An epigenetic mechanism for differential maturation of amygdala-prefrontal connectivity in childhood socio-emotional development

Abstract Functional connectivity between the amygdala and the medial prefrontal cortex (mPFC) has been identified as a neural substrate of emotion regulation that undergoes changes throughout development. Amygdala-mPFC connectivity has been well studied in adolescents and adults, with a mature profile typically emerging at 10 years of age. Maternal bonding in childhood has been shown to buffer amygdala reactivity and to influence the trajectory of amygdala-mPFC coupling, which in turn may impact socio-emotional dysfunction later in life. The oxytocinergic system is critical in the development of social behavior and maternal bonding. Early life parental care influences the methylation status of the oxytocin receptor (OXTRm) in animal models and humans, and higher OXTRm is associated with lower amygdala-PFC functional connectivity in adults. Using a neuroimaging-epigenetic approach, we investigated OXTRm as a biological marker of functional connectivity maturation in middle childhood. We find that higher levels of OXTRm are associated with a more adult-like functional connectivity profile. We also find that lower OXTRm blunts the association between amygdala-mPFC connectivity and future internalizing behaviors in early adolescence. These findings implicate OXTRm as a biological marker at the interface of the social environment and amygdala-mPFC coupling in emotional and behavioral regulation. Ultimately, identification of neurobiological markers may lead to earlier detection of children at risk for socio-emotional dysfunction.