In our study, childhood trauma had the least impact on heroin dependence. In contrast, we found a strong effect of childhood trauma on cocaine dependence. Although there was no main effect of GABRA2, severe childhood trauma was associated with cocaine dependence only in individuals with the rs11503014 11/12 genotypes. Preclinical studies support our findings: rats subjected to early life stress are more sensitive to cocaine, demonstrate increased cocaine self-administration (27,53–55) and, perhaps in line with this, have an altered pattern of distribution of GABAA receptor α2 subunits (25) that have been implicated in cocaine sensitization (56). Therefore, bases on these preclinical findings, one speculative explanation for the gene × environment (G×E) interaction in our study might be that if rs11503014 (or a tightly linked SNP) is indeed implicated in exon splicing and thus might influence GABRA2 expression, carriers of the variant allele might be more sensitive to early life stress and subsequent vulnerability to cocaine addiction. However, one caveat should be discussed. Due to the limited sample size and loss of power stemming from categorization of variables we did not
