Brain Receptor Function in Post-Traumatic Stress Disorder

The purpose of this study is to examine the function of cortisol receptors in post-traumatic stress disorder (PTSD). Patients with PTSD have neurobiological dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function. High corticotrophin releasing hormone (CRH) levels and decreased hippocampal volume are major features of the disorder. The mechanisms responsible for these alterations are not known. This study will evaluate the function of cortisol receptors to determine their roles in maintaining PTSD HPA axis dysregulation. Three groups of subjects will take part in the study: Patients with PTSD, healthy control subjects who were exposed to trauma in the past and remained healthy and healthy control subjects who were never traumatized At study entry, the cerebral spinal fluid (CSF) of all participants will be sampled and evaluated. Participants will also undergo a magnetic resonance imaging (MRI) scan of the brain as well as eye blink trace conditioning and neuropsychological tests. Participants will be admitted to the Clinical Center for two nights on three different occasions. At each overnight visits, blood levels of stress hormones will be measured every hour for 26 hours after medication or placebo are given. This will be the end of the study for both groups of healthy control subjects, with the exception that they may be asked to repeat neuropsychologic and eye blink tests after 12 weeks. Participants with PTSD will receive paroxetine for 10 weeks. After 10 weeks these participants will be reevaluated in exactly the same way as before treatment (except they will not repeat the MRI scan).