Neurobiology of Brain Disorders (eBook)

Biological Basis of Neurological and Psychiatric Disorders

Joseph T. Coyle, Lewis P. Rowland, Michael J. Zigmond (Herausgeber)

eBook Download: PDF | EPUB

2014 | 1. Auflage
824 Seiten
Elsevier Science (Verlag)
978-0-12-398280-3 (ISBN)

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

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

Front Cover 1
Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders 4
Copyright 5
Dedication 6
Contents 8
Preface 14
References 15
Acknowledgments 16
List of Contributors 18
Chapter 1 - An Introduction: A Clinical Neuroscientist and Disorders of the Brain 22
INTRODUCTION 22
LOCALIZATION OF LESIONS 23
IMAGING 23
SELECTIVE VULNERABILITY OF NEURONAL POPULATIONS 23
RECOVERY AFTER INJURY 24
STEM CELLS IN RECOVERY 25
BRAIN TRANSPLANTS 26
NEUROLOGY AS A THERAPEUTIC FIELD 26
ANIMAL MODELS OF HUMAN DISEASE 27
DEVELOPMENT OF NEW DRUGS 27
CLINICAL TRIALS 28
TRIALS IN ALZHEIMER DISEASE 28
BIOMARKERS OF DISEASE 29
PSYCHIATRIC DISEASE 30
GENETICS OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS 30
TEMPERAMENT AND DISEASE 31
CONCLUSION 31
References 32
Section I - DEVELOPMENTAL DISORDERS 34
Chapter 2 - Introduction 36
Chapter 3 - Developmental Disabilities and Metabolic Disorders 39
INTRODUCTION 40
BRAIN DEVELOPMENT 40
FUNCTIONAL DEVELOPMENT 43
ETIOLOGY 48
TECHNIQUES 51
PRINCIPLES OF MANAGEMENT 57
PRACTICE GUIDELINES 60
CONCLUSION 60
QUESTIONS FOR FURTHER RESEARCH 60
References 61
Chapter 4 - Attention Deficit/Hyperactivity Disorder 63
INTRODUCTION 63
CLINICAL DESCRIPTION 64
NEUROIMAGING STUDIES 64
EFFECTS OF ATTENTION DEFICIT/HYPERACTIVITY DISORDER TREATMENTS ON BRAIN FUNCTION 72
SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY AND POSITRON EMISSION TOMOGRAPHY STUDIES 72
CURRENT CLINICAL APPLICATIONS OF NEUROIMAGING STUDIES 73
FUTURE PERSPECTIVES IN THE NEUROIMAGING OF ATTENTION DEFICIT/HYPERACTIVITY DISORDER 73
EXPERIMENTAL ANIMAL MODELS 74
CONCLUSION 77
QUESTIONS FOR FURTHER RESEARCH 78
References 78
Chapter 5 - Down Syndrome: A Model for Chromosome Abnormalities 80
INTRODUCTION 80
DOWN SYNDROME 81
MOUSE MODELS OF DOWN SYNDROME 84
CLINICAL CHARACTERIZATION OF DOWN SYNDROME 85
DEVELOPMENT OF PHARMACOTHERAPY IN DOWN SYNDROME 93
CONCLUSION AND REMAINING ISSUES 96
Acknowledgments 97
References 97
Chapter 6 - Autism Spectrum Disorder 99
INTRODUCTION 99
HISTORY 100
CLINICAL FEATURES 101
DEFINITION AND CLASSIFICATION 103
