Zigmond / Coyle / Rowland Neurobiology of Brain Disorders

Biological Basis of Neurological and Psychiatric Disorders
1. Auflage 2014
ISBN: 978-0-12-398280-3
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 824 Seiten

Neurobiology of Brain Disorders is the first book directed primarily at basic scientists to offer a comprehensive overview of neurological and neuropsychiatric disease. This book links basic, translational, and clinical research, covering the genetic, developmental, molecular, and cellular mechanisms underlying all major categories of brain disorders. It offers students, postdoctoral fellows, and researchers in the diverse fields of neuroscience, neurobiology, neurology, and psychiatry the tools they need to obtain a basic background in the major neurological and psychiatric diseases, and to discern connections between basic research and these relevant clinical conditions. This book addresses developmental, autoimmune, central, and peripheral neurodegeneration; infectious diseases; and diseases of higher function. The final chapters deal with broader issues, including some of the ethical concerns raised by neuroscience and a discussion of health disparities. Included in each chapter is coverage of the clinical condition, diagnosis, treatment, underlying mechanisms, relevant basic and translational research, and key unanswered questions. Written and edited by a diverse team of international experts, Neurobiology of Brain Disorders is essential reading for anyone wishing to explore the basic science underlying neurological and neuropsychiatric diseases. - Links basic, translational, and clinical research on disorders of the nervous system, creating a format for study that will accelerate disease prevention and treatment - Covers a vast array of neurological disorders, including ADHD, Down syndrome, autism, muscular dystrophy, diabetes, TBI, Parkinson, Huntington, Alzheimer, OCD, PTSD, schizophrenia, depression, and pain - Illustrated in full color - Each chapter provides in-text summary points, special feature boxes, and research questions - Provides an up-to-date synthesis of primary source material

Autoren/Hrsg.

Zigmond, Michael J.

Coyle, Joseph T.

Rowland, Lewis P.

Inhaltsverzeichnis

1;Front Cover;1
2;Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders;4
3;Copyright;5
4;Dedication;6
5;Contents;8
6;Preface;14
6.1;References;15
7;Acknowledgments;16
8;List of Contributors;18
9;Chapter 1 - An Introduction: A Clinical Neuroscientist and Disorders of the Brain;22
9.1;INTRODUCTION;22
9.2;LOCALIZATION OF LESIONS;23
9.3;IMAGING;23
9.4;SELECTIVE VULNERABILITY OF NEURONAL POPULATIONS;23
9.5;RECOVERY AFTER INJURY;24
9.6;STEM CELLS IN RECOVERY;25
9.7;BRAIN TRANSPLANTS;26
9.8;NEUROLOGY AS A THERAPEUTIC FIELD;26
9.9;ANIMAL MODELS OF HUMAN DISEASE;27
9.10;DEVELOPMENT OF NEW DRUGS;27
9.11;CLINICAL TRIALS;28
9.12;TRIALS IN ALZHEIMER DISEASE;28
9.13;BIOMARKERS OF DISEASE;29
9.14;PSYCHIATRIC DISEASE;30
9.15;GENETICS OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS;30
9.16;TEMPERAMENT AND DISEASE;31
9.17;CONCLUSION;31
9.18;References;32
10;Section I - DEVELOPMENTAL DISORDERS;34
10.1;Chapter 2 - Introduction;36
10.2;Chapter 3 - Developmental Disabilities and Metabolic Disorders;39
10.2.1;INTRODUCTION;40
10.2.2;BRAIN DEVELOPMENT;40
10.2.3;FUNCTIONAL DEVELOPMENT;43
10.2.4;ETIOLOGY;48
10.2.5;TECHNIQUES;51
10.2.6;PRINCIPLES OF MANAGEMENT;57
10.2.7;PRACTICE GUIDELINES;60
10.2.8;CONCLUSION;60
10.2.9;QUESTIONS FOR FURTHER RESEARCH;60
10.2.10;References;61
10.3;Chapter 4 - Attention Deficit/Hyperactivity Disorder;63
10.3.1;INTRODUCTION;63
10.3.2;CLINICAL DESCRIPTION;64
10.3.3;NEUROIMAGING STUDIES;64
10.3.4;EFFECTS OF ATTENTION DEFICIT/HYPERACTIVITY DISORDER TREATMENTS ON BRAIN FUNCTION;72
10.3.5;SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY AND POSITRON EMISSION TOMOGRAPHY STUDIES;72
