Alcohol and the Nervous System

1st Edition, Volume 125 - October 8, 2014
Imprint: Elsevier
Editors: Edith V. Sullivan, Adolf Pfefferbaum
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 4 - 6 2 6 1 9 - 6
eBook ISBN:
9 7 8 - 0 - 4 4 4 - 6 2 6 2 2 - 6

Alcohol is the most widely used drug in the world, yet alcoholism remains a serious addiction affecting nearly 20 million Americans. Our current understanding of alcohol's ef… Read more

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Alcohol is the most widely used drug in the world, yet alcoholism remains a serious addiction affecting nearly 20 million Americans. Our current understanding of alcohol's effect on brain structure and related functional damage is being revolutionized by genetic research, basic neuroscience, brain imaging science, and systematic study of cognitive, sensory, and motor abilities. Volume 125 of the Handbook of Clinical Neurology is a comprehensive, in-depth treatise of studies on alcohol and the brain covering the basic understanding of alcohol's effect on the central nervous system, the diagnosis and treatment of alcoholism, and prospect for recovery. The chapters within will be of interest to clinical neurologists, neuropsychologists, and researchers in all facets and levels of the neuroscience of alcohol and alcoholism.

Handbook of Clinical Neurology 3rd Series
Foreword
Preface
Section 1: Introduction
- Chapter 1: Alcoholism: diagnosis, prognosis, epidemiology, and burden of the disease
  - Abstract
  - Natural history and clinical assessment
  - Diagnosis
  - Gauging prognosis
  - Other psychiatric assessment
  - Economic costs of problematic alcohol use
  - Economics and alcohol
  - Alcohol-related spending and other disease categories
  - Conclusion
- Chapter 2: Perspectives on the neuroscience of alcohol from the National Institute on Alcohol Abuse and Alcoholism
  - Abstract
  - Introduction
  - The division of neuroscience and behavior (DNB) and its mission
  - Genetics
  - Neuroadaptation
  - Behavior
  - Neurobehavioral, structural, and functional consequences of human alcoholism
  - Preclinical medications development
  - Future directions
Section 2: Animal models: neurochemistry and metabolism of alcohol
- Chapter 3: Neurocircuitry of alcohol addiction: synthesis from animal models
  - Abstract
  - Definitions and conceptual framework for neurocircuitry of alcoholism
  - Animal models for compulsive alcohol seeking
  - Animal models of motivation, withdrawal, and opponent process
  - Neurocircuits for the binge/intoxication stage associated with alcoholism
  - Neural substrates for the withdrawal/negative affect stage associated with alcoholism
  - Neural substrates for executive function deficits associated with alcoholism
  - Compulsivity in alcoholism: an allostatic view
  - Acknowledgments
- Chapter 4: Metabolism
  - Abstract
  - Overview
  - Ethanol metabolism
  - Systemic pharmacokinetics and pharmacokinetic modeling
  - Summary
  - Acknowledgments
- Chapter 5: Use of animal models of alcohol-related behavior
  - Abstract
  - Introduction
  - Pharmacologic considerations
  - AUD is behaviorally and genetically complex
  - What can be modeled?
  - Choice of non-human animal species
  - Alcohol-related phenotypes
  - Assessing alcohol sensitivity
  - Assessing alcohol tolerance or sensitization
  - Assessing alcohol dependence
  - Assessing alcohol reinforcement
  - Modeling genetic risk in non-human animals
  - Can behavior genetics reveal the structure of ethanol-related behavior?
  - Acknowledgments
Section 3: Molecular basis of alcoholism
- Chapter 6: Molecular basis of alcoholism
  - Abstract
  - Molecular mechanisms underlying acute and chronic alcoholism
  - Summary and future directions
Section 4: Neurologic signs and consequences
- Chapter 7: Alcohol: intoxication and poisoning – diagnosis and treatment
  - Abstract
  - Introduction
  - The effects of ethanol on organ systems
  - Diagnosis
  - Differential diagnosis
  - Treatment
- Chapter 8: Acute withdrawal: diagnosis and treatment
  - Abstract
  - Introduction
  - Symptoms and signs
  - Comorbid disorders