EPIDEMIOLOGY 103
NATURAL HISTORY 104
DIFFERENTIAL DIAGNOSIS 106
ASSESSMENT 107
NEUROPSYCHOLOGICAL PROFILE/COGNITIVE FUNCTIONING 107
NEUROBIOLOGY 108
NEUROIMAGING 110
NEUROPHYSIOLOGY 111
NEUROPATHOLOGY 111
NEUROCHEMISTRY 112
GENETIC AND ENVIRONMENTAL RISK FACTORS 113
TREATMENT 115
FUTURE DIRECTIONS 115
Acknowledgment 117
References 117
Chapter 7 - Rett Syndrome: From the Involved Gene(s) to Treatment 119
INTRODUCTION 119
CLINICAL FEATURES OF RETT SYNDROME AND OTHER MECP2-RELATED DISORDERS 120
DIAGNOSIS AND CLINICAL MANAGEMENT OF RETT SYNDROME 121
GENETICS OF RETT SYNDROME: MECP2 GENE, PATHOGENIC MUTATIONS, AND PHENOTYPIC OUTCOME 122
MECP2 MOUSE MODELS RECAPITULATING HUMAN MECP2-RELATED PATHOLOGIES 125
MECP2 EXPRESSION DURING BRAIN DEVELOPMENT: ROLE IN NEURONAL MATURATION AND/OR MAINTENANCE OF THE MATURE STATE 128
NEUROMORPHOLOGICAL AND NEUROPHYSIOLOGICAL CONSEQUENCES OF MECP2 DYSFUNCTION 128
RETT SYNDROME: NOT SOLELY A NEURONAL DISEASE 130
MECP2: A MULTIFUNCTIONAL PROTEIN WHOSE PATHOGENIC MECHANISMS REMAIN UNSOLVED 131
MECP2 RESEARCH: FROM BENCH TO BEDSIDE 134
CONCLUSION AND FUTURE CHALLENGES 136
Acknowledgments 138
References 138
Chapter 8 - Fragile X-Associated Disorders 141
INTRODUCTION 141
RNA TOXICITY IN PREMUTATION CARRIERS 142
FRAGILE X SYNDROME 143
CLINICAL MANIFESTATIONS OF THE FRAGILE X PREMUTATION 144
PSYCHIATRIC MORBIDITY OF THE FRAGILE X PREMUTATION 146
CONCLUSION 148
AREAS FOR FUTURE RESEARCH 148
Acknowledgments 149
References 149
Section II - DISEASES OF THE PERIPHERAL NERVOUS SYSTEM 152
Chapter 9 - Introduction 154
Chapter 10 - Myasthenia Gravis 156
INTRODUCTION 156
IMMUNOPATHOGENESIS 158
DEFECT IN NEUROMUSCULAR TRANSMISSION 162
ANIMAL MODELS OF MYASTHENIA GRAVIS 163
EPIDEMIOLOGY AND GENETICS 164
CLINICAL PHENOTYPE 165
DIAGNOSIS 167
TREATMENT 168
CONCLUSION 170
References 171
Chapter 11 - Muscular Dystrophy 172
INTRODUCTION 172
PATHOPHYSIOLOGY AND GENETICS 173
EPIDEMIOLOGY 179
CLINICAL MANIFESTATIONS 180
DIAGNOSIS 182
GENETIC COUNSELING 183
TREATMENT AND OUTCOMES 183
CONCLUSION 185
Acknowledgments 186
References 186
Chapter 12 - Peripheral Neuropathies 188
PERIPHERAL NERVOUS SYSTEM BIOLOGY 188
CLINICAL MANIFESTATION AND DIAGNOSTIC MODALITIES IN PERIPHERAL NEUROPATHIES 193
INHERITED NEUROPATHIES 194
IMMUNE-MEDIATED NEUROPATHIES 200
OTHER NEUROPATHIES 206
CONCLUSION 208
QUESTIONS FOR FURTHER RESEARCH 208
References 209
Chapter 13 - Diabetes and Cognitive Dysfunction 210
DIABETES MELLITUS 210
