Age effects on cortisol levels in depressed patients with and without comorbid post-traumatic stress disorder, and healthy volunteers

Background: Post-traumatic stress disorder (PTSD) and major depression are frequently comorbid. Age and major depression are associated with higher cortisol levels and dexamethasone resistance, whereas PTSD is associated with lower cortisol and dexamethasone supersensitivity. Therefore, we examined the effect of age on the hypothalamic–pituitary–adrenal (HPA) system in depressed patients with and without PTSD. Methods: Thirty-one depressed patients without PTSD, 12 depressed patients with PTSD, and 23 healthy volunteers were studied on 2 days. Subjects received single-blind placebo on day 1 and fenfluramine on day 2. Cortisol levels were drawn before challenge and for 5 h thereafter. Results: Cortisol levels increase with age in depressed patients without PTSD but not in depressed patients with PTSD or in healthy volunteers. Number of previous major depressive episodes was a predictor of the cortisol response to fenfluramine administration in depressed patients without PTSD. Conclusions: The results of our study highlight the importance of considering age in psychobiology. Further research is needed to fully delineate the role of age in abnormalities of the HPA axis found in major depression and PTSD.