The Application of Genetic Micro-Trial Technology to Tailor an Adolescent Drug Abuse Program

Introduction. To personalize interventions, it is necessary to identify for each client, candidate genes, biomarkers, neurocognitive processes and environmental exposure indicators that provide the means for identifying which interventions are provide optimal benefits. A micro-trial is a randomized proximal change experiment that tests the degree to which a specialized intervention(s) can affect malleability of a key risk/protective mechanism that is causally linked to the distal outcome of interest. The explanatory power of the micro-trial can be further enhanced by incorporating personal characteristics that moderate the intervention(s) effects, including genetic, physiologic, neurocognitive, and behavior characteristics. A ‘genetically-informed’ micro-trial, for example, can be employed to help determine what specific intervention provides optimal impact on a key mechanism for change for individuals with different genetic variants.

Methods. We describe an emerging study that uses micro-trial technology to inform personalization of adolescent drug abuse prevention. The study is enrolling adolescents (ages 13-16) who are referred to a counseling center because of a recent drug use incident. Youth are randomized to one of two EBIs that promote healthy decision-making as a strategy to reduce drug use, albeit using different structural frameworks. One intervention is the Teen Intervene-Brief Program (TI-B; Winters & Leitten, 2007), the second is the Cognitive Behavioral Coping Skills Program (CBCS: Garrett & Kaminer, 2009; Kaminer et al., 1998; 2002). Our micro-trial seeks to test whether impaired decision-making as measured by delay discounting (an important trait/risk mechanism among those susceptible to drug use) can be differentially influenced by two evidence-based interventions (EBIs) and whether intervention effects vary as a function of pre-intervention scores on delay discounting and genetic polymorphisms. The genetic variables of interest are: DRD4, DRD2, COMT, DAT1/SLC6A3, MAOA, DBH, SLC6A4/5-HTT/SERT, and SLC6A2/NET.

Conclusions. If specific genetic polymorphisms and/or theoretically-based bio-behavioral processes such as impaired decision-making (delay discounting) can be shown to moderate intervention effects on drug abuse outcomes, these variables can be used to inform personalization by matching clients to specific interventions that offer the best opportunities for optimizing response.