomical Basis of Apathy
- Prefrontal Cortex in Primates
- Prefrontal Cortex in Humans
- Motivation and Reward System: Basal Ganglia Structures and Corticostriatal Loop
- Structural and Functional Connectivity in Apathy
- Dopamine Regulation in Motivation and Reward System
- Apathy in Neuropsychiatric Diseases
- Genetics Studies of Apathy
- Summary
- Chapter 22. Emotional Dysfunction in Psychopathology and Neuropathology: Neural and Genetic Pathways
- Emotional Dysfunction in Psychopathology and Neuropathology: Neural and Genetic Pathways
- Emotions and Emotional Processes Emotions: Short and Discrete
- Emotional Processes
- Emotional Functioning: Neural Pathways
- Emotional Reactivity
- Emotion Regulation
- Emotional Affiliation
- Emotion Functioning: Genetic Pathways
- Model of the Genetic Pathway
- Emotional Reactivity
- Emotion Regulation
- Emotional Affiliation
- Neural and Genetic Pathways: Clinical Implications
- Emotional Dysfunction in Psychopathology and Neuropathology
- Emotion in Diagnosis
- Emotion in Treatment
- Chapter 23. The Anatomy of Delusion
- Introduction and Definition
- Phenomenology and Anatomy
- Content-Specific Delusions
- Genetics
- Chapter 24. Beyond Dopamine: The Role of the Serotonergic System and Treatments in Understanding and Treating Visual Hallucinations in Parkinson Disease
- Simple Versus Complex Visual Hallucinations
- The Visual Pathway and Mechanisms of Disruption Leading to Visual Hallucinations
- Complex Visual Hallucinations: The Role of Lesion Location
- Synucleinopathy and Visual Hallucinations
- The Serotonergic System and Visual Hallucinations
- Pharmacological Interventions for Visual Hallucinations in Parkinson Disease
- Summary
- Chapter 13. The Molecular Landscape of the Developing Human Central Nervous System
- Section III. Clinical Phenomenologie
- Chapter 25. Risk Overlap Between Clinical Disorders
- Introduction
- Clinical Neuroscience, Neurology, and Psychiatry
- The Diseases and Disorders in Section III
- Overlap
- Genomics as a Way to Understand Risk Overlap
- Wielding Genomic Tools
- The Genetic Architectures of Section III Entities
- Risk Overlap
- Conclusion
- Financial Conflicts of Interest
- List of URLs
- Chapter 26. The NIMH Research Domain Criteria Project: Toward an Integrated Neuroscience of Mental Disorders
- Introduction
- Why Research Domain Criteria?
- Research Domain Criteria Process and Structure
- Intermediate Phenotypes and Endophenotypes
- Loosening the Constraints of Research
- Research Domain Criteria and Genetics
- Meeting in the Middle
- Research Domain Criteria and Big Data
- Summary and Conclusions
- Competing Interests
- Chapter 27. Schizophrenia
- Introduction
- Heritability and Genetic Architecture
- The Genomics Era
- Genome-Wide Association Studies
- Structural Variation Studies
- Sequencing Studies
- Next Steps in Gene Discovery
- Circuits and Pathways
- Future Directions
- Chapter 28. The Emergence and Underlying Neurobiology of Psychosis
- Introduction
- The Clinical Emergence of Psychosis
- Clinical Phenotype to Endophenotype
- Neurocognition
- Neuroimaging
- Neurodevelopmental Perspective
- Links to Genomics: Challenges and Future Directions
- Chapter 29. Autism Spectrum Disorder: Genes to Pathways to Circuits
- Introduction
- Genetics and Genomics
- From Genes to Biology in Autism Spectrum Disorder
- Conclusions
- Chapter 30. Molecular Architecture and Neurobiology of Bipolar Disorder
- Descriptive Epidemiology
- Comorbidity
- Genetic Epidemiology
- Molecular Genetics
- Intermediate Traits and the Biology of Bipolar Disorder
- Neuroimaging Intermediate Traits
- Summary and Conclusions
- Chapter 31. Conceptualizing Major Depression: From Genes to Neuroanatomy to Epidemiology
- Prevalence of Major Depressive Disorder
- Risk Factors for Major Depressive Disorder
- Diagnostic Heterogeneity in Major Depressive Disorder
