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, 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. 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 saliva-derived OXTRm as a biological marker of structural and functional connectivity maturation in 57 typically developing children (P < 0.05). We utilized seed-based connectivity analysis during a novel abstract movie paradigm and find that higher levels of OXTRm are associated with a more adult-like functional connectivity profile. Concurrently, more adult-like functional connectivity was associated with higher reported self-control and more diffusion streamlines between the amygdala and mPFC. OXTRm mediates the association between structural and functional connectivity with higher levels of OXTRm being associated with more streamlines. Lastly, 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 connectivity in emotional and behavioral regulation. Ultimately, identification of neurobiological markers may lead to earlier detection of children at risk for socio-emotional dysfunction.

Early origins of health and disease risk: The case for investigating adverse exposures and biological aging in utero, across childhood, and into adolescence

“…Epigenetic age clocks assess age-related changes in DNA methylation patterns, providing insights into cellular age and the potential impact of environmental exposures. Exposure to stress prenatally and across childhood can lead to epigenetic modifications that affect cellular and molecular processes involved in aging (e.g., DNA repair, inflammation, and cellular senescence; Horvath & Raj, 2018), possibly via their impact on brain circuitry involved in emotion regulation, construction and function of stress response systems, and the responsiveness of the immune system to challenge (Chen et al, 2021;Jiang et al, 2019;Skyberg et al, 2023).…”