Sullivan / Pfefferbaum Alcohol and the Nervous System

1. Auflage 2014
ISBN: 978-0-444-62622-6
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 704 Seiten

Reihe: Handbook of Clinical Neurology

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. - The first focused reference specifically on alcohol and the brain - Details our current understanding of how alcohol impacts the central nervous system - Covers clinical and social impact of alcohol abuse disorders and the biomedical consequences of alcohol abuse - Includes section on neuroimaging of neurochemical markers and brain function

Autoren/Hrsg.

Sullivan, Edith V.

Pfefferbaum, Adolf

Inhaltsverzeichnis

1;Front Cover;1
2;Alcohol and the Nervous System;4
3;Copyright;5
4;Handbook of Clinical Neurology 3rd Series;6
5;Foreword;8
6;Preface;10
7;Contributors;12
8;Contents;16
9;Section 1: Introduction;20
9.1;Chapter 1: Alcoholism: Diagnosis, Prognosis, Epidemiology, and Burden Of the Disease;22
9.1.1;Natural History and Clinical Assessment;22
9.1.1.1;Alcoholism Frequency;22
9.1.1.2;Practical Typology;23
9.1.2;Diagnosis;23
9.1.2.1;Alcohol Use History;23
9.1.2.2;Making a Diagnosis;24
9.1.2.2.1;Physiologic Dependence: Tolerance And withdrawal;24
9.1.2.2.1.1;Tolerance;24
9.1.2.2.1.2;Withdrawal;25
9.1.2.2.2;Loss of Control Phenomenon;25
9.1.2.2.3;Social Or Physical Decline;26
9.1.3;Gauging Prognosis;26
9.1.3.1;Positive Versus Negative;26
9.1.3.2;Diagnosis is Prognosis;27
9.1.3.3;Abuse Rather than Dependence;27
9.1.3.4;Behavioral Versus Hepatic Diagnosis;27
9.1.3.5;Assessing Ambivalence and Continuing Loss Of Control risk;27
9.1.3.6;Social Stability;28
9.1.3.7;Vaillant's Four Prognostic Factors;28
9.1.3.7.1;Structured time;28
9.1.3.7.2;A Rehabilitation Relationship;28
9.1.3.7.3;Sources of Hope Or self-esteem;28
9.1.3.7.4;A Negative Behavioral Reinforcer;28
9.1.3.8;Summing Up Prognosis;29
9.1.4;Other Psychiatric Assessment;29
9.1.4.1;Dsm-5 and Alcoholism Diagnosis: Progress Or Old Wine in a New Bottle?;29
9.1.5;Economic Costs of Problematic Alcohol use;30
9.1.5.1;Cost of Illness: Clarifying the Concept;30
9.1.5.2;Cost: Contribution By Category;30
9.1.5.3;Interpretation: Cost Consequences;30
9.1.6;Economics and Alcohol;31
9.1.7;Alcohol-related Spending and Other Disease Categories;31
9.1.8;Conclusion;31
9.1.9;References;31
9.2;Chapter 2: Perspectives on the Neuroscience of Alcohol From the National Institute on Alcohol Abuse and Alcoholism;34
9.2.1;Introduction;34
9.2.2;The Division of Neuroscience and Behavior (Dnb) and Its Mission;34
9.2.3;Genetics;35
9.2.4;Neuroadaptation;36
9.2.5;Behavior;38
9.2.6;Neurobehavioral, Structural, and Functional Consequences of Human Alcoholism;40
9.2.7;Preclinical Medications Development;41
9.2.8;Future Directions;43
9.2.9;References;44
10;Section 2: Animal Models: Neurochemistry and Metabolism of Alcohol;50
10.1;Chapter 3: Neurocircuitry of Alcohol Addiction: Synthesis From animal models;52
10.1.1;Definitions and Conceptual Framework for Neurocircuitry of Alcoholism;52
10.1.2;Animal Models for Compulsive Alcohol Seeking;53
10.1.3;Animal Models of Motivation, Withdrawal, and Opponent Process;55
10.1.4;Neurocircuits for the Binge/intoxication Stage Associated With Alcoholism;57
10.1.5;Neural Substrates for the Withdrawal/negative Affect Stage Associated With Alcoholism;59
10.1.5.1;Within-system Neuroadaptations That Contribute to the Compulsivity Associated With the Dark Side of Alcoholism;59
10.1.5.2;Between-system Neuroadaptations That Contribute to Compulsivity Associated With the Dark Side of Alcoholism;60
10.1.6;Neural Substrates for Executive Function Deficits Associated With alcoholism;63
10.1.7;Compulsivity in Alcoholism: An allostatic view;65
10.1.8;Acknowledgments;66
10.1.9;References;67
10.2;Chapter 4: Metabolism;74
10.2.1;Overview;74
10.2.2;Ethanol Metabolism;74
10.2.2.1;Hepatic Ethanol Metabolism;74
10.2.2.1.1;Genetic Factors: Genetic Variants And gender;76
10.2.2.1.1.1;Genetic Variation in Adh, Aldh2, Cyp2E1 and Ethanol Metabolism;76
10.2.2.1.2;Genetic Predisposition to Alcoholism;76
10.2.2.1.2.1;Effects of Gender on Alcohol Metabolism;77
10.2.2.1.3;Fasting;77
10.2.2.1.4;Protein Malnutrition;77
10.2.2.1.5;Effect of Fat Content Or Composition Of diet;77
10.2.2.1.6;Effect of Dietary Ethanol;78
10.2.2.1.7;Miscellaneous Dietary Effects;78
10.2.2.1.8;Endocrine Effects;78
10.2.2.2;Gastrointestinal and Other Tissue Metabolism of Ethanol;78
10.2.2.2.1;Alcohol-metabolizing Enzymes In the nervous system;79
10.2.3;Systemic Pharmacokinetics and Pharmacokinetic Modeling;79
10.2.3.1;Overview - Absorption, first-pass Metabolism, Distribution, and Elimination;79
10.2.3.1.1;Compartmental/phenomenologic Modeling;80
10.2.3.1.2;Physiologically Based Modeling;81
10.2.4;Summary;82
10.2.5;Acknowledgments;84
10.2.6;References;84
10.3;Chapter 5: Use of Animal Models of alcohol-related Behavior;90
10.3.1;Introduction;90
10.3.2;Pharmacologic Considerations;90
10.3.3;Aud is Behaviorally and Genetically Complex;91
10.3.4;What Can Be Modeled?;91
10.3.5;Choice of non-human Animal species;91
10.3.6;Alcohol-related Phenotypes;91
10.3.7;Assessing Alcohol Sensitivity;92
10.3.8;Assessing Alcohol Tolerance Or sensitization;92
10.3.9;Assessing Alcohol Dependence;93
10.3.10;Assessing Alcohol Reinforcement;93
10.3.11;Modeling Genetic Risk in non-human Animals;94
10.3.11.1;Rodent Lines Selectively Bred for Alcohol responses;95
10.3.11.1.1;Alcohol Preference Selections;95
10.3.11.1.1.1;Congruent Findings in Rat Preference Selections;95
10.3.11.1.1.2;Findings From High (Hap) and Low (Lap) alcohol-preferring mice;97
10.3.11.1.2;Selection for Drinking in The dark;98
10.3.11.1.3;Selection for Locomotor Response to Ethanol;98
