HPA axis regulation in posttraumatic stress disorder: A meta-analysis focusing on potential moderators

Posttraumatic stress disorder (PTSD) is often associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Previous findings are inconsistent, possibly due to trauma exposure of controls or different hormone measurement methods. We investigated cortisol, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) in adults with clinical PTSD under basal or challenged conditions (Prospero registration no. CRD42016041690). A search of PubMed, Scopus, Medline, PsycINFO, Pilots/ProQuest, and Web of Science resulted in 108 included studies (N = 6484). Morning and 24 h cortisol were significantly lower in PTSD than in controls (g = -0.21; 95% CI: -0.42-(-0.01); g = -0.31; CI: -0.60-(-0.03)). Significant cortisol increases occurred after awakening in PTSD (g = 0.40; CI: 0.13-0.67) and in non-exposed controls (g = 0.96; CI: 0.59-1.33). Evening DHEA was significantly higher in PTSD than in non-exposed controls (g = 0.58; CI: 0.17-0.99). All groups showed large cortisol suppression effects after dexamethasone administration. Overall, the potential moderators investigated did not reveal a consistent pattern of HPA alterations.