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

The authors assessed the contributions of early life stress (ELS) and childhood cortisol levels to adolescent resting-state functional connectivity. In females, ELS predicted increased cortisol levels in childhood, which predicted decreased amygdala-ventromedial prefrontal cortex (vmPFC) functional connectivity. Amygdala-vmPFC connectivity was inversely correlated with anxious sympotms and positively correlated with depressive symptoms. Early life stress (ELS) and function of the hypothalamic-pituitary-adrenal axis predict later psychopathology. Animal studies and cross-sectional human studies suggest that this process might operate through amygdala–ventromedial prefrontal cortex (vmPFC) circuitry implicated in the regulation of emotion. Here we prospectively investigated the roles of ELS and childhood basal cortisol amounts in the development of adolescent resting-state functional connectivity (rs-FC), assessed by functional connectivity magnetic resonance imaging (fcMRI), in the amygdala-PFC circuit. In females only, greater ELS predicted increased childhood cortisol levels, which predicted decreased amygdala-vmPFC rs-FC 14 years later. For females, adolescent amygdala-vmPFC functional connectivity was inversely correlated with concurrent anxiety symptoms but positively associated with depressive symptoms, suggesting differing pathways from childhood cortisol levels 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.