  - Treatment
  - Treatment of severe symptoms
  - Other management considerations
  - Summary
- Chapter 9: Neurochemical mechanisms of alcohol withdrawal
  - Abstract
  - Introduction
  - Signs and symptoms of the alcohol withdrawal syndrome
  - Neurochemical adaptations produced by chronic alcohol and withdrawal
  - Conclusions
  - Acknowledgments
- Chapter 10: Molecular and neurologic responses to chronic alcohol use
  - Abstract
  - Introduction
  - Molecular mechanisms of chronic alcohol action on the brain
  - Neurology of chronic alcohol action in the central nervous system
  - Conclusions
  - Acknowledgment
Section 5: Neuropsychology
- Chapter 11: Methods of association and dissociation for establishing selective brain–behavior relations
  - Abstract
  - Historic background
  - Single dissociation model: lesion studies
  - Double dissociation model: lesion studies
  - Double dissociation model in conditions affecting multiple neural systems
  - Acknowledgment
- Chapter 12: Profiles of impaired, spared, and recovered neuropsychologic processes in alcoholism
  - Abstract
  - Introduction
  - The participants and the tests
  - The impaired, the spared, and the recovered
  - Profiles of damage and repair
  - The five functional domains
  - Summary and conclusions
  - Acknowledgments
- Chapter 13: Component processes of memory in alcoholism: pattern of compromise and neural substrates
  - Abstract
  - Working memory and executive functions
  - Episodic memory
  - Semantic memory
  - Perceptual memory
  - Procedural memory
  - Factors contributing to the heterogeneity of memory disorders in alcoholism
  - Reversibility of alcohol-related memory disorders
  - Clinical implications of memory disorders in the treatment of alcohol dependence
  - Conclusion
- Chapter 14: Decision making, risky behavior, and alcoholism
  - Abstract
  - Decision making, risky behavior, and alcoholism
  - Poor executive control leads to poor decision making
  - Strong appetitive drive leads to poor decision making
  - Other aspects of behavior related to poor decision making in alcoholics
  - Neural correlates of decision making and risky behavior in alcoholism
  - Brain function associated with decision making in binge drinking
  - Brain function associated with decision making in active drinkers with alcohol dependence
  - Brain function associated with decision making in short-term abstinent alcoholics
  - Brain function associated with decision making in individuals at risk for alcoholism
  - Brain function associated with decision making in long-term abstinent alcoholics
- Chapter 15: Motor systems and postural instability
  - Abstract
  - Introduction
  - Postural control in healthy individuals
  - Prenatal exposure to alcohol
  - Acute alcohol intoxication: neurologic and behavioral changes in postural control
  - Chronic alcoholism: long-term motor and neurologic effects
  - Influence of length of alcohol dependence and sobriety
  - Recovery
  - Conclusion
- Chapter 16: Sex differences in alcohol-related neurobehavioral consequences
  - Abstract
  - Introduction
  - Neurobehavioral consequences of acute alcohol administration
  - Neurobehavioral consequences associated with alcoholism
  - Other considerations pertinent to exploring sex differences and alcohol effects
Section 6: Neuroimaging of brain macrostructure and microstructure
- Chapter 17: Structural and microstructral imaging of the brain in alcohol use disorders
  - Abstract
  - Introduction
  - Structural magnetic resonance imaging
  - Structural MRI findings in syndromes associated with alcoholism
  - Structural MRI findings in uncomplicated alcoholism
  - Structural MRI findings in recovery from alcoholism
  - Diffusion tensor imaging
  - DTI Findings in syndromes associated with alcoholism
  - DTI Findings in uncomplicated alcoholism
  - DTI Findings in recovery from alcoholism
  - Conclusion
Section 7: Neuroimaging of neurochemical markers
- Chapter 18: Molecular imaging in alcohol dependence
  - Abstract
  - Introduction
  - Review of imaging methods
  - Dopamine and alcohol dependence
  - Gaba and alcohol dependence