10.3.6;CURRENT CLINICAL APPLICATIONS OF NEUROIMAGING STUDIES;73
10.3.7;FUTURE PERSPECTIVES IN THE NEUROIMAGING OF ATTENTION DEFICIT/HYPERACTIVITY DISORDER;73
10.3.8;EXPERIMENTAL ANIMAL MODELS;74
10.3.9;CONCLUSION;77
10.3.10;QUESTIONS FOR FURTHER RESEARCH;78
10.3.11;References;78
10.4;Chapter 5 - Down Syndrome: A Model for Chromosome Abnormalities;80
10.4.1;INTRODUCTION;80
10.4.2;DOWN SYNDROME;81
10.4.3;MOUSE MODELS OF DOWN SYNDROME;84
10.4.4;CLINICAL CHARACTERIZATION OF DOWN SYNDROME;85
10.4.5;DEVELOPMENT OF PHARMACOTHERAPY IN DOWN SYNDROME;93
10.4.6;CONCLUSION AND REMAINING ISSUES;96
10.4.7;Acknowledgments;97
10.4.8;References;97
10.5;Chapter 6 - Autism Spectrum Disorder;99
10.5.1;INTRODUCTION;99
10.5.2;HISTORY;100
10.5.3;CLINICAL FEATURES;101
10.5.4;DEFINITION AND CLASSIFICATION;103
10.5.5;EPIDEMIOLOGY;103
10.5.6;NATURAL HISTORY;104
10.5.7;DIFFERENTIAL DIAGNOSIS;106
10.5.8;ASSESSMENT;107
10.5.9;NEUROPSYCHOLOGICAL PROFILE/COGNITIVE FUNCTIONING;107
10.5.10;NEUROBIOLOGY;108
10.5.11;NEUROIMAGING;110
10.5.12;NEUROPHYSIOLOGY;111
10.5.13;NEUROPATHOLOGY;111
10.5.14;NEUROCHEMISTRY;112
10.5.15;GENETIC AND ENVIRONMENTAL RISK FACTORS;113
10.5.16;TREATMENT;115
10.5.17;FUTURE DIRECTIONS;115
10.5.18;Acknowledgment;117
10.5.19;References;117
10.6;Chapter 7 - Rett Syndrome: From the Involved Gene(s) to Treatment;119
10.6.1;INTRODUCTION;119
10.6.2;CLINICAL FEATURES OF RETT SYNDROME AND OTHER MECP2-RELATED DISORDERS;120
10.6.3;DIAGNOSIS AND CLINICAL MANAGEMENT OF RETT SYNDROME;121
10.6.4;GENETICS OF RETT SYNDROME: MECP2 GENE, PATHOGENIC MUTATIONS, AND PHENOTYPIC OUTCOME;122
10.6.5;MECP2 MOUSE MODELS RECAPITULATING HUMAN MECP2-RELATED PATHOLOGIES;125
10.6.6;MECP2 EXPRESSION DURING BRAIN DEVELOPMENT: ROLE IN NEURONAL MATURATION AND/OR MAINTENANCE OF THE MATURE STATE;128
10.6.7;NEUROMORPHOLOGICAL AND NEUROPHYSIOLOGICAL CONSEQUENCES OF MECP2 DYSFUNCTION;128
10.6.8;RETT SYNDROME: NOT SOLELY A NEURONAL DISEASE;130
10.6.9;MECP2: A MULTIFUNCTIONAL PROTEIN WHOSE PATHOGENIC MECHANISMS REMAIN UNSOLVED;131
10.6.10;MECP2 RESEARCH: FROM BENCH TO BEDSIDE;134
10.6.11;CONCLUSION AND FUTURE CHALLENGES;136
10.6.12;Acknowledgments;138
10.6.13;References;138
10.7;Chapter 8 - Fragile X-Associated Disorders;141
10.7.1;INTRODUCTION;141
10.7.2;RNA TOXICITY IN PREMUTATION CARRIERS;142
10.7.3;FRAGILE X SYNDROME;143
10.7.4;CLINICAL MANIFESTATIONS OF THE FRAGILE X PREMUTATION;144
10.7.5;PSYCHIATRIC MORBIDITY OF THE FRAGILE X PREMUTATION;146
10.7.6;CONCLUSION;148
10.7.7;AREAS FOR FUTURE RESEARCH;148
10.7.8;Acknowledgments;149
10.7.9;References;149
11;Section II - DISEASES OF THE PERIPHERAL NERVOUS SYSTEM;152
11.1;Chapter 9 - Introduction;154
11.2;Chapter 10 - Myasthenia Gravis;156
11.2.1;INTRODUCTION;156
11.2.2;IMMUNOPATHOGENESIS;158
11.2.3;DEFECT IN NEUROMUSCULAR TRANSMISSION;162
11.2.4;ANIMAL MODELS OF MYASTHENIA GRAVIS;163
11.2.5;EPIDEMIOLOGY AND GENETICS;164
11.2.6;CLINICAL PHENOTYPE;165
11.2.7;DIAGNOSIS;167
11.2.8;TREATMENT;168
11.2.9;CONCLUSION;170
11.2.10;References;171
11.3;Chapter 11 - Muscular Dystrophy;172
11.3.1;INTRODUCTION;172
11.3.2;PATHOPHYSIOLOGY AND GENETICS;173
11.3.3;EPIDEMIOLOGY;179
11.3.4;CLINICAL MANIFESTATIONS;180
11.3.5;DIAGNOSIS;182
11.3.6;GENETIC COUNSELING;183
11.3.7;TREATMENT AND OUTCOMES;183
11.3.8;CONCLUSION;185
11.3.9;Acknowledgments;186
11.3.10;References;186
11.4;Chapter 12 - Peripheral Neuropathies;188
11.4.1;PERIPHERAL NERVOUS SYSTEM BIOLOGY;188
11.4.2;CLINICAL MANIFESTATION AND DIAGNOSTIC MODALITIES IN PERIPHERAL NEUROPATHIES;193
11.4.3;INHERITED NEUROPATHIES;194
11.4.4;IMMUNE-MEDIATED NEUROPATHIES;200
11.4.5;OTHER NEUROPATHIES;206
11.4.6;CONCLUSION;208
11.4.7;QUESTIONS FOR FURTHER RESEARCH;208
11.4.8;References;209
11.5;Chapter 13 - Diabetes and Cognitive Dysfunction;210
11.5.1;DIABETES MELLITUS;210
11.5.2;COMPLICATIONS ASSOCIATED WITH DIABETES;211
11.5.3;UNDERLYING MECHANISMS LINKING DIABETES AND ALZHEIMER DISEASE;213