COMPLICATIONS ASSOCIATED WITH DIABETES 211
UNDERLYING MECHANISMS LINKING DIABETES AND ALZHEIMER DISEASE 213
ANIMAL MODELS OF DIABETES AND ALZHEIMER DISEASE 219
CONCLUSION 221
Acknowledgments 221
References 221
Section III - DISEASES OF THE CENTRAL NERVOUS SYSTEM AND NEURODEGENERATION 224
Chapter 14 - Introduction 226
Chapter 15 - Spinal Cord Injury 228
INTRODUCTION 228
TYPES OF INJURY AND GLIAL SCAR FORMATION 229
TIME-COURSE OF POSTINJURY CHANGES 229
CELL TYPES INVOLVED 230
ROLE OF THE EXTRACELLULAR MATRIX AND GROWTH INHIBITORS 232
CELL DEATH FOLLOWING SPINAL CORD INJURY 233
GENETIC AND EPIGENETIC CONTROL OF AXONAL GROWTH 233
INFLAMMATORY AND MALADAPTIVE IMMUNE RESPONSES AND THE BLOOD–BRAIN BARRIER 234
NEUROPATHIC PAIN AND AUTONOMIC DYSREFLEXIA 235
THERAPEUTIC TOOLS IN SPINAL CORD INJURY 235
QUESTIONS FOR FURTHER RESEARCH 238
References 239
Chapter 16 - Traumatic Brain Injury 240
INTRODUCTION: EPIDEMIOLOGY AND CLASSIFICATIONS 240
PRIMARY EFFECTS OF TRAUMATIC BRAIN INJURY 244
SECONDARY EFFECTS OF TRAUMATIC BRAIN INJURY 245
CHRONIC EFFECTS OF TRAUMATIC BRAIN INJURY 246
CONCLUSION 254
DIRECTIONS FOR FUTURE RESEARCH 255
Acknowledgments 255
References 255
Chapter 17 - Epilepsy 257
INTRODUCTION 257
CLASSIFICATION OF THE SEIZURES AND THE EPILEPSIES 260
MECHANISMS UNDERLYING SEIZURES 265
MECHANISMS OF EPILEPTOGENESIS AND EPILEPSY 274
TREATMENT OF EPILEPSY 277
SUMMARY 281
Acknowledgments 281
References 281
Chapter 18 - Amyotrophic Lateral Sclerosis 283
INTRODUCTION 283
DIAGNOSIS OF AMYOTROPHIC LATERAL SCLEROSIS 283
CLINICAL CHARACTERISTICS OF AMYOTROPHIC LATERAL SCLEROSIS 284
NATURAL HISTORY OF AMYOTROPHIC LATERAL SCLEROSIS 285
AVAILABLE TREATMENTS FOR AMYOTROPHIC LATERAL SCLEROSIS 285
NEUROBIOLOGICAL BASIS OF AMYOTROPHIC LATERAL SCLEROSIS 285
MODEL SYSTEMS OF AMYOTROPHIC LATERAL SCLEROSIS TOXICITY 295
FUTURE DIRECTIONS 299
Acknowledgments 300
References 300
Chapter 19 - Parkinson Disease and Other Synucleinopathies 302
INTRODUCTION 303
CLINICAL FEATURES OF PARKINSON DISEASE 303
DIAGNOSIS OF PARKINSON DISEASE 305
ETIOLOGY OF PARKINSON DISEASE: CLUES FROM EPIDEMIOLOGY AND GENETICS 306
TREATMENT OF PARKINSON DISEASE 317
CONCLUSION 322
References 322
Chapter 20 - Huntington Disease 324
OVERVIEW OF HUNTINGTON DISEASE 324
ANIMAL MODELS OF HUNTINGTON DISEASE 328
NEUROPATHOLOGY OF HUNTINGTON DISEASE 328
NEUROBIOLOGY OF HUNTINGTON DISEASE 330
TREATMENT OF HUNTINGTON DISEASE 337
OTHER CAG REPEAT DISORDERS 338
QUESTIONS FOR FURTHER RESEARCH 340
