Handbook of Schizophrenia Spectrum Disorders, Volume I - Conceptual Issues and Neurobiological Advances

Foreword

Schizophrenia Spectrum Disorders: Insights from Views Across 100 years

Contents

Contributors

1 The Schizophrenia Construct After 100 Years of Challenges

The Schizophrenia Construct

A Unitary Concept

Categorical Models

Dimensional Models

Genetic Epidemiology

Familiality of Schizophrenia

Candidate Genes

Endophenotype Model Challenges

Current Challenges

Conclusions and Future Directions

References

2 Diagnosis and Classification of the Schizophrenia Spectrum Disorders

Introduction

Historical Aspects of Classification

Nosological Overview of the Schizophrenia Spectrum Disorders

Schizophrenia

Brief Psychotic Disorders

Schizoaffective Disorder

Personality Disorders

Schizotypal

Schizoid

Paranoid

Other Disorders

Bipolar Disorder with Psychotic Features

Major Depressive Disorder with Psychotic Features

Delusional Disorder

Obsessive Compulsive Disorder

Pervasive Developmental Disorders

Psychosis-Risk Syndromes

Critiques of Current Nosology

Differences Across Psychiatric Manuals

Validity of Existing Diagnostic Constructs

Reliability

Distinction of Disorders Within the Psychotic Spectrum

Organization of the Meta-Structure of Psychotic Disorders

Refining Schizophrenia Subtypes

Dimensional Representations

Use of More Proximal Indicators of Disorders

Etiology Related Classification

Cognition in Psychotic Disorders

Characterizing the Risk Syndrome for Psychosis

Culture and Ethnicity

Future Directions

Schizophrenia

Schizoaffective Disorder

Attenuated Psychotic Symptoms Syndrome

Personality Disorders

References

3 Toward a Multidimensional Continuum Model of Functional Psychoses for Research Purposes

Statement of Conundrum

Proof-of-Concept for a Multidimensional Continuum Model

Symptom Dimensions

Toward a Unitary Pathogenetic Mechanism

Conclusions and Future Directions

References

4 Irving Gottesman and the Schizophrenia Spectrum

Early Career

Heritability of Personality

The Maudsley Twin Study on Schizophrenia

The Schizoidia Concept

In Denmark 1972–1973: The Twin Study on Criminality

The Danish Dual Mating Study

The Professorships and the Books

The Discordant Twins' Offspring Study

The New Dual Mating Study

Endophenotypes

Recognition

References

5 Schizotypy: Reflections on the Bridge to Schizophrenia and Obstacles on the Road Ahead to Etiology and Pathogenesis

Reactions

Schizotypic Pathology/Schizophrenia Connection: Considering the ''Damn Strange Coincidence'' Argument

Leverage Gained with the Schizotypy Model

Reflections

Neuroimaging and Schizotypy/Schizophrenia: Selling Bridges v. Building Them. Where Are We, Are You Sure?

Major Impediments to Our Future Progress in Our Understanding Schizotypy and Schizophrenia

The Problem of Heterogeneity

The Problem of Rating in Schizotypy and Schizophrenia Research

Conclusions and Future Directions

References

6 Autistic Spectrum Disorders and Schizophrenia

Introduction

Autistic Spectrum Disorders: Diagnosis and Sub-types and Phenomenology

Epidemiology

Etiology

Genetics

Endophenotypes

Neuropathology and Brain Imaging

Infection and Immune Dysfunction

Early Recognition

Interventions

Psychosocial and Educational Interventions

Pharmacological Interventions

Autism and Schizophrenia: Co-morbid Association and Phenotypic Variations

Conclusions and Future Directions

References

7 One Hundred Years of Insanity: Genomic, Psychological, and Evolutionary Models of Autism in Relation to Schizophrenia

Introduction

"Autism" from Bleuler to the DSM

Phenotypic Structure of Autism and Schizophrenia Spectrum

Alternative Models for the Relationship of Schizophrenia with Autism

Conclusions and Future Directions

References

8 Quantifying the Dynamics of Central Systemic Degeneration in Schizophrenia

Background and Significance

Schizophrenia – A Complex Unsolved Problem

A Diseased Complex System?