  - Opioid receptors and alcohol dependence
  - Serotonin and alcohol dependence
  - Cannabinoid receptors and alcohol dependence
  - Conclusions
- Chapter 19: Brain proton magnetic resonance spectroscopy of alcohol use disorders
  - Abstract
  - Introduction
  - Neurochemicals measured by ¹H MRS and basic MRS methods
  - ¹H MRS of alcohol use disorders
  - Effects of common substance use comorbidities on ¹H MRS measures in alcohol use disorders
  - Current and future ¹H MRS research in alcohol use disorders
  - Acknowledgments
Section 8: Neuroimaging of brain function
- Chapter 20: Cognition, emotion, and attention
  - Abstract
  - Cognition, attention, and emotion in alcohol abuse and dependence
  - Concepts of attention and their neural correlates
  - Attentional control systems interact with emotion and reward systems
  - Attention and memory
  - Alcoholism – A neural disconnection syndrome?
  - Functional networks of attention and cognition
  - Conclusion
- Chapter 21: The neurobiology of alcohol craving and relapse
  - Abstract
  - Introduction
  - Alcohol-related neuroadaptations
  - Clinical neurobiology of craving and relapse in chronic alcoholism
  - Factors increasing alcohol craving and relapse risk
  - Conclusions
- Chapter 22: Compensatory recruitment of neural resources in chronic alcoholism
  - Abstract
  - What are compensatory mechanisms?
  - Alcoholism-related increases and differences in activity and functional connectivity
  - Are alcoholism-related increases in functional activity and connectivity compensatory?
  - Conclusion
  - Acknowledgment
Section 9: Neuroelectrophysiology
- Chapter 23: Understanding alcohol use disorders with neuroelectrophysiology
  - Abstract
  - Introduction
  - Continuous electroencephalogram
  - Event-related potentials
  - Event-related oscillations
  - Acute effects of alcohol on the brain in social drinkers
  - Effects of binge drinking on electrophysiology
  - Chronic alcoholism and neuroelectrophysiology
  - Electrophysiologic measures as endophenotypes
  - Conclusion
  - Acknowledgment
- Chapter 24: Alcohol and the sleeping brain
  - Abstract
  - Introduction
  - Acute effects of alcohol on sleep
  - Sleep in alcoholism
  - Alcohol dependence and sleep in adolescence
  - Sleep homeostasis and circadian problems with alcohol abuse
  - Evoked potentials during sleep
  - Possible neurochemical mechanisms of the acute and chronic alcohol effects on sleep EEG
  - Familial predisposition for alcoholism effects on sleep?
  - A role for sleep in treatment, recovery, and relapse
  - Conclusion
  - Acknowledgments
Section 10: Fetal alcohol spectrum disorder
- Chapter 25: Neurobehavioral, neurologic, and neuroimaging characteristics of fetal alcohol spectrum disorders
  - Abstract
  - Introduction
  - Neuropsychologic characteristics
  - Neuroimaging characteristics
  - Conclusion
  - Acknowledgments
- Chapter 26: Fetal alcohol spectrum disorder: pathogenesis and mechanisms
  - Abstract
  - Introduction
  - Cell death
  - Cell cycle and proliferation
  - Cell migration
  - Cell morphogenesis
  - Gene expression changes
  - Reactive oxygen species-mediated damage
  - Retinoid and sonic hedgehog signaling
  - Conclusion
- Chapter 27: Current hypotheses on the mechanisms of alcoholism
  - Abstract
  - Alcoholism is a disease characterized by continued use despite negative consequences
  - Diminished executive function in the alcoholic is consistent with a compromise of prefrontal cortex function
  - Alcohol and innate immune system activation
  - Risk factors that contribute to the progression of alcohol dependence
  - Conclusions
Section 11: Adolescent drinking
- Chapter 28: The effect of alcohol use on human adolescent brain structures and systems
  - Abstract
  - Introduction
  - Brain structural changes in adolescent alcohol use
  - Brain function differences in adolescent alcohol users
  - Neurocognitive performance in adolescent alcohol users
  - Summary and conclusions
  - Acknowledgments
Section 12: Other topics
- Chapter 29: Peripheral systems: neuropathy
  - Abstract
  - History and prevalence
  - Clinical features
