Interaction of CD38 Variant and Chronic Interpersonal Stress Prospectively Predicts Social Anxiety and Depression Symptoms Over 6 Years

Variation in the CD38 gene, which regulates secretion of the neuropeptide oxytocin, has been associated with several social phenotypes. Specifically, rs3796863 Aallele carriers have demonstrated increased social sensitivity. In 400 older adolescents, we used trait-state-occasion modeling to investigate how rs3796863 genotype, baseline ratings of chronic interpersonal stress, and their gene–environment (G×E) interaction predicted trait social anxiety and depression symptoms over 6 years. We found significant G×E effects for CD38 A-carrier genotypes and chronic interpersonal stress at baseline predicting greater social anxiety and depression symptoms. A significant G×E effect of smaller magnitude was also found for C/Cgenotype and chronic interpersonal stress predicting greater depression; however, this effect was small compared with the main effect of chronic interpersonal stress. Thus, in the context of chronic interpersonal stress, heightened social sensitivity associated with the rs3796863 Aallele may prospectively predict risk for social anxiety and (to a lesser extent) depression.