Alcohol and the Nervous System - Handbook of Clinical Neurology

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Alcohol and the Nervous System

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Handbook of Clinical Neurology 3rd Series

Foreword

Preface

Contributors

Contents

Section 1: Introduction

Chapter 1: Alcoholism: Diagnosis, Prognosis, Epidemiology, and Burden Of the Disease

Natural History and Clinical Assessment

Alcoholism Frequency

Practical Typology

Diagnosis

Alcohol Use History

Making a Diagnosis

Physiologic Dependence: Tolerance And withdrawal

Tolerance

Withdrawal

Loss of Control Phenomenon

Social Or Physical Decline

Gauging Prognosis

Positive Versus Negative

Diagnosis is Prognosis

Abuse Rather than Dependence

Behavioral Versus Hepatic Diagnosis

Assessing Ambivalence and Continuing Loss Of Control risk

Social Stability

Vaillant's Four Prognostic Factors

Structured time

A Rehabilitation Relationship

Sources of Hope Or self-esteem

A Negative Behavioral Reinforcer

Summing Up Prognosis

Other Psychiatric Assessment

Dsm-5 and Alcoholism Diagnosis: Progress Or Old Wine in a New Bottle?

Economic Costs of Problematic Alcohol use

Cost of Illness: Clarifying the Concept

Cost: Contribution By Category

Interpretation: Cost Consequences

Economics and Alcohol

Alcohol-related Spending and Other Disease Categories

Conclusion

References

Chapter 2: Perspectives on the Neuroscience of Alcohol From the National Institute on Alcohol Abuse and Alcoholism

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

References

Section 2: Animal Models: Neurochemistry and Metabolism of Alcohol

Chapter 3: Neurocircuitry of Alcohol Addiction: Synthesis From animal models

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

Within-system Neuroadaptations That Contribute to the Compulsivity Associated With the Dark Side of Alcoholism

Between-system Neuroadaptations That Contribute to Compulsivity Associated With the Dark Side of Alcoholism

Neural Substrates for Executive Function Deficits Associated With alcoholism

Compulsivity in Alcoholism: An allostatic view

Acknowledgments

References

Chapter 4: Metabolism

Overview

Ethanol Metabolism

Hepatic Ethanol Metabolism

Genetic Factors: Genetic Variants And gender

Genetic Variation in Adh, Aldh2, Cyp2E1 and Ethanol Metabolism

Genetic Predisposition to Alcoholism

Effects of Gender on Alcohol Metabolism

Fasting

Protein Malnutrition

Effect of Fat Content Or Composition Of diet

Effect of Dietary Ethanol

Miscellaneous Dietary Effects

Endocrine Effects

Gastrointestinal and Other Tissue Metabolism of Ethanol

Alcohol-metabolizing Enzymes In the nervous system

Systemic Pharmacokinetics and Pharmacokinetic Modeling

Overview - Absorption, first-pass Metabolism, Distribution, and Elimination

Compartmental/phenomenologic Modeling

Physiologically Based Modeling

Summary

Acknowledgments

References

Chapter 5: Use of Animal Models of alcohol-related Behavior

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

Rodent Lines Selectively Bred for Alcohol responses

Alcohol Preference Selections

Congruent Findings in Rat Preference Selections

Findings From High (Hap) and Low (Lap) alcohol-preferring mice

Selection for Drinking in The dark

Selection for Locomotor Response to Ethanol

Lines Selected to Be Ethanol Withdrawal Seizure-Prone (Wsp) Or -Resistant (Wsr)

Long Sleep (Ls) and Short Sleep (Ss) mice

Alcohol-tolerant (At) and non-tolerant (Ant) rats

Studies With Inbred Strains

Can Behavior Genetics Reveal the Structure of ethanol-related Behavior?

