GRIK1 genotype and daily expectations of alcohol's positive effects moderate the reduction of heavy drinking by topiramate.

Using retrospective reports obtained during treatment visits in 138 heavy drinkers, we found that topiramate's reduction of heavy drinking was moderated by a polymorphism (rs2832407) in GRIK1, which encodes the GluK1 kainate subunit (Kranzler et al., 2014a). A subsequent analysis of that 12-week topiramate treatment trial showed similar effects of medication and genotype on daily drinking reports obtained via interactive voice response technology (IVR; Kranzler et al., 2014b). Specifically, rs2832407*C-allele homozygotes treated with topiramate reported lower levels of drinking than those receiving placebo. This group also had the largest decreases in the expected positive effects of drinking (i.e., expectancies) and desire to drink. To extend that analysis, which focused on how mean levels of desire and expectancies changed over time with treatment, we used a within-person approach to examine whether daily variation in expectancies and desire to drink interact with topiramate treatment and genotype to predict nighttime drinking levels. In contrast to the previous analysis (Kranzler et al., 2014b), here we focus on whether alcohol expectancies and desire to drink moderate the effects of topiramate on drinking. Results showed a 3-way interaction of daily expectancies with genotype and medication, such that the protective effect of topiramate on nighttime drinking among rs2832407*C-allele homozygotes was decreased on days characterized by relatively high levels of anticipated positive effects of alcohol. There was no moderating effect of desire to drink or negative alcohol expectancies. Thus, there is specific moderation of the effects of topiramate by both genotype and cognitive process.