10.3.11.1.4;Lines Selected to Be Ethanol Withdrawal Seizure-Prone (Wsp) Or -Resistant (Wsr);98
10.3.11.1.5;Long Sleep (Ls) and Short Sleep (Ss) mice;99
10.3.11.1.6;Alcohol-tolerant (At) and non-tolerant (Ant) rats;99
10.3.11.2;Studies With Inbred Strains;99
10.3.12;Can Behavior Genetics Reveal the Structure of ethanol-related Behavior?;100
10.3.13;Acknowledgments;101
10.3.14;References;101
11;Section 3: Molecular Basis of Alcoholism;106
11.1;Chapter 6: Molecular Basis of Alcoholism;108
11.1.1;Molecular Mechanisms Underlying Acute and Chronic Alcoholism;108
11.1.1.1;Introduction;108
11.1.1.2;Primary Targets;108
11.1.1.3;DNA;109
11.1.1.4;Neurotransmitter Systems;112
11.1.1.4.1;Glutamate;112
11.1.1.4.2;Dopamine;114
11.1.1.4.3;GABA(A);114
11.1.1.4.4;GABA(B);115
11.1.1.4.5;Serotonin (5-Ht);116
11.1.1.5;Big Potassium (Bk) Channels;117
11.1.1.6;Transcription Factors;117
11.1.1.7;microRnas;118
11.1.1.8;Synaptic MRna Translation and MicroRnas;118
11.1.1.9;Neuroimmune;119
11.1.2;Summary and Future Directions;120
11.1.3;References;124
12;Section 4: Neurologic Signs and Consequences;132
12.1;Chapter 7: Alcohol: Intoxication and Poisoning - Diagnosis and Treatment;134
12.1.1;Introduction;134
12.1.2;The Effects of Ethanol on Organ Systems;134
12.1.2.1;Nervous System;134
12.1.2.2;Gastrointestinal System;135
12.1.2.3;Cardiovascular System;135
12.1.2.4;Other Effects;135
12.1.3;Diagnosis;136
12.1.3.1;Clinical Features;136
12.1.3.2;Blood Alcohol Concentration;136
12.1.3.3;Alcohol Flush Reaction;136
12.1.3.4;Idiosyncratic Alcohol Intoxication;137
12.1.4;Differential Diagnosis;137
12.1.4.1;Hepatic Encephalopathy;137
12.1.4.2;Wernicke-Korsakoff Syndrome;138
12.1.5;Treatment;138
12.1.6;References;139
12.2;Chapter 8: Acute withdrawal: diagnosis and treatment;142
12.2.1;Introduction;142
12.2.2;Symptoms And signs;142
12.2.2.1;Hangover;142
12.2.2.2;Tremor;142
12.2.2.3;Hallucinosis;142
12.2.2.4;Abnormal Movements;143
12.2.2.5;Seizures;143
12.2.2.6;Delirium Tremens;144
12.2.3;Comorbid Disorders;144
12.2.4;Treatment;145
12.2.4.1;Non-pharmacologic Therapy;145
12.2.4.2;Pharmacotherapy;145
12.2.4.2.1;Benzodiazepines;145
12.2.4.2.2;Phenobarbital;146
12.2.4.2.3;Anticonvulsants;146
12.2.4.2.4;Baclofen;146
12.2.4.2.5;Gamma-hydroxybutyric acid;146
12.2.4.2.6;Neuroleptics;146
12.2.4.2.7;Beta-blockers and alpha-2-agonists;147
12.2.4.2.8;Ethanol;147
12.2.4.2.9;N-methyl-d-aspartate Receptor Blockers;147
12.2.4.2.10;Other Pharmacotherapies;147
12.2.5;Treatment of Severe Symptoms;147
12.2.5.1;Seizures;147
12.2.5.2;Delirium Tremens;147
12.2.6;Other Management Considerations;148
12.2.7;Summary;148
12.2.8;References;148
12.3;Chapter 9: Neurochemical Mechanisms of Alcohol Withdrawal;152
12.3.1;Introduction;152
12.3.2;Signs and Symptoms of the Alcohol Withdrawal Syndrome;153
12.3.2.1;Cns Hyperexcitability;153
12.3.2.2;Autonomic Nervous System Hyperactivity;153
12.3.2.3;Sleep Disturbances;154
12.3.2.4;Measures of Psychologic Discomfort And negative Affect;154
12.3.2.4.1;Anxiety;154
12.3.2.4.2;Heightened Stress Responsiveness;155
12.3.2.4.3;Anhedonia/dysphoria;155
12.3.3;Neurochemical Adaptations Produced By Chronic Alcohol And withdrawal;156
12.3.3.1;Adaptations in Amino Acid Neurotransmitter Systems;156
12.3.3.1.1;Glutamate;157
12.3.3.1.2;Gaba;158
12.3.3.2;Adaptations in Monoamine Systems;158
12.3.3.2.1;Dopamine;158
12.3.3.2.2;Norepinephrine;159
12.3.3.2.3;Serotonin;159
12.3.3.3;Adaptations in Neuropeptide Systems;160
12.3.3.3.1;Corticotropin-releasing factor;160
12.3.3.3.2;Neuropeptide Y;161
12.3.3.3.3;Opioid Polypeptides;161
12.3.3.3.4;Nociceptin;162
12.3.3.3.5;Other Neuropeptides;162
12.3.3.4;Adaptations in Ion Channels;162
12.3.3.4.1;Voltage-gated Ca2+ Channels;162
12.3.3.4.2;Small-conductance Ca2+-activated K+ Channels;163
12.3.3.4.3;Large-conductance voltage- and Ca2+-activated K+ Channels;163
12.3.3.4.4;A-type K+ Channels;164
12.3.4;Conclusions;164
12.3.5;Acknowledgments;165
12.3.6;References;165
12.4;Chapter 10: Molecular and Neurologic Responses to Chronic Alcohol use;176
12.4.1;Introduction;176
12.4.2;Molecular Mechanisms of Chronic Alcohol Action on The brain;176
12.4.2.1;Genetic Contributions to Alcoholism;177
12.4.2.2;Modulation of Gene Expression With chronic alcohol;177
12.4.2.3;Persistence of Gene Expression Changes - Role for Epigenetic Regulation?;178
12.4.3;Neurology of Chronic Alcohol Action in the Central Nervous System;179
12.4.3.1;Overview of Clinical Syndromes;179
12.4.3.2;Alcohol Blackouts;179
12.4.3.3;Craving;180
12.4.3.4;Tolerance and Dependence;181
12.4.3.5;Alcohol Withdrawal Syndrome Overview;181
12.4.3.6;Withdrawal Seizures;182
12.4.3.7;Delirium Tremens;182
12.4.3.8;Wernicke-Korsakoff Syndrome;183
12.4.3.9;Cerebellar Degeneration;184
12.4.3.10;Primary Alcoholic Dementia;184
12.4.3.11;Central Pontine Myelinolysis;185
12.4.3.12;Marchiafava-Bignami Disease;186
12.4.4;Conclusions;186
12.4.5;Acknowledgment;186
12.4.6;References;186
13;Section 5: Neuropsychology;192
13.1;Chapter 11: Methods of Association and Dissociation for Establishing Selective Brain-behavior Relations;194
13.1.1;Historic Background;194
13.1.2;Single Dissociation Model: Lesion studies;195
13.1.3;Double Dissociation Model: Lesion studies;195
13.1.4;Double Dissociation Model in Conditions Affecting Multiple Neural Systems;196
13.1.4.1;Between-groups model;196
13.1.4.2;Within-group model;196
13.1.4.3;Multiple Dissociations and Relevance to Establishing Network Selectivity;199
13.1.5;Acknowledgment;199
13.1.6;References;199
13.2;Chapter 12: Profiles of Impaired, Spared, and Recovered Neuropsychologic Processes in Alcoholism;202
13.2.1;Introduction;202
13.2.2;The Participants and The tests;202
13.2.2.1;Characteristics of the Participants;202
13.2.2.2;Assessing Neuropsychologic Functions And the brain;203