Acknowledgments

References

Section 3: Molecular Basis of Alcoholism

Chapter 6: Molecular Basis of Alcoholism

Molecular Mechanisms Underlying Acute and Chronic Alcoholism

Introduction

Primary Targets

DNA

Neurotransmitter Systems

Glutamate

Dopamine

GABA(A)

GABA(B)

Serotonin (5-Ht)

Big Potassium (Bk) Channels

Transcription Factors

microRnas

Synaptic MRna Translation and MicroRnas

Neuroimmune

Summary and Future Directions

References

Section 4: Neurologic Signs and Consequences

Chapter 7: Alcohol: Intoxication and Poisoning - Diagnosis and Treatment

Introduction

The Effects of Ethanol on Organ Systems

Nervous System

Gastrointestinal System

Cardiovascular System

Other Effects

Diagnosis

Clinical Features

Blood Alcohol Concentration

Alcohol Flush Reaction

Idiosyncratic Alcohol Intoxication

Differential Diagnosis

Hepatic Encephalopathy

Wernicke-Korsakoff Syndrome

Treatment

References

Chapter 8: Acute withdrawal: diagnosis and treatment

Introduction

Symptoms And signs

Hangover

Tremor

Hallucinosis

Abnormal Movements

Seizures

Delirium Tremens

Comorbid Disorders

Treatment

Non-pharmacologic Therapy

Pharmacotherapy

Benzodiazepines

Phenobarbital

Anticonvulsants

Baclofen

Gamma-hydroxybutyric acid

Neuroleptics

Beta-blockers and alpha-2-agonists

Ethanol

N-methyl-d-aspartate Receptor Blockers

Other Pharmacotherapies

Treatment of Severe Symptoms

Seizures

Delirium Tremens

Other Management Considerations

Summary

References

Chapter 9: Neurochemical Mechanisms of Alcohol Withdrawal

Introduction

Signs and Symptoms of the Alcohol Withdrawal Syndrome

Cns Hyperexcitability

Autonomic Nervous System Hyperactivity

Sleep Disturbances

Measures of Psychologic Discomfort And negative Affect

Anxiety

Heightened Stress Responsiveness

Anhedonia/dysphoria

Neurochemical Adaptations Produced By Chronic Alcohol And withdrawal

Adaptations in Amino Acid Neurotransmitter Systems

Glutamate

Gaba

Adaptations in Monoamine Systems

Dopamine

Norepinephrine

Serotonin

Adaptations in Neuropeptide Systems

Corticotropin-releasing factor

Neuropeptide Y

Opioid Polypeptides

Nociceptin

Other Neuropeptides

Adaptations in Ion Channels

Voltage-gated Ca2+ Channels

Small-conductance Ca2+-activated K+ Channels

Large-conductance voltage- and Ca2+-activated K+ Channels

A-type K+ Channels

Conclusions

Acknowledgments

References

Chapter 10: Molecular and Neurologic Responses to Chronic Alcohol use

Introduction

Molecular Mechanisms of Chronic Alcohol Action on The brain

Genetic Contributions to Alcoholism

Modulation of Gene Expression With chronic alcohol

Persistence of Gene Expression Changes - Role for Epigenetic Regulation?

Neurology of Chronic Alcohol Action in the Central Nervous System

Overview of Clinical Syndromes

Alcohol Blackouts

Craving

Tolerance and Dependence

Alcohol Withdrawal Syndrome Overview

Withdrawal Seizures

Delirium Tremens

Wernicke-Korsakoff Syndrome

Cerebellar Degeneration

Primary Alcoholic Dementia

Central Pontine Myelinolysis

Marchiafava-Bignami Disease

Conclusions

Acknowledgment

References

Section 5: Neuropsychology

Chapter 11: Methods of Association and Dissociation for Establishing Selective Brain-behavior Relations

Historic Background

Single Dissociation Model: Lesion studies

Double Dissociation Model: Lesion studies

Double Dissociation Model in Conditions Affecting Multiple Neural Systems

Between-groups model

Within-group model

Multiple Dissociations and Relevance to Establishing Network Selectivity

Acknowledgment

References

Chapter 12: Profiles of Impaired, Spared, and Recovered Neuropsychologic Processes in Alcoholism

Introduction

The Participants and The tests

Characteristics of the Participants

Assessing Neuropsychologic Functions And the brain

The Impaired, the Spared, And the recovered

Impairments

Spared Functions and Compensation

Recovery

Profiles of Damage And repair

General Neuropsychologic Abilities

Widespread Brain Damage in Alcoholism

Frontocerebellar and Mesocorticolimbic Structures

The Five Functional Domains

Memory

Impairments

Compensation and Recovery

Executive Functions

Impairments

Compensation and Recovery

Emotion and Psychosocial Skills

Impairments

Compensation and Recovery

Visuospatial Cognition

Impairments

Compensation and Recovery

Psychomotor Abilities

Impairments

Compensation and Recovery

Summary and Conclusions

Acknowledgments

References

Chapter 13: Component Processes of Memory in Alcoholism: Pattern of Compromise and Neural Substrates

