Neurobiology of Brain Disorders - 1st Edition - ISBN: 9780123982704, 9780123982803

Neurobiology of Brain Disorders

1st Edition

Biological Basis of Neurological and Psychiatric Disorders

Editors: Michael Zigmond Joseph Coyle Lewis Rowland
eBook ISBN: 9780123982803
Hardcover ISBN: 9780123982704
Imprint: Academic Press
Published Date: 25th November 2014
Page Count: 824
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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.

Key Features

  • 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


Advanced students in neuroscience (molecular/cellular, behavioral, systems, cognitive, theoretical/computational, and developmental), neurobiology, neurology, and psychiatry, as well as neuroscience faculty, researchers, and postdoctoral fellows interested in becoming more involved in clinically related research

Table of Contents

  • Dedication
  • Preface
  • Acknowledgments
  • List of Contributors
  • Chapter 1. An Introduction: A Clinical Neuroscientist and Disorders of the Brain
    • Introduction
    • Localization of Lesions
    • Imaging
    • Selective Vulnerability of Neuronal Populations
    • Recovery After Injury
    • Stem Cells in Recovery
    • Brain Transplants
    • Neurology as a Therapeutic Field
    • Animal Models of Human Disease
    • Development of New Drugs
    • Clinical Trials
    • Trials in Alzheimer Disease
    • Biomarkers of Disease
    • Psychiatric Disease
    • Genetics of Neurological and Psychiatric Disorders
    • Temperament and Disease
    • Conclusion
  • Section I. Developmental Disorders
    • Chapter 2. Introduction
    • Chapter 3. Developmental Disabilities and Metabolic Disorders
      • Introduction
      • Brain Development
      • Functional Development
      • Etiology
      • Techniques
      • Principles of Management
      • Practice Guidelines
      • Conclusion
      • Questions for Further Research
    • Chapter 4. Attention Deficit/Hyperactivity Disorder
      • Introduction
      • Clinical Description
      • Neuroimaging Studies
      • Effects of Attention Deficit/Hyperactivity Disorder Treatments on Brain Function
      • Single-Photon Emission Computed Tomography and Positron Emission Tomography Studies
      • Current Clinical Applications of Neuroimaging Studies
      • Future Perspectives in the Neuroimaging of Attention Deficit/Hyperactivity Disorder
      • Experimental Animal Models
      • Conclusion
      • Questions for Further Research
    • Chapter 5. Down Syndrome: A Model for Chromosome Abnormalities
      • Introduction
      • Down Syndrome
      • Mouse Models of Down Syndrome
      • Clinical Characterization of Down Syndrome
      • Development of Pharmacotherapy in Down Syndrome
      • Conclusion and Remaining Issues
    • Chapter 6. Autism Spectrum Disorder
      • Introduction
      • History
      • Clinical Features
      • Definition and Classification
      • Epidemiology
      • Natural History
      • Differential Diagnosis
      • Assessment
      • Neuropsychological Profile/Cognitive Functioning
      • Neurobiology
      • Neuroimaging
      • Neurophysiology
      • Neuropathology
      • Neurochemistry
      • Genetic and Environmental Risk Factors
      • Treatment
      • Future Directions
    • Chapter 7. Rett Syndrome: From the Involved Gene(s) to Treatment
      • Introduction
      • Clinical Features of Rett Syndrome and Other MECP2-Related Disorders
      • Diagnosis and Clinical Management of Rett Syndrome
      • Genetics of Rett Syndrome: MECP2 Gene, Pathogenic Mutations, and Phenotypic Outcome
      • Mecp2 Mouse Models Recapitulating Human MECP2-Related Pathologies
      • MeCP2 Expression During Brain Development: Role in Neuronal Maturation and/or Maintenance of the Mature State
      • Neuromorphological and Neurophysiological Consequences of MeCP2 Dysfunction
      • Rett Syndrome: Not Solely a Neuronal Disease
      • MeCP2: A Multifunctional Protein Whose Pathogenic Mechanisms Remain Unsolved
      • MeCP2 Research: From Bench to Bedside
      • Conclusion and Future Challenges
    • Chapter 8. Fragile X-Associated Disorders
      • Introduction
      • RNA Toxicity in Premutation Carriers
      • Fragile X Syndrome
      • Clinical Manifestations of the Fragile X Premutation
      • Psychiatric Morbidity of the Fragile X Premutation