13.2.3;The Impaired, the Spared, And the recovered;203
13.2.3.1;Impairments;203
13.2.3.2;Spared Functions and Compensation;203
13.2.3.3;Recovery;204
13.2.4;Profiles of Damage And repair;204
13.2.4.1;General Neuropsychologic Abilities;204
13.2.4.2;Widespread Brain Damage in Alcoholism;205
13.2.4.3;Frontocerebellar and Mesocorticolimbic Structures;206
13.2.5;The Five Functional Domains;206
13.2.5.1;Memory;207
13.2.5.1.1;Impairments;207
13.2.5.1.2;Compensation and Recovery;216
13.2.5.2;Executive Functions;216
13.2.5.2.1;Impairments;217
13.2.5.2.2;Compensation and Recovery;218
13.2.5.3;Emotion and Psychosocial Skills;218
13.2.5.3.1;Impairments;219
13.2.5.3.2;Compensation and Recovery;220
13.2.5.4;Visuospatial Cognition;220
13.2.5.4.1;Impairments;220
13.2.5.4.2;Compensation and Recovery;221
13.2.5.5;Psychomotor Abilities;221
13.2.5.5.1;Impairments;221
13.2.5.5.2;Compensation and Recovery;222
13.2.6;Summary and Conclusions;222
13.2.7;Acknowledgments;223
13.2.8;References;223
13.3;Chapter 13: Component Processes of Memory in Alcoholism: Pattern of Compromise and Neural Substrates;230
13.3.1;Working Memory and Executive functions;230
13.3.1.1;Definition;230
13.3.1.2;Slave Systems of Working Memory;230
13.3.1.3;Central Executive of Working Memory;230
13.3.1.4;Neural Substrates of Working Memory In alcoholism;231
13.3.1.5;Working Memory in Korsakoff's Syndrome;232
13.3.2;Episodic Memory;233
13.3.2.1;Definition;233
13.3.2.2;Encoding and Retrieval Processes;233
13.3.2.3;Contextual Memory, Source Memory, And prospective Memory;233
13.3.2.4;Metamemory;234
13.3.2.5;Episodic Memory and Executive Functions;234
13.3.2.6;Neural Substrates of Episodic Memory Deficits in Alcoholism;234
13.3.2.7;Autobiographical Memory;234
13.3.2.8;Episodic Memory in Korsakoff's Syndrome;235
13.3.3;Semantic Memory;235
13.3.3.1;Definition;235
13.3.3.2;New Semantic Learning;236
13.3.3.3;Semantic Memory in Korsakoff's Syndrome;236
13.3.4;Perceptual Memory;236
13.3.4.1;Definition;236
13.3.4.2;Implicit Perceptual Learning;236
13.3.4.3;Perceptual Memory in Korsakoff's Syndrome;237
13.3.5;Procedural Memory;237
13.3.5.1;Definition;237
13.3.5.2;Cognitive Procedural Learning;237
13.3.5.3;Visuomotor Procedural Learning;237
13.3.5.4;Procedural Memory in Korsakoff's Syndrome;237
13.3.6;Factors Contributing to the Heterogeneity of Memory Disorders in Alcoholism;238
13.3.6.1;Age;238
13.3.6.2;Gender;238
13.3.6.3;Alcohol Use Pattern;238
13.3.6.4;Smoking Status;238
13.3.6.5;Nutritional Status;238
13.3.6.6;Psychiatric Comorbidity;238
13.3.6.7;Treatment-naïve Versus treatment-seeking Patients;239
13.3.7;Reversibility of alcohol-related Memory Disorders;239
13.3.7.1;Uncomplicated Alcoholism;239
13.3.7.2;Korsakoff's Syndrome;240
13.3.8;Clinical Implications of Memory Disorders in the Treatment of Alcohol Dependence;240
13.3.9;Conclusion;240
13.3.10;References;240
13.4;Chapter 14: Decision Making, Risky Behavior, and Alcoholism;246
13.4.1;Decision Making, Risky Behavior, and Alcoholism;246
13.4.2;Poor Executive Control Leads to Poor Decision Making;246
13.4.3;Strong Appetitive Drive Leads to Poor Decision Making;247
13.4.4;Other Aspects of Behavior Related to Poor Decision Making in Alcoholics;248
13.4.5;Neural Correlates of Decision Making and Risky Behavior in Alcoholism;249
13.4.6;Brain Function Associated With Decision Making in Binge Drinking;249
13.4.7;Brain Function Associated With Decision Making in Active Drinkers With Alcohol Dependence;249
13.4.8;Brain Function Associated With Decision Making in short-term Abstinent Alcoholics;250
13.4.9;Brain Function Associated With Decision Making in Individuals At Risk for Alcoholism;251
13.4.10;Brain Function Associated With Decision Making in long-term Abstinent Alcoholics;252
13.4.11;References;253
13.5;Chapter 15: Motor Systems and Postural Instability;256
13.5.1;Introduction;256
13.5.2;Postural Control in Healthy Individuals;256
13.5.3;Prenatal Exposure to Alcohol;257
13.5.4;Acute Alcohol Intoxication: Neurologic and Behavioral Changes in Postural Control;258
13.5.4.1;Chemical Effects of Ethanol On postural control;258
13.5.4.2;Instability During Acute Intoxication;259
13.5.4.3;The Cerebellum in Acute Alcohol Intoxication;260
13.5.5;Chronic Alcoholism: long-term Motor and Neurologic Effects;260
13.5.5.1;Motor Symptoms;260
13.5.5.2;Excessive Sway and Postural tremor;260
13.5.5.3;Visual and Tactile cues;261
13.5.5.4;Neurologic Changes in Chronic Alcoholism;262
13.5.5.5;Cortical Changes;263
13.5.5.6;Corpus Callosum;263
13.5.5.7;Cerebellum;264
13.5.5.8;Pons and Thalamus;264
13.5.5.9;Peripheral Nervous System;265
13.5.6;Influence of Length of Alcohol Dependence and Sobriety;265
13.5.6.1;Influence Of age;265
13.5.6.2;Sexual Dimorphism;266
13.5.7;Recovery;266
13.5.8;Conclusion;268
13.5.9;References;268
13.6;Chapter 16: Sex Differences in alcohol-related Neurobehavioral Consequences;272
13.6.1;Introduction;272
13.6.2;Neurobehavioral Consequences of Acute Alcohol Administration;274
13.6.2.1;Neuropsychological/behavioral Consequences;274
13.6.2.2;Neurophysiologic Consequences;277
13.6.2.3;Neuroimaging Correlates of Acute Alcohol Administration;278
13.6.2.4;Section summary;279
13.6.3;Neurobehavioral Consequences Associated With Alcoholism;279
13.6.3.1;General notes;279
13.6.3.2;Neuropsychologic Concomitants;279
13.6.3.3;Neurophysiologic Concomitants: Eeg;281
13.6.3.4;Neurophysiologic Concomitants: Erp;282
13.6.3.5;Neuroimaging Concomitants: Structural;283
13.6.3.6;Neuroimaging Concomitants: Functional And metabolic Contrasts;285
13.6.4;Other Considerations Pertinent to Exploring Sex Differences And alcohol Effects;286
13.6.5;References;286
14;Section 6: Neuroimaging of Brain Macrostructure and Microstructure;292