  - Electrodiagnostic studies
  - Other laboratory studies
  - Neuropathology
  - Differential diagnosis
  - Pathogenesis
  - Molecular mechanisms
  - Prognosis and treatment
  - Summary and future directions
- Chapter 30: Pharmacologic treatment of alcoholism
  - Abstract
  - Introduction
  - Neurochemical targets for medication treatment
  - Opioid antagonists
  - Gaba/glutamatergic medications
  - Serotonergic medications
  - Dopaminergic medications
  - Cholinergic/nicotine acting drugs
  - Combination pharmacotherapy
  - Treatment of AUD with co-occurring mood or anxiety disorders
  - Pharmacogenetics and endophenotype predictors
  - Use of neuroimaging to identify new drugs and targets
  - Newer targets for medication development
  - The future
- Chapter 31: Alcohol–medical drug interactions
  - Abstract
  - Introduction
  - Pharmacokinetic interactions
  - Pharmacodynamic interactions
  - Interaction of alcohol with currently tested medications for the treatment of alcoholism
  - Concluding remarks
- Chapter 32: Genetics of alcoholism
  - Abstract
  - Genetic variations contribute to risk of alcoholism
  - Defining the phenotype
  - Genetic approaches for identifying variants that affect risk for alcoholism
  - Candidate gene studies
  - Linkage studies followed by positional candidate gene analyses
  - Genomewide association studies to identify common variants
  - Rare variants
  - Conclusions
  - Acknowledgments
- Chapter 33: Co-occurring psychiatric disorders and alcoholism
  - Abstract
  - Introduction
  - The relationship between alcohol use disorders and other psychopathology
  - Identifying psychopathology in AUD patients
  - Neurobiologic mechanisms involved in comorbidities
  - Treatment and outcomes in comorbidity
  - Conclusion
- Chapter 34: Hepatic encephalopathy in alcoholic cirrhosis
  - Abstract
  - Introduction
  - Neuropathology of HE
  - Pathophysiology of HE in alcoholic cirrhosis
  - Therapeutic advances
  - Summary
  - Acknowledgments
- Chapter 35: Neuropathology of alcoholism
  - Abstract
  - Introduction
  - Alcohol neurotoxicity
  - Complicating pathologies
  - Structural changes in ARBD
  - Neuronal loss in ARBD
  - Molecular differences
  - Neurotransmitters and their receptors
  - Genetics and genomics
  - Gene expression
  - Proteomics
  - Summary
  - Acknowledgments
- Chapter 36: Genetic differences in response to alcohol
  - Abstract
  - Response to alcohol as an endophenotype of alcohol use disorder
  - Heritability of level of response to alcohol
  - Genetic influences on level of response to alcohol
  - Alcohol metabolism and genetic variations of alcohol-metabolizing enzymes
  - Conclusions
- Chapter 37: Epidemiology of drinking, alcohol use disorders, and related problems in US ethnic minority groups
  - Abstract
  - Introduction
  - Brief historic overview
  - What the chapter will cover
  - Drinking among whites, blacks, and hispanics
  - Alcohol use disorders and other problems among whites, blacks, and hispanics
  - Drinking, alcohol use disorders, and other problems among hispanic national groups
  - Drinking, alcohol use disorders, and other problems among asian americans
  - Drinking, alcohol use disorders, and other problems among american indians and alaska natives
  - A theory about health disparities: cumulative adversities
  - Conclusions
- Chapter 38: Alcohol and the law
  - Abstract
  - Interventions to reduce alcohol-related consequences
  - Alcohol taxes and price controls
  - Policies targeting alcohol-impaired driving
  - Restrictions on alcohol availability
  - Minimum legal drinking age laws
  - Information and education on alcohol use
  - Recovery-oriented policy
  - Alcohol and violence
  - Alcohol and criminal responsibility
  - Alcohol and decision making
  - Conclusion
  - Acknowledgment
- Chapter 39: Clinical management of alcohol use disorders in the neurology clinic
  - Abstract
  - Introduction
  - What is sbirt?
  - What is the evidence that sbirt works?
  - Screening
  - Screening results
  - Brief intervention
  - Referral to treatment
  - Neurologic medical comorbidity
  - Conclusion
Index