Working Memory and Executive functions

Definition

Slave Systems of Working Memory

Central Executive of Working Memory

Neural Substrates of Working Memory In alcoholism

Working Memory in Korsakoff's Syndrome

Episodic Memory

Definition

Encoding and Retrieval Processes

Contextual Memory, Source Memory, And prospective Memory

Metamemory

Episodic Memory and Executive Functions

Neural Substrates of Episodic Memory Deficits in Alcoholism

Autobiographical Memory

Episodic Memory in Korsakoff's Syndrome

Semantic Memory

Definition

New Semantic Learning

Semantic Memory in Korsakoff's Syndrome

Perceptual Memory

Definition

Implicit Perceptual Learning

Perceptual Memory in Korsakoff's Syndrome

Procedural Memory

Definition

Cognitive Procedural Learning

Visuomotor Procedural Learning

Procedural Memory in Korsakoff's Syndrome

Factors Contributing to the Heterogeneity of Memory Disorders in Alcoholism

Age

Gender

Alcohol Use Pattern

Smoking Status

Nutritional Status

Psychiatric Comorbidity

Treatment-naïve Versus treatment-seeking Patients

Reversibility of alcohol-related Memory Disorders

Uncomplicated Alcoholism

Korsakoff's Syndrome

Clinical Implications of Memory Disorders in the Treatment of Alcohol Dependence

Conclusion

References

Chapter 14: Decision Making, Risky Behavior, and Alcoholism

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

References

Chapter 15: Motor Systems and Postural Instability

Introduction

Postural Control in Healthy Individuals

Prenatal Exposure to Alcohol

Acute Alcohol Intoxication: Neurologic and Behavioral Changes in Postural Control

Chemical Effects of Ethanol On postural control

Instability During Acute Intoxication

The Cerebellum in Acute Alcohol Intoxication

Chronic Alcoholism: long-term Motor and Neurologic Effects

Motor Symptoms

Excessive Sway and Postural tremor

Visual and Tactile cues

Neurologic Changes in Chronic Alcoholism

Cortical Changes

Corpus Callosum

Cerebellum

Pons and Thalamus

Peripheral Nervous System

Influence of Length of Alcohol Dependence and Sobriety

Influence Of age

Sexual Dimorphism

Recovery

Conclusion

References

Chapter 16: Sex Differences in alcohol-related Neurobehavioral Consequences

Introduction

Neurobehavioral Consequences of Acute Alcohol Administration

Neuropsychological/behavioral Consequences

Neurophysiologic Consequences

Neuroimaging Correlates of Acute Alcohol Administration

Section summary

Neurobehavioral Consequences Associated With Alcoholism

General notes

Neuropsychologic Concomitants

Neurophysiologic Concomitants: Eeg

Neurophysiologic Concomitants: Erp

Neuroimaging Concomitants: Structural

Neuroimaging Concomitants: Functional And metabolic Contrasts

Other Considerations Pertinent to Exploring Sex Differences And alcohol Effects

References

Section 6: Neuroimaging of Brain Macrostructure and Microstructure

Chapter 17: Structural and Microstructral Imaging of the Brain in Alcohol Use Disorders

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

Whole-brain Analysis

Region of Interest Analysis

Quantitative Fiber Tracking and Tractography

DTI Findings in Syndromes Associated With Alcoholism

DTI Findings in Uncomplicated Alcoholism

DTI Findings in Recovery From Alcoholism

Conclusion

References

Section 7: Neuroimaging of Neurochemical Markers

Chapter 18: Molecular Imaging in Alcohol Dependence

Introduction

Review of Imaging Methods

Dopamine and Alcohol Dependence

The Dopamine Receptor in Alcohol Dependence

Neurochemical Imaging of Dopamine Receptors in Alcohol Dependence

Alcohol Dependence and Presynaptic Dopamine

Dopamine Synthesis in Alcohol Dependence

The Dopamine Transporter in Alcohol Dependence

Acute Alcohol Intoxication and Dopamine Imaging

Gaba and Alcohol Dependence

Opioid Receptors and Alcohol Dependence

Serotonin and Alcohol Dependence

Cannabinoid Receptors And alcohol Dependence

Conclusions

References

Chapter 19: Brain Proton Magnetic Resonance Spectroscopy of Alcohol Use disorders

