LAUSR

BACKGROUND The impact of combined variants of Oxytocin Receptor (OXTR) and G protein β3 subunit genes was investigated in relation to retrospective reports of childhood as well as contemporary adult separation anxiety (SA), based on evidence of a β/γ dimer-mediated signaling for OXTR. METHODS A case-control association study (225 healthy adults and 188 outpatients with depression) was performed to establish Risk-Combined Genotype (RCG) of the studied variants (OXTR rs53576 and the functional Gβ3 subunit rs5443). Current SA was evaluated by the ASA-27 and retrospective childhood symptoms by the SASI. GG genotype of OXTR rs53576 combined with T-carrier genotype of Gβ3 rs5443 represented the RCG. RESULTS Compared to non-RCG, those with RCG had significantly higher levels of childhood and adult SA. The RCG was significantly associated with childhood SA threshold score (OR=2.85, 90%CI: 1.08-7.50). Childhood SA was, in turn, strongly associated with a threshold SA score in adulthood (OR=15.58; 95% CI: 4.62-52.59). LIMITATIONS Although the overall sample size is sizable, comparisons among subgroups with specific combination of alleles are based on relatively small numbers. CONCLUSIONS Our study indicates that variations in OXTR and Gβ3 genes are specifically associated with presence and severity of SA in childhood and adulthood, but not with depression or anxiety in general. Because there is increasing interest in oxytocin in social behavior, the gene-SA associations identified have potential translational and clinical relevance.