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Rachel Yehuda, PhD; David Boisoneau; Martin T. Lowy, PhD; Earl L. Giller, Jr, MD, PhD

Arch Gen Psychiatry. 1995;52(7):583-593.

Abstract
Background
Our previous studies have suggested that combat veterans with posttraumatic stress disorder (PTSD) have alterations in hypothalamic-pituitary-adrenal axis functioning that are different from the well-documented biological changes observed in major depressive disorder and following exposure to stress.

Methods
In the present study, we examined cortisol and lymphocyte glucocorticoid receptor number before and after the administration of 0.50 and 0.25 mg of dexamethasone in 14 combat veterans with PTSD, 12 combat veterans without PTSD, and 14 nonpsychiatric healthy men. All subjects were medication free at the time of testing and none met diagnostic criteria for major depression or substance dependence.

Results
Combat veterans with PTSD suppressed cortisol to a greater extent than did combat veterans without PTSD and normal controls in response to both doses of dexamethasone. Differences in cortisol suppression could not be attributed to substance dependence history or differences in dexamethasone bioavailability. Combat veterans with PTSD showed a larger number of baseline glucocorticoid receptors compared with normal men. Combat veterans without PTSD also had a larger number of baseline glucocorticoid receptors compared with normal men and in fact were comparable to combat veterans with PTSD on this measure. However, only veterans with PTSD showed a decrease in lymphocyte glucocorticoid receptor number following dexamethasone administration.

Conclusion
The data support the hypothesis of an enhanced negative feedback sensitivity of the hypothalamic-pituitary-adrenal axis in PTSD.

Author Affiliations
From the Departments of Psychiatry, Mount Sinai School of Medicine and Bronx Veterans Affairs Medical Center, New York, NY (Dr Yehuda), and University of Connecticut Health Center, Farmington (Mr Boisoneau); the Burroughs Wellcome Co, Research Triangle Park, NC (Dr Lowy), and CNS Research, Pfizer Inc, Groton, Conn (Dr Giller).

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