One limitation of our design is the absence of samples from control subjects with a history of child abuse. Notably, child abuse predicts ACTH responses to stress11. However, the best predictor of HPA responses to stress is the interaction between a developmental history of child abuse and stress in adulthood. One interpretation for such findings is that childhood adversity might alter the development of systems that serve to regulate stress responses, such as hippocampal glucocorticoid receptor expression, and thus enhance the effect of stress in adulthood and vulnerability for mood disorders11. Rodent models provide evidence for a direct effect of variations in forebrain glucocorticoid receptor expression and the behavioral characteristics of depression. Mice bearing a brain-specific glucocorticoid receptor knockdown show behavioral alterations that mimic some of the features of depression6,7,34.