Introduction

Neurochemicals Measured By 1H Mrs and Basic Mrs Methods

1H Mrs of Alcohol Use Disorders

Cross-sectional 1H Mrs

Longitudinal 1H Mrs During Alcohol Abstinence

Gaba and Glu Concentrations in Alcohol Use disorders

Treatment-seeking Vs treatment-naïve alcohol-dependent Individuals

Effects of Common Substance Use Comorbidities on 1H Mrs Measures in Alcohol Use Disorders

Smoking Comorbidity

Other Substance Use Comorbidity

Current and Future 1H Mrs Research in Alcohol Use Disorders

1H Mrs Correlates of Relapse In Aud

Neuroimaging Genetics

Knowledge Gaps and Outlook

Acknowledgments

References

Section 8: Neuroimaging of Brain Function

Chapter 20: Cognition, Emotion, and Attention

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

References

Chapter 21: The Neurobiology of Alcohol Craving and Relapse

Introduction

Alcohol-related Neuroadaptations

Striatal Dopamine Transmission

Neuronal Hyperexcitability

Clinical Neurobiology of Craving and Relapse in Chronic Alcoholism

Alcohol Craving

Incentive Salience and Craving

Positively Reinforced Craving

Negatively Reinforced Craving

Alcohol Relapse

Functional Alterations Associated With Relapse

Structural Alterations Associated With Relapse

Factors Increasing Alcohol Craving and Relapse risk

Alcohol Or Alcohol cue

Stress

Stress and the Development of Alcoholism

Stress Sensitivity, Alcohol Craving, and Relapse

Conclusions

References

Chapter 22: Compensatory Recruitment of Neural Resources In chronic alcoholism

What are Compensatory Mechanisms?

Alcoholism-related Increases and Differences in Activity and Functional Connectivity

Default Mode Network in Alcoholism

Intrinsic Functional Networks

Frontocerebellar Structural and Functional Connectivity

Are alcoholism-related Increases in Functional Activity and Connectivity Compensatory?

Factors Contributing to Compensatory Mechanisms

Is there a Continuum in Compensatory Mechanisms?

Neuroplastic Changes Possibly Underlying Compensatory Mechanisms

Conclusion

Acknowledgment

References

Section 9: Neuroelectrophysiology

Chapter 23: Understanding Alcohol Use Disorders With Neuroelectrophysiology

Introduction

Continuous Electroencephalogram

Event-related Potentials

Event-related Oscillations

Acute Effects of Alcohol on the Brain in Social Drinkers

Acute Effects of Alcohol On Eeg

Acute Effects of Alcohol On Erps

Acute Effects of Alcohol On Eros

Effects of Binge Drinking On electrophysiology

Binge Drinking And Eeg

Binge Drinking And Erps

Chronic Alcoholism and Neuroelectrophysiology

Chronic Alcoholism and Resting Eeg

Theta band

Alpha band

Beta band

Interhemispheric Coherence

Chronic Alcoholism and event-related Potentials

Attention - N100 and Mismatch Negativity

Target Detection (oddball tasks)

Recovery With Abstinence

Response Inhibition (Go/NoGo tasks)

Error Monitoring and Response Evaluation

Semantic Processing

Chronic Alcoholism and event-related Oscillations

Electrophysiologic Measures As endophenotypes

EEG Phenotypes

Eros as Endophenotypes

Conclusion

Acknowledgment

References

Chapter 24: Alcohol and the Sleeping brain

Introduction

Acute Effects of Alcohol On sleep

Acute Effects of Alcohol on Sleep: Repeated Administration

Acute Alcohol: Sleep Eeg data

Sleep in Alcoholism

Alcoholism: Sleep Eeg data

Sex Effects in the Impact of Alcohol And alcoholism On sleep

Alcohol Dependence and Sleep In adolescence

Sleep Homeostasis and Circadian Problems With Alcohol abuse

Evoked Potentials During sleep

Sleep-evoked Responses in Alcoholism

Links Between Sleep Eeg Effects and Altered Brain Structure in Alcoholism

Possible Neurochemical Mechanisms of the Acute And chronic Alcohol Effects On sleep Eeg

Neurochemistry of Acute Alcohol Effects

Neurochemistry of Alcoholism Effects

Familial Predisposition for Alcoholism Effects On sleep?

