Effects of Hydrocortisone in Patients With Post-Traumatic Stress Disorder

Patients with post traumatic stress disorder (PTSD) related to combat or civilian trauma have been found to have small hippocampal volume, and deficits in hippocampal mediated memory, compared to the controls. However, it is not clear if the smaller hippocampi are a consequence of the extreme trauma and PTSD, or a risk factor in the development of PTSD. Researchers supporting the causal hypothesis have proposed that increased levels of cortisol during the traumatic experience could be neurotoxic to the hippocampus. Several studies have confirmed an increase in levels of cortisol during stress. However, plasma and urine measures of cortisol in patients with PTSD are mixed; with reports of increased decreased or normal cortisol. The possibility that increased sensitivity of the Type II or glucocorticoid receptors to circulating cortisol could lead to neurotoxic damage to the hippocampus, despite normal to low peripheral levels of cortisol has been proposed. Furthermore, increased sensitivity of the glucocorticoid receptor in PTSD could lead to stronger negative feedback inhibition, thereby offering a mechanism for the paradoxical observation of lower ACTH and cortisol levels in PTSD. Studies attempting to test the glucocorticoid receptor super sensitivity theory in PTSD confirmed the presence of increased number and sensitivity of lymphocyte glucocorticoid receptors in patients compared to healthy subjects. However, there are currently no published reports investigating central glucocorticoid sensitivity in patients with PTSD. A recent study in healthy subjects and Alzheimer's disease demonstrated that central glucocorticoid receptor sensitivity can be measured by hydrocortisone mediated inhibition of glucose metabolism measured by positron emission tomography (PET) and 2-deoxy-2\[F\]fluoro-D-glucose (FDG). We propose to evaluate the metabolic, cognitive, and behavioral effects of hydrocortisone or placebo administration in patients with PTSD, subjects who have experienced trauma but do not develop PTSD (trauma controls) and healthy subjects.