14.1;Chapter 17: Structural and Microstructral Imaging of the Brain in Alcohol Use Disorders;294
14.1.1;Introduction;294
14.1.2;Structural Magnetic Resonance Imaging;294
14.1.3;Structural MRI Findings In syndromes Associated With alcoholism;296
14.1.4;Structural MRI Findings in Uncomplicated Alcoholism;297
14.1.5;Structural MRI Findings in Recovery From Alcoholism;299
14.1.6;Diffusion Tensor Imaging;300
14.1.6.1;Whole-brain Analysis;301
14.1.6.2;Region of Interest Analysis;301
14.1.6.3;Quantitative Fiber Tracking and Tractography;301
14.1.7;DTI Findings in Syndromes Associated With Alcoholism;302
14.1.8;DTI Findings in Uncomplicated Alcoholism;302
14.1.9;DTI Findings in Recovery From Alcoholism;303
14.1.10;Conclusion;303
14.1.11;References;303
15;Section 7: Neuroimaging of Neurochemical Markers;310
15.1;Chapter 18: Molecular Imaging in Alcohol Dependence;312
15.1.1;Introduction;312
15.1.2;Review of Imaging Methods;313
15.1.3;Dopamine and Alcohol Dependence;313
15.1.3.1;The Dopamine Receptor in Alcohol Dependence;313
15.1.3.2;Neurochemical Imaging of Dopamine Receptors in Alcohol Dependence;313
15.1.3.3;Alcohol Dependence and Presynaptic Dopamine;315
15.1.3.4;Dopamine Synthesis in Alcohol Dependence;316
15.1.3.5;The Dopamine Transporter in Alcohol Dependence;316
15.1.3.6;Acute Alcohol Intoxication and Dopamine Imaging;316
15.1.4;Gaba and Alcohol Dependence;317
15.1.5;Opioid Receptors and Alcohol Dependence;318
15.1.6;Serotonin and Alcohol Dependence;320
15.1.7;Cannabinoid Receptors And alcohol Dependence;322
15.1.8;Conclusions;322
15.1.9;References;326
15.2;Chapter 19: Brain Proton Magnetic Resonance Spectroscopy of Alcohol Use disorders;332
15.2.1;Introduction;332
15.2.2;Neurochemicals Measured By 1H Mrs and Basic Mrs Methods;333
15.2.3;1H Mrs of Alcohol Use Disorders;336
15.2.3.1;Cross-sectional 1H Mrs;336
15.2.3.2;Longitudinal 1H Mrs During Alcohol Abstinence;340
15.2.3.3;Gaba and Glu Concentrations in Alcohol Use disorders;341
15.2.3.4;Treatment-seeking Vs treatment-naïve alcohol-dependent Individuals;342
15.2.4;Effects of Common Substance Use Comorbidities on 1H Mrs Measures in Alcohol Use Disorders;344
15.2.4.1;Smoking Comorbidity;344
15.2.4.2;Other Substance Use Comorbidity;346
15.2.5;Current and Future 1H Mrs Research in Alcohol Use Disorders;347
15.2.5.1;1H Mrs Correlates of Relapse In Aud;347
15.2.5.2;Neuroimaging Genetics;348
15.2.5.3;Knowledge Gaps and Outlook;349
15.2.6;Acknowledgments;350
15.2.7;References;350
16;Section 8: Neuroimaging of Brain Function;358
16.1;Chapter 20: Cognition, Emotion, and Attention;360
16.1.1;Cognition, Attention, And emotion in Alcohol Abuse And dependence;360
16.1.2;Concepts of Attention and Their Neural Correlates;360
16.1.3;Attentional Control Systems Interact With Emotion and Reward Systems;363
16.1.4;Attention and Memory;364
16.1.5;Alcoholism - A neural Disconnection Syndrome?;366
16.1.6;Functional Networks Of attention and Cognition;366
16.1.7;Conclusion;367
16.1.8;References;367
16.2;Chapter 21: The Neurobiology of Alcohol Craving and Relapse;374
16.2.1;Introduction;374
16.2.2;Alcohol-related Neuroadaptations;374
16.2.2.1;Striatal Dopamine Transmission;375
16.2.2.2;Neuronal Hyperexcitability;375
16.2.3;Clinical Neurobiology of Craving and Relapse in Chronic Alcoholism;376
16.2.3.1;Alcohol Craving;376
16.2.3.1.1;Incentive Salience and Craving;376
16.2.3.1.2;Positively Reinforced Craving;376
16.2.3.1.3;Negatively Reinforced Craving;377
16.2.3.2;Alcohol Relapse;377
16.2.3.2.1;Functional Alterations Associated With Relapse;378
16.2.3.2.2;Structural Alterations Associated With Relapse;378
16.2.4;Factors Increasing Alcohol Craving and Relapse risk;379
16.2.4.1;Alcohol Or Alcohol cue;380
16.2.4.2;Stress;381
16.2.4.2.1;Stress and the Development of Alcoholism;381
16.2.4.2.2;Stress Sensitivity, Alcohol Craving, and Relapse;381
16.2.5;Conclusions;383
16.2.6;References;384
16.3;Chapter 22: Compensatory Recruitment of Neural Resources In chronic alcoholism;388
16.3.1;What are Compensatory Mechanisms?;388
16.3.2;Alcoholism-related Increases and Differences in Activity and Functional Connectivity;390
16.3.2.1;Default Mode Network in Alcoholism;392
16.3.2.2;Intrinsic Functional Networks;392
16.3.2.3;Frontocerebellar Structural and Functional Connectivity;394
16.3.3;Are alcoholism-related Increases in Functional Activity and Connectivity Compensatory?;394
16.3.3.1;Factors Contributing to Compensatory Mechanisms;395
16.3.3.2;Is there a Continuum in Compensatory Mechanisms?;395
16.3.3.3;Neuroplastic Changes Possibly Underlying Compensatory Mechanisms;395
16.3.4;Conclusion;397
16.3.5;Acknowledgment;397
16.3.6;References;397
17;Section 9: Neuroelectrophysiology;400
17.1;Chapter 23: Understanding Alcohol Use Disorders With Neuroelectrophysiology;402
17.1.1;Introduction;402
17.1.2;Continuous Electroencephalogram;402
17.1.3;Event-related Potentials;403
17.1.4;Event-related Oscillations;403
17.1.5;Acute Effects of Alcohol on the Brain in Social Drinkers;405
17.1.5.1;Acute Effects of Alcohol On Eeg;405
17.1.5.2;Acute Effects of Alcohol On Erps;408
17.1.5.3;Acute Effects of Alcohol On Eros;412
17.1.6;Effects of Binge Drinking On electrophysiology;413
17.1.6.1;Binge Drinking And Eeg;413
17.1.6.2;Binge Drinking And Erps;414
17.1.7;Chronic Alcoholism and Neuroelectrophysiology;415
17.1.7.1;Chronic Alcoholism and Resting Eeg;415
17.1.7.1.1;Theta band;415
17.1.7.1.2;Alpha band;415
17.1.7.1.3;Beta band;416
17.1.7.1.3.1;Interhemispheric Coherence;416
17.1.7.2;Chronic Alcoholism and event-related Potentials;416
17.1.7.2.1;Attention - N100 and Mismatch Negativity;416
17.1.7.2.2;Target Detection (oddball tasks);417
17.1.7.2.2.1;Recovery With Abstinence;417
