Adverse effects of excessive drinking are widespread in terms of the increased health care, loss of productivity, crime, accidents, and myriad emotional and personal costs. Understanding the factors that contribute to the development and persistence of excessive alcohol consumption is crucial for improved prevention, education and intervention strategies. The goal of our study is to evaluate the role of subjective and physiologic responses to alcohol in the escalation and maintenance of excessive drinking in adults. Our paradigm integrates human laboratory alcohol challenge with longitudinal assessment of drinking and related behaviors to discern whether alcohol responses predict future drinking problems in young heavy drinkers versus light drinker controls. In the last award phase, we also provided an initial laboratory re-examination of alcohol responses 5 years after initial testing to determine the stability or change in alcohol responses over time and how they relate to drinking behaviors. Thus far, findings from our carefully designed laboratory and intermediate-term follow-up investigation has advanced new discoveries and challenged existing paradigms. Compared with light drinkers, heavy social drinkers have greater sensitivity to alcohol's stimulating and rewarding (liking, wanting) effects and lower sensitivity to sedative effects. These effects predicted future binge drinking through six years of follow-up. As the sample is now aging to their thirties, a developmental period when binge drinking is less normative, we now propose several extensions of the longitudinal aspects of the study.
In Aim 1, we will extend follow-up during early middle adulthood in our existing cohorts (n=290) to discern binge drinking severity, alcohol use disorder symptoms, and drinking consequences during this transitional phase and evaluate the role of early-adult stimulating, rewarding, and sedating alcohol responses in predicting these behaviors.
In Aim 2, we will conduct a second re-examination testing of alcohol response one decade after initial testing. This will enable full direct and longitudinal tests of incentive-sensitization, reward sensitivity and low response models of the development of addictive behavior.
In Aim 3, we propose to conduct alcohol challenge testing in a new cohort of persons with alcohol dependence who are not seeking treatment (n=104) and compare them to existing heavy and light drinker cohorts (n=290). The information from this translational laboratory and longitudinal investigation will provide an evidence-based test of the role of alcohol response to escalations and maintenance of excessive drinking. Results have already advanced our knowledge of how alcohol responses predict future course of drinking, and the proposed extensions and new directions will further elucidate new empirical insights into the propensity for excessive and harmful drinking.

Public Health Relevance

Understanding the factors contributing to development and persistence of excessive alcohol consumption is crucial for improved prevention, education and intervention strategies. Our unique integration of human laboratory alcohol challenge and longitudinal assessment of drinking behaviors and consequences over time will provide critical tests of the prospective role of stimulating, rewarding, and sedating alcohol responses to escalations and maintenance of excessive drinking.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Risk, Prevention and Intervention for Addictions Study Section (RPIA)
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Matochik, John A
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University of Chicago
Schools of Medicine
United States
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Rueger, Sandra Y; Hu, Hongxing; McNamara, Patrick et al. (2015) Differences in subjective response to alcohol in heavy- and light-drinking Chinese men versus Caucasian American men. Addiction 110:91-9
King, Andrea C; McNamara, Patrick J; Hasin, Deborah S et al. (2014) Alcohol challenge responses predict future alcohol use disorder symptoms: a 6-year prospective study. Biol Psychiatry 75:798-806
Roche, Daniel J O; Palmeri, Michael D; King, Andrea C (2014) Acute alcohol response phenotype in heavy social drinkers is robust and reproducible. Alcohol Clin Exp Res 38:844-52
Rueger, Sandra Y; King, Andrea C (2013) Validation of the brief Biphasic Alcohol Effects Scale (B-BAES). Alcohol Clin Exp Res 37:470-6
Sivasithamparam, Janani; Visk, Carly A; Cohen, Ezra E W et al. (2013) Modifiable risk behaviors in patients with head and neck cancer. Cancer 119:2419-26
Morean, Meghan E; de Wit, Harriet; King, Andrea C et al. (2013) The drug effects questionnaire: psychometric support across three drug types. Psychopharmacology (Berl) 227:177-92
Childs, Emma; Roche, Daniel J O; King, Andrea C et al. (2012) Varenicline potentiates alcohol-induced negative subjective responses and offsets impaired eye movements. Alcohol Clin Exp Res 36:906-14
King, Andrea C; de Wit, Harriet; McNamara, Patrick J et al. (2011) Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking. Arch Gen Psychiatry 68:389-99
Sripada, Chandra Sekhar; Angstadt, Mike; McNamara, Patrick et al. (2011) Effects of alcohol on brain responses to social signals of threat in humans. Neuroimage 55:371-80
King, Andrea; McNamara, Patrick; Angstadt, Michael et al. (2010) Neural substrates of alcohol-induced smoking urge in heavy drinking nondaily smokers. Neuropsychopharmacology 35:692-701

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