DAT1 and alcohol use: differential responses to life stress during adolescence

Abstract

Stressful life events can impact both substance use initiation and the quantity of substances consumed by adolescents; however, the effect of stress on substance use may be contingent on other factors including social support, peers, and genotype. DAT1, a polymorphic dopamine transporter gene, is one such factor that may be responsible for differential susceptibility to cumulative life pressures. Data from the National Longitudinal Study of Adolescent Health were utilized to determine whether adolescents with the 10-repeat allele are more likely to respond to life stresses by engaging in alcohol use than those without the allele. Respondents’ self-reports of key stressors were used to create a composite life stress scale. The interaction of this measure with the number of 10-repeat DAT1 alleles was evaluated in series of logistic regression models. A significant interaction emerged between stressful life experiences and DAT1 for alcohol use among females, but this pattern was not seen in males. Females with the 10-repeat allele appear to be more sensitive to life stress as compared to those without the allele. It appears that variation in the DAT1 gene may help explain why some women are more likely to consume alcohol when confronted with stress. It, however, does not appear to condition the reaction of men, in terms of alcohol use, to stress.

Keywords:

• alcohol
• DAT1
• stress
• gene X environment interaction
• adolescent alcohol use
• gender differences

Acknowledgments

This research uses data from Add Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill and funded by Grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. Special acknowledgment is due to Ronald R. Rindfuss and Barbara Entwistle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health Web site (http://www.cpc.unc.edu/addhealth). No direct support was received from Grant P01-HD31921 for this analysis.

Notes

1. A potential rGE was assessed for each component stressor primarily to ensure the presented results are not inappropriately confounded. In some cases, a passive rGE is theoretically viable (parental problems), whereas other component stressors may be more easily conceptually linked to an active rGE (victimization) and others to an evocative rGE (negative school experiences). In other cases, there may not have been clear reason to suspect a potential rGE. Regardless, each potential rGE was evaluated to ensure statistical accuracy – not because of underlying theoretical expectations. As a result, no portion of this preliminary check should be interpreted as victim blaming, but instead as related to methodological comprehensiveness. None of these associations were significant at the .05 level.

2. The analyses presented in this section were repeated with individual stress measures as opposed to the composite scale. Logistic regression models were estimated which included DAT1 genotype, each of the eight stressors, the four risk factors, the three protective factors, the four demographic variables, and a GxE interaction term as predictors and alcohol use as the dependent variable. To avoid multicolinearity, the interaction of each stressor with DAT1 genotype was entered into a separate model. Appendix 2 depicts the coefficient and standard errors of each of these terms (other predictors are omitted to allow for a parsimonious display of results). Only one individual stressor emerges as significant at the p < .05 level (parental maltreatment among females). However, this information should not be interpreted as an indication that parental maltreatment was the driving force behind the results presented in the text. As discussed earlier, stressors may have an incremental effect whereby the sum of stress is more important than the source(s) of the stress. Parental maltreatment is certainly an important stressor, but an examination of the table also demonstrates that other terms are trending toward significance and likely contributed to the significant interaction between cumulative adversity and DAT1 (albeit that these contributions may have been too small to identify in isolation in a sample of this size).

Additional information

Funding

Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [grant number P01-HD31921], with cooperative funding from 23 other federal agencies and foundations.