Denis McCarthy - US grants

The proposed study intends to test a model of risk for alcoholism that integrates disinhibited personality with social learning factors. Previous work has focused heavily on risk in men, with an attendant focus on sociopathic traits more prevalent in men. Some research with men has identified a personality characteristic, neurotic extroversion (NE) to related to disinhibition: experimental tests have shown this personality style to predict reward-focused responding with less attention to punishment. The study will test this model: NE leads to disinhibition, as measured by disinhibited task performance. Problem drinking becomes likely when this disinhibited style combines with specific learning about alcohol in the form of high positive expectancies for alcohol's effects. NE and expectancy will each have incremental validity in predicting drinking, expectancy will meditate the influence of NE on drinking, and level of NE may moderate the demonstrated expectancy-drinking relationship.

APPLICANT'S ABSTRACT: Cognitions regarding drinking and driving have been shown to be predictive of drinking and driving behavior in adolescents. However, no studies have assessed these variables in adolescents who have not begun to drive. As cognitions about a behavior form prior to engaging in that behavior, measuring cognitions of non-driving adolescents can be a crucial step in improving our understanding of how these cognitions develop. The proposed project will explore relationships among a variety of cognitions about drinking, driving, and drinking and driving, behavior. Data will be collected from two samples of adolescents - one of licensed drivers, and one of adolescents who have not obtained a drivers' license. The non-licensed group is hypothesized to have more negative cognitions concerning drinking and driving, and more positive cognitions about alternatives to drinking and driving. A model of the relationships among these cognitive risk variables and their relationship with drinking and driving behavior will be estimated. Finally, mediating and moderating models will also be tested. This research is intended to provide data critical to the theoretical model of the role of cognitions on drinking and driving, and to lay the groundwork for a larger program of research to track changes in these cognitions longitudinally. Improving our understanding of the development of these cognitive risk variables can have important implications for prevention and intervention programs, particularly for programs focused on drivers-in-training.

DESCRIPTION (provided by applicant): Polymorphisms of alcohol metabolizing enzymes (ADH, ALDH) have been found to influence risk for alcohol dependence and heavy alcohol consumption. These polymorphisms are thought to influence alcohol behavior by altering the metabolism of alcohol, and influencing individual differences in alcohol response. Genetic variants in ADH and ALDH alleles occur at different rates in different ethnic groups. ADH/1B*3 alleles have been identified only in individuals of African decent and some Native American groups. In Native Americans, ADH1B*3 alleles have been found to protect against alcohol dependence. In African Americans, these alleles are negatively associated with family history of alcoholism, and protect against alcohol-related birth defects. The proposed project will test the role of ADH1B*3 alleles in the alcohol dependence risk process in African Americans. It is hypothesized that ADH1B*3 protects against alcohol dependence by influencing level of response to alcohol, and by influencing alcohol-related learning. One-hundred and thirty African American participants will be recruited for an alcohol challenge study. Participants will be genotyped for ADH1B, as well as additional ADH/ALDH polymorphisms. This sample size should be sufficient to obtain approximately 30 participants with ADH1B*3 alleles. Data on alcohol use, alcohol abuse/dependence symptoms, alcohol expectancies, family history of alcoholism and exposure to alcohol modeling in the family environment will be collected prior to the alcohol challenge visit. The proposed project has four principal aims. One is to test whether ADH1B*3 alleles are associated with increased response to alcohol in African Americans. Second, to test whether those with ADH1B*3 alleles differ in their alcohol expectancies. We will also test whether differences in expectancies are a function of differences in alcohol response and/or familial models of alcohol use. Finally, a mediation model will be tested, hypothesizing that the protective effect of ADH1B*3 alleles on alcoholism risk is mediated by differences in alcohol expectancies.

