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Relations among Posttraumatic Stress Disorder, Comorbid Major Depression, and HPA Function: A Systematic Review and Meta-Analysis
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    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.

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    1 F31 MH084425-01A1/MH/NIMH NIH HHS/United States
    1 UL1RR024975/RR/NCRR NIH HHS/United States
    F31 MH084425/MH/NIMH NIH HHS/United States
    F31 MH084425-01A1/MH/NIMH NIH HHS/United States
    G12 RR003032/RR/NCRR NIH HHS/United States
    KL2 RR024977/RR/NCRR NIH HHS/United States
    R01 DA017805/DA/NIDA NIH HHS/United States
    R01 MH064735/MH/NIMH NIH HHS/United States
    R01 MH064735-04/MH/NIMH NIH HHS/United States
    R01 MH068391/MH/NIMH NIH HHS/United States
    R01 MH068391-06/MH/NIMH NIH HHS/United States
    R01 MH069940/MH/NIMH NIH HHS/United States
    R01 MH069940-05/MH/NIMH NIH HHS/United States
    R01HM069940/HM/NCHM CDC HHS/United States
    R01MH068391/MH/NIMH NIH HHS/United States
    R01MH64735/MH/NIMH NIH HHS/United States
    RC1 MH088329/MH/NIMH NIH HHS/United States
    RC1 MH088329-02/MH/NIMH NIH HHS/United States
    RC1MH088329/MH/NIMH NIH HHS/United States
    T32 MH018921/MH/NIMH NIH HHS/United States
    T32 MH018921-20/MH/NIMH NIH HHS/United States
    T32MH18921/MH/NIMH NIH HHS/United States
    TL1 RR024978/RR/NCRR NIH HHS/United States
    UL1 RR024975/RR/NCRR NIH HHS/United States
    UL1 RR024975-01/RR/NCRR NIH HHS/United States
    UL1RR024975-01/RR/NCRR NIH HHS/United States
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