A Role for Sleep in Treatment, Recovery, and Relapse

Conclusion

Acknowledgments

References

Section 10: Fetal alcohol spectrum disorder

Chapter 25: Neurobehavioral, neurologic, and neuroimaging characteristics of fetal alcohol spectrum disorders

Introduction

Neuropsychologic characteristics

Cognitive abilities

General intellectual function

Academic achievement

Executive function

Language

Learning and memory

Cognitive processing speed and attention

Behavioral characteristics

Problem behaviors

Psychopathology

Social skills and social communication

Neurologic characteristics

Sensory integration and processing

Motor skills

Seizure activity

Sleep pathology

Using neurobehavioral data to identify individuals affected by prenatal alcohol exposure

Neuroimaging characteristics

Global structural abnormalities

Cerebral volume and shape

Cerebrospinal fluid

White matter

Gray matter

Regional brain abnormalities

Corpus callosum

Cerebellum

Hippocampus

Basal ganglia

Additional subcortical structures

Functional brain abnormalities

Electrophysiologic studies

Functional magnetic resonance imaging

Attention

Verbal learning

Spatial working memory

Response inhibition

Number processing

Default mode network

Functional connectivity

Metabolic neuroimaging studies

Conclusion

Acknowledgments

References

Chapter 26: Fetal Alcohol Spectrum Disorder: Pathogenesis and Mechanisms

Introduction

Cell death

Cell Cycle and Proliferation

Cell Migration

Cell Morphogenesis

Gene Expression Changes

Genetic

Epigenetic

Reactive Oxygen species-mediated Damage

Retinoid and Sonic Hedgehog Signaling

Conclusion

References

Chapter 27: Current Hypotheses on the Mechanisms of Alcoholism

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

Human Prefrontal Cortex Case Studies

Alcohol-induced Neurodegeneration

Alcohol Alters the Neurotrophin/neuroimmune Balance

Alcohol and Innate Immune System Activation

Alcohol Activates the Neuroimmune Signaling system

Induction of Neuroimmune Cascades Contributes to addiction-like Behaviors

Risk Factors That Contribute To the Progression of Alcohol Dependence

Genetic Contribution to Alcohol Dependence

Adolescent Onset of Alcohol Consumption

Disorders of Pfc Function

Conclusions

References

Section 11: Adolescent Drinking

Chapter 28: The Effect of Alcohol Use on Human Adolescent Brain Structures and Systems

Introduction

Adolescent Brain Development

Prevalence of Adolescent Alcohol Use And drinking Patterns

Brain Structural Changes In adolescent Alcohol use

Gray-matter Volume

Cortical Thickness

White-matter Integrity

Brain Function Differences In adolescent Alcohol users

Genetics, Vulnerability, and Brain Function

Cue Reactivity, Level of Response, and Brain Function

Neurocognitive Performance In adolescent Alcohol users

Summary and Conclusions

Acknowledgments

References

Section 12: Other Topics

Chapter 29: Peripheral Systems: Neuropathy

History and Prevalence

Clinical Features

Electrodiagnostic Studies

Other Laboratory Studies

Neuropathology

Differential Diagnosis

Pathogenesis

Thiamine Deficiency in Humans

Deficiency of B vitamins Other than Thiamine

Lead In wine

Animal Studies of Alcoholic Neuropathy And nutritional Deficiency

Molecular Mechanisms

Acetaldehyde and Oxidative Stress

Glial Dysfunction

The Role of Insulin and insulin-like Growth Factor (Igf) in Alcoholic Neuropathy

Nociceptor Signaling Via Protein Kinase C (Pkc)

