Abi-Dargham / Guillin Integrating the Neurobiology of Schizophrenia

1. Auflage 2007
ISBN: 978-0-08-047508-0
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band Volume 78, 480 Seiten

Reihe: International Review of Neurobiology

This book examines the role that dopamine plays in schizophrenia, examining its role in not only the symptoms of the disease but also in its treatment. It also reviews all neurotransmitters that have been implicated in schizophrenia, exploring the genetic data, clinical data implicating the transmitter, and the preclinical data exploring how a transmitter may interact with dopamine and contribute to the dopaminergic phenotype observed in the illness. This book will serve as an educational tool for instructors, a guide for clinicians, and be of interest to researchers. It is a good reference for researchers specialized in one particular area and interested in learning about other areas of pathology in schizophrenia and how they may all feed into each other. The book concludes with an overall integrative model assembling as many of these elements as possible.

Autoren/Hrsg.

Abi-Dargham, Anissa

Guillin, Olivier

Inhaltsverzeichnis

1;Front Cover;1
2;Integrating the Neurobiology of Schizophrenia;4
3;Copyright Page;5
4;Contents;6
5;Contributors;12
6;Preface;14
6.1;References;17
7;Chapter 1: Neurobiology of Dopamine in Schizophrenia;18
7.1;I. Introduction;18
7.2;II. Dopaminergic System in the Brain;20
7.2.1;A. Dopaminergic Projections;20
7.2.2;B. Dopaminergic Receptors;23
7.3;III. Evidence Supporting Alterations of DA Systems in Schizophrenia;26
7.3.1;A. Pharmacological Evidence;26
7.3.2;B. Postmortem Studies;30
7.3.3;C. Imaging Studies;32
7.4;IV. Conclusions;42
7.5;References;43
8;Chapter 2: The Dopamine System and the Pathophysiology of Schizophrenia: A Basic Science Perspective;58
8.1;I. Introduction;59
8.2;II. Neuroanatomy of DA Systems;59
8.3;III. DA Neuron Activity and Release;62
8.4;IV. Cellular Actions of DA;66
8.5;V. Roles of DA on Cognitive and Affective Functions;68
8.6;VI. Development and Maturation of the DA System;70
8.7;VII. DA Deficits in Schizophrenia;72
8.8;VIII. Conclusions;75
8.9;References;75
9;Chapter 3: Glutamate and Schizophrenia: Phencyclidine, N-Methyl-D-Aspartate Receptors, and Dopamine–Glutamate Interactions;86
9.1;I. Introduction;87
9.2;II. Glutamatergic Physiology;88
9.2.1;A. Glutamate-Dopamine Comparisons;89
9.2.2;B. Glutamate Receptors;89
9.2.3;C. NMDA Receptors;89
9.2.4;D. AMPA/Kainate Receptors;91
9.2.5;E. Metabotropic Receptors;92
9.3;III. Glutamatergic Models of Schizophrenia;92
9.3.1;A. Symptom Patterns Following NMDA Antagonist Administration;93
9.3.2;B. Cognitive Deficits Following NMDA Antagonist Treatment;95
9.3.3;C. In Vivo Findings in Schizophrenia Based on Dopamine Receptor Occupancy;96
9.3.4;D. Postmortem Findings;98
9.4;IV. Clinical Studies with NMDA Agonists;98
9.4.1;A. NMDA Receptor Glycine-Site Agonists;100
9.4.2;B. Glycine Transport Inhibitors;103
9.4.3;C. Other Ionotropic Targets;105
9.4.4;D. Metabotropic Receptors;106
9.4.5;E. Group I Receptors;106
9.4.6;F. Group II Metabotropic Agonists;107
9.5;V. Potential Causes of Glutamatergic Dysfunction in Schizophrenia;107
9.5.1;A. Dopamine-Glutamate Interactions;108
9.5.2;B. Linkage-Association Studies in Schizophrenia;111
9.5.3;C. Environmental and Neurochemical Factors;112
9.6;VI. Future Research and Treatment Implications;113
9.7;Acknowledgments;113
9.8;References;113
10;Chapter 4: Deciphering the Disease Process of Schizophrenia: the.Contribution of Cortical Gaba Neurons;126
10.1;I. Working Memory Impairments: A Core Feature of Schizophrenia;126
10.2;II. Working Memory Impairments and Altered GABA Neurotransmission in the DLPFC;127
10.3;III. Potential Pathogenetic Mechanisms for Cell Type-Specific Alterations in GABA Neurons;135
10.3.1;A. Reduced Excitatory Drive via NMDA Receptors;135
10.3.2;B. Reduced Neurotrophin Signaling;136
