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Interaction of genes and environment

more informative than blanket statements that would suggest in a generic way that environment and genes come together to create risk for substance use and abuse. In particular, we have almost a mandate from this body of work to consider the psychosocial environment of initiation and early usage of substances in adolescence as a template for targeted inter- ventions that could focus on social processes (eg, parenting, sibling, and peer influences). Intervention scientists, in turn, are given a platform to consider how their interventions may in turn be conceptualized as a possible blockade for genetically moderated progression of use through adoles- cence and beyond. Of course, at this point this is simply a model*an attractive heuristic that refines the role of the intervention scientist in the postgenomic era of research on substance use.

INTERPLAY BETWEEN PSYCHOSOCIAL INTERVENTION AND GENETIC RISK The intersection of the psychosocial intervention perspec-

tive and the genetic epidemiological framework demonstrates and anticipates a novel direction for future work. When we think of finding implications for intervention from genetically informative studies, we often reflect on the utility of tailoring interventions to high risk groups. The idea would be that once we understand which youth are at high genetic risk, we could orient interventions to them. There are, however, two intriguing alternatives to consider.

One alternative is that the targets of psychosocial interven-

tion could, in principle, negate the importance and impact of the individual differences in risk conveyed by having parti- cular risk alleles*without knowing anything about which genetic markers are implicated. For illustrative purposes, let’s take this to the extreme. Imagine that a given psychosocial intervention could eliminate use of substances in adolescents who had initiated substances and begun to engage in sporadic use. If we take an extreme view of the developmental genetic epidemiological model, we would hypothesize that activation of systems of risk genes would not occur and the related negative impacts on the maturing adolescent brain would be circumvented. In this case, a psychosocial inter- vention would be completely effective in ‘‘preventing’’ gene expression, but it would be unnecessary to actually target specific risk genes; in fact, they could remain anonymous and the intervention would still work as long as it reduced and ideally terminated adolescent substance use.

A second alternative is that future intervention science could

begin to incorporate genetic markers into clinical trials, especially given the reality that it would prove enormously difficult to completely prevent initiation of substance use in adolescence. Note though that this is different from saying that genetic markers would be used to tailor interventions toward high-risk youth based on measured genetic risk. Rather, a suggestion has been made that interventions could provide ‘‘microtrials,’’ relatively brief and focused environ- mental manipulations, which offer many design advantages such as those derived from randomization that offer a strong 53

platform for examining genetically moderated sensitivity to immediate environmental change delivered by a psychosocial intervention.35

This perspective draws on the now decade long work on

gene X environment interaction in the developmental sciences. This research initiative has been cast in a very compelling manner because it is rooted in the idea that the environment may work differently depending on genetically influenced levels of susceptibility. For example, the growing data base on the serotonin transporter gene and its involve- ment in risk for mood disorders is currently oriented toward an understanding of genetic sensitivity to the environment and particularly stressors.36 Although the robustness of the empirical findings to date have been debated,37 the critically important conceptual point for intervention science is the idea that individuals may respond differently to the environ- ment based on genetic differences.

Recently, this idea has been reinterpreted as differential

susceptibility to the environment, with genetic differences representing the degree of plasticity to environmental influ- ence.38,39 In this approach, genes are seen not as a potential diathesis (as has been the classic model), but rather as an indicator of likelihood of responsivity to the environment. The key concept for intervention science is that the youth who are most likely to respond poorly to environmental risk factors may also be the ones who would respond most robustly to positive environmental influences such as those delivered via intervention. In this regard, it is important to recognize that recent thinking in the field suggests that adolescence may be a particularly important developmental period in which the social factors that promote initiation begin to interact with genetic liability for progression to higher levels of use.40

Building on this idea, there have recently been extremely

interesting and forward looking studies showing genetic moderation of preventive intervention effects on youth risk behaviors.4144 This work evaluated the effects of one promising family centered intervention*the Strong African American Families Program (SAAF). The SAAF is a preventive intervention that emphasizes the promotion of regulated, communicative parenting, particularly with reference to buffering the likelihood of engaging in risk behavior in early adolescence.45

Focusing on the serotonin transporter gene, recent studies

have shown that the SAAF is not only successful in reducing a number of risk behaviors*including substance use*but also that the prevention can have positive effects on youth at high genetic risk .4144 The findings reported in these papers are consistent with both the heightened attention given to gene X environment interaction as well as the differential suscept- ibility perspective. What should be most appreciated by intervention scientists and practitioners is that psychosocial interventions may currently offer opportunities to examine directly how adolescents with putative high genetic risk for substance abuse and dependence may be particularly and positively reactive to environmental attempts to change their behavior.

M&B 2011; 2:(1). July 2011

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