Relation of Promoter Methylation of the Oxytocin Gene to Stressful Life Events and Depression Severity.

Oxytocin (OT) is a neuropeptide associated with trauma, sociality, and depression. Despite the widely accepted assumption of OT playing a role in the etiology of mood and anxiety disorders, associations between stressful life events, depression, and epigenetic regulation of the gene coding for OT (OXT) have not yet been investigated. We therefore aimed to examine the interrelations of stressful life events, depression severity, and methylation of the promoter region of OXT in a sample of N = 146 inpatients suffering from major depression. We found significant negative associations of stressful life events with mean methylation status as well as with methylation status of single CpG sites in the promoter region of OXT. There was no association between depression severity and OXT methylation. However, there were significant sex differences in methylation status of OXT with women showing higher methylation rates than men, putatively suggesting that in depression OXT is less activated in females compared to males. These results speak against an association of OXT methylation and depression severity, but support the assumption of a dysregulation of the OT system due to life stress. Our findings further emphasize the importance of including sex as an important factor in the investigation of the interrelations between OXT, stress, and depression.