17.1.7.2.3;Response Inhibition (Go/NoGo tasks);418
17.1.7.2.4;Error Monitoring and Response Evaluation;418
17.1.7.2.5;Semantic Processing;419
17.1.7.3;Chronic Alcoholism and event-related Oscillations;421
17.1.8;Electrophysiologic Measures As endophenotypes;422
17.1.8.1;EEG Phenotypes;422
17.1.8.2;Eros as Endophenotypes;423
17.1.9;Conclusion;424
17.1.10;Acknowledgment;424
17.1.11;References;424
17.2;Chapter 24: Alcohol and the Sleeping brain;434
17.2.1;Introduction;434
17.2.2;Acute Effects of Alcohol On sleep;435
17.2.2.1;Acute Effects of Alcohol on Sleep: Repeated Administration;435
17.2.2.2;Acute Alcohol: Sleep Eeg data;436
17.2.3;Sleep in Alcoholism;437
17.2.3.1;Alcoholism: Sleep Eeg data;437
17.2.3.2;Sex Effects in the Impact of Alcohol And alcoholism On sleep;438
17.2.4;Alcohol Dependence and Sleep In adolescence;439
17.2.5;Sleep Homeostasis and Circadian Problems With Alcohol abuse;440
17.2.6;Evoked Potentials During sleep;440
17.2.6.1;Sleep-evoked Responses in Alcoholism;441
17.2.6.2;Links Between Sleep Eeg Effects and Altered Brain Structure in Alcoholism;441
17.2.7;Possible Neurochemical Mechanisms of the Acute And chronic Alcohol Effects On sleep Eeg;442
17.2.7.1;Neurochemistry of Acute Alcohol Effects;443
17.2.7.2;Neurochemistry of Alcoholism Effects;443
17.2.8;Familial Predisposition for Alcoholism Effects On sleep?;443
17.2.9;A Role for Sleep in Treatment, Recovery, and Relapse;444
17.2.10;Conclusion;445
17.2.11;Acknowledgments;446
17.2.12;References;446
18;Section 10: Fetal alcohol spectrum disorder;452
18.1;Chapter 25: Neurobehavioral, neurologic, and neuroimaging characteristics of fetal alcohol spectrum disorders;454
18.1.1;Introduction;454
18.1.2;Neuropsychologic characteristics;454
18.1.2.1;Cognitive abilities;454
18.1.2.1.1;General intellectual function;454
18.1.2.1.2;Academic achievement;457
18.1.2.1.3;Executive function;457
18.1.2.1.4;Language;457
18.1.2.1.5;Learning and memory;458
18.1.2.1.6;Cognitive processing speed and attention;458
18.1.2.2;Behavioral characteristics;459
18.1.2.2.1;Problem behaviors;459
18.1.2.2.2;Psychopathology;459
18.1.2.2.3;Social skills and social communication;459
18.1.2.3;Neurologic characteristics;460
18.1.2.3.1;Sensory integration and processing;460
18.1.2.3.2;Motor skills;460
18.1.2.3.3;Seizure activity;462
18.1.2.3.4;Sleep pathology;462
18.1.2.3.5;Using neurobehavioral data to identify individuals affected by prenatal alcohol exposure;462
18.1.3;Neuroimaging characteristics;463
18.1.3.1;Global structural abnormalities;463
18.1.3.1.1;Cerebral volume and shape;464
18.1.3.1.2;Cerebrospinal fluid;464
18.1.3.1.3;White matter;468
18.1.3.1.4;Gray matter;468
18.1.3.2;Regional brain abnormalities;468
18.1.3.2.1;Corpus callosum;468
18.1.3.2.2;Cerebellum;470
18.1.3.2.3;Hippocampus;470
18.1.3.2.4;Basal ganglia;470
18.1.3.2.5;Additional subcortical structures;471
18.1.3.3;Functional brain abnormalities;471
18.1.3.3.1;Electrophysiologic studies;471
18.1.3.3.2;Functional magnetic resonance imaging;471
18.1.3.3.3;Attention;471
18.1.3.3.4;Verbal learning;471
18.1.3.3.5;Spatial working memory;471
18.1.3.3.6;Response inhibition;472
18.1.3.3.7;Number processing;473
18.1.3.3.8;Default mode network;473
18.1.3.3.9;Functional connectivity;473
18.1.3.3.10;Metabolic neuroimaging studies;473
18.1.4;Conclusion;473
18.1.5;Acknowledgments;474
18.1.6;References;474
18.2;Chapter 26: Fetal Alcohol Spectrum Disorder: Pathogenesis and Mechanisms;482
18.2.1;Introduction;482
18.2.2;Cell death;483
18.2.3;Cell Cycle and Proliferation;485
18.2.4;Cell Migration;485
18.2.5;Cell Morphogenesis;485
18.2.6;Gene Expression Changes;487
18.2.6.1;Genetic;487
18.2.6.2;Epigenetic;487
18.2.7;Reactive Oxygen species-mediated Damage;488
18.2.8;Retinoid and Sonic Hedgehog Signaling;488
18.2.9;Conclusion;489
18.2.10;References;491
18.3;Chapter 27: Current Hypotheses on the Mechanisms of Alcoholism;496
18.3.1;Alcoholism is a Disease Characterized By Continued Use Despite Negative Consequences;496
18.3.2;Diminished Executive Function in the Alcoholic is Consistent With a Compromise of Prefrontal Cortex Function;497
18.3.2.1;Human Prefrontal Cortex Case Studies;497
18.3.2.2;Alcohol-induced Neurodegeneration;498
18.3.2.3;Alcohol Alters the Neurotrophin/neuroimmune Balance;499
18.3.3;Alcohol and Innate Immune System Activation;500
18.3.3.1;Alcohol Activates the Neuroimmune Signaling system;502
18.3.3.2;Induction of Neuroimmune Cascades Contributes to addiction-like Behaviors;505
18.3.4;Risk Factors That Contribute To the Progression of Alcohol Dependence;506
18.3.4.1;Genetic Contribution to Alcohol Dependence;506
18.3.4.2;Adolescent Onset of Alcohol Consumption;508
18.3.4.3;Disorders of Pfc Function;509
18.3.5;Conclusions;510
18.3.6;References;511
19;Section 11: Adolescent Drinking;518
19.1;Chapter 28: The Effect of Alcohol Use on Human Adolescent Brain Structures and Systems;520
19.1.1;Introduction;520
19.1.1.1;Adolescent Brain Development;520
19.1.1.2;Prevalence of Adolescent Alcohol Use And drinking Patterns;520
19.1.2;Brain Structural Changes In adolescent Alcohol use;520
19.1.2.1;Gray-matter Volume;520
19.1.2.2;Cortical Thickness;521
19.1.2.3;White-matter Integrity;521
19.1.3;Brain Function Differences In adolescent Alcohol users;522
19.1.3.1;Genetics, Vulnerability, and Brain Function;524
19.1.3.2;Cue Reactivity, Level of Response, and Brain Function;525
19.1.4;Neurocognitive Performance In adolescent Alcohol users;526
19.1.5;Summary and Conclusions;527
19.1.6;Acknowledgments;527
19.1.7;References;527
20;Section 12: Other Topics;530
20.1;Chapter 29: Peripheral Systems: Neuropathy;532
20.1.1;History and Prevalence;532
20.1.2;Clinical Features;532
20.1.3;Electrodiagnostic Studies;533
