Handbook of Neurochemistry and Molecular Neurobiology: Schizophrenia (Springer Reference)

Handbook of Neurochemistry and Molecular Neurobiology......Page 1
Copy Right......Page 3
Preface......Page 4
Table of Contents......Page 6
Contributors......Page 8
001......Page 12
Event-Related Potentials (ERPs) in the Study of Schizophrenia: How Preclinical ERP Studies have Contributed to our Understandi......Page 533
2 Overview of Prefrontal DA......Page 15
3 Prefrontal DA and Cognition......Page 16
4.1 Clinical Studies......Page 17
4.3.1 Extrastriatal D1 Receptors......Page 18
4.3.2 Extrastriatal D2 Receptors......Page 19
6 Significance and Therapeutic Implications......Page 21
References......Page 23
Cholinergic Mechanisms in Schizophrenia......Page 28
2 Acetylcholine......Page 29
5 Hippocampal Function and Schizophrenia......Page 30
4.1 Postmortem Studies......Page 31
5 Pharmacological Studies......Page 33
5.3 Muscarinic Agonists......Page 34
5.5 Muscarinic Receptors as Therapeutic Targets......Page 36
7 Nicotinic Receptors and the Pathophysiology of Schizophrenia......Page 37
7.2 Nicotinic Agonist Development for Therapeutic Intervention......Page 39
7.3 Phase 1 Proof-of-Concept Trial of DMXB-A for Neurocognitive and Neurophysiological Deficits in Schizophrenia......Page 40
References......Page 41
Glutamatergic Approaches to the Conceptualization and Treatment of Schizophrenia......Page 50
1 Introduction......Page 52
2.1 Presynaptic Glutamatergic Mechanisms......Page 53
2.2.1 NMDA Receptors......Page 55
2.3 Metabotropic Receptors......Page 58
3 Evidence for NMDA Dysfunction in Schizophrenia......Page 59
3.1 Symptom Patterns Following NMDA Antagonist Administration......Page 60
3.2 Neurocognitive Effects of NMDA Antagonist Treatment......Page 69
3.3 NMDA Antagonist Effects on Sensory Processing......Page 72
3.4 Dopamine-Glutamate Interactions......Page 73
4 Glutamatergic Models of Schizophrenia......Page 74
4.2 Environmental and Neurochemical Factors......Page 75
4.3.2 NMDA Receptor-Hypofunction (NRH) Model......Page 76
4.3.3 Glutamatergic Hyperfunction......Page 77
2.1 Biology of N-acetylaspartate (NAA) and Magnetic Resonance Spectroscopy of NAA......Page 416
5.1 NMDA Receptor Glycine-site Agonists......Page 78
5.2 Early Studies - Glycine......Page 79
5.2.1 D-serine......Page 80
5.2.3 NMDA Agonists in Combination with Clozapine......Page 81
5.3 Glycine Transport Inhibitors......Page 82
5.5 Metabotropic Receptors......Page 83
5.5.2 Group II Metabotropic Agonists......Page 84
6 Future Research and Treatment Implications......Page 85
References......Page 86
004......Page 102
Hippocampus......Page 104
2 Association and Meta-Analysis of G72/G30 in Schizophrenia and Bipolar Disorder......Page 105
3 Human-Mouse ERP Homology......Page 112
3.1 Biological Role of Glutamate and the NMDA Receptor Hypofunction Hypothesis of Schizophrenia......Page 425
5 Structural Asymmetry of Auditory Regions in Normal and Schizophrenia Brains......Page 114
References......Page 115
Dysbindin-1 and Its Protein Family......Page 118
1 Introduction......Page 121
2.1 Family Membership Criteria......Page 122
2.2 Paralogs and Their Isoforms......Page 124
2.2.2 Dysbindin-2 (=Dysbindin Domain-Containing Protein 2, DBNDD2)......Page 135
3 Components of Dysbindin Family Members and Their Predicted Phosphorylation Sites......Page 136
3.2 Coiled Coil Domain (CCD) and Its Leucine Zipper (LZ) Motif......Page 137
3.3 Carboxy Terminal Region (CTR)......Page 148
3.3.2 PEST Domain (PD)......Page 149
4 Intracellular Localization of Dysbindin Family Members and Their Functional Implications......Page 150
4.1 Unlikely Sites......Page 151
4.2 Likely Sites: Cytoplasmic, Cytoskeletal, and Synaptic......Page 152
4.3 Nuclear Localization......Page 153
5.2.1 Changes in the CCD and its LZ Motif......Page 154
6.1.1 The DTNBP1 Gene......Page 157
6.1.3 Transcriptional Regulation......Page 161
6.2.1 Expression in Normal Tissues......Page 164
6.3 Protein Expression in Mammalian Tissues......Page 168
6.3.1 Western Blotting......Page 170
6.3.2.3 Central Nervous System (CNS)......Page 173
6.3.2.3.1 Sensory Relay Nuclei......Page 178
6.3.2.3.5 Hippocampal Formation......Page 179