11.5.4;ANIMAL MODELS OF DIABETES AND ALZHEIMER DISEASE;219
11.5.5;CONCLUSION;221
11.5.6;Acknowledgments;221
11.5.7;References;221
12;Section III - DISEASES OF THE CENTRAL NERVOUS SYSTEM AND NEURODEGENERATION;224
12.1;Chapter 14 - Introduction;226
12.2;Chapter 15 - Spinal Cord Injury;228
12.2.1;INTRODUCTION;228
12.2.2;TYPES OF INJURY AND GLIAL SCAR FORMATION;229
12.2.3;TIME-COURSE OF POSTINJURY CHANGES;229
12.2.4;CELL TYPES INVOLVED;230
12.2.5;ROLE OF THE EXTRACELLULAR MATRIX AND GROWTH INHIBITORS;232
12.2.6;CELL DEATH FOLLOWING SPINAL CORD INJURY;233
12.2.7;GENETIC AND EPIGENETIC CONTROL OF AXONAL GROWTH;233
12.2.8;INFLAMMATORY AND MALADAPTIVE IMMUNE RESPONSES AND THE BLOOD–BRAIN BARRIER;234
12.2.9;NEUROPATHIC PAIN AND AUTONOMIC DYSREFLEXIA;235
12.2.10;THERAPEUTIC TOOLS IN SPINAL CORD INJURY;235
12.2.11;QUESTIONS FOR FURTHER RESEARCH;238
12.2.12;References;239
12.3;Chapter 16 - Traumatic Brain Injury;240
12.3.1;INTRODUCTION: EPIDEMIOLOGY AND CLASSIFICATIONS;240
12.3.2;PRIMARY EFFECTS OF TRAUMATIC BRAIN INJURY;244
12.3.3;SECONDARY EFFECTS OF TRAUMATIC BRAIN INJURY;245
12.3.4;CHRONIC EFFECTS OF TRAUMATIC BRAIN INJURY;246
12.3.5;CONCLUSION;254
12.3.6;DIRECTIONS FOR FUTURE RESEARCH;255
12.3.7;Acknowledgments;255
12.3.8;References;255
12.4;Chapter 17 - Epilepsy;257
12.4.1;INTRODUCTION;257
12.4.2;CLASSIFICATION OF THE SEIZURES AND THE EPILEPSIES;260
12.4.3;MECHANISMS UNDERLYING SEIZURES;265
12.4.4;MECHANISMS OF EPILEPTOGENESIS AND EPILEPSY;274
12.4.5;TREATMENT OF EPILEPSY;277
12.4.6;SUMMARY;281
12.4.7;Acknowledgments;281
12.4.8;References;281
12.5;Chapter 18 - Amyotrophic Lateral Sclerosis;283
12.5.1;INTRODUCTION;283
12.5.2;DIAGNOSIS OF AMYOTROPHIC LATERAL SCLEROSIS;283
12.5.3;CLINICAL CHARACTERISTICS OF AMYOTROPHIC LATERAL SCLEROSIS;284
12.5.4;NATURAL HISTORY OF AMYOTROPHIC LATERAL SCLEROSIS;285
12.5.5;AVAILABLE TREATMENTS FOR AMYOTROPHIC LATERAL SCLEROSIS;285
12.5.6;NEUROBIOLOGICAL BASIS OF AMYOTROPHIC LATERAL SCLEROSIS;285
12.5.7;MODEL SYSTEMS OF AMYOTROPHIC LATERAL SCLEROSIS TOXICITY;295
12.5.8;FUTURE DIRECTIONS;299
12.5.9;Acknowledgments;300
12.5.10;References;300
12.6;Chapter 19 - Parkinson Disease and Other Synucleinopathies;302
12.6.1;INTRODUCTION;303
12.6.2;CLINICAL FEATURES OF PARKINSON DISEASE;303
12.6.3;DIAGNOSIS OF PARKINSON DISEASE;305
12.6.4;ETIOLOGY OF PARKINSON DISEASE: CLUES FROM EPIDEMIOLOGY AND GENETICS;306
12.6.5;TREATMENT OF PARKINSON DISEASE;317
12.6.6;CONCLUSION;322
12.6.7;References;322
12.7;Chapter 20 - Huntington Disease;324
12.7.1;OVERVIEW OF HUNTINGTON DISEASE;324
12.7.2;ANIMAL MODELS OF HUNTINGTON DISEASE;328
12.7.3;NEUROPATHOLOGY OF HUNTINGTON DISEASE;328
12.7.4;NEUROBIOLOGY OF HUNTINGTON DISEASE;330
12.7.5;TREATMENT OF HUNTINGTON DISEASE;337
12.7.6;OTHER CAG REPEAT DISORDERS;338
12.7.7;QUESTIONS FOR FURTHER RESEARCH;340
12.7.8;References;340
12.8;Chapter21 - Alzheimer Disease;342
12.8.1;INTRODUCTION;342
12.8.2;NEUROPATHOLOGY OF ALZHEIMER DISEASE;346
12.8.3;GENETICS AND MOLECULAR BIOLOGY OF ALZHEIMER DISEASE;347
12.8.4;CURRENT AND FUTURE THERAPIES FOR ALZHEIMER DISEASE;351
12.8.5;CONCLUSION;357
12.8.6;QUESTIONS FOR FURTHER RESEARCH;358
12.8.7;Acknowledgments;358
12.8.8;References;358
12.9;Chapter 22 - Cerebrovascular Disease – Stroke;360
12.9.1;DEFINITION OF STROKE;360
12.9.2;BRAIN LESIONS CAUSED BY CEREBROVASCULAR DISEASE;360
12.9.3;VASCULAR PATHOLOGIES CAUSING BRAIN ISCHEMIA AND HEMORRHAGE;365
12.9.4;FACTORS AFFECTING TISSUE SURVIVAL IN PATIENTS WITH BRAIN ISCHEMIA AND INFARCTION;373
12.9.5;DEATH OF CELLS IN THE CNS, AND NEUROPROTECTIVE AND REPARATIVE MECHANISMS;375
12.9.6;QUESTIONS FOR FURTHER RESEARCH;376
12.9.7;References;376
12.10;Chapter 23 - Prion Diseases;377
12.10.1;INTRODUCTION;377
12.10.2;CAUSES AND PATHOGENESIS OF PRION DISEASES;378
12.10.3;KURU;380
12.10.4;CREUTZFELDT–JAKOB DISEASE;382
12.10.5;VARIANT CREUTZFELDT–JAKOB DISEASE;386
12.10.6;GERSTMANN–STRÄUSSLER–SCHEINKER DISEASE;391
