The neurobiology of schizophrenia / edited by Ted Abel, Thomas Nickl-Jockschat.

Format:

Book

Contributor:

Abel, Ted, editor.

Nickl-Jockschat, Thomas, editor.

Language:

English

Subjects (All):

Schizophrenia.

Neurobiology.

Schizophrenia--physiopathology.

Brain Chemistry--physiology.

Medical Subjects:

Schizophrenia--physiopathology.

Brain Chemistry--physiology.

Physical Description:

1 online resource (470 pages)

Edition:

1st ed.

Place of Publication:

Amsterdam, Netherlands : Academic Press, 2016.

Summary:

The Neurobiology of Schizophrenia begins with an overview of the various facets and levels of schizophrenia pathophysiology, ranging systematically from its genetic basis over changes in neurochemistry and electrophysiology to a systemic neural circuits level. When possible, the editors point out connections between the various systems. The editors also depict methods and research strategies used in the respective field. The individual backgrounds of the two editors promote a synthesis between basic neuroscience and clinical relevance.- Provides a comprehensive overview of neurobiological aspects of schizophrenia- Discusses schizophrenia at behavioral, cognitive, clinical, electrophysiological, molecular, and genetic levels- Edited by a translational researcher and a psychiatrist to promote synthesis between basic neuroscience and clinical relevance- Elucidates connections between the various systems depicted, when possible

Contents:

Front Cover

The Neurobiology of Schizophrenia

Copyright Page

Contents

List of Contributors

Acknowledgments

I. Introduction

1 Historical and Clinical Overview: Implications for Schizophrenia Research

Introduction

A Brief History of the Definition of Schizophrenia

Lessons From Therapeutic Approaches

References

II. The Genetic and Epigenetic Basis of Schizophrenia

2 Progress and Prospects for Endophenotypes for Schizophrenia in the Time of Genomics, Epigenetics, Oscillatory Brain Dynam ...

Endophenotypes in Schizophrenia: Current Status

An Emerging Frontier for Endophenotypes: Epigenetics

A New Frontier for Endophenotypes: Brain Connectivity Dynamics

Limitations and Future Directions

3 Insights From Genome-Wide Association Studies (GWAS)

The Pre-GWAS Era: Linkage and Candidate Gene Association Studies

The Developments That Made GWAS Possible

The Principle of GWAS

GWAS Findings in Schizophrenia

Genetic Relationship Between Schizophrenia and Other Psychiatric Disorders

Were GWAS of Schizophrenia Successful So Far and Should They Continue?

Future Directions

4 Sequencing Approaches to Map Genes Linked to Schizophrenia

Introduction and Background

Next-Generation Sequencing

Exome Versus Whole Genome

Sequencing Studies to Date

Conclusions

5 Epigenetic Approaches to Define the Molecular and Genetic Risk Architectures of Schizophrenia

An Epigenetic Link Between Environmental Risk Factors and Schizophrenia

Evidence From Human Studies

Evidence From Animal Studies

DNA Methylation in Schizophrenia

DNA Methylation and Gene Regulation in the Brain

DNA Methylation Changes in Schizophrenia.

Studies in the Peripheral Tissue and Possible Epigenetic Biomarkers in Schizophrenia

Epigenetic Approaches to the Molecular and Genetic Risk Architectures of Schizophrenia

Do Epigenetic Mechanisms Contribute to Long-Lasting Alterations in Gene Expression in Schizophrenia Brain?

Functional Neuroepigenomics Could Inform About Disease-Associated Genetic Risk Polymorphisms

Higher-Order Chromatin and the Genetic Risk Architecture of Schizophrenia

Epigenetic Mechanisms and the Treatment of Schizophrenia

Chromatin-Modifying Drugs: A Future Treatment for Schizophrenia?

Comprehensive, Region-Specific, and Cell Type-Specific Epigenome Mappings in the Brain

Larger and More Ambitious Clinical Studies

Acknowledgment

6 Exploring Neurogenomics of Schizophrenia With Allen Institute for Brain Science Resources

Introduction to the Portal

Mouse Atlas Resources

Common Reference Space in the Mouse Brain

Integrated Search and Visualization in the Allen Brain Atlas

The Mouse Developmental Atlas

Connectivity in the Mouse Brain

Human Atlas Resources

The Allen Human Brain Atlas

BrainSpan Atlas of the Developing Human Brain

NIH Blueprint NON-HUMAN Primate Atlas

Beyond the Atlases

Applications of the Allen Institute for Brain Science Resources in Schizophrenia Research

III. The Neurochemical Basis of Schizophrenia

7 The Dopamine Hypothesis of Schizophrenia: Current Status

Introduction: History of the Dopamine Hypothesis

Dopamine Receptor Occupancy Studies

Molecular Imaging Studies of Dopaminergic Neurotransmission in Schizophrenia

Prefrontal-Subcortical Dopamine Dysregulation

Ketamine Psychosis

Conclusion: Beyond the Dopamine Hypothesis

References.