6.3.2.3.6 Neocortex......Page 186
6.4.1 Mutations in Sdy Mice and the HPS-7 Case......Page 187
6.4.2 Abnormalities in Sdy Mice......Page 188
6.4.3 Does the Sdy Mouse Model Aspects of Schizophrenia?......Page 198
6.5.9 Motor Functions?......Page 212
6.5.1 Spermatogenesis......Page 201
6.5.3 Anti-Apoptosis in Neurons......Page 202
6.5.4 Growth of Axons, Dendrites, and Dendritic Spines......Page 204
6.5.5 AP-3 Cargo Transport to LROs and Synaptic Vesicles......Page 205
6.5.6 Synaptic Vesicle Release......Page 207
6.5.7 Postsynaptic Receptor Trafficking......Page 210
6.5.10 Cognition......Page 213
6.6.1 Association of DTNBP1 Variants with Schizophrenia......Page 214
6.6.2 Gene and Protein Expression of Dysbindin-1 in Schizophrenia......Page 221
6.6.3 Potential Contributions of Altered Dysbindin-1 Expression to Neurobiological and Clinical Features of Schizophrenia......Page 223
7 Synopsis......Page 228
Acknowledgments......Page 230
References......Page 231
006......Page 253
1.1 Human Genetic Studies on Neuregulin 1 Gene......Page 254
1.2 Correlation of the Expression of Neuregulin 1 and the Disease State of Schizophrenia......Page 256
1.3 Neuregulin 1 Gene and Psychoses......Page 257
2.2 The Neuregulin Subfamily......Page 258
2.3 Neuregulin 1: Isoform Diversity......Page 259
2.4 Neuregulin 1: Functional Diversity......Page 260
3.1 Mouse Models for Schizophrenia?......Page 261
3 Cytoarchitectonic Asymmetries of Human Auditory Areas......Page 367
3.2 Neuregulin 1/ErbB Signaling and Synaptic Maturation......Page 262
3.3 Using Mutant Mice for Nrg1 to Model Disease Endophenotypes......Page 264
3.5 Type III Neuregulin 1 Heterozygous Mutant Mice as a Model for Understanding Disease Conditions, and for Testing Therapeuti......Page 267
4.1 Catechol-O-methyltransferase (COMT) and Schizophrenia......Page 395
References......Page 269
Synaptic Vesicle Associated Proteins and Schizophrenia......Page 277
1 Introduction......Page 278
2 Neurotransmission at Chemical Synapses......Page 279
3.1 Synapsins......Page 280
3.2 Synaptotagmins......Page 281
3.3 Synaptophysin I and its Homologs......Page 282
3.4 SNARE Proteins and Their Regulators......Page 285
4 Potential Roles of Synaptic Vesicle Associated Proteins in the Etiology of Schizophrenia......Page 287
5 Discussion......Page 288
7 Aggression and Violence and the Prefrontal Lobe......Page 289
Redox Dysregulation in Schizophrenia: Genetic Susceptibility and Pathophysiological Mechanisms......Page 295
1.1 Etiopathogeny......Page 296
1.2 Pathophysiology......Page 297
1.3 Oxidative Stress in Schizophrenia......Page 298
1.4 Glutathione (GSH) Function and Metabolism......Page 300
2.2 GCL Dysregulation Under Oxidative Stress Conditions......Page 302
2.3 Decrease of GCLC Protein Expression......Page 303
3 Potential Contribution of GSH Deficit to Schizophrenia Pathophysiology......Page 304
3.1.2.1 Hypofunction of NMDA-R......Page 305
3.2 GSH Deficit During Early Postnatal Development......Page 306
3.2.2 Cognitive Functions......Page 307
4.1 Clinical Trial with N-Acetyl Cysteine (NAC)......Page 308
2.1 Neuroimaging/Gross Postmortem Studies......Page 519
5 GSH Deficit in the Broader Context of Schizophrenia Research......Page 309
Acknowledgements......Page 312
009......Page 322
2 Hippocampal Volume and Shape......Page 325
3 Cellular Mechanisms of Hippocampal Dysfunction in Schizophrenia......Page 326
3.2 Glutamatergic Hippocampal Neurons......Page 329
4 The Genetic Basis of Hippocampal Abnormalities in Schizophrenia......Page 330
5.1 Hippocampal Activity at Rest in Schizophrenia......Page 331
5.3 Hippocampal Activity and Cognitive Function in Schizophrenia......Page 332
6 Conclusion: The Role of the Hippocampus in Schizophrenia......Page 333
References......Page 335
Early-Stage Visual Processing Deficits in Schizophrenia......Page 340
1 Introduction......Page 341
2 Electrophysiological Studies......Page 344
3 Behavioral Studies......Page 349
6 Endophenotypes......Page 351
7 Anatomical Studies......Page 352
8 Effects on Higher Level Function......Page 354
References......Page 355
Auditory Cortex Anatomy and Asymmetry in Schizophrenia......Page 362