10.4;IV. Connecting Alterations in PV-Positive Neurons to Working Memory Impairments: Decreased Gamma Band Synchrony in Schizophrenia;139
10.5;V. Treatment Implications;140
10.6;Acknowledgments;141
10.7;References;141
11;Chapter 5: Alterations of Serotonin Transmission in Schizophrenia;150
11.1;I. Introduction;150
11.2;II. Alteration of 5-HT Receptors in Schizophrenia;151
11.2.1;A. 5-HT Transporters;151
11.2.2;B. 5-HT1A Receptors;158
11.2.3;C. 5-HT2 Receptors;159
11.2.4;D. Other Receptors;161
11.3;III. Pharmacological Manipulation of 5-HT Transmission in Schizophrenia;158
11.3.1;A. 5-HT Precursors;158
11.3.2;B. 5-HT Depleting Agents;158
11.3.3;C. 5-HT2A Agonism: LSD and "Model" Psychosis;159
11.3.4;D. 5-HT2A Antagonism, Clozapine, and Atypicality;161
11.3.5;E. Action of Antipsychotic Drugs at Other Serotonergic Receptors;164
11.4;IV. 5-HT-DA Interactions Relevant to Schizophrenia;166
11.4.1;A. VTA DA Neurons Activity;166
11.5;V. Discussions;168
11.6;References;170
12;Chapter 6: Serotonin and Dopamine Interactions in Rodents and Primates: Implications for Psychosis and Antipsychotic Drug Development;182
12.1;I. Introduction;183
12.2;II. Dopamine and 5-HT Receptors;184
12.3;III. Psychomotor Stimulants: A Dopamine-Serotonin Interaction "Case Study";185
12.4;IV. Monoaminergic Nuclei Interactions;187
12.5;V. Serotonin and Dopamine in the Thalamus;189
12.6;VI. Dopamine and Serotonin in the Striatum;191
12.7;VII. Dopamine and Serotonin in the Hippocampal Formation;193
12.8;VIII. Dopamine and Serotonin in the Prefrontal Cortex/Neocortex;194
12.9;IX. Animal Models;198
12.10;X. Conclusions;200
12.11;References;200
13;Chapter 7: Cholinergic Circuits and Signaling in the Pathophysiology of Schizophrenia;210
13.1;I. Introduction;211
13.2;II. ACh in Brain Regions Implicated in Schizophrenia;212
13.2.1;A. Cholinergic Pathways Within the Ventral Striatum;214
13.2.2;B.Cholinergic Projections in Prefrontal Cortex and Hippocampus;215
13.3;III. Physiology of ACh Circuits and Signaling in Brain Regions Implicated in Schizophrenia Pathology;215
13.3.1;A. ACh Receptors in the CNS;215
13.3.2;B. Physiology of ACh Circuits in Striatum;217
13.3.3;C. Physiology of ACh Circuits in PFC and Hippocampus;219
13.4;IV. Developmental and Genetic Deficits in Schizophrenia That May Influence Function and Assembly of Cholinergic Systems;220
13.4.1;A. Development of Cholinergic Systems;220
13.4.2;B. Potential Role of Neuregulin 1;221
13.5;V. Clinical and Preclinical Evidence for Deficits in Components of Brain Cholinergic Systems in Schizophrenia;223
13.5.1;A. Deficits in Components of Muscarinic Cholinergic Transmission;223
13.5.2;B. Deficits in Components of Nicotinic Cholinergic Transmission;224
13.5.3;C. Deficits in Cholinergic Innervation;224
13.5.4;D. Summary;224
13.6;VI. Evidence for Cholinergic Contributions to Schizophrenia Pathophysiology from Clinical and Preclinical Psychopharmacology;225
13.6.1;A. ACh Release, Muscarinic Blockade, Partial Agonists, and "Atypicality";225
13.6.2;B. Both Procholinergic and Anticholinergic Compounds May Ameliorate or Worsen Different Symptom Domains;226
13.6.3;C. Nicotine Ameliorates a Wide Range of Deficits Seen in Schizophrenia;228
13.6.4;D. Despite Clear Effects of Other Cholinergic Compounds, Cholinesterase Inhibitors Are Not Proven Adjuncts in the Treatment of Schizophrenia;229
13.7;VII. Conclusions;230
13.8;References;231
14;Chapter 8: Schizophrenia and the alpha7 Nicotinic Acetylcholine Receptor;242
14.1;I. Introduction;243
14.2;II. Neurobiological and Neurogenetic Evidence for a Link Between the alpha7 Nicotinic Acetylcholine Receptor and Schizophrenia;243
14.3;III. The Prototypic alpha7 Nicotinic Agonist, Nicotine, and Schizophrenia;245
14.4;IV. The Search for an alpha7 Nicotinic Acetylcholine Receptor Agonist;250
14.5;V. The Phase 1 Study of DMXBA in Schizophrenia;251
14.6;References;254
15;Chapter 9: Histamine And Schizophrenia;264
15.1;I. Introduction;265