12.10.7;LABORATORY TESTS;392
12.10.8;CONCLUSION;393
12.10.9;QUESTIONS FOR FURTHER RESEARCH;393
12.10.10;References;394
13;Section IV - INFECTIOUS AND IMMUNE-MEDIATED DISEASES AFFECTING THE NERVOUS SYSTEM;396
13.1;Chapter 24 - Introduction;398
13.2;Chapter 25 - Role of Inflammation in Neurodegenerative Diseases;401
13.2.1;INTRODUCTION;401
13.2.2;MICROGLIA: CONVERGENCE POINT FOR PROMOTING OR COMPROMISING NEURONAL SURVIVAL;402
13.2.3;T-LYMPHOCYTES: NEUROPROTECTION AND NEUROTOXICITY;404
13.2.4;PARKINSON DISEASE;405
13.2.5;ALZHEIMER DISEASE;408
13.2.6;AMYOTROPHIC LATERAL SCLEROSIS;411
13.2.7;CONCLUSION;414
13.2.8;References;415
13.3;Chapter 26 - Role of Inflammation in Psychiatric Disease;417
13.3.1;INTRODUCTION;417
13.3.2;EVIDENCE THAT THE IMMUNE SYSTEM IS INVOLVED IN PSYCHIATRIC DISEASE PATHOGENESIS;418
13.3.3;EVIDENCE THAT PATTERNS OF CNS ACTIVITY ASSOCIATED WITH PSYCHIATRIC DISEASE AFFECT IMMUNE FUNCTIONING IN HEALTH-RELEVANT WAYS;429
13.3.4;EVIDENCE THAT ENVIRONMENTAL FACTORS THAT PROMOTE PSYCHIATRIC MORBIDITY MAY DO SO BY ALTERING IMMUNE FUNCTION;433
13.3.5;EVIDENCE THAT PSYCHIATRIC CONDITIONS ARE ASSOCIATED WITH ALTERATIONS IN PERIPHERAL AND CNS IMMUNE ACTIVITY;437
13.3.6;References;441
13.4;Chapter 27 - Infections and Nervous System Dysfunction;443
13.4.1;INTRODUCTION;443
13.4.2;MICROBE–HOST CELL INTERACTIONS;444
13.4.3;IMMUNE RESPONSES TO INVADING PATHOGENS;445
13.4.4;INVASION OF PATHOGENS IN THE NERVOUS SYSTEM;448
13.4.5;PATHOGENS CAUSING NERVOUS SYSTEM DYSFUNCTION;450
13.4.6;FUTURE DIRECTIONS;462
13.4.7;Acknowledgments;463
13.4.8;References;463
13.5;Chapter 28 - Pathobiology of CNS Human Immunodeficiency Virus Infection;465
13.5.1;INTRODUCTION;466
13.5.2;HUMAN IMMUNODEFICIENCY VIRUS GENETICS AND GENOMIC ORGANIZATION OF HIV-1;466
13.5.3;LIFE CYCLE OF THE HUMAN IMMUNODEFICIENCY VIRUS;468
13.5.4;ESTABLISHMENT OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION;469
13.5.5;ENTRY OF HUMAN IMMUNODEFICIENCY VIRUS INTO THE CNS;469
13.5.6;CNS HUMAN IMMUNODEFICIENCY VIRUS INFECTION BY CELL TYPE;473
13.5.7;CNS ESCAPE AND VIRAL LATENCY;475
13.5.8;MECHANISMS OF CNS INJURY;477
13.5.9;CNS METABOLIC COMPLICATIONS OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION;480
13.5.10;EXPERIMENTAL MODELS;482
13.5.11;CLINICAL MANIFESTATIONS OF CNS HUMAN IMMUNODEFICIENCY VIRUS INFECTION;483
13.5.12;EFFECTS OF COMBINATION ANTIRETROVIRAL THERAPY ON CNS HUMAN IMMUNODEFICIENCY VIRUS PATHOLOGY;484
13.5.13;CONCLUSION AND FUTURE CHALLENGES;485
13.5.14;Acknowledgments;485
13.5.15;References;485
13.6;Chapter 29 - Autoimmune and Paraneoplastic Neurological Disorders;488
13.6.1;INTRODUCTION;489
13.6.2;THE IMMUNE SYSTEM;489
13.6.3;PATHOGENIC MECHANISMS OF NEURAL ANTIGEN-SPECIFIC AUTOIMMUNITY;490
13.6.4;AUTOIMMUNE AND PARANEOPLASTIC NEUROLOGICAL DISEASES;504
13.6.5;LEVELS OF THE NEURAXIS AFFECTED BY PARANEOPLASTIC AND AUTOIMMUNE SYNDROMES;506
13.6.6;CONCLUSION;515
13.6.7;FUTURE DIRECTIONS;515
13.6.8;References;516
13.7;Chapter 30 - Multiple Sclerosis;518
13.7.1;INTRODUCTION;518
13.7.2;ETIOLOGY OF MULTIPLE SCLEROSIS;521
13.7.3;IMMUNE PATHOGENESIS OF MULTIPLE SCLEROSIS;525
13.7.4;CLINICAL FEATURES OF MULTIPLE SCLEROSIS;531
13.7.5;PROGRESSIVE MULTIPLE SCLEROSIS AS AN UNMET NEED;532
13.7.6;TREATMENT OF MULTIPLE SCLEROSIS;533
13.7.7;FUTURE DIRECTIONS;539
13.7.8;References;540
14;Section V - DISEASES OF HIGHER FUNCTION;542
14.1;Chapter 31 - Introduction;544
14.1.1;References;545
14.2;Chapter 32 - Disorders of Higher Cortical Function;546
14.2.1;INTRODUCTION: FROM NEUROPSYCHOLOGY TO MENTAL STRUCTURE;547
14.2.2;LANGUAGE DISORDERS;548
14.2.3;MEMORY DISORDERS: AMNESIA;550
14.2.4;DISORDERS OF MOVEMENT EXECUTION: APRAXIA;551
14.2.5;DISORDERS OF VISUAL RECOGNITION: AGNOSIA;553
14.2.6;DISORDERS OF SPATIAL REPRESENTATION: UNILATERAL NEGLECT;556
14.2.7;CONSCIOUS AWARENESS;558
14.2.8;FUTURE DIRECTIONS;561
14.2.9;References;561
14.3;Chapter 33 - Disorders of Frontal Lobe Function;563