1 Introduction......Page 363
2.1 Monkey Auditory Areas......Page 364
2.2 Human Auditory Areas......Page 365
4 Altered Cellular Anatomy of Auditory Areas in Schizophrenia......Page 369
5.1 Structural Asymmetry of Heschls\' Gyrus......Page 371
5.2 Heschl\'s Gyrus Structural Changes in Schizophrenia......Page 373
5.3 Structural Asymmetry of the Planum Temporale......Page 374
5.4 Planum Temporale Structural Changes in Schizophrenia......Page 375
5.5 Superior Temporal Gyrus Structural Changes and Schizophrenia......Page 377
6 Pharmacological Models of Treatment......Page 381
References......Page 382
The Role of Prefrontal Abnormalities in Schizophrenia......Page 391
2.1 Prefrontally-mediated Cognitive Abnormalities......Page 393
2.3 DLPFC Neuroanatomical Findings......Page 394
5 Prefrontal White Matter Abnormalities......Page 396
6.2 Inferior Frontal Cortex and Social Cognition......Page 397
7.1 Introduction......Page 398
7.4 MAO-A and Aggression......Page 399
7.6.2.1 Structural Studies......Page 400
References......Page 401
013......Page 411
Magnetic Resonance Spectroscopy......Page 413
1 Principles of Magnetic Resonance Spectroscopy......Page 414
2.2 N-acetylaspartate (NAA) in Schizophrenia......Page 419
3.2 1H MRS Studies of Glutamate and Glutamine in Schizophrenia......Page 427
3.3 Biological Role of gamma-aminobutyric Acid (GABA) and Involvement in Schizophrenia......Page 430
3.4 1H MRS of GABA in Schizophrenia......Page 432
4.2 Early Studies of Phospholipid Changes in Schizophrenia and the Membrane Phospholipid Hypothesis for the Pathogenesis of Sc......Page 433
4.3 Recent 31P MRS Studies of Phospholipids in Schizophrenia......Page 434
4.4 High-energy Phosphates in Schizophrenia......Page 435
5.1 Research Directions......Page 438
References......Page 440
Alterations of Neurotransmitter Receptors in Schizophrenia: Evidence from Postmortem Studies......Page 451
1.1.1 The Dopamine System......Page 452
1.1.2.3 Thalamus, Hippocampus......Page 454
1.2 Glutamate Receptors......Page 456
1.2.1.1 NMDA Receptors......Page 457
1.2.2.1 Cortex......Page 458
1.2.2.2 Hippocampus......Page 463
1.2.2.3 Thalamus......Page 465
1.3.1.1 GABAA Receptors......Page 467
1.3.2.1 Cortex......Page 468
1.4.1 The Serotonergic System......Page 470
1.4.2.2 Hippocampus, Amygdala, Striatum......Page 471
1.5.1.1 Nicotinic Receptors......Page 474
1.5.2.1 Cortex......Page 475
1.5.2.2 Striatum, Hippocampus, Thalamus......Page 477
1.6.2 Adrenoreceptor Expression in Schizophrenia......Page 478
1.7.2 Cannabinoid Receptor Expression in Schizophrenia......Page 479
1.8.2 Histamine Receptor Expression in Schizophrenia......Page 480
1.9.2 Sigma Receptors......Page 481
Summary......Page 482
References......Page 483
An Overview and Current Perspective on Family Studies of Schizophrenia......Page 501
2.2 Abnormalities in Obligate ERPs in Schizophrenia......Page 535
2.1 Focus on Families During the First Quarter of the Twentieth Century......Page 502
2.3 The Post-War Era and the Family (Late 1940s-1970s)......Page 503
3.1 The Adoption Studies (1960s-1970s)......Page 504
3.2 Molecular Genetics and the Family......Page 505
4.2 Imprinting and Anticipation......Page 506
5.3 Potential Cognitive Endophenotype Investigations......Page 507
6 The Family and Stigma......Page 508
4 Pharmacological Models of Psychosis......Page 540
016......Page 513
The Neurobiology of Negative Symptoms and the Deficit Syndrome......Page 515
1 A Brief History of Negative Symptoms and the Deficit Syndrome......Page 516
2.Summary......Page 520
3.2 Norepinephrine......Page 521
3.4 Glutamate......Page 522
3.5 Acetylcholine......Page 523
4.1 COMT......Page 524
5 Why Do We Know so Little?......Page 525
References......Page 526
2.4 Deviance and Novelty-Related ERPs......Page 536
3.3 Mouse Correlates of the Human P50......Page 537
3.4 Mouse Correlates of the Human N100 and P200......Page 538
3.5 Mouse Correlates of the Human Deviance-Related MMN and P300......Page 539
4.2 NMDA Antagonists - Ketamine......Page 541
4.4 Mixed Models - Bupropion......Page 542
5.2 DBA/2 Strain......Page 544
6.3 Novel Therapeutics......Page 545
6.3.2 Nicotine......Page 546
References......Page 547
Index......Page 553