Integrating the Neurobiology of Schizophrenia

Neurobiology of Dopamine in Schizophrenia

I Introduction

II Dopaminergic System in the Brain

III Evidence Supporting Alterations of DA Systems in Schizophrenia

IV Conclusions

The Dopamine System and the Pathophysiology of Schizophrenia: A Basic Science Perspective

I Introduction

II Neuroanatomy of DA Systems

III DA Neuron Activity and Release

IV Cellular Actions of DA

V Roles of DA on Cognitive and Affective Functions

VI Development and Maturation of the DA System

VII DA Deficits in Schizophrenia

VIII Conclusions

Glutamate and Schizophrenia: Phencyclidine, N-Methyl-d-Aspartate Receptors, and Dopamine–Glutamate Interactions

I Introduction

II Glutamatergic Physiology

III Glutamatergic Models of Schizophrenia

IV Clinical Studies with NMDA Agonists

V Potential Causes of Glutamatergic Dysfunction in Schizophrenia

VI Future Research and Treatment Implications

Deciphering the Disease Process of Schizophrenia: The Contribution of Cortical Gaba Neurons

I Working Memory Impairments: A Core Feature of Schizophrenia

II Working Memory Impairments and Altered GABA Neurotransmission in the DLPFC

III Potential Pathogenetic Mechanisms for Cell Type-Specific Alterations in GABA Neurons

IV Connecting Alterations in PV-Positive Neurons to Working Memory Impairments: Decreased Gamma Band Synchrony in Schizophrenia

V Treatment Implications

Alterations of Serotonin Transmission in Schizophrenia

I Introduction

II Alteration of 5-HT Receptors in Schizophrenia

III Pharmacological Manipulation of 5-HT Transmission in Schizophrenia

IV 5‐HT–DA Interactions Relevant to Schizophrenia

V Discussions

Serotonin and Dopamine Interactions in Rodents and Primates: Implications for Psychosis and Antipsychotic Drug Development

I Introduction

II Dopamine and 5-HT Receptors

III Psychomotor Stimulants: A Dopamine–Serotonin Interaction Case Study

IV Monoaminergic Nuclei Interactions

V Serotonin and Dopamine in the Thalamus

VI Dopamine and Serotonin in the Striatum

VII Dopamine and Serotonin in the Hippocampal Formation

VIII Dopamine and Serotonin in the Prefrontal Cortex/Neocortex

IX Animal Models

X Conclusions

Cholinergic Circuits and Signaling in the Pathophysiology of Schizophrenia

I Introduction

II ACh in Brain Regions Implicated in Schizophrenia

III Physiology of ACh Circuits and Signaling in Brain Regions Implicated in Schizophrenia Pathology

IV Developmental and Genetic Deficits in Schizophrenia That May Influence Function and Assembly of Cholinergic Systems

V Clinical and Preclinical Evidence for Deficits in Components of Brain Cholinergic Systems in Schizophrenia

VI Evidence for Cholinergic Contributions to Schizophrenia Pathophysiology from Clinical and Preclinical Psychopharmacology

VII Conclusions

Schizophrenia and the α7 Nicotinic Acetylcholine Receptor

I Introduction

II Neurobiological and Neurogenetic Evidence for a Link Between the α7 Nicotinic Acetylcholine Receptor and Schizophrenia

III The Prototypic α7 Nicotinic Agonist, Nicotine, and Schizophrenia

IV The Search for an α7 Nicotinic Acetylcholine Receptor Agonist

V The Phase 1 Study of DMXBA in Schizophrenia

Histamine and Schizophrenia

I Introduction

II The Histaminergic Neuronal System

III Changes in the Histaminergic System in Schizophrenia

IV Interactions of Antipsychotic Drugs with the Histaminergic System

V Role of Histaminergic Neurons in Schizophrenia

VI Conclusions

Cannabinoids and Psychosis

I Introduction

II Ancedotal Reports

III Epidemiological Studies

IV Pharmacological Studies

V Cannabis and Psychosis: Causality

VI Cannabinoid Receptor Dysfunction and Psychotic Disorders

VII Summary and Conclusions

Involvement of Neuropeptide Systems in Schizophrenia: Human Studies

I Introduction

II Cholecystokinin

III Corticotropin-Releasing Factor

IV Interleukins

V Neurotensin

VI Neuropeptide Y

VII Opioid Peptides

VIII Secretin

IX Somatostatin

X Vasoactive Intestinal Peptide

XI Tachykinins

XII Thyrotropin‐Releasing Hormone

XIII Other Peptides

XIV Conclusions

Acknowledgments

Brain-Derived Neurotrophic Factor in Schizophrenia and Its Relation With Dopamine

I Introduction

II Genetic Studies

III BDNF in the Serum of Patients with Schizophrenia

IV BDNF and TrkB Receptor in the Brain of Patients with Schizophrenia

V Dopamine–BDNF Interactions

VI Conclusions

Schizophrenia Susceptibility Genes: in Search of A Molecular Logic and Novel Drug Targets for A Devastating Disorder

I The Genetic Component of Schizophrenia

II Genes Identified Through Systematic Follow-Up of Linkage Signals

III Other Candidate Genes

IV Areas of Caution in the Interpretation and Generalization of Genetic Findings

V Future Directions of the Genetic Research: Advancing Our Understanding of How the Specific Genetic Factors Contribute Biologically to the Disease Process

Series Editors

Contributors to Volume 78

Preface

Index

Contents of Recent Volumes