Schizophrenia as a Degenerative Systemic Dysregulation

Theoretical Remarks

Quantifying Schizophrenia from Physiological Time Series

Nonlinear Analysis Methods and Physiological Data

Our Existing Nonlinear Analysis Results

Work in Progress

Conclusions: The Future of This Approach

Appendix 1: Simplified Schema of the Brain Circuitry Implicated in Schizophrenia Dysregulation

Appendix 2: Neural Complexity Layers that May Exhibit Suboptimal Dynamics in Schizophrenia

Appendix 3: Subject Recruitment and Data Collection

References

9 Schizophrenia Has a High Heritability, but Where Are the Genes?

Introduction

Likely Causes for Failure of Traditional Linkage/Candidate Gene Studies

The Genome-Wide Association Approach

Copy Number Variation in Schizophrenia

Common Disease, Common Variant or Rare Variant

The Dilemma of the Heterogeneous Sample

Reducing Genetic Heterogeneity Through Endophenotypes

Shared Genetic Susceptibility with Autism and Bipolar Disorder

Schizophrenia Research: Novel Approaches

Micro RNAs

Cytosine Methylation

Conclusion and Future Directions

References

10 Changes in Gene Expression in Subjects with Schizophrenia Associated with Disease Progression

Studies on the Human CNS Transcriptome: The First Indication of Progressive Changes in Gene Expression in Schizophrenia

Studies on the Human CNS Transcriptome: Outcomes from the Use of Microarrays

Studies on the Human CNS Transcriptome: Outcomes from Pooling Microarray Sets

Studies on the Human CNS Transcriptome: Moving Beyond Microarray Studies

Conclusions and Future Directions

References

11 Amino Acids in Schizophrenia – Glycine, Serine and Arginine

Introduction

Glycine

D-Serine

Arginine

Conclusions and Future Directions

References

12 Developmental Consequences of Prenatal Exposure to Maternal Immune Activation

Introduction

Epidemiologic Overview

Modeling Maternal Immune Activation

Live Pathogens

Pathogen-Free Inflammatory Agents

Pro-inflammatory Cytokines

Summary of Preclinical Models

Behavioral Consequences of Prenatal Immune Activation

Relevance to Positive Symptoms

Relevance to Cognitive Symptoms

Summary of Behavioral Consequences

Neurochemical Consequences of Prenatal Immune Activation

Dopamine

Glutamate

GABA

Overall Impact on Neurotransmitter Systems

Conclusions & Future Directions

References

13 Glutamatergic Neurotransmission Abnormalities and Schizophrenia

Introduction

Glutamatergic Neurotransmission

Glutamate Neurotransmission and Schizophrenia

NMDAR Antagonist Administration

Imaging Studies and Glutamate Hypothesis of Schizophrenia

Postmortem Brain Studies of NMD/AMPA/Kainate Receptors in Schizophrenia

Neurodevelopmental Model of Schizophrenia and NMDAR Hypofunction

Conclusions and Future Studies

References

14 Mathematical Models in Schizophrenia

Introduction

Mathematical Models with Implications in Schizophrenia

Conceptual Models

Correlative Models

Deterministic Models

Stochastic Models

Artificial Neural Networks

Mechanistically Based Models

Conclusions and Future Directions

References

15 Methamphetamine-Associated Psychosis: A Model for Biomarker Discovery in Schizophrenia

Introduction

Epidemiology of Methamphetamine

Acute and Chronic Effects of Methamphetamine

MAP Clinical Features

MAP Clinical Course

MAP Diagnosis

Biomarker Discovery

Genetic Biomarkers for MAP Susceptibility

Genetic Biomarkers of MAP Clinical Course

Conclusions and Future Directions

References

16 What Does Proteomics Tell Us About Schizophrenia?

Schizophrenia

Proteomics

Methods for Differential Proteome Studies

Two-dimensional Gel Electrophoresis

Shotgun Proteomics

Validation Experiments

Metabolomics

Proteomics of Schizophrenia Brain Tissue

Cytoskeleton-Related Proteins

Calcium Buffering

Oligodendrocyte Dysfunction

Energy Metabolism

Conclusions and Future Directions

References

17 The Role of 3a-Hydroxy-5a-Pregnan-20-One in Mediating the Development and/or Expression of Schizophrenia Spectrum Disorders: Findings in Rodents Models and Clinical Populations