Axonal Transport and the Cytoskeleton

Prognosis and Treatment

Summary and Future Directions

References

Chapter 30: Pharmacologic Treatment of Alcoholism

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

Depression

Bipolar Disorder

Anxiety Disorders

Summary

Pharmacogenetics And endophenotype Predictors

Use of Neuroimaging to Identify New Drugs and Targets

Newer Targets for Medication Development

The Future

References

Chapter 31: Alcohol-medical Drug Interactions

Introduction

Pharmacokinetic Interactions

Absorption and Distribution

Elimination

Oxidative Pathways of Alcohol Metabolism

Adh Family of Enzymes

CYP 450 System

ALDH System

Non-oxidative Pathways of Alcohol Metabolism

EtG/EtS

FAEE

PEth

Alcohol Metabolism in The Cns

Regulators of Alcohol Metabolism

Influence of Genetic Variability in Genes Encoding alcohol-metabolizing Enzymes

Adh genes

Aldh-coding genes

Cyp2E1-coding genes

Catalase-coding genes

Pharmacodynamic Interactions

Interaction of Alcohol With Currently Tested Medications for the Treatment of Alcoholism

Concluding Remarks

References

Chapter 32: Genetics of Alcoholism

Genetic Variations Contribute To risk of Alcoholism

Defining the Phenotype

Genetic Approaches for Identifying Variants That Affect Risk for Alcoholism

Candidate Gene Studies

Genes Involved in Alcohol Metabolism

Nicotinic Acetylcholine Receptors

Linkage Studies Followed By positional Candidate Gene analyses

Gaba-A Receptor genes

Genes on Chromosome 4

Genomewide Association Studies to Identify Common Variants

Rare Variants

Conclusions

Acknowledgments

References

Chapter 33: Co-occurring Psychiatric Disorders and Alcoholism

Introduction

The Relationship Between Alcohol Use Disorders and Other Psychopathology

Identifying Psychopathology In Aud Patients

Mood Disorders

Differentiating Primary Vs Secondary Mood Symptoms in co-occurring Conditions

Anxiety Disorders

Differentiating Anxiety From Mood Disorders

Personality Disorders (Axis Ii In Dsm)

Differentiating Mood From Personality Disorders

Organic Brain Disease

Drug Use Disorders

Neurobiologic Mechanisms Involved in Comorbidities

Treatment and Outcomes In comorbidity

Conclusion

References

Chapter 34: Hepatic Encephalopathy in Alcoholic Cirrhosis

Introduction

Neuropathology Of He

Pathophysiology of He In alcoholic Cirrhosis

Ammonia

Manganese

Inflammation

Brain Glucose and Energy Metabolism

The Gaba System and Neurosteroids

Serotonin

Histamine

Dopamine

Therapeutic Advances

Ammonia-lowering Strategies

Neuropharmacology

Liver Support Systems

Liver Transplantation

Summary

Acknowledgments

References

Chapter 35: Neuropathology of Alcoholism

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

References

Chapter 36: Genetic Differences in Response to Alcohol

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

Gamma-aminobutyric Acid A (Gaba) Receptor genes

Serotonin Transporter gene

Opioid Receptor gene

Nicotinic Acetylcholine Receptors gene

Interaction of Gene-environment And other factors

Alcohol Metabolism and Genetic Variations of alcohol-metabolizing Enzymes

Alcohol Dehydrogenase

Acetaldehyde Dehydrogenase

Conclusions

References

Chapter 37: Epidemiology of Drinking, Alcohol Use Disorders, and Related Problems in Us Ethnic Minority Groups

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

References

Chapter 38: Alcohol and The law

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

References

Chapter 39: Clinical Management of Alcohol Use Disorders In the neurology clinic

Introduction

What Is sbirt?

What is the Evidence That Sbirt works?

Screening

Screening Results

Brief Intervention

Precontemplation stage

Goal: to Move the Patient Toward Thinking About Change

Contemplation stage

Goal: to Encourage the Patient to Examine the Benefits and Risks of Change

Referral to Treatment

Neurologic Medical Comorbidity

Physical Examination

Acute Presentations

Blood Alcohol Concentration

Alcohol Withdrawal

Wernicke-Korsakoff Syndrome

Pellagra

Blackouts (retrograde Amnesia)

Central Pontine and Extrapontine Myelinolysis

Neuropathy

Cognitive Impairment

A Note About Alcohol Use as a Risk Factor For traumatic Brain Injury Or Recovery From Tbi

Conclusion

References

Index