14.3.1;INTRODUCTION;563
14.3.2;FRONTAL TOPOGRAPHY;563
14.3.3;CORTICAL MOTOR SYSTEMS;565
14.3.4;CORTICAL INFLUENCE ON THE AUTONOMIC NERVOUS SYSTEM;568
14.3.5;COGNITIVE FUNCTIONS OF THE FRONTAL CORTEX;569
14.3.6;EMOTION, MOTIVATION, AND SOCIAL BEHAVIOR;573
14.3.7;CONCLUSION AND QUESTIONS FOR FURTHER RESEARCH;576
14.3.8;References;577
14.4;Chapter 34 - Stress;579
14.4.1;INTRODUCTION;579
14.4.2;TYPES OF STRESS;580
14.4.3;DEFINITION OF STRESS, ALLOSTASIS, AND ALLOSTATIC LOAD;580
14.4.4;RESPONSE TO STRESSORS: PROTECTION AND DAMAGE;582
14.4.5;POSITIVE EFFECTS OF GLUCOCORTICOIDS ON NEURONAL FUNCTIONS AND STRUCTURE;582
14.4.6;STRESS IN THE NATURAL WORLD;583
14.4.7;CIRCADIAN DISRUPTION;583
14.4.8;KEY ROLE OF THE BRAIN IN RESPONSE TO STRESS;584
14.4.9;THE BRAIN AS A TARGET OF STRESS;584
14.4.10;TRANSLATION TO THE HUMAN BRAIN;585
14.4.11;EARLY LIFE EXPERIENCES;586
14.4.12;INTERVENTIONS THAT CHANGE THE BRAIN AND IMPROVE HEALTH;587
14.4.13;CONCLUSION;588
14.4.14;Acknowledgments;589
14.4.15;References;589
14.5;Chapter 35 - Addictions;591
14.5.1;INTRODUCTION;591
14.5.2;TRAJECTORY OF ADDICTIONS AND UNDERLYING NEUROBIOLOGY;593
14.5.3;ANIMAL BEHAVIORAL MODELS TO STUDY ADDICTIONS;594
14.5.4;RESEARCH TECHNIQUES IN HUMANS;596
14.5.5;BASIC NEUROBIOLOGY OF SELECTED ADDICTIONS;597
14.5.6;THE GENETICS OF ADDICTION;602
14.5.7;QUESTIONS FOR FURTHER RESEARCH;603
14.5.8;Acknowledgments;604
14.5.9;References;604
14.6;Chapter 36 - Sleep Disorders;606
14.6.1;INTRODUCTION TO SLEEP AND CIRCADIAN NEUROBIOLOGY;607
14.6.2;NEUROBIOLOGY OF SLEEP;608
14.6.3;CIRCADIAN REGULATION OF SLEEP;609
14.6.4;CIRCUITRY AND MOLECULAR ASPECTS OF SLEEP;612
14.6.5;CURRENT THEORIES ON WHY WE SLEEP;616
14.6.6;INTRODUCTION TO SLEEP DISORDERS;617
14.6.7;CIRCADIAN RHYTHM SLEEP DISORDERS;619
14.6.8;NARCOLEPSY;622
14.6.9;KLEINE–LEVIN SYNDROME;626
14.6.10;RESTLESS LEGS SYNDROME;627
14.6.11;RAPID EYE MOVEMENT SLEEP BEHAVIOR DISORDER;628
14.6.12;CONCLUSION AND QUESTIONS FOR FURTHER RESEARCH;630
14.6.13;References;631
14.7;Chapter 37 - Fear-Related Anxiety Disorders and Post-Traumatic Stress Disorder;633
14.7.1;INTRODUCTION;633
14.7.2;CLASSIFICATION OF ANXIETY DISORDERS;634
14.7.3;NEUROANATOMICAL BASIS OF ANXIETY DISORDERS;635
14.7.4;CLINICAL FEATURES AND PSYCHOBIOLOGY OF ANXIETY DISORDERS;637
14.7.5;CONCLUSION;639
14.7.6;QUESTIONS FOR FURTHER RESEARCH;640
14.7.7;References;640
14.8;Chapter 38 - Obsessive–Compulsive Disorder;642
14.8.1;INTRODUCTION;643
14.8.2;EPIDEMIOLOGY OF OBSESSIVE–COMPULSIVE DISORDER;643
14.8.3;CLINICAL CONSIDERATIONS IN OBSESSIVE–COMPULSIVE DISORDER;644
14.8.4;NATURAL HISTORY AND COURSE OF THE DISEASE;647
14.8.5;PATHOGENESIS OF OBSESSIVE–COMPULSIVE DISORDER;647
14.8.6;TREATMENT OF OBSESSIVE–COMPULSIVE DISORDER;653
14.8.7;OBSESSIVE–COMPULSIVE SPECTRUM DISORDERS;656
14.8.8;OBSESSIVE–COMPULSIVE DISORDER IN PEDIATRIC POPULATIONS;657
14.8.9;CONCLUSION;658
14.8.10;QUESTIONS FOR FURTHER RESEARCH;658
14.8.11;References;658
14.9;Chapter 39 - Schizophrenia;660
14.9.1;CLINICAL ASPECTS OF SCHIZOPHRENIA;660
14.9.2;DYSREGULATED NEUROTRANSMITTER SYSTEMS IN SCHIZOPHRENIA;662
14.9.3;GLIAL CELL ALTERATIONS IN SCHIZOPHRENIA;670
14.9.4;CONCLUSION;673
14.9.5;References;674
14.10;Chapter 40 - Bipolar Disorder;676
14.10.1;INTRODUCTION;676
14.10.2;SPECTRUM OF BIPOLAR DISORDER;677
14.10.3;GENETICS OF BIPOLAR DISORDER;677
14.10.4;EPIGENETICS OF BIPOLAR DISORDER;680
14.10.5;NEUROMORPHOLOGICAL CHANGES IN BIPOLAR DISORDER;680
14.10.6;NEUROBIOLOGICAL CHANGES IN BIPOLAR DISORDER;683
14.10.7;BEHAVIORAL MARKERS IN BIPOLAR DISORDER;690
14.10.8;CONCLUSION;692
14.10.9;References;693
14.11;Chapter 41 - Pain: From Neurobiology to Disease;695
14.11.1;INTRODUCTION;695
14.11.2;TERMINOLOGY OF PAIN;696
14.11.3;FACTORS AFFECTING THE EMERGENCE, PROGNOSIS, AND SEVERITY OF PAIN;698
14.11.4;NEUROBIOLOGY OF PAIN;701
14.11.5;INJURY-INDUCED PLASTICITY;703
14.11.6;LOSS OF HOMEOSTASIS;706
