We propose to investigate the underlying mechanisms that account for neurobiological dysregulation of HPA axis function in PTSD. Paradoxically, low or normal plasma and urinary cortisol despite high corticotrophin releasing hormone (CRH) levels are a major feature of this disorder. Some investigators report decreased hippocampal volume in patients with PTSD. The mechanisms responsible for these alterations are not known. One possibility is that patients with PTSD have an increased number of glucocorticoid receptors (GR) and/or increased GR sensitivity, causing hyper-suppression of HPA axis. Another possibility is that high CRH levels lead to increased mineralocorticoid receptor (MR) levels and this up-regulation of MR is responsible for the low cortisol secretion seen in PTSD. Elevated CRH levels could also result in reduced hippocampal volume.