20.1.4;Other Laboratory Studies;533
20.1.5;Neuropathology;534
20.1.6;Differential Diagnosis;535
20.1.7;Pathogenesis;535
20.1.7.1;Thiamine Deficiency in Humans;535
20.1.7.2;Deficiency of B vitamins Other than Thiamine;536
20.1.7.3;Lead In wine;536
20.1.7.4;Animal Studies of Alcoholic Neuropathy And nutritional Deficiency;537
20.1.8;Molecular Mechanisms;537
20.1.8.1;Acetaldehyde and Oxidative Stress;537
20.1.8.2;Glial Dysfunction;537
20.1.8.3;The Role of Insulin and insulin-like Growth Factor (Igf) in Alcoholic Neuropathy;538
20.1.8.4;Nociceptor Signaling Via Protein Kinase C (Pkc);538
20.1.8.5;Axonal Transport and the Cytoskeleton;539
20.1.9;Prognosis and Treatment;539
20.1.10;Summary and Future Directions;541
20.1.11;References;541
20.2;Chapter 30: Pharmacologic Treatment of Alcoholism;546
20.2.1;Introduction;546
20.2.2;Neurochemical Targets For medication Treatment;546
20.2.3;Opioid Antagonists;547
20.2.4;Gaba/glutamatergic Medications;548
20.2.5;Serotonergic Medications;549
20.2.6;Dopaminergic Medications;549
20.2.7;Cholinergic/nicotine Acting drugs;550
20.2.8;Combination Pharmacotherapy;550
20.2.9;Treatment of Aud With co-occurring Mood Or Anxiety Disorders;550
20.2.9.1;Depression;550
20.2.9.2;Bipolar Disorder;550
20.2.9.3;Anxiety Disorders;551
20.2.9.4;Summary;551
20.2.10;Pharmacogenetics And endophenotype Predictors;551
20.2.11;Use of Neuroimaging to Identify New Drugs and Targets;552
20.2.12;Newer Targets for Medication Development;554
20.2.13;The Future;556
20.2.14;References;557
20.3;Chapter 31: Alcohol-medical Drug Interactions;562
20.3.1;Introduction;562
20.3.2;Pharmacokinetic Interactions;562
20.3.2.1;Absorption and Distribution;563
20.3.2.2;Elimination;563
20.3.2.3;Oxidative Pathways of Alcohol Metabolism;565
20.3.2.3.1;Adh Family of Enzymes;565
20.3.2.3.2;CYP 450 System;565
20.3.2.3.3;ALDH System;569
20.3.2.4;Non-oxidative Pathways of Alcohol Metabolism;569
20.3.2.4.1;EtG/EtS;569
20.3.2.4.2;FAEE;569
20.3.2.4.3;PEth;569
20.3.2.5;Alcohol Metabolism in The Cns;569
20.3.2.6;Regulators of Alcohol Metabolism;570
20.3.2.7;Influence of Genetic Variability in Genes Encoding alcohol-metabolizing Enzymes;570
20.3.2.7.1;Adh genes;570
20.3.2.7.2;Aldh-coding genes;570
20.3.2.7.3;Cyp2E1-coding genes;571
20.3.2.7.4;Catalase-coding genes;571
20.3.3;Pharmacodynamic Interactions;571
20.3.4;Interaction of Alcohol With Currently Tested Medications for the Treatment of Alcoholism;572
20.3.5;Concluding Remarks;572
20.3.6;References;573
20.4;Chapter 32: Genetics of Alcoholism;580
20.4.1;Genetic Variations Contribute To risk of Alcoholism;580
20.4.2;Defining the Phenotype;580
20.4.3;Genetic Approaches for Identifying Variants That Affect Risk for Alcoholism;581
20.4.4;Candidate Gene Studies;581
20.4.4.1;Genes Involved in Alcohol Metabolism;581
20.4.4.2;Nicotinic Acetylcholine Receptors;583
20.4.5;Linkage Studies Followed By positional Candidate Gene analyses;584
20.4.5.1;Gaba-A Receptor genes;584
20.4.5.2;Genes on Chromosome 4;584
20.4.6;Genomewide Association Studies to Identify Common Variants;585
20.4.7;Rare Variants;586
20.4.8;Conclusions;586
20.4.9;Acknowledgments;587
20.4.10;References;587
20.5;Chapter 33: Co-occurring Psychiatric Disorders and Alcoholism;592
20.5.1;Introduction;592
20.5.2;The Relationship Between Alcohol Use Disorders and Other Psychopathology;592
20.5.3;Identifying Psychopathology In Aud Patients;593
20.5.3.1;Mood Disorders;593
20.5.3.1.1;Differentiating Primary Vs Secondary Mood Symptoms in co-occurring Conditions;596
20.5.3.2;Anxiety Disorders;597
20.5.3.2.1;Differentiating Anxiety From Mood Disorders;598
20.5.3.3;Personality Disorders (Axis Ii In Dsm);598
20.5.3.3.1;Differentiating Mood From Personality Disorders;599
20.5.3.4;Organic Brain Disease;600
20.5.3.5;Drug Use Disorders;600
20.5.4;Neurobiologic Mechanisms Involved in Comorbidities;601
20.5.5;Treatment and Outcomes In comorbidity;602
20.5.6;Conclusion;603
20.5.7;References;604
20.6;Chapter 34: Hepatic Encephalopathy in Alcoholic Cirrhosis;608
20.6.1;Introduction;608
20.6.2;Neuropathology Of He;610
20.6.3;Pathophysiology of He In alcoholic Cirrhosis;610
20.6.3.1;Ammonia;610
20.6.3.2;Manganese;611
20.6.3.3;Inflammation;612
20.6.3.4;Brain Glucose and Energy Metabolism;613
20.6.3.5;The Gaba System and Neurosteroids;613
20.6.3.6;Serotonin;614
20.6.3.7;Histamine;615
20.6.3.8;Dopamine;615
20.6.4;Therapeutic Advances;615
20.6.4.1;Ammonia-lowering Strategies;615
20.6.4.2;Neuropharmacology;616
20.6.4.3;Liver Support Systems;617
20.6.4.4;Liver Transplantation;617
20.6.5;Summary;617
20.6.6;Acknowledgments;618
20.6.7;References;618
20.7;Chapter 35: Neuropathology of Alcoholism;622
20.7.1;Introduction;622
20.7.2;Alcohol Neurotoxicity;622
20.7.3;Complicating Pathologies;622
20.7.4;Structural Changes In Arbd;624
20.7.5;Neuronal Loss In Arbd;625
20.7.6;Molecular Differences;627
20.7.7;Neurotransmitters and Their Receptors;627
20.7.8;Genetics and Genomics;627
20.7.9;Gene Expression;628
20.7.10;Proteomics;629
20.7.11;Summary;630
20.7.12;Acknowledgments;630
20.7.13;References;630
20.8;Chapter 36: Genetic Differences in Response to Alcohol;636
20.8.1;Response to Alcohol as an Endophenotype of Alcohol Use Disorder;636
20.8.2;Heritability of Level of Response to Alcohol;636
20.8.3;Genetic Influences on Level Of response to Alcohol;637
20.8.3.1;Gamma-aminobutyric Acid A (Gaba) Receptor genes;637
20.8.3.2;Serotonin Transporter gene;637
20.8.3.3;Opioid Receptor gene;638
20.8.3.4;Nicotinic Acetylcholine Receptors gene;638
20.8.3.5;Interaction of Gene-environment And other factors;638
20.8.4;Alcohol Metabolism and Genetic Variations of alcohol-metabolizing Enzymes;639
20.8.4.1;Alcohol Dehydrogenase;639
20.8.4.2;Acetaldehyde Dehydrogenase;641
20.8.5;Conclusions;643
