Oxytocin receptor expression and epigenetic regulation in the anterior cingulate cortex of individuals with a history of severe childhood abuse

Childhood abuse significantly increases the lifetime risk of negative mental health outcomes. The oxytocinergic system, which plays a role in complex social and emotional behaviors, has been shown to be sensitive to early-life experiences. While previous studies have investigated the relationship between early-life adversity and oxytocin, they did so with peripheral samples. We, therefore, aimed to characterize the relationship between early-life adversity and oxytocin receptor (OXTR) expression in the brain, using post-mortem human samples, as well as a rodent model of naturally occurring variation in early-life environment. Focusing on the dorsal anterior cingulate cortex, we compared OXTR expression and epigenetic regulation between MDD suicides with (N = 26) and without history of childhood abuse (N = 24), as well as psychiatrically healthy controls (N = 23). We also compared Oxtr expression in the cingulate cortex of adult rats raised by dams displaying high (N = 13) and low levels (N = 12) of licking and grooming (LG) behavior. Overall, our results indicate that childhood abuse associates with an upregulation of OXTR expression, and that similarly, this relationship is also observed in the cingulate cortex of adult rats raised by low-LG dams. Additionally, we found an effect of rs53576 genotype on expression, showing that carriers of the A variant also show upregulated OXTR expression. The effects of early-life adversity and rs53576 genotype on OXTR expression are, however, not explained by differences in DNA methylation within and around the MT region of the OXTR gene.