References 340
Chapter21 - Alzheimer Disease 342
INTRODUCTION 342
NEUROPATHOLOGY OF ALZHEIMER DISEASE 346
GENETICS AND MOLECULAR BIOLOGY OF ALZHEIMER DISEASE 347
CURRENT AND FUTURE THERAPIES FOR ALZHEIMER DISEASE 351
CONCLUSION 357
QUESTIONS FOR FURTHER RESEARCH 358
Acknowledgments 358
References 358
Chapter 22 - Cerebrovascular Disease – Stroke 360
DEFINITION OF STROKE 360
BRAIN LESIONS CAUSED BY CEREBROVASCULAR DISEASE 360
VASCULAR PATHOLOGIES CAUSING BRAIN ISCHEMIA AND HEMORRHAGE 365
FACTORS AFFECTING TISSUE SURVIVAL IN PATIENTS WITH BRAIN ISCHEMIA AND INFARCTION 373
DEATH OF CELLS IN THE CNS, AND NEUROPROTECTIVE AND REPARATIVE MECHANISMS 375
QUESTIONS FOR FURTHER RESEARCH 376
References 376
Chapter 23 - Prion Diseases 377
INTRODUCTION 377
CAUSES AND PATHOGENESIS OF PRION DISEASES 378
KURU 380
CREUTZFELDT–JAKOB DISEASE 382
VARIANT CREUTZFELDT–JAKOB DISEASE 386
GERSTMANN–STRÄUSSLER–SCHEINKER DISEASE 391
LABORATORY TESTS 392
CONCLUSION 393
QUESTIONS FOR FURTHER RESEARCH 393
References 394
Section IV - INFECTIOUS AND IMMUNE-MEDIATED DISEASES AFFECTING THE NERVOUS SYSTEM 396
Chapter 24 - Introduction 398
Chapter 25 - Role of Inflammation in Neurodegenerative Diseases 401
INTRODUCTION 401
MICROGLIA: CONVERGENCE POINT FOR PROMOTING OR COMPROMISING NEURONAL SURVIVAL 402
T-LYMPHOCYTES: NEUROPROTECTION AND NEUROTOXICITY 404
PARKINSON DISEASE 405
ALZHEIMER DISEASE 408
AMYOTROPHIC LATERAL SCLEROSIS 411
CONCLUSION 414
References 415
Chapter 26 - Role of Inflammation in Psychiatric Disease 417
INTRODUCTION 417
EVIDENCE THAT THE IMMUNE SYSTEM IS INVOLVED IN PSYCHIATRIC DISEASE PATHOGENESIS 418
EVIDENCE THAT PATTERNS OF CNS ACTIVITY ASSOCIATED WITH PSYCHIATRIC DISEASE AFFECT IMMUNE FUNCTIONING IN HEALTH-RELEVANT WAYS 429
EVIDENCE THAT ENVIRONMENTAL FACTORS THAT PROMOTE PSYCHIATRIC MORBIDITY MAY DO SO BY ALTERING IMMUNE FUNCTION 433
EVIDENCE THAT PSYCHIATRIC CONDITIONS ARE ASSOCIATED WITH ALTERATIONS IN PERIPHERAL AND CNS IMMUNE ACTIVITY 437
References 441
Chapter 27 - Infections and Nervous System Dysfunction 443
INTRODUCTION 443
MICROBE–HOST CELL INTERACTIONS 444
IMMUNE RESPONSES TO INVADING PATHOGENS 445
INVASION OF PATHOGENS IN THE NERVOUS SYSTEM 448
PATHOGENS CAUSING NERVOUS SYSTEM DYSFUNCTION 450
FUTURE DIRECTIONS 462
Acknowledgments 463
References 463
Chapter 28 - Pathobiology of CNS Human Immunodeficiency Virus Infection 465
INTRODUCTION 466
HUMAN IMMUNODEFICIENCY VIRUS GENETICS AND GENOMIC ORGANIZATION OF HIV-1 466