      • Conclusion
      • Areas for Future Research
  • Section II. Diseases of The Peripheral Nervous System
    • Chapter 9. Introduction
    • Chapter 10. Myasthenia Gravis
      • Introduction
      • Immunopathogenesis
      • Defect in Neuromuscular Transmission
      • Animal Models of Myasthenia Gravis
      • Epidemiology and Genetics
      • Clinical Phenotype
      • Diagnosis
      • Treatment
      • Conclusion
    • Chapter 11. Muscular Dystrophy
      • Introduction
      • Pathophysiology and Genetics
      • Epidemiology
      • Clinical Manifestations
      • Diagnosis
      • Genetic Counseling
      • Treatment and Outcomes
      • Conclusion
    • Chapter 12. Peripheral Neuropathies
      • Peripheral Nervous System Biology
      • Clinical Manifestation and Diagnostic Modalities in Peripheral Neuropathies
      • Inherited Neuropathies
      • Immune-Mediated Neuropathies
      • Other Neuropathies
      • Conclusion
      • Questions for Further Research
    • Chapter 13. Diabetes and Cognitive Dysfunction
      • Diabetes Mellitus
      • Complications Associated with Diabetes
      • Underlying Mechanisms Linking Diabetes and Alzheimer Disease
      • Animal Models of Diabetes and Alzheimer Disease
      • Conclusion
  • Section III. Diseases of the Central Nervous System and Neurodegeneration
    • Chapter 14. Introduction
    • Chapter 15. Spinal Cord Injury
      • Introduction
      • Types of Injury and Glial Scar Formation
      • Time-Course of Postinjury Changes
      • Cell Types Involved
      • Role of the Extracellular Matrix and Growth Inhibitors
      • Cell Death Following Spinal Cord Injury
      • Genetic and Epigenetic Control of Axonal Growth
      • Inflammatory and Maladaptive Immune Responses and the Blood–Brain Barrier
      • Neuropathic Pain and Autonomic Dysreflexia
      • Therapeutic Tools in Spinal Cord Injury
      • Questions for Further Research
    • Chapter 16. Traumatic Brain Injury
      • Introduction: Epidemiology and Classifications
      • Primary Effects of Traumatic Brain Injury
      • Secondary Effects of Traumatic Brain Injury
      • Chronic Effects of Traumatic Brain Injury
      • Conclusion
      • Directions for Future Research
    • Chapter 17. Epilepsy
      • Introduction
      • Classification of the Seizures and the Epilepsies
      • Mechanisms Underlying Seizures
      • Mechanisms of Epileptogenesis and Epilepsy
      • Treatment of Epilepsy
      • Summary
    • Chapter 18. Amyotrophic Lateral Sclerosis
      • Introduction
      • Diagnosis of Amyotrophic Lateral Sclerosis
      • Clinical Characteristics of Amyotrophic Lateral Sclerosis
      • Natural History of Amyotrophic Lateral Sclerosis
      • Available Treatments for Amyotrophic Lateral Sclerosis
      • Neurobiological Basis of Amyotrophic Lateral Sclerosis
      • Model Systems of Amyotrophic Lateral Sclerosis Toxicity
      • Future Directions
    • Chapter 19. Parkinson Disease and Other Synucleinopathies
      • Introduction
      • Clinical Features of Parkinson Disease
      • Diagnosis of Parkinson Disease
      • Etiology of Parkinson Disease: Clues from Epidemiology and Genetics
      • Treatment of Parkinson Disease
      • Conclusion
    • Chapter 20. Huntington Disease
      • Overview of Huntington Disease
      • Animal Models of Huntington Disease
      • Neuropathology of Huntington Disease
      • Neurobiology of Huntington Disease
      • Treatment of Huntington Disease
      • Other CAG Repeat Disorders
      • Questions for Further Research
    • Chapter 21. Alzheimer Disease
      • Introduction
      • Neuropathology of Alzheimer Disease
      • Genetics and Molecular Biology of Alzheimer Disease
      • Current and Future Therapies for Alzheimer Disease
      • Conclusion
      • Questions for Further Research
    • Chapter 22. Cerebrovascular Disease – Stroke
      • Definition of Stroke
      • Brain Lesions Caused by Cerebrovascular Disease
      • Vascular Pathologies Causing Brain Ischemia and Hemorrhage
      • Factors Affecting Tissue Survival in Patients with Brain Ischemia and Infarction
      • Death of Cells in the CNS, and Neuroprotective and Reparative Mechanisms
      • Questions for Further Research
    • Chapter 23. Prion Diseases
      • Introduction
      • Causes and Pathogenesis of Prion Diseases
      • Kuru
