Subjective Responses to Alcohol Consumption as Endophenotypes: Advancing Behavioral Genetics in Etiological and Treatment Models of Alcoholism

Abstract

Individual differences in subjective responses to alcohol consumption represent genetically mediated biobehavioral mechanisms of alcoholism risk (i.e., endophenotype). The objective of this review is three-fold: (1) to provide a critical review the literature on subjective response to alcohol and to discuss the rationale for its conceptualization as an endophenotype for alcoholism; (2) to examine the literature on the neurobiological substrates and associated genetic factors subserving individual differences in subjective response to alcohol; and (3) to discuss the treatment implications of this approach and to propose a framework for conceptualizing, and systematically integrating, endophenotypes into alcoholism treatment.

Keywords :

• alcohol
• subjective responses
• endophenotypes
• genetics
• pharmacogenetics
• behavioral marker
• craving
• alcoholism

THE AUTHORS

Lara A. Ray, Ph.D., is an assistant professor in the Department of Psychology at the University of California Los Angeles (UCLA). She received her doctorate in Clinical Psychology from the University of Colorado at Boulder and completed her clinical internship and fellowship at Brown University. Dr. Ray has received interdisciplinary training in behavioral genetics and her research focuses on the integration of clinical and experimental psychology, pharmacology, and behavioral genetics of addiction.

James MacKillop, Ph.D., is an assistant professor in the Department of Psychology at the University of Georgia. He conducts a program of research studying the determinants of addictive behavior using modern learning theory. This work emphasizes using behavioral economics to study addiction and the integration of genetic variables into behavioral approaches to addiction. Dr. MacKillop received a Ph.D. in clinical psychology from the State University of New York at Binghamton, completing a predoctoral clinical internship at the Brown University Training Consortium. He subsequently completed an NIAAA T32 postdoctoral fellowship in addictions research at Brown's Center for Alcohol and Addiction Studies and was a faculty member at the Center prior to joining the UGA faculty.

Peter M. Monti, Ph.D. Dr. Peter Monti is Donald G. Millar Distinguished Professor of Alcohol and Addiction Studies and Director, Center for Alcohol and Addiction Studies at Brown University. He is also a senior career research scientist for the Department of Veterans Affairs. A recognized leader in understanding the biobehavioral mechanisms that underlie addictive behavior as well as its prevention and treatment, Dr. Monti has published nearly 250 papers, monographs, and chapters primarily focused in the areas of assessment, mechanisms, early intervention, and treatment. His three major books, Treating Alcohol Dependence: A Coping Skills Training Guide, The Tobacco Dependence Treatment Handbook, and Adolescents, Alcohol and Substance Abuse, reflect the breadth of his contributions. He has held research grants from NIAAA, NIDA, and the VA. Dr. Monti is PI of Brown's NIAAA T32 Postdoctoral Training Program on Treatment and Early Intervention Research, currently in its 25th year. He has trained hundreds of students. Many of these have gone on to become leaders in the field.

Dr. Monti regularly serves on numerous scientific review committees, including those for NIAAA, NIDA, and the VA. He has served as chair of NIAAA's Portfolio Review Committee, and currently serves on the NIAAA's Extramural Advisory Board and on the NIH's National Advisory Council on Alcohol Abuse and Alcoholism. He has sat on numerous editorial boards and is Editor of the Brown University Digest of Addiction Theory and Application (DATA). Dr. Monti has received numerous awards for his research and scholarship. Most recently he was the recipient of the Distinguished Researcher Award from the Research Society on Alcoholism. He is currently immediate past President of the RSA.

Notes

1 The journal's style utilizes the category substance abuse as a diagnostic category. Substances are used or misused; living organisms are and can be abused. Editor's note.

2 Risk is hereby defined as the predisposition to developing alcoholism under certain environmental conditions, such as alcohol exposure.

3 Drinking level was defined using a composite drinking score averaging the number of standard drinks consumed per occasion and the average number of drinking occasions per month.

4 Treatment can be briefly and usefully defined as a planned, goal directed, temporally structured change process, of necessary quality, appropriateness and conditions (endogenous and exogenous; micro to macro levels)), which is bounded (culture, place, time, etc.) and can be categorized into professional-based, tradition-based, mutual-help based (AA,NA, etc.) and self-help (“natural recovery”) models. There are no unique models or techniques used with substance users, of whatever types and heterogeneities, which are not also used with non-substance users. In the West, with the relatively new ideology of “harm reduction” and the even newer Quality of Life (QOL) treatment-driven model there are now a new set of goals in addition to those derived from/associated with the older tradition of abstinence driven models. Editor's note.