Relations among posttraumatic stress disorder, comorbid major depression, and HPA function: A systematic review and meta-analysis

Exposure to traumatic stress is associated with increased risk for posttraumatic stress disorder (PTSD) and alterations of hypothalamic–pituitary–adrenocortical (HPA) function. Research linking traumatic stress with HPA function in PTSD has been inconsistent, however, in part due to (a) the inclusion of trauma-exposed individuals without PTSD (TE) in control groups and (b) a failure to consider comorbid major depressive disorder (MDD) and moderating variables. This meta-analysis of 47 studies (123 effect sizes, N = 6008 individuals) revealed that daily cortisol output was lower for PTSD (d = −.36, SE = .15, p = .008) and PTSD + MDD (d = −.65, SE = .25, p = .008) groups relative to no trauma controls (NTC); TE and NTC groups did not differ significantly from each other. Afternoon/evening cortisol was lower in TE (d = −.25, SE = .09, p = .007) and PTSD (d = −.27, SE = .12, p = .021) groups and higher in PTSD + MDD groups (d = .49, SE = .24, p = .041) relative to NTC. Post-DST cortisol levels were lower in PTSD (d = −.40, SE = .12, p < .001), PTSD + MDD (d = −.65, SE = .14, p < .001), and TE groups (d = −.53, SE = .14, p < .001) relative to NTC. HPA effect sizes were moderated by age, sex, time since index event, and developmental timing of trauma exposure. These findings suggest that enhanced HPA feedback function may be a marker of trauma-exposure rather than a specific mechanism of vulnerability for PTSD, whereas lower daily cortisol output may be associated with PTSD in particular.

► Daily cortisol output was lower for PTSD and PTSD + MDD groups relative to NTC. ► No significant differences between TE and NTC groups in daily cortisol output. ► Afternoon cortisol was lower in PTSD groups relative to NTC. ► Afternoon cortisol was higher in PTSD + MDD groups relative to NTC. ► Post-DST cortisol levels were lower in PTSD, PTSD + MDD, TE groups relative to NTC.