- Neuroanatomy of Major Depressive Disorder
- Functional Neuroimaging in Major Depressive Disorder
- Heritability
- Endophenotypes
- Genetics
- Treatment for Major Depression
- Conclusions
- Chapter 32. Speech and Language Disorders
- Introduction
- Language Networks and Pathways
- Neurodevelopmental Language Disorders
- Primary Progressive Aphasia
- Chapter 33. Molecular Pathways Leading to the Clinical Phenomenology of Frontotemporal Dementia
- Introduction to Frontotemporal Dementia and Associated Clinical Syndromes
- Three Unique Genetic Mechanisms Converging on Frontotemporal Dementia Spectrum Disorders
- Neuroanatomical Circuits and Clinical Syndromes in Autosomal Dominant Frontotemporal Lobar Degeneration
- Chapter 34. The Genetic Basis of Alzheimer's Disease: Findings From Genome-Wide Studies
- Introduction
- Genetics of Early-Onset Familial Alzheimer's Disease
- Amyloid Precursor Protein
- Presenilin Genes (PSEN1 and PSEN2)
- Other Early-Onset Familial Alzheimer's Disease Genes
- Late-Onset Sporadic Form of Alzheimer's Disease
- Apolipoprotein E
- ADAM Metallopeptidase Domain 10
- Triggering Receptor Expressed on Myeloid Cells 2
- CD33 (Myeloid Cell Surface Antigen CD33; Sialic Acid-Binding Immunoglobulin-Like Lectin 3)
- Cas Scaffolding Protein Family Member 4
- Complement Component (3b/4b) Receptor 1
- Bridging Integrator 1
- Clusterin
- Adenosine Triphosphate-Binding Cassette, Subfamily A (ABC1), Member 7
- Phosphatidylinositol-Binding Clathrin Assembly Protein
- Membrane-Spanning 4 Domain Subfamily A Members 4A and 6A
- CUGBP, Elav-Like Family Member 1
- Sortilin-Related Receptor, LDLR Class A Repeats Containing
- Inositol Polyphosphate-5-Phosphatase
- CD2-Associated Protein
- Major Histocompatibility Complex Class II, DRβ1 and 5
- EPH Receptor A1
- Myocyte Enhancer Factor 2C
- NME/NM23 Family Member 8
- Zinc Finger, CW Type With PWWP Domain 1
- Fermitin Family Member 2
- Protein Tyrosine Kinase 2β
- Ras and Rab Interactor 3 (RIN3) and Solute Carrier Family 24 Sodium/Potassium/Calcium Exchanger, Member 4 (SLC24A4)
- Conclusion
- Chapter 35. Posttraumatic Stress Disorder: From Circuits to Genes
- Introduction
- Clinical Aspects of Posttraumatic Stress Disorder Diagnosis
- Neural Circuits of Fear and Extinction, and Their Dysregulation in Posttraumatic Stress Disorder
- Genetic Studies of Posttraumatic Stress Disorder
- Conclusions
- Acknowledgment
- Disclosures
- Chapter 36. Neurodevelopmental Disorders, Causes, and Consequences
- Neurodevelopmental Disorders, Causes, and Consequences
- Causes of Disorders of Neurodevelopment
- Genetics of Neurodevelopmental Disorders
- Mechanisms of Action and Consequences on the Circuits of Cognition and Behavior
- Future Directions
- Chapter 37. Molecular Architecture and Neurobiology of the Epilepsies
- Introduction
- Progress in Epilepsy Genetics
- Genetic Architecture of the Epilepsies
- Voltage-Gated Channelopathies
- Ligand-Gated Channelopathies
- Vesicle Trafficking Dysregulation
- Miscellaneous Genes
- Interpretation
- Management/Therapeutic Implications
- Future Studies and Conclusion
- Chapter 38. Clinical Syndromes of Substance Use Disorder
- Introduction
- Overview of Substance Use Disorder
- Circuits and Pathways That Mediate Substance Abuse
- Cellular and Molecular Pathology of Substance Abuse
- Genetic Factors Contributing to Substance Use Disorder
- Conclusion
- Chapter 39. Immunologic and Genetic Aspects of Type 1 Narcolepsy
- Introduction to the Clinical Condition and Its Pathophysiology
- Type 1 Narcolepsy Is Caused by a Loss of Hypocretin Neurons
- Genetic Association of Narcolepsy With the Human Leukocyte Antigen
- Non–Human Leukocyte Antigen Genes Are Also Associated With Narcolepsy
- Narcolepsy in Association With Other Syndromic Genetic Disorders
- Is Type 1 Narcolepsy an Autoimmune Disease?