DESCRIPTION (provided by applicant): Driving after consuming alcohol continues to be a major public health problem, particularly for young adults, who report the highest rates of drinking and driving. Although changes in policy (minimum legal drinking age; per se laws) have been successful in reducing drinking and driving, individual difference factors predispose certain people to drive after drinking. Research clearly demonstrates that impulsivity is one such individual difference factor. However, to date the influence of impulsivity on drinking and driving has primarily been examined using questionnaire measures of impulsive personality traits. No previous study has examined individual differences in acute alcohol effects on behavioral measures of impulsivity and their association with drinking and driving behavior. The proposed project will test a model of drinking and driving as influenced by the acute effect of alcohol on two impulsivity constructs: behavioral inhibition (i.e., the ability to inhibit/suppress behavior) and impulsive decision making (i.e., the ability to make decisions in accordance with time and probability contingencies). Participants will be drawn from an ongoing longitudinal study (PI: Kenneth Sher, R37 AA07231) based on the longitudinal course of their drinking and driving behavior. All participants will complete multiple behavioral measures of impulsivity in two laboratory sessions (alcohol, no beverage control), as well as a 3 month follow-up assessment of their drinking and driving behavior and risk variables specific to drinking and driving. The proposed project has three specific aims: 1) Test the association of sober and intoxicated impulsivity with engagement in and persistence of drinking and driving. 2) Test how the effect of alcohol on impulsivity is moderated by other risk factors for alcohol use. 3) Test the interaction between impulsivity and risk factors specific to drinking and driving in determining drinking and driving behavior. Results of the proposed project can advance drinking and driving theory, research, and intervention by delineating the role of intoxicated impulsivity in drinking and driving decisions. PUBLIC HEALTH RELEVANCE: The proposed project is a laboratory study designed to test impulsivity following alcohol use and risk for drinking and driving. Greater impulsivity while intoxicated can increase the chance an individual would chose to drive, despite knowing the risks or even after experiencing negative consequences (e.g., arrest). Results of the project can help improve intervention and treatment strategies for drinking and driving, which may benefit from supplementing drinking and driving education with training to reduce impulsivity or increase self-regulation.

Project Summary Despite previous success in reducing alcohol impaired driving (AID), rates of alcohol-related motor vehicle crashes have not decreased significantly since the 1990s. Developing novel approaches to prevention/intervention is likely required to produce further progress. Building on laboratory findings from the original project (Acute Alcohol Effects on Impulsivity and Risk for Drinking and Driving), the proposed project is designed to bring this work out of the lab and into the natural drinking environment in which AID decisions are made. Participants will complete a laboratory alcohol administration session followed by six weeks of multi-method ambulatory assessment. The ambulatory assessment component will include participant report via smartphone, transdermal alcohol concentration (TAC) using the BACtrack biosensor, and location and movement data passively collected by the smartphone GPS/accelerometer. The combination of these methods will allow for the integration of subjective (e.g., perceived intoxication) and objective (e.g., TAC, calculated drinking location) data for each drinking episode. Aim 1 of the project is to test laboratory measures as prospective predictors of AID and examine the role of event-level influences on specific AID decisions. Aim 2 of the proposed project is to test the potential for a novel intervention to reduce AID using mobile technology. Participants will be randomly assigned to either a full ambulatory assessment or a minimal assessment control condition. The timing of the introduction of AA will also be manipulated within the full ambulatory assessment condition. This design will allow us to test whether the introduction of ambulatory assessment produces changes in AID behavior, as well as whether such changes persist once ambulatory assessment is discontinued. Changes made to the revised application are aimed at ensuring the achievement of both study aims. If Aim 2 is achieved and ambulatory assessment alters AID behavior, the combination of the minimal assessment control condition and the full assessment condition prior to the introduction of ambulatory assessment has sufficient sample size and power to test Aim 1 hypotheses.