20.8.6;References;643
20.9;Chapter 37: Epidemiology of Drinking, Alcohol Use Disorders, and Related Problems in Us Ethnic Minority Groups;648
20.9.1;Introduction;648
20.9.2;Brief Historic Overview;648
20.9.3;What the Chapter will Cover;649
20.9.4;Drinking Among Whites, Blacks, and Hispanics;649
20.9.5;Alcohol Use Disorders and Other Problems Among Whites, Blacks, and Hispanics;652
20.9.6;Drinking, Alcohol Use Disorders, and Other Problems Among Hispanic National Groups;654
20.9.7;Drinking, Alcohol Use Disorders, and Other Problems Among Asian americans;657
20.9.8;Drinking, Alcohol Use Disorders, and Other Problems Among american Indians And alaska Natives;658
20.9.9;A Theory About Health Disparities: cumulative Adversities;660
20.9.10;Conclusions;661
20.9.11;References;662
20.10;Chapter 38: Alcohol and The law;668
20.10.1;Interventions to Reduce alcohol-related Consequences;668
20.10.2;Alcohol Taxes and Price Controls;669
20.10.3;Policies Targeting alcohol-impaired Driving;670
20.10.4;Restrictions on Alcohol Availability;671
20.10.5;Minimum Legal Drinking Age laws;671
20.10.6;Information and Education On alcohol use;671
20.10.7;Recovery-oriented Policy;672
20.10.8;Alcohol and Violence;672
20.10.9;Alcohol and Criminal Responsibility;672
20.10.10;Alcohol and Decision Making;673
20.10.11;Conclusion;674
20.10.12;Acknowledgment;674
20.10.13;References;674
20.11;Chapter 39: Clinical Management of Alcohol Use Disorders In the neurology clinic;678
20.11.1;Introduction;678
20.11.2;What Is sbirt?;679
20.11.3;What is the Evidence That Sbirt works?;679
20.11.4;Screening;679
20.11.5;Screening Results;681
20.11.6;Brief Intervention;681
20.11.6.1;Precontemplation stage;683
20.11.6.1.1;Goal: to Move the Patient Toward Thinking About Change;683
20.11.6.2;Contemplation stage;683
20.11.6.2.1;Goal: to Encourage the Patient to Examine the Benefits and Risks of Change;683
20.11.7;Referral to Treatment;683
20.11.8;Neurologic Medical Comorbidity;684
20.11.8.1;Physical Examination;684
20.11.8.2;Acute Presentations;685
20.11.8.3;Blood Alcohol Concentration;685
20.11.8.4;Alcohol Withdrawal;685
20.11.8.5;Wernicke-Korsakoff Syndrome;685
20.11.8.6;Pellagra;686
20.11.8.7;Blackouts (retrograde Amnesia);686
20.11.8.8;Central Pontine and Extrapontine Myelinolysis;686
20.11.8.9;Neuropathy;686
20.11.8.10;Cognitive Impairment;686
20.11.8.11;A Note About Alcohol Use as a Risk Factor For traumatic Brain Injury Or Recovery From Tbi;687
20.11.9;Conclusion;687
20.11.10;References;687
21;Index;690

Leseproben

Chapter 1 Alcoholism
diagnosis, prognosis, epidemiology, and burden of the disease
Thomas P. Beresford1,2,*; Narin Wongngamnit1,3; Benjamin A. Temple1    1 Department of Psychiatry, School of Medicine, University of Colorado, Denver, CO, USA
2 Laboratory for Clinical and Translational Research in Psychiatry, Department of Veterans Affairs, Denver, CO, USA
3 Substance Abuse Treatment Program, Department of Veterans Affairs, Denver, CO, USA
* Correspondence to: Thomas P. Beresford, M.D., 1055 Clermont Street (116), Denver, CO 80220, USA. Tel: + 1-303-399-8020; x 3732 email address: [e-mail] Abstract
To the clinician, alcoholism can appear as an amorphous entity that is confusing with respect to diagnosis, treatment prognosis, and the role of the health professional, despite its high incidence and associated morbidities and mortality when unrecognized or untreated. This chapter focuses on the clinical application of current knowledge, with the aim of being useful to the practitioner in working directly with patients for whom alcoholism may or may not be an already identified problem. It briefly reviews large-scale studies and then focuses on diagnosis and prognosis assessment and decision making. Also considered are current controversies in nomenclature and the chapter ends with an economic perspective with respect to healthcare and cost to society. As the introductory chapter, the goal is to provide a context of the scope of alcoholism and attendant problems for the rest of the chapters. Keywords alcoholism alcohol dependence alcohol abuse diagnosis prognosis economic burden Natural history and clinical assessment
Alcoholism frequency
Alcoholism, known clinically in its most severe form as alcohol dependence (ALD), and in early course forms as alcohol abuse, affects as many as 7–10% of persons in the United States (Vaillant, 1995). It directly affects nearly one in every three families in the United States and carries with it considerable negative social stigma. Those suffering from it often appear to reject any help from others, or even to ignore the presence of the condition itself, in their struggle to give up alcohol use. Population studies offer some useful background insights to the practicing clinician but, as often characteristic of large epidemiologic studies, may not translate well into the care of specific patients. For example, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) conducted a two-stage prevalence study, the National Epidemiologic Survey on Alcohol Related Conditions (NESARC), in 2001–2002 and 2004–2005 (Hasin et al., 2007). Criteria for ALD and alcohol abuse were borrowed from the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV, 1994: American Psychiatric Association, 1994) and its fourth edition text revision (DSM-IV-TR: American Psychiatric Association, 2000) published in 2000, with little difference between the two. The same study group retrospectively compared the results with an NESARC predecessor conducted in 1991–1992 before the publication of the DSM-IV, the National Longitudinal Alcohol Epidemiologic Survey (NLAES). Owing to differing methods used in the two studies by the same researchers, they