The Etiology of Alcohol Use Disorders

1
The Etiology of Alcohol Use Disorders

• Kenneth J. Sher, Ph.D.
• Emily Grekin, Ph.D.
• University of Missouri-Columbia and the Midwest
  Alcoholism Research Center

2
Support of authors

• Research
• NIAAA (NIH)
• Professional Consulting/Reviewing
• NIH
• Approximately one dozen academic institutions and
  research centers
• Alcoholic Beverage Medical Research Foundation
• Joint Defense Group (alcohol industry sponsored
  legal defense)
• Investments
• No individual equity position in biotech or
  health-care related companies (either public or
  private)
• Mutual funds may, and often do, have positions in
  biotech and health care stocks

3
Topics to Be Reviewed

• Definitions of alcohol-related constructs
• Epidemiology of alcohol use, problems, and
  dependence
• Importance of life course and developmental
  perspectives
• Presumed etiological mechanisms
• Individual differences in susceptibility
• Environmental factors
• Towards an integrated perspective

4
Definitions of Alcohol-related Constructs

• Consumption-based measures
• Frequency, quantity, and Q-F
• Frequency of heavy drinking
• Problematic alcohol involvement
• Alcohol-related consequences
• Alcohol dependence syndrome
• DSM-IV alcohol use disorders
• Alcohol dependence
• Alcohol abuse

5
DSM-IV Dependence Criteria

• Tolerance
• Withdrawal
• Using in larger amounts/over a longer time period
  than intended
• Persistent desire to cut down/control
• Great deal of time spent obtaining/using/recoverin
  g
• Important activities given up/reduced
• Continued drinking despite physical/psychological
  problems that are caused/exacerbated by alcohol

6
DSM-IV Abuse Criteria

• Failure to fulfill major role obligations
• Recurrent use in physically hazardous situations
• Recurrent alcohol-related legal problems
• Continued drinking despite social/interpersonal
  problems that are caused/exacerbated by alcohol
• Criteria for alcohol dependence not met

7
Problems with the AUD Definitions

• Polythetic criteria
• Diagnostic orphans
• Diagnostic imposters
• Continuum or categories

8
Alcohol Use and AUDs in the Population

• Importance of epidemiologic data
• Framing the problem
• Providing etiological clues
• Data from NESARC (2002)
• Prevalence of use
• Prevalence of heavy drinking
• Prevalence of AUDs

9
Epidemiology of Use and Abstention
Percent
10
Epidemiology of Heavy Use
Heavy Use Women gt 1 drink / day
Men gt 2 drinks / day
Percent
11
12-mo. Prevalence of DSM-IV AUD Diagnoses
Men
Women
12
Epidemiological Context

• Alcohol use rapidly increases during adolescence,
  peaking in the early-mid 20s
• AUDs show roughly a similar pattern
• Implications
• Etiological theory needs to address the
  developmental processes that can help explain
  this strong, age-graded phenomenon
• Processes responsible for desistence (offset) are
  important for understanding the population
  prevalence and persistence

13
Meta-models of AUD Etiology

• Pharmacological Vulnerability
• Affect Regulation
• Negative affect regulation (self-medication)
• Positive affect regulation (reward seeking)
• Deviance/Disinhibition

14
Meta-models of AUD Etiology

• Pharmacological Vulnerability
• Affect Regulation
• Negative affect regulation (self-medication)
• Positive affect regulation (reward seeking)
• Deviance/Disinhibition

15
Pharmacological Vulnerability

• Premise Individual differences in alcohol
  effects are related to risk for developing AUDs
• Insensitivity/tolerance to punishing effects
• Insensitivity/tolerance to reinforcing effects
• Sensitivity to reinforcing effects
• Sensitivity to disinhibition

16
Pharmacological Vulnerability Insensitivity to
Punishing Effects

• Alcohol-related flushing and its relation to
  drinking rates and AUDs
• ADH polymorphisms
• ALDH polymorphisms
• Other forms of alcohol-related punishment
• Headaches and other symptoms?
• Hangover?