Introduction

Biosynthesis and Metabolism of 3a,5a-THP

Genes Implicated in 3a,5a-THP Dysregulation

Mechanisms of Action of 3a,5a-THP

Animal Models of Schizo-Affective Disorders and Alterations in 3a,5a-THP

Stress-Responding and 3a,5a-THP

Schizo-Affective Disorders and Stress-Responding

Prenatal Stress and 3a,5a-THP

Effects of Prenatal Stress on Offspring Before Puberty

Sex Differences in 3a,5a-THP and Incidence and Symptom Manifestation of Schizophrenia

Interactions of Therapeutics and Neurosteroids in Schizophrenia

Anti-psychotics, Anti-depressants and 3a,5a-THP

3a,5a-THP Actions in the PFC, Hippocampus, and/or VTA to Mediate Behaviors

3a,5a-THP's Biosynthesis and Social Approach

P, 3a,5a-THP and Social Approach/Avoidance Behaviors

P, 3a,5a-THP and Socially-Relevant Cognitive Performance

Social Isolation and 3a,5a-THP

Maternal Separation Stress and 3a,5a-THP

Hippocampal Lesions and Schizo-Affective Behaviors

Dopamine in Schizo-Affective Disorders

Dopamine Transporter Knock-Out Mouse Model

Cocaine, Schizo-Affective Disorders and 3a,5a-THP

Methamphetamine, Endoplasmic Reticulum, and Schizo-Affective Disorders

Other Genetic Mutations in Schizo-Affective Disorders

Conclusions and Future Directions

References

18 Neural Substrates of Emotion Dysfunctions in Patients with Schizophrenia Spectrum Disorders

Introduction

Emotion Induction

Visual Emotion Induction

Olfactory Emotion Induction

Emotion Recognition

Recognizing Emotional Facial Expressions

Interpreting Emotional Prosody

Interaction of Emotion and Cognition

Emotional Self-Concept

Conclusions and Future Directions

References

19 Brain Morphological Abnormalities at the Onset of Schizophrenia and Other Psychotic Disorders: A Review of the Evidence

Introduction

Schizophrenia

Bipolar Disorder

Schizophrenia Compared with Affective Psychoses

Schizophrenia Compared with Schizophrenia Spectrum Disorders

Trajectories of Brain Abnormalities and Specificity of Brain Morphologic Changes in Schizophrenia and BD

Conclusions and Future Directions

References

20 Mapping Prodromal Psychosis

Introduction

Definition of the High Risk for Psychosis

Structural Neuroimaging

Structural MRI in Established Psychosis

Grey Matter Volume Abnormalities in Prodromal Psychosis: Cross Sectional Studies

Grey Matter Changes During the Transition to Psychosis: Longitudinal Studies

Functional Neuroimaging

fMRI in Established Psychosis

Neurofunctional Correlates of an Enhanced Risk to Psychosis

Neurofunctional Mapping of Psychosis Transition

Neurophysiological Correlates of Antipsychotic Treatments in Early Psychosis

Brain Connectivity in the Pre-psychotic Phases

fMRI and Longitudinal Outcomes in Subjects at High Risk for Psychosis

Neurochemical Imaging

Dopamine

Dopamine and Psychosis

Dopamine Dysregulation Prior to the Onset of Psychosis

The Revised Dopamine Hypothesis of Schizophrenia

Glutamate

Glutamate in Established Psychosis

Glutamate Dysfunction in Prodromal Psychosis

Integration of Neuroimaging Findings Across Modalities

Conclusions

References

Afterword

The Future of the Schizophrenia Construct and Acquisition of New Knowledge

References

Contents to Volume II

Contents to Volume III

Contributors to Volume II

Contributors to Volume III

Index