      • Creutzfeldt–Jakob Disease
      • Variant Creutzfeldt–Jakob Disease
      • Gerstmann–Sträussler–Scheinker Disease
      • Laboratory Tests
      • Conclusion
      • Questions for Further Research
  • Section IV. Infectious and Immune-Mediated Diseases Affecting the Nervous System
    • Chapter 24. Introduction
    • Chapter 25. Role of Inflammation in Neurodegenerative Diseases
      • Introduction
      • Microglia: Convergence Point for Promoting or Compromising Neuronal Survival
      • T-Lymphocytes: Neuroprotection and Neurotoxicity
      • Parkinson Disease
      • Alzheimer Disease
      • Amyotrophic Lateral Sclerosis
      • Conclusion
    • Chapter 26. Role of Inflammation in Psychiatric Disease
      • Introduction
      • Evidence THAT the Immune System is Involved in Psychiatric Disease Pathogenesis
      • Evidence that Patterns of CNS Activity Associated with Psychiatric Disease Affect Immune Functioning in Health-Relevant Ways
      • Evidence that Environmental Factors that Promote Psychiatric Morbidity May Do So By Altering Immune Function
      • Evidence that Psychiatric Conditions Are Associated with Alterations in Peripheral and CNS Immune Activity
    • Chapter 27. Infections and Nervous System Dysfunction
      • Introduction
      • Microbe–Host Cell Interactions
      • Immune Responses to Invading Pathogens
      • Invasion of Pathogens in the Nervous System
      • Pathogens Causing Nervous System Dysfunction
      • Future Directions
    • Chapter 28. Pathobiology of CNS Human Immunodeficiency Virus Infection
      • Introduction
      • Human Immunodeficiency Virus Genetics and Genomic Organization of HIV-1
      • Life Cycle of the Human Immunodeficiency Virus
      • Establishment of Human Immunodeficiency Virus Infection
      • Entry of Human Immunodeficiency Virus into the CNS
      • CNS Human Immunodeficiency Virus Infection by Cell Type
      • CNS Escape and Viral Latency
      • Mechanisms of CNS Injury
      • CNS Metabolic Complications of Human Immunodeficiency Virus Infection
      • Experimental Models
      • Clinical Manifestations of CNS Human Immunodeficiency Virus Infection
      • Effects of Combination Antiretroviral Therapy on CNS Human Immunodeficiency Virus Pathology
      • Conclusion and Future Challenges
    • Chapter 29. Autoimmune and Paraneoplastic Neurological Disorders
      • Introduction
      • The Immune System
      • Pathogenic Mechanisms of Neural Antigen-Specific Autoimmunity
      • Autoimmune and Paraneoplastic Neurological Diseases
      • Levels of the Neuraxis Affected by Paraneoplastic and Autoimmune Syndromes
      • Conclusion
      • Future Directions
    • Chapter 30. Multiple Sclerosis
      • Introduction
      • Etiology of Multiple Sclerosis
      • Immune Pathogenesis of Multiple Sclerosis
      • Clinical Features of Multiple Sclerosis
      • Progressive Multiple Sclerosis as an Unmet Need
      • Treatment of Multiple Sclerosis
      • Future Directions
  • Section V. Diseases of Higher Function
    • Chapter 31. Introduction
    • Chapter 32. Disorders of Higher Cortical Function
      • Introduction: From Neuropsychology to Mental Structure
      • Language Disorders
      • Memory Disorders: Amnesia
      • Disorders of Movement Execution: Apraxia
      • Disorders of Visual Recognition: Agnosia
      • Disorders of Spatial Representation: Unilateral Neglect
      • Conscious Awareness
      • Future Directions
    • Chapter 33. Disorders of Frontal Lobe Function
      • Introduction
      • Frontal Topography
      • Cortical Motor Systems
      • Cortical Influence on the Autonomic Nervous System
      • Cognitive Functions of the Frontal Cortex
      • Emotion, Motivation, and Social Behavior
      • Conclusion and Questions for Further Research
    • Chapter 34. Stress
      • Introduction
      • Types of Stress
      • Definition of Stress, Allostasis, and Allostatic Load
      • Response to Stressors: Protection and Damage
      • Positive Effects of Glucocorticoids on Neuronal Functions and Structure
      • Stress in the Natural World
      • Circadian Disruption
      • Key Role of the Brain in Response to Stress
      • The Brain as a Target of Stress
      • Translation to the Human Brain
      • Early Life Experiences
      • Interventions that Change the Brain and Improve Health
      • Conclusion