14.11.7;HOPE FOR THE MAGIC BULLET;706
14.11.8;TREATMENT OF PAIN;706
14.11.9;CONCLUSION;711
14.11.10;References;712
14.12;Chapter 42 - Migraine;714
14.12.1;INTRODUCTION;714
14.12.2;THE MIGRAINE SPECTRUM: AN OVERVIEW OF CLINICAL MANIFESTATIONS;715
14.12.3;MIGRAINE MECHANISMS;716
14.12.4;MIGRAINE AND ALLOSTATIC LOAD;726
14.12.5;CONCLUSION;727
14.12.6;QUESTIONS FOR FURTHER RESEARCH;727
14.12.7;Acknowledgments;727
14.12.8;References;727
14.13;Chapter 43 - Depression and Suicide;730
14.13.1;INTRODUCTION;730
14.13.2;EPIDEMIOLOGICAL OBSERVATIONS IN DEPRESSION AND SUICIDE;731
14.13.3;PATHOGENIC FACTORS IN DEPRESSION AND SUICIDE;735
14.13.4;GENETIC FACTORS IN DEPRESSION AND SUICIDE;736
14.13.5;GENE BY ENVIRONMENT INTERACTIONS IN STRESS, DEPRESSION, AND SUICIDE;739
14.13.6;NEUROTRANSMITTER SYSTEMS IN MAJOR DEPRESSION AND SUICIDAL BEHAVIOR;740
14.13.7;CELL PLASTICITY AND SURVIVAL IN DEPRESSION AND SUICIDE;742
14.13.8;NEUROANATOMICAL CHANGES IN DEPRESSION AND SUICIDE;744
14.13.9;RESILIENCE, DEPRESSION, AND SUICIDE;747
14.13.10;CONCLUSION;749
14.13.11;References;749
15;Section VI - DISEASES OF THE NERVOUS SYSTEM AND SOCIETY;752
15.1;Chapter 44 - Introduction;754
15.1.1;References;755
15.2;Chapter 45 - Advances in Ethics for the Neuroscience Agenda;756
15.2.1;INTRODUCTION;756
15.2.2;RESEARCH WITH ANIMALS;757
15.2.3;SHARING DATA AND RESOURCES;758
15.2.4;INCIDENTAL FINDINGS;761
15.2.5;NEUROSCIENCE COMMUNICATION;762
15.2.6;NEUROETHICS FOR NEUROSCIENCE;764
15.2.7;CONCLUSION;766
15.2.8;Acknowledgments;767
15.2.9;References;767
15.3;Chapter 46 - Burden of Neurological Disease;769
15.3.1;INTRODUCTION;769
15.3.2;BASIC CONCEPTS IN EPIDEMIOLOGY;769
15.3.3;CEREBROVASCULAR DISEASE;771
15.3.4;PRIMARY NEOPLASMS;773
15.3.5;EPILEPSY AND SEIZURE DISORDERS;774
15.3.6;DEMENTIA;775
15.3.7;PARKINSON DISEASE;776
15.3.8;MULTIPLE SCLEROSIS;776
15.3.9;OVERVIEW OF NEUROLOGICAL DISORDERS;781
15.3.10;CONCLUSION AND FUTURE DIRECTIONS;784
15.3.11;References;784
15.4;Chapter 47 - Stress, Health, and Disparities;786
15.4.1;RACIAL DISPARITIES IN HEALTH;786
15.4.2;STRESS, STRESSORS, AND THEIR ROLE IN HEALTH;789
15.4.3;UNDERSTANDING RACIAL DIFFERENCES IN HEALTH: A ROLE FOR STRESS?;794
15.4.4;RESEARCH IMPLICATIONS;797
15.4.5;CLINICAL IMPLICATIONS;798
15.4.6;CONCLUSION;799
15.4.7;References;799
16;Index;802

Leseproben

Preface
Interest in understanding the basis of neurological and psychiatric disorders is thousands of years old. People of China and India, as well as the Egyptians and Greeks, all had ideas about how the brain worked and what caused the occasional functional abnormalities that they observed. Moreover, they often developed interventions to relieve symptoms, if not treat the disease. Indeed, the origins of neuroscience probably go back even farther. For example, trephination of the skull is thought to have been practiced as long as 7000 years ago and may have been designed to release evil spirits believed to be the cause of brain disorders. Since then, some of the ancient treatments have been found to be quite effective and have even served as the basis for much more recent interventions. However, the modern era of inquiry into the neurobiological basis of brain disorders did not begin until the nineteenth century. Several milestones along the path of that inquiry can be identified; here we mention just a few. Rauwolfia serpentina is a shrub from which the people of India have been making a medicinal tea for thousands of years.1,2 Among the many conditions for which it was used was “moon disease”, which we now recognize as psychosis. In the early 1950s it was determined that most of the tranquilizing effects of the plant extracts resulted from a compound that was named reserpine. Over the next decade, Arvid Carlsson and colleagues, working first at the US National Institutes of Health, then at the University of Lund, and finally at the University of