Articles

An Integrative Approach for Studying the Etiology of Alcoholism and Other Addictions

T. Jacob^a1, K.J. Sher^a2, K.K. Bucholz^a3, W.T. True^a4, E.J. Sirevaag^a5, J. Rohrbaugh^a6, E. Nelson^a7, R.J. Neuman^a8, R.D. Todd^a9, W.S. Slutske^a10, J.B. Whitfield^a11, K.M. Kirk^a12, N.G. Martin^a13, P.A.F. Madden^a14 and A.C. Heath^a15 c1

^a1 Palo Alto Veterans Administration, Palo Alto, California, USA.

^a2 Missouri Alcoholism Research Center, Department of Psychology, University of Missouri, Columbia, Missouri, USA.

^a3 Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, USA.

^a4 Missouri Alcoholism Research Center, School of Public Health, Saint-Louis University, St. Louis, Missouri, USA.

^a5 Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, USA; Also:Siteman Cancer Center, Washington University School of Medicine, St.Louis, USA.

^a6 Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, USA; Also:Siteman Cancer Center, Washington University School of Medicine, St.Louis, USA.

^a7 Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, USA.

^a8 Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, USA.

^a9 Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, USA.

^a10 Missouri Alcoholism Research Center, Department of Psychology, University of Missouri, Columbia, Missouri, USA.

^a11 Royal Prince Alfred Hospital, Sydney, Australia; Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.

^a12 Department of Psychiatry, The University of Queensland, Brisbane, Australia; Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.

^a13 Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.

^a14 Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, USA; Also:Siteman Cancer Center, Washington University School of Medicine, St.Louis, USA.

^a15 Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, USA; Also:Siteman Cancer Center, Washington University School of Medicine, St.Louis, USA. andrew@matlock.wuSTL.edu

Abstract

Studies of alcoholism etiology often focus on genetic or psy-chosocial approaches, but not both. Greater understanding of the etiology of alcohol, tobacco and other addictions will come from integration of these research traditions. A research approach is outlined to test three models for the etiology of addictions — behavioral undercontrol, pharmacologic vulnerability, negative affect regulation — addressing key questions including (i) mediators of genetic effects, (ii) genotype-environment correlation effects, (iii) genotype x environment interaction effects, (iv) the developmental unfolding of genetic and environmental effects, (v) subtyping including identification of distinct trajectories of substance involvement, (vi) identification of individual genes that contribute to risk, and (vii) the consequences of excessive use. By using coordinated research designs, including prospective assessment of adolescent twins and their siblings and parents; of adult substance dependent and control twins and their MZ and DZ cotwins, the spouses of these pairs, and their adolescent offspring; and of regular families; by selecting for gene-mapping approaches sibships screened for extreme concordance or discordance on quantitative indices of substance use; and by using experimental (drug challenge) as well as survey approaches, a number of key questions concerning addiction etiology can be addressed. We discuss complementary strengths and weaknesses of different sampling strategies, as well as methods to implement such an integrated approach illustrated for the study of alcoholism etiology. A coordinated program of twin and family studies will allow a comprehensive dissection of the interplay of genetic and environmental risk-factors in the etiology of alcoholism and other addictions.

(Received February 05 2001)

(Accepted February 12 2001)

Correspondence:

^c1 Address for correspondence: A.C. Heath, Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, 40 N. Kingshighway, Suite One, St. Louis, MO 63108, USA.