    • Chapter 35. Addictions
      • Introduction
      • Trajectory of Addictions and Underlying Neurobiology
      • Animal Behavioral Models to Study Addictions
      • Research Techniques in Humans
      • Basic Neurobiology of Selected Addictions
      • The Genetics of Addiction
      • Questions for Further Research
    • Chapter 36. Sleep Disorders
      • Introduction to Sleep and Circadian Neurobiology
      • Neurobiology of Sleep
      • Circadian Regulation of Sleep
      • Circuitry and Molecular Aspects of Sleep
      • Current Theories on Why We Sleep
      • Introduction to Sleep Disorders
      • Circadian Rhythm Sleep Disorders
      • Narcolepsy
      • Kleine–Levin Syndrome
      • Restless Legs Syndrome
      • Rapid Eye Movement Sleep Behavior Disorder
      • Conclusion and Questions for Further Research
    • Chapter 37. Fear-Related Anxiety Disorders and Post-Traumatic Stress Disorder
      • Introduction
      • Classification of Anxiety Disorders
      • Neuroanatomical Basis of Anxiety Disorders
      • Clinical Features and Psychobiology of Anxiety Disorders
      • Conclusion
      • Questions for Further Research
    • Chapter 38. Obsessive–Compulsive Disorder
      • Introduction
      • Epidemiology of Obsessive–Compulsive Disorder
      • Clinical Considerations in Obsessive–Compulsive Disorder
      • Natural History and Course of the Disease
      • Pathogenesis of Obsessive–Compulsive Disorder
      • Treatment of Obsessive–Compulsive Disorder
      • Obsessive–Compulsive Spectrum Disorders
      • Obsessive–Compulsive Disorder in Pediatric Populations
      • Conclusion
      • Questions for Further Research
    • Chapter 39. Schizophrenia
      • Clinical Aspects of Schizophrenia
      • Dysregulated Neurotransmitter Systems in Schizophrenia
      • Glial Cell Alterations in Schizophrenia
      • Conclusion
    • Chapter 40. Bipolar Disorder
      • Introduction
      • Spectrum of Bipolar Disorder
      • Genetics of Bipolar Disorder
      • Epigenetics of Bipolar Disorder
      • Neuromorphological Changes in Bipolar Disorder
      • Neurobiological Changes in Bipolar Disorder
      • Behavioral Markers in Bipolar Disorder
      • Conclusion
    • Chapter 41. Pain: From Neurobiology to Disease
      • Introduction
      • Terminology of Pain
      • Factors Affecting the Emergence, Prognosis, and Severity of Pain
      • Neurobiology of Pain
      • Injury-Induced Plasticity
      • Loss of Homeostasis
      • Hope for the Magic Bullet
      • Treatment of Pain
      • Conclusion
    • Chapter 42. Migraine
      • Introduction
      • The Migraine Spectrum: An Overview of Clinical Manifestations
      • Migraine Mechanisms
      • Migraine and Allostatic Load
      • Conclusion
      • Questions for Further Research
    • Chapter 43. Depression and Suicide
      • Introduction
      • Epidemiological Observations in Depression and Suicide
      • Pathogenic Factors in Depression and Suicide
      • Genetic Factors in Depression and Suicide
      • Gene By Environment Interactions in Stress, Depression, and Suicide
      • Neurotransmitter Systems in Major Depression and Suicidal Behavior
      • Cell Plasticity and Survival in Depression and Suicide
      • Neuroanatomical Changes in Depression and Suicide
      • Resilience, Depression, and Suicide
      • Conclusion
  • Section VI. Diseases of the Nervous System and Society
    • Chapter 44. Introduction
    • Chapter 45. Advances in Ethics for the Neuroscience Agenda
      • Introduction
      • Research with Animals
      • Sharing Data and Resources
      • Incidental Findings
      • Neuroscience Communication
      • Neuroethics for Neuroscience
      • Conclusion
    • Chapter 46. Burden of Neurological Disease
      • Introduction
      • Basic Concepts in Epidemiology
      • Cerebrovascular Disease
      • Primary Neoplasms
      • Epilepsy and Seizure Disorders
      • Dementia
      • Parkinson Disease
      • Multiple Sclerosis
      • Overview of Neurological Disorders
      • Conclusion and Future Directions
    • Chapter 47. Stress, Health, and Disparities
      • Racial Disparities in Health
      • Stress, Stressors, and their Role in Health
      • Understanding Racial Differences in Health: A Role for Stress?
      • Research Implications
      • Clinical Implications
      • Conclusion
  • Index


