Serial CSF Corticotropin-Releasing Hormone Levels and Adrenocortical Activity in Combat Veterans With Posttraumatic Stress Disorder

OBJECTIVE: The authors sought to carefully test, by using a technique of continuous CSF sampling, the hypothesis that basal elevations in CSF corticotropin-releasing hormone (CRH) concentrations exist in patients with posttraumatic stress disorder (PTSD). They also sought to assess the relationship among PTSD symptoms, adrenocortical activity, and CSF CRH levels. METHOD: CSF was withdrawn by means of a flexible, indwelling subarachnoid catheter over a 6-hour period, and hourly CSF concentrations of CRH were determined for 11 well-characterized combat veterans with PTSD and 12 matched normal volunteers. Twenty-four-hour urinary-free cortisol excretion was also determined. PTSD and depressive symptoms were correlated with the neuroendocrine data. RESULTS: Mean CSF CRH levels were significantly greater in PTSD patients than in normal subjects (55.2 [SD=16.4] versus 42.3 pg/ml [SD=15.6]). No correlation was found between CSF CRH concentrations and PTSD symptoms. While there was no significant difference between groups in 24-hour urinary-free cortisol excretion, the correlation between 24-hour urinary-free cortisol excretion and PTSD symptoms was negative and significant. CONCLUSIONS: By using a serial CSF sampling technique, the authors found high basal CSF CRH concentrations and normal 24-hour urinary-free cortisol excretion in combat veterans with PTSD, a combination that appears to be unique among psychiatric conditions studied to date.