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

D.G. Baker^1,2 , S.A. West², W.E. Nicholson³, N.N. Ekhator^1,2, J.W. Kasckow^1,2
K.K. Hill¹, A.B. Bruce¹, E.C. Somoza^1,2, D.N. Orth³, T.D. Geracioti1,²

From the Psychiatry Service, Cincinnati Veterans Affairs Medical Center¹ and the Department of Psychiatry, University of Cincinnati College of Medicine² and the Department of Medicine³, Vanderbilt University Medical Center, Nashville, TN

Objective: We sought to carefully test the hypothesis that basal cerebrospinal fluid (CSF) corticotropin releasing hormone (CRH) hyperactivity exists in patients with posttraumatic stress disorder (PTSD) by using a technique of continuous CSF sampling. We also sought to assess the relationship between PTSD symptoms, adrenocortical activity and CSF CRH.

Methods: We withdrew CSF via a flexible, indwelling subarachnoid catheter over a six-h period and determined hourly CSF concentrations of CRH in 11 well characterized combat veterans with PTSD and 12 matched normal volunteers. Urine was obtained for urinary free cortisol (UFC) determination. PTSD and depressive symptoms were correlated with the neuroendocrine data.

Results: Mean CSF CRH was significantly greater in PTSD patients compared with controls (55.19 + 16.42 pg/ml v.s. 42.24 + 15.60 pg/ml, [F(1,18)= 6.04, p< .05]). A significant positive correlation was observed between CSF CRH concentrations and depressive symptoms (r = .63, df =9, p =.05) but not between CSF CRH concentrations and PTSD symptoms. While there were no significant differences between groups in 24-h UFC concentrations, the correlation between 24h UFC concentrations and PTSD symptoms (r = -.72, df = 9, p < .02) was negative and significant.

Conclusions: Using a serial CSF sampling technique, we found high basal CSF CRH concentrations and normal 24-h urinary free cortisol excretion in combat veterans with PTSD, a combination which appears to be unique among psychiatric conditions studied to date. Elevated concentration of CSF CRH may be related to the persistent irritability and anxiety of our patients. It will prove of interest to characterize the responsivity of CSF CRH to provocative challenge in patients with PTSD.

Keywords: Cerebrospinal fluid (CSF), Corticotropin-Releasing Hormone (CRH) or Corticotropin-Releasing Factor (CRF), Posttraumatic Stress Disorder (PTSD)

Acknowledgments: This work was supported by a VA Central Office Research Funds (Dr. Geracioti).