Article

King AC, de Wit H, McNamara PJ, Cao D. Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking. Arch Gen Psychiatry. 68: 389-399

Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL 60637, USA.
Archives of general psychiatry (Impact Factor: 14.48). 04/2011; 68(4):389-99. DOI: 10.1001/archgenpsychiatry.2011.26
Source: PubMed

ABSTRACT

Excessive consumption of alcohol is a major problem in the United States and abroad. Despite many years of study, it is unclear why some individuals drink alcohol excessively while others do not. It has been postulated that either lower or greater acute responses to alcohol, or both, depending on the limb of the breath alcohol concentration curve, contribute to propensity for alcohol misuse.
To prospectively assess the relationship of acute alcohol responses to future binge drinking.
Within-subject, double-blind, placebo-controlled, multidose laboratory alcohol challenge study with intensive follow-up. Each participant completed 3 randomized sessions examining responses to a high (0.8 g/kg) and low (0.4 g/kg) alcohol dose and placebo, followed by quarterly assessments for 2 years examining drinking behaviors and alcohol diagnoses.
Participants recruited from the community.
High-risk heavy social drinkers aged 21 to 35 years who habitually engage in weekly binge drinking (n = 104) and light drinker controls (n = 86).
We conducted 570 laboratory sessions with a subsequent 99.1% follow-up (1506 of 1520).
Biphasic Alcohol Effects Scale, Drug Effects Questionnaire, cortisol response, Timeline Follow-Back, Drinker Inventory of Consequences-Recent, and DSM-IV alcohol abuse and dependence.
Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers. Among the heavy drinkers, greater positive effects and lower sedative effects after alcohol consumption predicted increased binge drinking frequency during follow-up. In turn, greater frequency of binge drinking during follow-up was associated with greater likelihood of meeting diagnostic criteria for alcohol abuse and dependence.
The widely held low level response theory and differentiator model should be revised: in high-risk drinkers, stimulant and rewarding alcohol responses even at peak breath alcohol concentrations are important predictors of future alcohol problems.
clinicaltrials.gov Identifier: NCT00961792.