LIFE CYCLE OF THE HUMAN IMMUNODEFICIENCY VIRUS 468
ESTABLISHMENT OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION 469
ENTRY OF HUMAN IMMUNODEFICIENCY VIRUS INTO THE CNS 469
CNS HUMAN IMMUNODEFICIENCY VIRUS INFECTION BY CELL TYPE 473
CNS ESCAPE AND VIRAL LATENCY 475
MECHANISMS OF CNS INJURY 477
CNS METABOLIC COMPLICATIONS OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION 480
EXPERIMENTAL MODELS 482
CLINICAL MANIFESTATIONS OF CNS HUMAN IMMUNODEFICIENCY VIRUS INFECTION 483
EFFECTS OF COMBINATION ANTIRETROVIRAL THERAPY ON CNS HUMAN IMMUNODEFICIENCY VIRUS PATHOLOGY 484
CONCLUSION AND FUTURE CHALLENGES 485
Acknowledgments 485
References 485
Chapter 29 - Autoimmune and Paraneoplastic Neurological Disorders 488
INTRODUCTION 489
THE IMMUNE SYSTEM 489
PATHOGENIC MECHANISMS OF NEURAL ANTIGEN-SPECIFIC AUTOIMMUNITY 490
AUTOIMMUNE AND PARANEOPLASTIC NEUROLOGICAL DISEASES 504
LEVELS OF THE NEURAXIS AFFECTED BY PARANEOPLASTIC AND AUTOIMMUNE SYNDROMES 506
CONCLUSION 515
FUTURE DIRECTIONS 515
References 516
Chapter 30 - Multiple Sclerosis 518
INTRODUCTION 518
ETIOLOGY OF MULTIPLE SCLEROSIS 521
IMMUNE PATHOGENESIS OF MULTIPLE SCLEROSIS 525
CLINICAL FEATURES OF MULTIPLE SCLEROSIS 531
PROGRESSIVE MULTIPLE SCLEROSIS AS AN UNMET NEED 532
TREATMENT OF MULTIPLE SCLEROSIS 533
FUTURE DIRECTIONS 539
References 540
Section V - DISEASES OF HIGHER FUNCTION 542
Chapter 31 - Introduction 544
References 545
Chapter 32 - Disorders of Higher Cortical Function 546
INTRODUCTION: FROM NEUROPSYCHOLOGY TO MENTAL STRUCTURE 547
LANGUAGE DISORDERS 548
MEMORY DISORDERS: AMNESIA 550
DISORDERS OF MOVEMENT EXECUTION: APRAXIA 551
DISORDERS OF VISUAL RECOGNITION: AGNOSIA 553
DISORDERS OF SPATIAL REPRESENTATION: UNILATERAL NEGLECT 556
CONSCIOUS AWARENESS 558
FUTURE DIRECTIONS 561
References 561
Chapter 33 - Disorders of Frontal Lobe Function 563
INTRODUCTION 563
FRONTAL TOPOGRAPHY 563
CORTICAL MOTOR SYSTEMS 565
CORTICAL INFLUENCE ON THE AUTONOMIC NERVOUS SYSTEM 568
COGNITIVE FUNCTIONS OF THE FRONTAL CORTEX 569
EMOTION, MOTIVATION, AND SOCIAL BEHAVIOR 573
CONCLUSION AND QUESTIONS FOR FURTHER RESEARCH 576
References 577
Chapter 34 - Stress 579
INTRODUCTION 579
TYPES OF STRESS 580
DEFINITION OF STRESS, ALLOSTASIS, AND ALLOSTATIC LOAD 580
RESPONSE TO STRESSORS: PROTECTION AND DAMAGE 582
POSITIVE EFFECTS OF GLUCOCORTICOIDS ON NEURONAL FUNCTIONS AND STRUCTURE 582
STRESS IN THE NATURAL WORLD 583
CIRCADIAN DISRUPTION 583