Göteborg, Sweden, demonstrated that the effects of this natural product were due to its depletion of the neurotransmitter dopamine from the striatum, as described in the Nobel Lecture by Arvid Carlsson.3 This led to several key observations, including the discovery by Oleh Hornykiewicz in Vienna that Parkinson disease (PD) was associated with a loss of striatal dopamine and that many of the motor symptoms of PD could be reversed by administration of the dopamine precursor, L-dopa (see Chapter 19).3,4 The use of reserpine as a treatment for psychosis, together with the discovery of chlorpromazine for the treatment of schizophrenia and the realization in 1963 that it, too, acted by reducing dopaminergic transmission,5 led to the focus on reducing dopaminergic transmission to treat schizophrenia (see Chapter 39). Likewise, the observation that a loss of dopamine was associated with PD, and that the behavior of reserpinized animals and patients with PD could both be improved by L-dopa, resulted in the use of drugs that activate dopamine receptors in the treatment of PD. This sequence of events, conducted over a period of less than 10 years, is a landmark in the use of behavioral and neurochemical approaches for studying the nervous system, and was largely responsible for initiating the twin fields of neuropharmacology and biological psychiatry. There have been many other such moments in the emergence of biological approaches to neurological and psychiatric disorders. For example, Ernst Wilhelm von Brücke and colleagues, as well as their students (e.g. Sigmund Freud), working in Austria during the latter half of the nineteenth century, were among the first to apply laboratory methods to the study of the nervous system and to suggest that behavior could be understood through an understanding of biological events. The introduction of electrophysiology into neuroscience can be traced as far back as the seventeenth century to the work of Jan Swammerdam in Holland, although it is Luigi Galvani, working in Italy in the nineteenth century using nerve–muscle preparations, who is usually credited with initiating electrophysiology as an approach for understanding how the nervous system functions.6 Neuropathology was introduced by Paul Oscar Blocq and Georges Marinesco in the late nineteenth century in Paris. During a postmortem examination, they found a tumor in the contralateral substantia nigra of a patient who had exhibited the symptoms of PD, as reviewed by Catala and Poirier.7 In short, many of the principal tools for understanding the neurobiology of brain disorders – neuropathology, histochemistry, electrophysiology, biochemistry, and behavior – gradually emerged over the past 250 years as a result of investigators working in many different areas of the world. In the 1970s, two more approaches were added, molecular neurobiology and brain imaging. (For an excellent treatise on the history of neuroscience, see Origins of Neuroscience: A History of Explorations into Brain Function, by Stanley Finger,8 and excellent articles in The Journal of the History of Neuroscience. For a timeline and an extensive bibliography of the history of neuroscience, see also the website of Eric Chudler at the University of Washington.9 Additional material can be found on the website of the Society for Neuroscience.10) Our decision to assist in the teaching of the neuroscience of brain disorders by preparing this textbook began to take shape over three decades ago. The Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts (USA) twice played a role in the origins of the project, as it has in the development of neuroscience more generally.11,12 The first event occurred on a rainy weekend afternoon in 1979, when Edward Kravitz invited two individuals to speak on the neurobiology course that he was co-teaching there. They were Nancy Wexler, then a program