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    • "Several lines of evidence support this conclusion . First, trajectories of subjective response over time as a function of ASQ scores (Figs 1–3) showed that higher ASQ-Light scores were associated with greater stimulation, consistent with modified differentiator model predictions (King et al., 2011 ), whereas higher ASQ-Heavy scores predicted lower sedation and subjective intoxication ratings. Second, in models directly comparing the predictive utility of the ASQ and SRE, the ASQ afforded the best prediction of both stimulation and sedation. "
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    ABSTRACT: Background: Variability in sensitivity to the acute effects of alcohol is an important risk factor for the development of alcohol use disorder (AUD). The most commonly used retrospective self-report measure of sensitivity, the Self-Rating of the Effects of Alcohol form (SRE), queries a limited number of alcohol effects and relies on respondents’ ability to recall experiences that might have occurred in the distant past. Here, we investigated the construct validity of an alternative measure that queries a larger number of alcohol effects, the Alcohol Sensitivity Questionnaire (ASQ), and compared it to the SRE in predicting momentary subjective responses to an acute dose of alcohol. Method: Healthy young adults (N = 423) completed the SRE and the ASQ and then were randomly assigned to consume either alcohol or a placebo beverage (between-subjects manipulation). Stimulation and sedation (Biphasic Alcohol Effects Scale) and subjective intoxication were measured multiple times after drinking. Results: Hierarchical linear models showed that the ASQ reliably predicted each of these outcomes following alcohol but not placebo consumption, provided unique prediction beyond that associated with differences in recent alcohol involvement, and was preferred over the SRE (in terms of model fit) in direct model comparisons of stimulation and sedation. Conclusions: The ASQ compared favorably with the better-known SRE in predicting increased stimulation and reduced sedation following an acute alcohol challenge. The ASQ appears to be a valid self-report measure of alcohol sensitivity and therefore holds promise for identifying individuals at-risk for AUD and related problems. Key Words: Alcohol Sensitivity, Level of Response, Subjective Alcohol Effects, Alcohol Challenge, Model Comparison.
    Full-text · Article · Jan 2016 · Alcoholism Clinical and Experimental Research
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    • "Several lines of evidence support this 22 conclusion. First, trajectories of subjective response over time as a function of ASQ scores (seeFigures 1-3) showed that higher ASQ-Light scores were associated with greater stimulation, 1 consistent with modified differentiator model predictions (King et al., 2011), whereas higher 2 ASQ-Heavy scores predicted lower sedation and subjective intoxication ratings. Second, in 3 models directly comparing the predictive utility of the ASQ and SRE, the ASQ afforded the best 4 prediction of both stimulation and sedation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Variability in sensitivity to the acute effects of alcohol is an important risk factor for the development of alcohol use disorder (AUD). The most commonly used retrospective self-report measure of sensitivity, the Self-Rating of the Effects of Alcohol form (SRE), queries a limited number of alcohol effects and relies on respondents’ ability to recall experiences that might have occurred in the distant past. Here, we investigated the construct validity of an alternative measure that queries a larger number of alcohol effects, the Alcohol Sensitivity Questionnaire (ASQ), and compared it to the SRE in predicting momentary subjective responses to an acute dose of alcohol. Method. Healthy young adults (N = 423) completed the SRE and the ASQ and then were randomly assigned to consume either alcohol or a placebo beverage (between-subjects manipulation). Stimulation and sedation (Biphasic Alcohol Effects Scale) and subjective intoxication were measured multiple times after drinking. Results. Hierarchical linear models showed that the ASQ reliably predicted each of these outcomes following alcohol but not placebo consumption, provided unique prediction beyond that associated with differences in recent alcohol involvement, and was preferred over the SRE (in terms of model fit) in direct model comparisons of stimulation and sedation. Conclusions. The ASQ compared favorably with the better-known SRE in predicting increased stimulation and reduced sedation following an acute alcohol challenge. The ASQ appears to be a valid self-report measure of alcohol sensitivity and therefore holds promise for identifying individuals at-risk for AUD and related problems.
    Full-text · Article · Jan 2016 · Alcoholism Clinical and Experimental Research
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    • "However, it was not until recently that a large longitudinal study established the predictive utility of alcohol-induced stimulation and sedation as measured with the BAES during a controlled and blinded oral alcohol challenge with regard to the propensity for heavy drinking and alcohol problems (King et al., 2011, 2014). Specifically, this landmark study demonstrated that individuals who engaged in regular, binge-drinking behavior experienced greater stimulant/pleasant effects during the rising BAC limb than light drinkers, and this heightened alcohol stimulation and reward sensitivity robustly predicted more alcohol use disorder symptoms over time and was associated with greater binge-drinking frequency at 2-(King et al., 2011) and 6-year follow-ups (King et al., 2014). Additionally, heavy drinkers reported lower sensitivity to the sedative effects of alcohol across the duration of BAC, which in turn was also associated with a higher number of alcohol use disorder symptoms at 2-and 6-year follow-ups (King et al., 2014). "
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    ABSTRACT: Background: Individual differences in the subjective experience of the pharmacological effects of alcohol have long been implicated in the likelihood that one will drink heavily and develop alcoholism. The theme of this conceptual review and perspective article is to synthesize the literature on subjective responses to alcohol and to set an agenda for the next generation of research in the area. Specifically, we contend that in order for subjective response to alcohol to play a prominent role in alcoholism research, it is critical that it be studied as a multimodal phenotype. Methods: First, we review the human research on subjective response to alcohol measured under controlled laboratory conditions and draw recommendations for the application of these findings to understanding alcoholism neurobiology in humans. Second, we highlight multimodal approaches, including studies of the genetic and neural substrates of individual differences in subjective response to alcohol. Third, we review treatment implications with a focus on subjective response to alcohol as an intervention target. Upon review of the research on subjective response to alcohol across levels of analyses, we provide recommendations for leveraging these phenotypes in a systematic and methodologically rigorous fashion that can address central questions about alcoholism etiology, disease progression, and personalized treatment. Discussion: The approach recommended herein is largely consistent with the Research Domain Criteria (RDoC) initiative across the National Institute of Mental Health. The defining feature of such domains is that they inform behavior yet be amenable to examination through multiple units of analysis, such as molecular, genetic, circuit-level, and behavioral measurements. To that end, we contend that subjective response to alcohol represents a behaviorally and biologically plausible phenotype upon which to build using the RDoC framework for understanding alcohol use disorder.
    Full-text · Article · Jan 2016 · Alcoholism Clinical and Experimental Research
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