Studies that have conducted quantitative analysis of the sleep electroencephalogram (EEG) have demonstrated decreased delta sleep in
PTSD. Elevations in both hypothalamic (neurohormonal) and extrahypothalamic (
neurotransmitter)
corticotropin releasing factor (CRF) release is associated with decreased delta sleep activity. We present data from several studies examining the effect of
metyrapone administration on the sleep EEG in
PTSD and control subjects. Plasma
ACTH,
cortisol, and 11-deoxycorticol were obtained the morning following polysomnographic sleep recordings before and after
metyrapone administration. Delta sleep was measured by period amplitude analysis. The results demonstrate: a) decreased delta sleep in male subjects with
PTSD; b)
metyrapone administration resulted in an activation of the sleep EEG and a robust decrease in quantitative delta sleep; c) the sleep and endocrine (increase in
ACTH) responses to
metyrapone were significantly decreased in
PTSD in two different study samples; and d) the
metyrapone-related disruption to sleep in both samples was predicted by the increase in
ACTH measured the following morning. These findings strongly suggest that the delta sleep response to
metyrapone is a measure of the brain response to a hypothalamic CRF challenge. The attenuated delta sleep and endocrine response to
metyrapone challenge in
PTSD is consistent with a model of enhanced negative feedback regulation or downregulation of
CRF receptors in an environment of chronically increased CRF activity.