BackgroundOxytocin has received much attention as a pro-social and anxiolytic neuropeptide. In human studies, the G-allele of a common variant (rs53576) in the oxytocin receptor gene (OXTR) has been associated with protective properties such as reduced stress response and higher receptiveness for social support. In contrast, recent studies suggest a detrimental role of the rs53576 G-allele in the context of childhood maltreatment. To further elucidate the role of OXTR, gene by maltreatment (GxE) interactions on brain structure and function were investigated.Methodsn = 309 healthy participants genotyped for OXTR rs53576 underwent structural as well as functional MRI during a common emotional face-matching task. Childhood maltreatment was assessed with the Childhood Trauma Questionnaire (CTQ). Gray matter volumes were investigated by means of voxel-based morphometry (VBM) across the entire brain.ResultsStructural MRI data revealed a strong interaction of rs53576 genotype and CTQ-scores, mapping specifically to the bilateral ventral striatum. GG homozygotes but not A-allele carriers showed strong gray matter reduction with increasing CTQ-scores. In turn, lower ventral striatum gray matter volumes were associated with lower reward dependence, a pro-social trait. Furthermore, the G-allele was associated with increased amygdala responsiveness to emotional facial expressions.ConclusionsThe findings suggest that the G-allele constitutes a vulnerability factor for specific alterations of limbic brain structure in individuals with adverse childhood experiences, complemented by increased limbic responsiveness to emotional interpersonal stimuli. While oxytocinergic signalling facilitates attachment and bonding in supportive social environments, this attunement for social cues may turn disadvantageous under early adverse conditions.Disclosure of interestThe author has not supplied his declaration of competing interest.