KEY ROLE OF THE BRAIN IN RESPONSE TO STRESS 584
THE BRAIN AS A TARGET OF STRESS 584
TRANSLATION TO THE HUMAN BRAIN 585
EARLY LIFE EXPERIENCES 586
INTERVENTIONS THAT CHANGE THE BRAIN AND IMPROVE HEALTH 587
CONCLUSION 588
Acknowledgments 589
References 589
Chapter 35 - Addictions 591
INTRODUCTION 591
TRAJECTORY OF ADDICTIONS AND UNDERLYING NEUROBIOLOGY 593
ANIMAL BEHAVIORAL MODELS TO STUDY ADDICTIONS 594
RESEARCH TECHNIQUES IN HUMANS 596
BASIC NEUROBIOLOGY OF SELECTED ADDICTIONS 597
THE GENETICS OF ADDICTION 602
QUESTIONS FOR FURTHER RESEARCH 603
Acknowledgments 604
References 604
Chapter 36 - Sleep Disorders 606
INTRODUCTION TO SLEEP AND CIRCADIAN NEUROBIOLOGY 607
NEUROBIOLOGY OF SLEEP 608
CIRCADIAN REGULATION OF SLEEP 609
CIRCUITRY AND MOLECULAR ASPECTS OF SLEEP 612
CURRENT THEORIES ON WHY WE SLEEP 616
INTRODUCTION TO SLEEP DISORDERS 617
CIRCADIAN RHYTHM SLEEP DISORDERS 619
NARCOLEPSY 622
KLEINE–LEVIN SYNDROME 626
RESTLESS LEGS SYNDROME 627
RAPID EYE MOVEMENT SLEEP BEHAVIOR DISORDER 628
CONCLUSION AND QUESTIONS FOR FURTHER RESEARCH 630
References 631
Chapter 37 - Fear-Related Anxiety Disorders and Post-Traumatic Stress Disorder 633
INTRODUCTION 633
CLASSIFICATION OF ANXIETY DISORDERS 634
NEUROANATOMICAL BASIS OF ANXIETY DISORDERS 635
CLINICAL FEATURES AND PSYCHOBIOLOGY OF ANXIETY DISORDERS 637
CONCLUSION 639
QUESTIONS FOR FURTHER RESEARCH 640
References 640
Chapter 38 - Obsessive–Compulsive Disorder 642
INTRODUCTION 643
EPIDEMIOLOGY OF OBSESSIVE–COMPULSIVE DISORDER 643
CLINICAL CONSIDERATIONS IN OBSESSIVE–COMPULSIVE DISORDER 644
NATURAL HISTORY AND COURSE OF THE DISEASE 647
PATHOGENESIS OF OBSESSIVE–COMPULSIVE DISORDER 647
TREATMENT OF OBSESSIVE–COMPULSIVE DISORDER 653
OBSESSIVE–COMPULSIVE SPECTRUM DISORDERS 656
OBSESSIVE–COMPULSIVE DISORDER IN PEDIATRIC POPULATIONS 657
CONCLUSION 658
QUESTIONS FOR FURTHER RESEARCH 658
References 658
Chapter 39 - Schizophrenia 660
CLINICAL ASPECTS OF SCHIZOPHRENIA 660
DYSREGULATED NEUROTRANSMITTER SYSTEMS IN SCHIZOPHRENIA 662
GLIAL CELL ALTERATIONS IN SCHIZOPHRENIA 670
CONCLUSION 673
References 674
Chapter 40 - Bipolar Disorder 676
INTRODUCTION 676
SPECTRUM OF BIPOLAR DISORDER 677
GENETICS OF BIPOLAR DISORDER 677
EPIGENETICS OF BIPOLAR DISORDER 680
NEUROMORPHOLOGICAL CHANGES IN BIPOLAR DISORDER 680
NEUROBIOLOGICAL CHANGES IN BIPOLAR DISORDER 683
BEHAVIORAL MARKERS IN BIPOLAR DISORDER 690
CONCLUSION 692
References 693
Chapter 41 - Pain: From Neurobiology to Disease 695
