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

Abstract

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=6,008 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.

Autonomic and inflammatory consequences of posttraumatic stress disorder and the link to cardiovascular disease

“…Chronic stress can lead to a breakdown of the negative feedback systems of the HPA axis, promoting reduced CRH and cortisol, which profoundly affect the long-term psychological state of affected individuals. This is endorsed by a meta-analysis showing decreased CRH and cortisol levels in individuals with psychiatric illness, including PTSD (76). Although it is clear that long-term elevations in HPA activity contribute to psychopathology, the associated increases in ANG II production and the influence of ANG II on psychiatric disorders, such as PTSD, are unknown.…”

The neural diathesis-stress model of schizophrenia revisited: An update on recent findings considering illness stage and neurobiological and methodological complexities

“…In contrast, there is evidence that individuals with PTSD, like those with psychosis, are characterized by a blunted CAR (Chida and Steptoe, 2009). However, decreased cortisol levels during the day have been consistently reported among PTSD patients relative to controls (Morris et al, 2012). Yet another picture emerges in panic disorder patients, who show little or no alteration in basal cortisol levels and a normal CAR, but a distinctive non-responsiveness to a psychosocial stressor (Petrowski et al, 2010).…”

Emotional and psychological trauma in refugees arriving in Germany in 2015

“…11 Even with the limitation of current methods, it has already been shown that with growing age, as well as with depression or in PTSD, the HPA axis may be subject to a 'load factor' whereby greater HPA activity in old age is accompanied by an increase in physical capacity. [12][13][14][15] Chronic changes in endogenous glucocorticoid production are typically a result of prolonged stress exposure. Patients with depression, generalized anxiety disorders or PTSD may exhibit disrupted HPA axis activity.…”