5-HTTLPR genotype and daily negative mood moderate the effects of sertraline on drinking intensity

We previously reported moderating effects of age of onset of alcohol dependence (AD) and a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter protein in a sample of 134 individuals participating in a 12-week, placebo-controlled trial of sertraline. To understand more fully the effects seen in that study, we examined moderation by negative moods reported each evening, with nighttime drinking intensity (i.e. the number of standard drinks consumed at night) as the dependent variable. We found a daily anxiety × age of onset × 5-HTTLPR polymorphism × medication interaction, which reflected a daily anxiety × medication group effect for early-onset individuals homozygous for the high-expression (L') allele, but not others. Specifically, on days characterized by relatively high levels of anxiety, early-onset L' homozygotes receiving placebo reduced their drinking intensity significantly. In contrast, early-onset L' homozygotes treated with sertraline non-significantly increased their drinking intensity. These findings implicate anxiety as a key moderator of the observed pharmacogenetic effects. These findings have important implications because of the high prevalence of AD and the frequency with which SSRIs are prescribed to treat the disorders.