cannot be considered strictly equivalent with respect to population estimates of alcoholism, but they approximate each other with sufficient similarity to offer prevalence comparison over time. For example, in the NLAES, the percentage of ALD Americans was 4.38 while alcohol abuse was 3.03. In the NESARC, the corresponding figures were 3.81 and 4.65. The combined percent point prevalence totals for ALD plus alcohol abuse are NLAES 7.41 and NESARC 8.46, suggesting an estimated increase in prevalence of problematic alcohol use in 1.5% of the population between the two surveys, from 1992 and 2005. According to the author's (TB) calculations from these frequency data, a prevalence increase of 1.5% translates to some 4.4 million Americans, allowing for the estimated increase in the US population itself over those years. If the same rate persists today, the estimated increase alone would be 5.9 million Americans. Added to the 2005 NESARC base of 25 million, this results in a total of nearly 31 million ALD or alcohol-abusing persons in the United States, or about 10% of the present population. The figures speak to the magnitude of the problem and we will discuss its economic implications further below. From another viewpoint, the Centers for Disease Control and Prevention (CDC) 2008–2010 National Health Interview Survey (NHIS) is another recent source of detailed alcohol epidemiology figures (Schoenborn et al., 2013). That survey found that rates of use, abuse, and dependence varied by age, gender, location, socioeconomic status, marital status, and ethnicity. The NHIS reports that only one-fifth of American adults are lifetime abstainers from alcohol use. However, many more women abstain than men (26.5% against 14.7%). Young Americans are more likely to drink than others. Also of note is the higher likelihood (35.1%) for adults aged 18–24 years than any other group to have had more than five drinks in one sitting some time in a year. White adults were more likely to drink than other groups: 67.8% versus 52.5% of Black adults and 48% of Asians. Interestingly, level of education was positively correlated with drinking. While 77.3% of those with graduate degrees were current drinkers, only 46.8% without high school diplomas were. Finally, the Midwest had the highest number of current drinkers at 68.6%, while the South had the fewest, with 61%. Practical typology
For the neurologist, psychiatrist, or other health professional, more practical, disease course-based characteristics of ALD appear more pertinent. The vast majority of ALD cases, for example, involve alcohol as the primary, and often only, drug of sustained, uncontrolled use. Research reports refer to this as primary ALD; it has accrued other synonyms such as type 1 (Cloninger et al., 1981), type A (Brown et al., 1994), or late-onset (Wetterling et al., 2003) alcoholism. By contrast, polydrug dependence – that is, addiction to two or more substances, not including nicotine, that may include alcohol as one of the dependence substances – affects about 0.5% of adults in the United States. Viewed from the perspective of alcoholism research, this group refers to type 2, type B, or early-onset alcoholism. Although the distinction between the two clinical groups with respect to their abstinence prognoses has been known for many years, many clinical programs fail to take this distinction into account. For example, liver transplant programs that separate the two types in follow-up studies demonstrate high rates of abstinence in the primary ALD group after transplant while those that do not make this distinction often report much lower abstinence rates (Lucey, 2007). Prior research on non-transplant samples demonstrates that the much more common primary ALD persons will enjoy a better prognosis than the polydrug-dependent group (Vaillant, 1995). Table 1.1 summarizes some of the characteristic differences between the two in brief form. Table 1.1 Characteristic differences between primary alcohol and polydrug dependence Primary alcohol dependence Polydrug dependence 7–10% US population 0.5% US population Alcohol primary dependence Polysubstance dependence Normal childhood Deprivation/abuse in childhood No conduct disorder Conduct disorder symptoms before age 15 Regular use: late teens, 20s Polydrug dependence: teens No characteristic personality diagnosis before addictive use Adult personality disorder diagnoses concurrent with use Natural remission: 30%/year Natural remission: 10%/year With treatment: 45%/year With treatment: 10%/year It is important to keep in perspective that alcoholism has been viewed in many model systems over many centuries, ranging from moral failing to medical illness, with many other models between. (See the lead author's Science Update installments on the website of the National Council on Alcoholism and Drug Dependence, beginning in November 2013, for a brief historic overview.) The present discussion refers to alcoholism in the disease model and as an illness that courses over decades, and rather than a few weeks, months, or even years. This occurs for two practical reasons: (1) it allows application of the methods of clinical science to a ubiquitous, and deadly, condition; and (2) it provides patients with an all-important sense of hope. Quoting one, “It is much easier to think of myself as an ill person trying to get better than as a bad person trying to become good.” Nonetheless, it is important to recall that other models provide useful discussions from other points of view with helpful contributions from time to time. Physicians have a particularly critical role to play in applying the principles of clinical science with...