This application proposes to continue, refine, and disseminate a nine week summer research program in alcohol and addiction research. The program, the ?MU Alcohol Research Training Summer School? (MU- ARTSS) at the University of Missouri, is targeted at undergraduate students with the goal of preparing trainees for graduate training in health-related scientific disciplines focusing on alcohol and addiction research. The program recruit seven students annually, drawn from a national pool of applicants, and with a major emphasis on recruiting students from under-represented groups in STEM and biomedical disciplines (i.e., ethnic and racial minority, economically disadvantaged, and first-generation college students). The MU-ARTSS program consists of a one-week intensive set of didactic lectures on alcohol research. Didactic topics include: introduction to and overview of addiction research, epidemiology, genetics, neuropharmacology, neurophysiology, individual differences, assessment and treatment, responsible conduct of research, and human subjects issues. In addition, trainees will attend laboratory demonstrations of addiction-relevant research protocols, including mobile and ambulatory assessment, structural and functional neuroimaging, and laboratory administration of alcohol to human subjects. Following this week of didactics, students will complete an eight-week internship in the lab of a mentor conducting alcohol research. Through the internship period, MU-ARTSS trainees will attend a weekly seminar series covering specific research skills and professional development issues. A weekly ?movie night? will be hosted by the program Co-Director, and will showcase notable films about alcohol spanning more than 80 years of film history, allowing for less-formal discussion and exploration of clinical phenomena related to alcohol and addiction, and the role and portrayal of alcohol in society. The MU-ARTSS program will be supplemented by additional training programs and experiences offered by the MU-Summer Research Internship Program (MU-SRIP). Partnering with MU-SRIP affords our trainees an opportunity to interact with research faculty and students across multiple scientific disciplines and in multiple venues including a Professional Development series, further instruction in the responsible conduct of research, a lecture series, and a formal end-of-the-program poster session. The program draws on the large number of active alcohol research programs in MU?s Department of Psychological Sciences. The focus of MU- ARTSS on undergraduate education also provides an important complement to the alcohol training emphasis at the graduate and postdoctoral levels (currently supported, in part, by a T32 to Co-Director Sher). To date, 12 MU-ARTSS interns have completed their undergraduate degrees, and of these, 7 are enrolled in Ph.D. programs, 1 in an M.D. program, and 2 in Master's programs, all in STEM fields. Based on these initial successes, the current proposal aims to continue refining MU-ARTSS recruitment and curriculum activities, and importantly, begin disseminating materials and outcome data produced by the program.

High levels of alcohol consumption clearly place individuals at great risk and present a significant health and economic burden to society. Emerging evidence indicates that many young adults engage in what can be called extreme drinking (i.e., drinking at levels likely to lead to BACs > .16). Despite recent attention to extreme drinking5,6, we know surprisingly little about this behavior beyond associations revealed by cross?sectional studies that rely exclusively on retrospective self?report. The proposed study is designed to provide some of the first comprehensive data about influences on the extreme drinking phenotype, and to compare these with those identified for the typical binge drinking phenotype. Whether there are unique causes and correlates of extreme drinking (compared to binge drinking) is an empirical question that has not been tested. There are challenges to investigating extreme drinking, including 1) overcoming the limitations of retrospective self?report, 2) adequately measuring personological and environmental influences, and 3) capturing the temporal associations of these diverse influences and their impact on extreme drinking occasions. The proposed project is designed to meet these challenges using a combination of laboratory, genetic, and ecological momentary assessment (EMA) methods. Our multi?method approach will combine laboratory alcohol administration, EMA, and real?time BAC assessment to capture the interplay between a broad range of potential influences on extreme drinking, extend our investigation outside the lab and into the natural drinking environment, and explore the temporal associations of influences on extreme drinking. We focus on four core constructs central to current theoretical models of addiction that are hypothesized to influence substance use through in?the?moment processes: reward sensitivity (RS), incentive salience (IS), impulsivity/loss of control (Imp), and negative affectivity (NA). We will recruit a sample of 400 young adults (ages 21?29), ascertained from a statewide DMV database, who have a recent legal action with a recorded BAC consistent with extreme drinking (? .12). Using a longitudinal burst design, we will follow participants over a 12?month period, with five self?report assessments and four, two?week EMA bursts. A baseline laboratory session will assess behavioral, trait, and electrophysiological markers of core study constructs. We aim to (1) Evaluate the validity and utility of real?time assessments for identifying extreme drinking and alcohol?related behavior. This aim could inform estimation methods for characterizing extreme drinking and guide refinement of definitions of problematic drinking profiles. (2) Characterize the structural influence of stable individual differences, transient intra?individual factors, and environmental variables on risky, binge, and extreme drinking occasions and alcohol?related negative consequences. This aim will reveal the incremental validity of state (EMA) and trait (lab; baseline questionnaires; polygenic risk scores [PRSs] when applicable) indices of core study constructs in predicting extreme drinking occasions within and between individuals; as well as test their interaction with specific contextual factors to predict extreme drinking behavior. (3) Identify multidimensional profiles associated with stable or highly variable binge and extreme drinking behavior. Our longitudinal burst design allows us to test hypotheses about the stability of drinking behavior over time.