8 The PSD: A Microdomain for Converging Molecular Abnormalities in Schizophrenia

The Postsynaptic Density, the Hub of Postsynaptic Signaling

Dendritic Spines

The Postsynaptic Density

Signaling Pathways in the PSD

NMDA receptors

AMPA receptors

mGluRs

Proteomic Landscape of the PSD

Evidence Supporting the Role of the PSD in Schizophrenia

Genetic Evidence

Postmortem Evidence for PSD Dysregulation in Schizophrenia

Dendritic spine alterations

Dysregulations in PSD Proteins and Their Signaling in Schizophrenia

PSD as a Microdomain for Converging Molecular Alterations in Schizophrenia

Summary and Future Directions

9 Targeting Cognitive Deficits in Schizophrenia via GABAA Receptors: Focus on α2, α3, and α5 Receptor Subtypes

Excitatory and Inhibitory Tuning

Multiplicity of GABAA Receptors

Maturation of GABAA Receptors

GABAA Receptor Subtypes in Cortical Period Plasticity

GABAA Receptor Genetics and Schizophrenia

Deficits of GABAergic Cortical Interneurons and Impaired Cortical Oscillations in Schizophrenia

Physiological and Pharmacological Functions of GABAA Receptor Subtypes

Attempts to Enhance Cognition via α2/α3 GABAA Receptor Modulation

Inhibition of Dopaminergic Neurons by α3-Containing GABAA Receptors

Indirect Inhibition of Dopaminergic Neurons by α5-Containing GABAA Receptors

Multispecific Modulation of α2-, α3-, and α5-Containing GABAA Receptors

Proof-of-Concept Clinical Study With the Partial Positive Allosteric Modulator Bretazenil

α5-Negative Allosteric Modulators and Cognition Enhancement

IV. The Biochemical Basis of Schizophrenia

10 Metabolomics of Schizophrenia

Lipidomics in Schizophrenia

Energy Metabolism in Schizophrenia

Outlook

11 The Role of Inflammation and the Immune System in Schizophrenia

Inflammatory Mechanisms in the CNS

Microglia as an Important Cellular Basis of Inflammation in the CNS

Kindling and Sensitization of the Immune Response: The Basis for the Stress-Induced Inflammatory Response in Psychiatric Di ...

The Vulnerability-Stress-Inflammation Model of Schizophrenia

The Immune Dysbalance in Schizophrenia Is Associated With Chronic Inflammation

The Impact of Inflammation on Neurotransmitters in Schizophrenia

The Possible Role of Infection in Schizophrenia

CNS Volume Loss in Imaging Studies: A Consequence of an Inflammatory Process?

Cyclooxygenase-2 Inhibition as an Anti-Inflammatory Therapeutic Approach in Schizophrenia

Further Immune-Related Substances in the Therapy of Schizophrenia

Methodological Aspects of the Response to Immune-Based Therapy in Schizophrenia

Statement of Conflict of Interest

12 Proteomics of Schizophrenia

Biomarkers

Postmortem Studies

Protein Interaction Pathways and Signaling Networks

Embryonic Brain

V. The Electro-Physiological Basis of Schizophrenia

13 EEG and MEG Probes of Schizophrenia Pathophysiology

Measures of Inhibitory Failure

P50 Auditory Sensory Gating

Neurobiology of P50 suppression

P50 suppression and schizophrenia

Prepulse Inhibition of Startle

PPI methodology

Neurobiology of PPI

PPI and schizophrenia

Measures of Aberrant Salience Detection

Mismatch Negativity

MMN measurement

Neurobiology of MMN

Mismatch negativity and schizophrenia

P300

P300 methodology

Neurobiology of P300

P300 and schizophrenia

Measures of Abnormal Gamma Band Oscillations

Measuring Neural Oscillations.

Neurobiology of Gamma Oscillations

Gamma Oscillations and Schizophrenia

Conclusion

14 Cellular and Circuit Models of Increased Resting State Network Gamma Activity in Schizophrenia

Studies in Schizophrenia

Resting State Brain Activity

Electroencephalography

Magnetoencephalography

Functional Magnetic Resonance Imaging

Findings in Disease

Resting State Network and Gamma Oscillations in Schizophrenia

Power and Coherence of Brain Activity

Inherent Noise and Relationship to Symptoms in Schizophrenia

Circuit Models and Evidence in Humans

Interneuron Network Gamma Generation

The Pyramidal and Interneuron Model of Generating Gamma Oscillations

Animal Models of a Noisy Brain

Defining Baseline Gamma in Animal Models

Animal Models of Schizophrenia With Relation to Resting Gamma Activity

In Vitro Examination of Animal Models of Increased Resting Gamma

Relating Behavior to EEG/LFP Validation of Models

Summary and Conclusions

VI. The Structure and Function of Neural Circuits in Schizophrenia

15 Computational Neuroanatomy of Schizophrenia

Methods for Computational Neuroanatomy

Region of Interest Versus Voxel-Based Analysis

Regional Tissue Volumetrics

Optimally Discriminant Voxel-Based Analysis

Multivariate Pattern Analysis (MVPA) and Machine Learning

Topography of Reduced Brain Volumes in Schizophrenia

Single-Subject Classification: From Computational Neuroanatomy of Schizophrenia to Individualized Diagnostic Tests

Single-Subject Differentiation Between the Psychosis Prodrome and the At-Risk for Mental Psychosis Without Subsequent Disea ...

Are SCZ-Like NeuroanAtomical Patterns Possibly Endophenotypes of Disease?

16 Brain Computations in Schizophrenia.

The Bayesian Brain, Precision, and Hierarchical Models.

Notes:

Includes bibliographical references at the end of each chapters and index.

Description based on print version record.

ISBN:

0-12-801877-1

0-12-801829-1