The interaction between OXTR rs2268493 and perceived maternal care is associated with amygdala-dorsolateral prefrontal effective connectivity during explicit emotion processing.

ABSTRACT

Previous studies have indicated a link between socio-emotional processing and the oxytocin receptor. In this regard, a single nucleotide polymorphism in the oxytocin receptor coding gene (OXTR rs2268493) has been linked with lower social functioning, increased risk for autism spectrum disorders (ASDs) and with post-mortem OXTR mRNA expression levels. Indeed, the levels of expression of OXTR in brain regions involved in emotion processing are also associated with maternal care. Furthermore, maternal care has been associated with emotional correlates. Taken together, these previous findings suggest a possible combined effect of rs2268493 and maternal care on emotion-related brain phenotypes. A crucial biological mechanism subtending emotional processing is the amygdala-dorsolateral prefrontal cortex (DLPFC) functional connection. On this basis, our aim was to investigate the interaction between rs2268493 and maternal care on amygdala-DLPFC effective connectivity during emotional evaluation. We characterized through dynamic causal modeling (DCM) patterns of amygdala-DLPFC effective connectivity during explicit emotion processing in healthy controls (HC), profiled based on maternal care and rs2268493 genotype. In the whole sample, right top-down DLPFC-to-amygdala pattern was the most likely directional model of effective connectivity. This pattern of connectivity was the most likely for all rs2268493/maternal care subgroups, except for thymine homozygous (TT)/low maternal care individuals. Here, a right bottom-up amygdala-to-DLPFC was the most likely directional model. These results suggest a gene by environment interaction mediated by the oxytocin receptor on biological phenotypes relevant to emotion processing.