The hippocampus plays a role in modulating activity of the HPA axis via a negative feedback system that involves glucocorticoid binding to receptors in the hippocampus (Herman et al. 2005; Jacobson and Sapolsky, 1991). In rodents, smaller hippocampal volume is associated with heightened glucocorticoid levels and blunted negative feedback (Hibberd et al. 2000; Meaney et al. 1995, 1996). Consistent with the role of the hippocampus in modulating HPA activity, hippocampal volume is typically found to be inversely correlated with glucocorticoid levels in humans (Tessner et al. 2007; Wiedenmayer et al. 2006). In addition, the medial frontal cortex and anterior cingulate is involved in glucocorticoid regulation (Brake et al. 2000; Diorio et al. 1993; Sullivan and Gratton, 2002), and it appears that smaller cingulate cortex volumes may be associated with HPA axis dysregulation (MacLullich et al. 2006).
