1. ¹Department of Psychiatry, Yale University School of Medicine & VA National Center for PTSD, Clinical Neuroscience Division, VA Boston Healthcare System, West Haven, CT, USA
2. ²Department of Psychiatry, Boston University School of Medicine & VA National Center for PTSD, Womens' Health Sciences Division, VA Boston Healthcare System, Boston, MA, USA
3. ³School of Public Health, New York Medical College, The Learning Center, Valhalla, NY, USA
4. ⁴Mood and Anxiety Disorders Branch, National Institute of Mental Health, Bethesda, MD, USA

Correspondence: Dr A M Rasmusson, Psychiatry Service/116A, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA. Tel: 203-932-5711, ext. 2483 or 2464; Fax: 203-937-3886; Page 203-867-3132; E-mail: ann.rasmusson@yale.edu

Received 22 September 2003; Revised 8 January 2004; Accepted 27 January 2004; Published online 16 June 2004.

Abstract

We recently found increased adrenal cortisol responses to adrenocorticotropic hormone (ACTH)_1–24 and increased pituitary ACTH and adrenal cortisol responses to corticotropin-releasing factor in premenopausal women with chronic post-traumatic stress disorder (PTSD) compared to healthy nontraumatized subjects. This pattern of hypothalamic–pituitary–adrenal axis (HPA) hyper-reactivity has been previously seen in healthy individuals treated with the antiglucocorticoid mifepristone. We therefore investigated whether endogenous plasma levels of antiglucocorticoids such as dehydroepiandrosteroine (DHEA) and progesterone were increased in premenopausal women with PTSD at baseline or in response to adrenal activation by ACTH_1-24. The study revealed that DHEA responses to 250 g ACTH_1-24 were increased in 13 PTSD subjects compared to 13 healthy nontraumatized subjects, while DHEA levels were generally increased in the PTSD subjects compared to seven healthy traumatized subjects. Cortisol responses to ACTH_1-24 were also higher in the women with PTSD, while progesterone levels and responses were not different among the three groups. In addition, among the PTSD subjects, the peak change in DHEA in response to ACTH_1-24 was negatively correlated with the total Clinician Administered PTSD Scale score, while the peak DHEA to cortisol ratio was inversely associated with negative mood symptoms measured by the Profile of Mood States scale. This work suggests that an increased capacity for DHEA release in response to extreme adrenal activation may influence the pattern of HPA axis adaptation to extreme stress, as well as mitigate the severity of PTSD and negative mood symptoms in premenopausal women with PTSD.