Changes in Salivary Cortisol During Psychotherapy for Posttraumatic Stress Disorder: A Pilot Study in 30 Veterans

Background: Convergent evidence suggests that the hypothalamic-pituitary-adrenal (HPA) axis is disrupted in posttraumatic stress disorder (PTSD) and that HPA axis normalization may be associated with symptom improvement. Thus, the current study was designed to test the association between HPA axis reactivity and treatment response in psychotherapy for PTSD.

Methods: Thirty returning veterans with DSM-IV-TR PTSD were randomly assigned to receive 10 sessions of prolonged exposure therapy or present-centered therapy as part of a previously published randomized clinical trial (2008–2010). Treatment groups were collapsed for the current analyses. Salivary cortisol was collected 3 times during 3 therapy sessions. Cortisol reactivity was calculated by area under the curve with respect to ground. Hierarchical linear modeling was used to measure longitudinal change in salivary cortisol nested within patients and to test the effects of treatment responder status at both levels.

Results: Session number was significant in the final model, indicating linear increases in cortisol output across sessions (β = 1.06, P = .02). In addition, responder status significantly predicted slope of cortisol reactivity across sessions (β = 1.35, P = .04). Compared to high responders, low responders exhibited a 1.35 (μg/dL) mean increase in cortisol reactivity between sessions. Responder status accounted for 6% of the previously unexplained variance in cortisol reactivity.

Conclusions: As compared to high treatment responders, low treatment responders showed greater increases in salivary cortisol output over the course of treatment. These results indicate that increases in HPA axis reactivity over the course of psychotherapy may be associated with worse treatment response. Future work is needed to investigate how modulation of HPA axis reactivity may be targeted in order to optimize PTSD treatment outcomes.

Trial Registration: identifier: NCT00475241

J Clin Psychiatry 2017;78(5):599–603