17
Pharmacological Vulnerability Insensitivity to
Reinforcement

• Low sensitivity and risk for alcoholism
• Laboratory findings
• Prospective findings
• Question of type of effect
• Reinforcement or punishment?
• Question of BAC Limb
• Findings generalized or specific to descending
  limb?

18
Pharmacological Vulnerability Sensitivity to
Reinforcement

• Positive Reinforcement
• Increased arousal
• Negative Reinforcement
• Stress response dampening
• Other measures of effect of alcohol on mood and
  emotion

19
Pharmacological Vulnerability Sensitivity to
Disinhibition

• Alcohol impairs inhibitory responses
• On motor tasks (e.g., go/no-go)
• On provoked aggression tasks (e.g., TAP, point
  subtraction task)
• Possible mechanism disruption of executive
  functioning
• Baseline executive functioning may moderate
  alcohol/aggression relationship

20
Pharmacological Vulnerability Rapprochement
21
Meta-models of AUD Etiology

• Pharmacological Vulnerability
• Affect Regulation
• Negative affect regulation (self-medication)
• Positive affect regulation (reward seeking)
• Deviance/Disinhibition

22
Affect RegulationNegative Mood Regulation

• Premise Alcohol relieves negative moods
• Evidence for
• Anxiolytic effects of ethanol in some lab models
• Coping motives and tension reduction
  expectancies and their relation to drinking
• Studies of stress induced drinking
• Diary studies of drinking and stress/emotions
• High comorbidity between anxiety and mood
  disorders and AUDs
• Correlation between negative affectivity/neurotici
  sm and drinking problems

23
Affect RegulationNegative Mood Regulation

• Evidence against
• Weak correlation between Q-F measures and mood
  states
• Not all lab preparations demonstrate
  antidepressant or anxiolytic effects
• Complexities
• Dose dependency
• Effects of chronic alcohol consumption on
  affective toneallostasis
• Range of emotion-regulation strategies available

24
Affect RegulationNegative Mood Regulation

• Alcohol can help regulate negative moods and
  emotions but
• Not for all people
• Not at all doses
• Not in all situations
• Protracted heavy consumption may lead to mood
  dysregulationregardless of original motivation

25
Affect RegulationPositive Mood Regulation

• Premise Alcohol increases positive moods
• Evidence for
• Low-moderate doses increase reports of
  stimulation and euphoriaat least early in the
  course of intoxication
• Enhancement motives and generalized
  expectancies for alcohol as a positively
  transforming substance are commonly endorsed
  correlate with both consumption and problems
• Reward seeking (e.g., novelty seeking) is a
  strong correlate of alcohol consumption

26

• Premise Alcohol increases positive moods
• Complexities
• Alcohol effects seem to be somewhat context
  dependent (e.g., effects are dose- dependent,
  person-dependent, subject to tolerance, etc.)
• Descending limb effects are typically not
  positively reinforcing

27
Meta-models of AUD Etiology

• Pharmacological Vulnerability
• Affect Regulation
• Negative affect regulation (self-medication)
• Positive affect regulation (reward seeking)
• Deviance/Disinhibition

28
Deviance/Disinhibition

• Premise Pathological alcohol use is just a facet
  of a larger syndrome of externalizing behavior
• Evidence for
• Abundance of psychometric work showing that
  alcohol involvement is associated with a wide
  range of other problem behaviors
• Personality traits associated with disinhibition
  a strong correlate of AUDs
• Behavior-genetic studies show a strong genetic
  correlation between AUDs and other forms of
  externalizing behavior

29
Deviance/Disinhibition


30
Deviance/Disinhibition
31
Deviance/Disinhibition

• Evidence against
• No real evidence against but not all individuals
  suffering from AUDs have an externalizing
  symptom pictureclearly doesnt explain all cases
  of AUDs
• Complexities
• Externalizing behavior can be a determinant as
  well as a consequence of alcohol involvement
• Acutely
• Chronically

