Metyrapone blocks
cortisol synthesis, which results in the stimulation of hypothalamic cortiocotropin-releasing factor (CRF) and a reduction in delta sleep. We examined the effect of
metyrapone administration on endocrine and sleep measures in male subjects with and without chronic
PTSD. We hypothesized that
metyrapone would result in a decrease in delta sleep and that the magnitude of this decrease would be correlated with the endocrine response. Finally, we utilized the delta sleep response to
metyrapone as an indirect measure of hypothalamic CRF activity and hypothesized that
PTSD subjects would have decreased delta sleep at baseline and a greater decrease in delta sleep induced by
metyrapone. Three nights of polysomnography were obtained in 24 male subjects with combat-related
PTSD and 18 male combat-exposed normal controls. On day 3,
metyrapone was administered during normal waking hours until habitual sleep onset preceding night 3. Endocrine responses to
metyrapone were measured in plasma obtained the morning following sleep recordings, the day before and after administration. Repeated measures ANOVAs were conducted to compare the endocrine and sleep response to
metyrapone in
PTSD and controls.
PTSD subjects had significantly less delta sleep as indexed by stages 3 and 4, and total delta integrated amplitude prior to
metyrapone administration. There were no differences in premetyrapone
cortisol or
ACTH levels in
PTSD vs controls.
PTSD subjects had a significantly decreased
ACTH response to
metyrapone compared to controls.
Metyrapone caused an increase in awakenings and a marked decrease in quantitative measures of delta sleep that was significantly greater in controls compared to
PTSD. The decline in delta sleep was significantly associated with the magnitude of increase in both
11-deoxycortisol and
ACTH. The results suggest that the delta sleep response to
metyrapone is a measure of the brain response to increases in hypothalamic CRF. These data also suggest that the
ACTH and sleep EEG response to hypothalamic CRF is decreased in
PTSD.