Pre-treatment cortisol awakening response predicts symptom reduction in posttraumatic stress disorder after treatment

Psychoneuroendocrinology. 2017 Aug;82:1-8. doi: 10.1016/j.psyneuen.2017.04.010. Epub 2017 Apr 27.


Dysfunction of the HPA-axis has frequently been found in the aftermath of trauma exposure with or without PTSD. Decreasing HPA-axis reactivity to different stress cues has been reported during PTSD treatment. The cortisol awakening response (CARi) is a well-validated, standardized measure of HPA-axis reactivity which can be easily acquired in the clinical setting. Whether CARi changes over time in traumatized individuals are specific to PTSD treatment is unknown. Furthermore, a possible role for the baseline CARi in predicting symptom reduction after treatment in PTSD has not been examined before. To answer these questions, a cohort study was conducted in which the awakening cortisol was measured in both PTSD (N=41) and non-PTSD (N=25) combat-exposed male subjects. Measurements took place at inclusion and 6-8 months after inclusion for both the PTSD and the non-PTSD group. During the 6-8 months interval, PTSD patients received trauma-focused focused psychotherapy, whereas non-PTSD patients received no treatment. We found a decrease in the CARi over time in both groups, suggesting it was not specific to PTSD or the effect of treatment. Therefore, caution is warranted when attributing diminished HPA-axis reactivity over time to effects of PTSD treatment. Second, CARi prior to treatment predicted PTSD symptom reduction (CAPS score change) after treatment, and accounted for 10% of the variance, even when adjusted for changes in depressive symptoms and medication use during the study period. A putative role emerges for CARi as a predictive biomarker of symptom reduction in male individuals with combat-related PTSD.

Keywords: Biomarker; Cortisol awakening response; Gortisol; HPA-axis; Neuroendocrinology; PTSD; Trauma; Treatment; Veterans.

MeSH terms

  • Adult
  • Cohort Studies
  • Depression
  • Humans
  • Hydrocortisone / analysis*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / physiopathology
  • Predictive Value of Tests
  • Psychotherapy
  • Saliva
  • Stress Disorders, Post-Traumatic / diagnosis
  • Stress Disorders, Post-Traumatic / metabolism*
  • Stress Disorders, Post-Traumatic / therapy*


  • Hydrocortisone