• Cory A Burghy, Diane E Stodola, Paula L Ruttle, Erin K Molloy, Jeffrey M Armstrong, Jonathan A Oler, Michelle E Fox, Andrea S Hayes, Ned H Kalin, Marilyn J Essex, Richard J Davidson, and Rasmus M Birn.
• Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, Wisconsin, USA. caburghy@wisc.edu
• Nat. Neurosci. 2012 Dec 1; 15 (12): 1736-41.

AbstractEarly 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.

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