An Increased Capacity for Adrenal DHEA Release is Associated with Decreased Avoidance and Negative Mood Symptoms in Women with PTSD

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 ACTH1-24. The study revealed that DHEA responses to 250 microg ACTH1-24 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 ACTH1-24 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 ACTH1-24 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.

Hypothalamic–Pituitary–Adrenal Axis Activity and Sleep in Posttraumatic Stress Disorder

“…However, other constituents that parallel cortisol release from the adrenal gland, such as dehydroepiandrosterone (DHEA), could be involved in sleep regulation. Consistent with this hypothesis, DHEA has recently been associated with sleep disturbances and symptom load in PTSD (Rasmusson et al, 2004;Sondergaard et al, 2002).…”

Biomarkers for the Diagnosis, Prognosis, and Evaluation of Treatment Efficacy for Traumatic Brain Injury

“…However, it is unclear if this ratio is a marker for symptom severity or if it is related to symptom improvement. 115 Because TBI can alter the function of the hypothalamic-pituitary-adrenal axis, it remains to be determined if the degree and/or a combination of these changes can be used to differentiate people with mild TBI from those with PTSD.…”

Neuroactive Steroids are Altered in Schizophrenia and Bipolar Disorder: Relevance to Pathophysiology and Therapeutics

“…It is also possible that subjects with schizophrenia and bipolar disorder may be physiologically resistant to DHEA actions in some manner (potentially resulting in the increased formation of this neuroactive steroid), or that there is dysregulation in a feedback system involving the hypothalamic-pituitaryadrenal (HPA) axis. Specifically, DHEA increases following corticotrophin-releasing hormone (CRH) (Genazzani et al, 1998;Bernardi et al, 2000) and ACTH administration (Rasmusson et al, 2004) in humans, and therefore persistent DHEA elevations may reflect a prolonged upregulation of the HPA axis. DHEA also demonstrates antiglucocorticoid actions (Kimonides et al, 1999;Karishma and Herbert, 2002;Hu et al, 2000;Kalimi et al, 1994), supporting a role for DHEA in HPA axis regulation.…”