- Involvement of Environmental Factors in Narcolepsy
- H1N1 Pandemrix Vaccination Leading to an Increase in Narcolepsy Incidence
- Perspectives
- Chapter 40. Genomic Landscape of Brain Tumors
- Introduction
- Meningiomas
- Gliomas
- Medulloblastomas
- Ependymal Tumors
- Summary
- Chapter 41. White Matter Disorders
- Introduction
- History of White Matter Research
- White Matter Anatomy
- Clinical Syndromes
- Chapter 42. Amyotrophic Lateral Sclerosis 1 and Many Diseases
- Introduction
- Epidemiology
- Clinical Features
- Clinical Subtypes of Amyotrophic Lateral Sclerosis
- Amyotrophic Lateral Sclerosis Anatomy
- Amyotrophic Lateral Sclerosis Pathology
- Amyotrophic Lateral Sclerosis Genetics by Putative Mechanism
- Amyotrophic Lateral Sclerosis Models
- Discussion and Future Directions
- Chapter 43. Eating Disorders
- Clinical Syndromes
- Human Genetic Research
- Neural Circuit Dissection of Feeding Behavior Related to Eating Disorders
- Concluding Remarks
- Chapter 25. Risk Overlap Between Clinical Disorders
- Section IV. Clinical Translation and Drug Development
- Chapter 44. Psychiatric Pharmacogenomics: Translating Genomics
- Definition and Overview
- Connection to Genomics in Psychiatry and Implications for Architecture
- Challenges
- Principal Findings by Therapeutic Area
- Efforts at Clinical Translation
- Applications in Clinical Investigation
- Policy and Regulatory Considerations
- Emerging Directions
- Chapter 44. Psychiatric Pharmacogenomics: Translating Genomics
- Index
- No. of pages: 796
- Language: English
- Edition: 1
- Published: June 7, 2016
- Imprint: Academic Press
- Hardback ISBN: 9780128001059
- eBook ISBN: 9780128005309
TL
Thomas Lehner
BM
Bruce L. Miller
Dr. Miller holds the A.W. and Mary Margaret Clausen Distinguished Professorship in Neurology at the University of California, San Francisco (UCSF). He directs the busy UCSF dementia center where patients in the San Francisco Bay Area and beyond receive comprehensive clinical evaluations. His goal is the delivery of model care to all of the patients who enter the clinical and research programs at the UCSF Memory and Aging Center (MAC).
Dr. Miller is a behavioral neurologist focused on dementia with special interests in brain and behavior relationships as well as the genetic and molecular underpinnings of disease. His work in frontotemporal dementia (FTD) emphasizes both the behavioral and emotional deficits that characterize these patients, while simultaneously noting the visual creativity that can emerge in the setting of FTD. He is the principal investigator of the NIH-sponsored Alzheimer’s Disease Research Center (ADRC) and program project on FTD called Frontotemporal Dementia: Genes, Imaging and Emotions. He oversees a healthy aging program, which includes an artist in residence program. In addition, he helps lead two philanthropy-funded research consortia, the Tau Consortium and Consortium for Frontotemporal Research, focused on developing treatments for tau and progranulin disorders, respectively. Also, he works with the National Football League to help with the education and assessment of players related to brain health. Dr. Miller teaches extensively, runs the Behavioral Neurology Fellowship at UCSF, and oversees visits of more than 50 foreign scholars every year.
Dr. Miller has received many awards including the Potamkin Award from the American Academy of Neurology, the Raymond Adams Lecture at the American Neurological Association, the Elliot Royer Award from the San Francisco Neurological community, the UCSF Annual Faculty Research Lectureship in Clinical Science, the UCSF Academic Senate Distinction in Mentoring Award, Distinguished Service to Minorities, from Charles Drew University, and the Gene D. Cohen Research Award in Creativity and Aging from the National Center for Creative Aging. He has authored The Human Frontal Lobes, The Behavioral Neurology of Dementia, Frontotemporal Dementia and over 600 other publications regarding dementia. He has been featured in Fortune magazine and The New York Times, as well as on "Charlie Rose," "PBS NewsHour" and other media. For more than three decades, Dr. Miller has been the scientific director for the philanthropic organization The John Douglas French Alzheimer’s Foundation, a private philanthropic organization that funds basic science research in Alzheimer’s disease.
MS
Matthew W. State
Dr. State received his undergraduate and medical degrees at Stanford University, completed his residency in psychiatry and fellowship in child psychiatry at the UCLA Neuropsychiatric Institute, and earned a PhD in genetics from Yale University. He was on the faculty at Yale from 2001 to 2013 where he was the Donald J. Cohen Professor of Child Psychiatry, Psychiatry and Genetics and the Co-Founder and Co-Director of the Yale Program on Neurogenetics. He is currently the Oberndorf Family Distinguished Professor and Chair of Psychiatry at UCSF and Director of the Langley Porter Psychiatric Institute and Hospital.