This proposal is the first of several phases in a line of research on the biology of sleep disturbances in Post Traumatic Stress Disorder (PTSD). This proposal aims to examine the relationship between sleep architecture, particularly slow wave sleep, and hypothalamic-pituitary-adrenal axis activity in chronic PTSD. The investigators will study medication-free, non-substance abusing male and female Vietnam theater veterans with chronic PTSD with and without concurrent Major Depressive Disorder (MDD). They will examine the effects of metyrapone, an antiglucocorticoid agent that enhances slow wave sleep, on sleep architecture in PTSD subjects with and without MDD. The major aims of this study will be met with a two group design whose main comparisons will be between PTSD with current MDD (N=50) and PTSD without lifetime MDD (N=50). The investigators will test if differences in HPA activity contribute to the variability in sleep physiology in PTSD. The study will involve 5 nights of ambulatory polysomnography: 2 at home, and 3 in a hospital observation unit where 23 hour urinary free cortisol and a metyrapone challenge will be performed. The home sleep and hospital sleep are separated by 3 nights. The order of home vs. hospital sleep studies will be counterbalanced to study order effects in adaptation to recording equipment and hospitalization. A third group of combat veteran controls without lifetime PTSD or MDD (N=20) will be recruited to allow an examination of the effect of PTSD on ambulatory sleep measures and adaptation to recording equipment and hospital setting. The control group will be studied with ambulatory polysomnography for 4 nights: 2 at home, and 2 in the hospital with no metyrapone challenge. Finally, the study will validate wrist actigraphy against ambulatory polysomnography and provide data on 24 hour sleep-wake activity levels in PTSD.