15.2;II. The Histaminergic Neuronal System;266
15.2.1;A. Organization;266
15.2.2;B. Metabolism of Histamine;268
15.2.3;C. Histamine Receptors;271
15.2.4;D. Histaminergic Neuron Activity and Its Control;277
15.2.5;E. Physiological Roles of Histaminergic Neurons;279
15.3;III. Changes in the Histaminergic System in Schizophrenia;281
15.3.1;A. Genetic Studies;281
15.3.2;B. Histamine Neuron Activity;282
15.4;IV. Interactions of Antipsychotic Drugs with the Histaminergic System;284
15.4.1;A. Interactions of APDs with Histamine Receptors;284
15.4.2;B. Modulation of Histamine Neuron Activity by APDs;286
15.5;V. Role of Histaminergic Neurons in Schizophrenia;286
15.6;VI. Conclusions;289
15.7;References;289
16;Chapter 10: Cannabinoids and Psychosis;306
16.1;I. Introduction;307
16.2;II. Ancedotal Reports;308
16.2.1;A. Autobiographical Accounts;308
16.2.2;B. Surveys of Cannabis Users;310
16.2.3;C. Psychosis in Cannabis Users from Community Samples;311
16.2.4;D. Naturalistic Case Series;311
16.3;III. Epidemiological Studies;314
16.4;IV. Pharmacological Studies;320
16.5;V. Cannabis and Psychosis: Causality;329
16.6;VI. Cannabinoid Receptor Dysfunction and Psychotic Disorders;331
16.7;VII. Summary and Conclusions;334
16.8;Acknowledgments;335
16.9;References;335
17;Chapter 11: Involvement of Neuropeptide Systems in Schizophrenia: Human Studies;344
17.1;I. Introduction;345
17.2;II. Cholecystokinin;346
17.3;III. Corticotropin-Releasing Factor;354
17.4;IV. Interleukins;361
17.5;V. Neurotensin;363
17.6;VI. Neuropeptide Y;365
17.7;VII. Opioid Peptides;366
17.7.1;A. Endorphins;366
17.7.2;B. Dynorphin;367
17.7.3;C. Enkephalins;367
17.8;VIII. Secretin;368
17.9;IX. Somatostatin;368
17.10;X. Vasoactive Intestinal Peptide;369
17.11;XI. Tachykinins;369
17.12;XII. Thyrotropin-Releasing Hormone;370
17.13;XIII. Other Peptides;371
17.14;XIV. Conclusions;373
17.15;Acknowledgments;374
17.16;References;374
18;Chapter 12: Brain-Derived Neurotrophic Factor in Schizophrenia and Its Relation With Dopamine;394
18.1;I. Introduction;394
18.2;II. Genetic Studies;396
18.3;III. BDNF in the Serum of Patients with Schizophrenia;399
18.4;IV. BDNF and TrkB Receptor in the Brain of Patients with Schizophrenia;399
18.5;V. Dopamine-BDNF Interactions;402
18.5.1;A. BDNF Supports the Survival and the Differentiation of Dopaminergic Neurons;402
18.5.2;B. BDNF in the GABA-Containing Local Circuit Neurons of the Prefrontal Cortex;402
18.5.3;C. Functional Interplay Between BDNF and Dopamine;403
18.5.4;D. BDNF Controls the Expression of the Dopamine D3 Receptor;403
18.6;VI. Conclusions;405
18.7;References;406
19;Chapter 13: Schizophrenia Susceptibility Genes: in Search of A Molecular Logic and Novel Drug Targets for A Devastating Disorder;414
19.1;I. The Genetic Component of Schizophrenia;415
19.2;II. Genes Identified Through Systematic Follow-Up of Linkage Signals;416
19.2.1;A. Proline Dehydrogenase;416
19.2.2;B. Dystrobrevin-Binding Protein 1;418
19.2.3;C. Neuregulin 1;419
19.2.4;D. G72;420
19.2.5;E. Disrupted in Schizophrenia 1;420
19.2.6;F. Carboxyl-Terminal PDZ Ligand of Neuronal Nitric Oxide Synthase;421
19.2.7;G. ZDHHC8;421
19.2.8;H. Trace Amine Receptor 6;422
19.2.9;I. Epsin 4;422
19.2.10;J. (GABA)A Receptor Subunit Gene Cluster;422
19.3;III. Other Candidate Genes;423
19.3.1;A. Catechol-O-Methyltransferase;423
19.3.2;B. Regulator of G-Protein Signaling 4;423
19.3.3;C. Calcineurin Gamma Catalytic Subunit;424
19.3.4;D. AKT1;424
19.4;IV. Areas of Caution in the Interpretation and Generalization of Genetic Findings;425
19.5;V. Future Directions of the Genetic Research: Advancing Our Understanding of How the Specific Genetic Factors Contribute Biologically to the Disease Process;426
19.5.1;A. Animal Models;427
19.5.2;B. Genetic Interactions;428
19.5.3;C. Understanding Disease Pathophysiology;429
19.5.4;D. Mechanism-Based Therapies;430
19.6;Acknowledgments;431
19.7;References;431
20;Index;440
21;Contents of Recent Volumes;456