Edith V. Sullivan

Edith V. Sullivan is Professor of Psychiatry and Behavioral Sciences at Stanford University School of Medicine. She received her B.A., M.A., and Ph.D. in experimental psychology from the University of Connecticut. Following graduate school, she was a research scientist in the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology (MIT) and the Ashton Graybiel Spatial Orientation Laboratory at Brandeis University. As a neuropsychologist with expertise in neuroimaging, Dr. Sullivan has championed putting the "neuro" into neuropsychology and has done so in her research and through her editorship of Neuropsychology Review. Her research combines quantitative brain imaging and assessment of component processes of neuropsychological functions to the study of neuropsychiatric diseases and normal function over the life span. Dr. Sullivan's interest in brain related conditions grew out of her experience as a researcher at MIT in the late 1970s to mid-1980s. There, she had the opportunity to work with the famous amnesic patient, H.M. Inspired by the component processes approach used in lesion research, she has applied these concepts to dissect impairments in cognitive and motor function in patients without focal lesions. Her early work focused on Parkinson’s disease, Alzheimer’s disease, and schizophrenia. Over the last two decades, the mainstay of her research has been on both normal aging and alcoholism-related brain injury in human nonamnesic and amnesic alcoholism and animal models of excessive alcohol exposure. Her research has resulted in identification of brain circuitry disrupted in alcoholism and elucidation of spared circuits that have the potential to enable functional recovery with sobriety.

Dr. Sullivan is the author of more than 250 peer-reviewed papers and numerous chapters and reviews. She serves on the editorial board of Alcoholism: Clinical and Experimental Research, Brain Imaging and Behavior, Hippocampus, Frontiers of Neuroscience, and Neurobiology of Aging. She is the recipient of several NIH funding awards, including the Senior Scientist Research and Mentorship Award, a grant for international collaborations on alcoholism research, and an NIAAA MERIT award for studies of neural circuitry modification in alcoholism focused on frontocerebellar systems. She also received the NIAAA Keller Award.

Affiliations and expertise

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA

Adolf Pfefferbaum

Adolf Pfefferbaum is Distinguished Scientist and founding Director of the Neuroscience Program of SRI International and Professor Emeritus, Stanford University School of Medicine. He received his M.D. from the University of California, San Francisco, completed Internship in Medicine at Barnes Hospital in St. Louis, was Research Associate at the NIH, and did Residency training at Stanford.

For nearly 40 years, Dr. Pfefferbaum has combined medical clinical skills with scientific rigor and creativity to develop and apply electrophysiology and neuroimaging approaches for identifying in vivo brain markers of the effects of long-term, alcohol dependence. His longitudinal neuroimaging studies using quantitative magnetic resonance imaging (MRI) have revealed alcoholism's scope and limits of recovery of brain structure and function. With diffusion tensor imaging to quantify the microstructure of white matter, Dr. Pfefferbaum has shown fiber degradation in alcoholic men that related to memory and attention; in alcoholic women, fiber compromise occurs in normal-appearing white matter. His seminal contribution using functional MRI revealed that alcoholics recruit broader areas of brain than controls to perform at equivalent levels on working memory tasks. In addition to naturalistic studies of human alcoholism, Dr. Pfefferbaum has an active research program using rodent models of alcoholism, employing macrostructural, microstructural, and functional imaging enabling translational research.

Dr. Pfefferbaum has been the principal investigator on numerous NIH-funded grants, including a Merit Award from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). He has also served the NIAAA as a member and chair of the Alcohol Biomedical Research Review Committee and of the Center Reviews and Special Emphasis Panels. Most recently, he was named a member of the NIAAA National Advisory Council. Dr. Pfefferbaum is a member of a number of scientific societies and is a fellow of the American College of Neuropsychopharmacology. He is on the editorial board of Alcoholism: Clinical and Experimental Research, Psychiatry Research, and was co-editor of Psychiatry Research: Neuroimaging for many years. He has published more than 350 peer-reviewed papers and 50 chapters and reviews. His many honors include Phi Beta Kappa, Phi Kappa Phi, and Alpha Omega Alpha. In recognition of his innovative work in electrophysiology, the American Psychiatric Electrophysiology Association presented him with a Career Contribution Award. His scientific contributions to our understanding of alcoholism have been acknowledged through reception of the Keller Award from the NIAAA and the Begleiter Award for Research Excellence from the Research Society on Alcoholism.

Affiliations and expertise

Neuroscience Program, SRI International, Menlo Park, CA, USA

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