INTRODUCTION 695
TERMINOLOGY OF PAIN 696
FACTORS AFFECTING THE EMERGENCE, PROGNOSIS, AND SEVERITY OF PAIN 698
NEUROBIOLOGY OF PAIN 701
INJURY-INDUCED PLASTICITY 703
LOSS OF HOMEOSTASIS 706
HOPE FOR THE MAGIC BULLET 706
TREATMENT OF PAIN 706
CONCLUSION 711
References 712
Chapter 42 - Migraine 714
INTRODUCTION 714
THE MIGRAINE SPECTRUM: AN OVERVIEW OF CLINICAL MANIFESTATIONS 715
MIGRAINE MECHANISMS 716
MIGRAINE AND ALLOSTATIC LOAD 726
CONCLUSION 727
QUESTIONS FOR FURTHER RESEARCH 727
Acknowledgments 727
References 727
Chapter 43 - Depression and Suicide 730
INTRODUCTION 730
EPIDEMIOLOGICAL OBSERVATIONS IN DEPRESSION AND SUICIDE 731
PATHOGENIC FACTORS IN DEPRESSION AND SUICIDE 735
GENETIC FACTORS IN DEPRESSION AND SUICIDE 736
GENE BY ENVIRONMENT INTERACTIONS IN STRESS, DEPRESSION, AND SUICIDE 739
NEUROTRANSMITTER SYSTEMS IN MAJOR DEPRESSION AND SUICIDAL BEHAVIOR 740
CELL PLASTICITY AND SURVIVAL IN DEPRESSION AND SUICIDE 742
NEUROANATOMICAL CHANGES IN DEPRESSION AND SUICIDE 744
RESILIENCE, DEPRESSION, AND SUICIDE 747
CONCLUSION 749
References 749
Section VI - DISEASES OF THE NERVOUS SYSTEM AND SOCIETY 752
Chapter 44 - Introduction 754
References 755
Chapter 45 - Advances in Ethics for the Neuroscience Agenda 756
INTRODUCTION 756
RESEARCH WITH ANIMALS 757
SHARING DATA AND RESOURCES 758
INCIDENTAL FINDINGS 761
NEUROSCIENCE COMMUNICATION 762
NEUROETHICS FOR NEUROSCIENCE 764
CONCLUSION 766
Acknowledgments 767
References 767
Chapter 46 - Burden of Neurological Disease 769
INTRODUCTION 769
BASIC CONCEPTS IN EPIDEMIOLOGY 769
CEREBROVASCULAR DISEASE 771
PRIMARY NEOPLASMS 773
EPILEPSY AND SEIZURE DISORDERS 774
DEMENTIA 775
PARKINSON DISEASE 776
MULTIPLE SCLEROSIS 776
OVERVIEW OF NEUROLOGICAL DISORDERS 781
CONCLUSION AND FUTURE DIRECTIONS 784
References 784
Chapter 47 - Stress, Health, and Disparities 786
RACIAL DISPARITIES IN HEALTH 786
STRESS, STRESSORS, AND THEIR ROLE IN HEALTH 789
UNDERSTANDING RACIAL DIFFERENCES IN HEALTH: A ROLE FOR STRESS? 794
RESEARCH IMPLICATIONS 797
CLINICAL IMPLICATIONS 798
CONCLUSION 799
References 799
Index 802

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...

Erscheint lt. Verlag	6.1.2015
Sprache	englisch
Themenwelt	Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie
Themenwelt	Medizin / Pharmazie ► Medizinische Fachgebiete ► Psychiatrie / Psychotherapie
ISBN-10	0-12-398280-4 / 0123982804
ISBN-13	978-0-12-398280-3 / 9780123982803

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