Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence

Previous work demonstrates that early life stress (ELS) and HPA-axis function predict later psychopathology. Animal work and cross-sectional human studies suggest that this process might operate through amygdala-ventromedial prefrontal cortical (vmPFC) circuitry implicated in emotion regulation. The current study prospectively investigated the roles of ELS and childhood basal cortisol in the development of adolescent resting-state functional connectivity (fcMRI) in the amygdala-PFC circuit. In females only, greater ELS predicted increased childhood cortisol levels, which, in turn, predicted decreased amygdala-vmPFC fcMRI 14 years later. Further, for females, amygdala-vmPFC fcMRI was inversely correlated with concurrent anxious symptoms, but positively associated with depressive symptoms, suggesting differing pathways from childhood cortisol function through adolescent amygdala-vmPFC functional connectivity to anxiety and depression. These data highlight that, for females, the effects of ELS and early HPA-axis function may be detected much later in the intrinsic processing of emotion-related brain circuits.