32
Etiological Processes

• Multiple etiological processes likely operating
• Pharmacological vulnerability
• Affect regulation
• Deviance proneness/Disinhibition
• These processes are likely overlapping
• Suggest multiple opportunities for prevention and
  treatment

33
Risk at the Individual Level

• Individual difference variables bias individuals
  towards different etiological processes
• Family history
• Personality
• Comorbid psychopathology
• Alcohol expectancies and drinking motives

34
Risk at the Individual Level Family History of
Alcoholism

• Family history of alcoholism represents one of
  the best established risk factors for alcohol
  dependence
• Genetic epidemiological studies indicate a
  substantial role of heredity
• Several specific genes appear to convey risk for
  alcohol dependence

35
Risk at the Individual Level Personality

• Two broad personality traits appear to be related
  to risk for AUDs
• Traits related to disinhibition/behavioral
  undercontrol
• Traits related to neuroticism/negative
  emotionality
• Traits demonstrated to be important prospectively
  and to mediate some degree of genetic risk

36
Risk at the Individual Level Personality
37
Risk at the Individual Level Comorbid
Psychopathology

• A wide range of childhood and adult disorders
  associated with risk for alcohol dependence
• Childhood and adolescent disorders
• ADHD
• Conduct Disorder
• Mood Disorders

38
Risk at the Individual Level Comorbid
Psychopathology

• Adult disorders
• Anxiety Disorders
• Depression
• Bipolar Disorder
• Substance Use Disorders
• The special case of tobacco dependence

39
Comorbid Disorders in Individuals with
DSM-III-R Alcohol Dependence
Kessler et al, 1997
40
Risk at the Individual Level Drinking
Motivation

• Drinking motives and alcohol outcome expectancies
  are potent predictors of alcohol involvement
• Alcohol outcome expectancies
• Beliefs individuals hold concerning the expected
  outcomes of drinking
• Drinking motives
• Reasons individuals give for drinking

41
Risk at the Individual Level Drinking
Motivation

• Domains of alcohol outcome expectancies

42
Risk at the Individual Level Drinking
Motivation

• Domains of drinking motives

43
Risk at the Individual Level Drinking
Motivation

• These motivational constructs differentially
  relate to drinking outcomes in complex ways
• Enhancement motives
• Associated with externalizing traits and predicts
  problem drinking only through consumption
• Coping motives
• Associated with negative affectivity and predicts
  problem drinking above and beyond its association
  with consumption

44
Risk at the Individual Level Drinking
Motivation

• These types of constructs may provide important
  mediational links between dispositional variables
  and actual drinking behavior
• Expectancies change dynamically, even prior to
  drinking, and may represent an important
  modifiable risk factor

45
Risk at the Environmental Level

• Prenatal exposures
• Rearing environment/Parenting
• Modeling of use
• Monitoring
• Nurturance/warmth
• Abuse and neglect
• Peer environment
• Life events
• Alcohol advertising
• Policy surrounding sales and intoxicated behavior
• Culture

46
Risk at the Environmental Level Some Conceptual
Issues

• Environment is a multifaceted domain
• Biological environment
• Interpersonal environment
• Policy environment
• Cultural environment
• Individuals seek out and create their own
  environments
• E.g., Greek organizations on college campuses

47
Risk at the Environmental Level Some Conceptual
Issues

• Person X Environment Interactionism
• G x E
• More general cases of interactions with
  environment
• Distal Environment vs. Proximal Environment
• Effects on traits
• Effects on behavioral expression

48
Towards an Integrated Etiological Perspective

• Etiological analyses can be conducted at multiple
  levels of analysis
• Etiological pathways can be conceptualized that
  link molecular processes (e.g., receptor
  sensitivity, gene expression) to alcohol seeking
  but
• Numerous instigating and inhibitory processes
  need to be considered

49
Towards an Integrated Etiological Perspective
(contd)

• Etiological mechanisms can be organizing
  principles for understanding the function of
  specific risk factors
• Etiological heterogeneity ?
• Wide ranging correlates
• Heterogeneity in syndrome and course?
• Multiple opportunities for prevention and
  treatment