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About the Editor

Michael Zigmond

Michael Zigmond

Affiliation: Professor of Neurology, Department of Neurology, University of Pittsburgh, Pennsylvania, U.S.A

Over the past year, Dr. Zigmond and his research team have continued their studies of cellular and animal models to examine Parkinson's disease (PD), which they believe is a multi-factorial disorder. A major focus of the lab is the role of intracellular signaling cascades in determining the viability of dopamine (DA) neurons. They hypothesize, for example, that trophic factors such as GDNF and oxidative stress can both stimulate intracellular survival cascades, including those involving MAP kinases. They further believe that endogenous trophic factor expression can be enhanced by exercise which in turn can be neuroprotective. And they have evidence that protection also can derive from acute exposure to low levels of a neurotoxin, a form of preconditioning. Last year their work included studies of the impact of oxidative stress induced by 6-hydroxydopamine (6-OHDA), a DA analogue that is concentrated in DA cells and rapidly breaks down to form reactive oxygen species. Results from these and other studies suggest that DA neurons react to stress by initiating a set of protective responses. Learning more about these responses may provide insights into new treatment modalities for PD.

In the coming year, Dr. Zigmond will continue to focus on understanding the strategies DA neurons use to reduce their vulnerability to intracellular stress. For example, studies are underway to determine if inhibition of trophic actor action or of kinase activation will block neuroprotection seen with exercise or GDNF or increase 6-OHDA toxicity. Some of these studies involve the preparation of molecular biological tools that maintain kinases in a constitutively or dominant negative state and/or localize a kinase to the cytoplasm or the nucleus. In addition, histochemical methods are being developed to quantify kinase levels in different cellular compartments of identified cells.

Affiliations and Expertise

Department of Neurology, University of Pittsburgh, Pennsylvania, U.S.A.

Joseph Coyle

Joseph T. Coyle, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA

Affiliations and Expertise

McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA

Lewis Rowland

Affiliations and Expertise

Columbia University, New York, U.S.A.


"This terrific book provides very broad coverage of the neurobiological basis of common neurological and psychiatric disorders...highly recommended to anyone who wants to keep up to date with the basic sciences involved in neuropsychiatric disorders. Score: 88 - 3 Stars" --Doody's