officer at the US National Institute of Neurological Diseases and Stroke, and Marjorie Guthrie, the widow of Woody Guthrie. Marjorie spoke movingly about how Woody’s Huntington disease affected him and their entire family; Nancy also commented on the disease. After the presentations, Marjorie, Nancy (who was to become the president of the Huntington’s Disease Foundation and whose family has also suffered from that condition), Ed, Michael Zigmond, and several others on the course went to “The Captain Kidd”, a popular hangout in Woods Hole, to continue the discussion. The group immediately began to talk about how moving the presentations by Marjorie and Nancy had been and how valuable it would be to expose others in the field to such experiences. Ed took this idea and ran with it, obtaining funding from the National Institutes of Health to underwrite the “Neurobiology of Disease” workshop now held each year just before the annual meeting of the Society for Neuroscience. The second event was a six-day workshop for faculty on teaching about the neurobiology of disease in which the three editors of the present textbook (and many others) taught during August 2011. The objective was to provide the participants with information and instructional methods that would allow them to go back to their home institutions and mount, or substantially improve, a course on the neurobiology of disorders. Much of the impetus for moving from courses to a textbook – and a few of the book’s authors (Ann McKee, Robert Brown) and consultants (Gerald Fischbach, Donald Price) – arose from that workshop. The hope was – and remains – that through this book still others will be able to develop courses on the neurobiology of disease. This textbook is not complete; there are separate chapters on the role of inflammation but not mitochondrial dysfunction, on PD but not Tourette syndrome, on depression but not anxiety, on traumatic brain injury, but not brain tumors. These and several other topics must await a second edition. But this raises the question: Why this abiding interest in helping to stimulate training in the neurobiology of disease? It is not because we believe that basic research in this field is less important than research that more directly confronts disease. On the contrary, virtually all of our current understanding of the biological basis of brain disorders stems from discoveries made in basic science laboratories, as the examples given at the beginning of this Preface indicate (see also the excellent series of pamphlets produced by the Society for Neuroscience, “Research and Discoveries”13). However, knowing more about disorders of the nervous system can motivate researchers to work even harder, and who among us does not want their work to eventually make a difference in the lives of others? Moreover, we firmly believe in the aphorism of Louis Pasteur that “chance favors the prepared mind”. We hope this textbook will aid in that preparation. Michael J. Zigmond, PhD Lewis P. Rowland, MD Joseph T. Coyle, MD References
1. Sen G, Bose K. Rauwolfia serpentina, a new Indian drug for insanity and hypertension. Indian Med World. 1931;21:194–201. 2. Lele R.D. Beyond reverse pharmacology: mechanism-based screening of Ayurvedic drugs. Ayurveda Integr Med. 2010;1:257–265. 3. Carlsson A. A half-century of neurotransmitter research: impact on neurology and psychiatry (Nobel Lecture). Chembiochem. 2001;2:484–493 For a video of this lecture, see http://www.nobelprize.org/nobel_prizes/medicine/laureates/2000/carlsson-lecture.html. 4. Hornykiewicz O. The discovery of dopamine deficiency in the parkinsonian brain. J Neural Transm Suppl. 2006;70:9–15. 5. Baumeister A.A. The chlorpromazine enigma. J Hist Neurosci. 2013;22:14–29. 6. Verkhratsky A, Krishtal O.A, Petersen O.H. From Galvani to patch clamp: the development of electrophysiology. Pflugers...