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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=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.

SUBMITTER: Morris MC

PROVIDER: S-EPMC3340453 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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

Morris Matthew C MC Compas Bruce E BE Garber Judy J

Clinical psychology review 20120210 4

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 (1 ...[more]

PMID: 22459791

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Project description:BackgroundSexual assault is implicated in several adverse psychological and physical health outcomes, including posttraumatic stress disorder (PTSD) and depression. Neurobiological research has shown variations related to the hypothalamic-pituitary-adrenal (HPA) axis, immune alterations, metabolic function, and brain circuitry. Although these mechanisms have been extensively studied, the results have demonstrated different outcomes in PTSD.MethodsWe compared the plasma adrenocorticotropin (ACTH) and salivary cortisol levels of fifty-eight women with PTSD developed after sexual assault to those of forty-four female controls with no history of trauma. We also evaluated the psychiatric diagnosis and symptom severity of PTSD and depression. The participants' clinical conditions were associated with their hormonal levels to assess whether symptom severity was related to hormonal imbalance.ResultsA large percentage of sexually assaulted women had PTSD and comorbid depression. The ACTH levels were higher in the PTSD group than the control group and increased as PTSD severity increased, considering depressive symptoms, measured by the Beck Depression Inventory (BDI) (p < 0.0001), as well as PTSD symptoms, measured by subscale D of the Clinician-Administered PTSD Scale (CAPS-5) (p = 0.045) and the CAPS-5 total scale (p = 0.026). Cortisol levels measured at 10 pm were higher for the PTSD group than the control group (p = 0.045, p = 0.037, respectively), and the cortisol awakening response showed elevated cortisol levels for the PTSD group.ConclusionsThese results show a correlation between symptom severity and HPA axis imbalance in patients with PTSD. Elevated ACTH and an elevated cortisol response in patients with comorbid depressive symptoms were the opposite of the expected response for patients with PTSD only. This association leads to the hypothesis that the neurobiological alterations of PTSD are related to the type of symptoms presented and their severity. These manifestations likely influence the disease course, prognosis and response to treatment. These outcomes highlight the need to discuss particular neurobiological alterations in patients with PTSD developed after sexual assault, mainly those with severe depressive symptoms.

Project description:BackgroundPosttraumatic stress disorder is a debilitating psychiatric disorder characterized by symptoms of intrusive re-experiencing of trauma, avoidance and hyper-arousal. Diagnosis and treatment of PTSD is further complicated by concurrently occurring disorders, the most frequent being major depressive disorder and anxiety disorders. Previous research highlights that attentional processing in posttraumatic stress disorder is associated with substantial interference by emotional stimuli, a phenomenon also observed in these concurrently occurring psychiatric disorders. However, the diagnosis-relevance of this interference remains elusive. Here, we investigated the emotional Stroop interference for diagnosis-related stimuli, generally negative stimuli, and generally positive stimuli in posttraumatic stress disorder, major depressive disorder and anxiety disorders.MethodsWe performed a systematic database search in PubMed (Medline), Cochrane Library and PsycINFO on emotional Stroop performance in individuals with a diagnosis of posttraumatic stress disorder, major depressive disorder or anxiety disorders separately. Mean effect sizes, standard errors and confidence intervals were estimated for each clinical group and healthy control group comparison using random effect models.ResultsAs compared to healthy control group, the posttraumatic stress disorder group displayed greater interference by diagnosis-related stimuli and positive stimuli but not for generally negative stimuli. The major depressive disorder and anxiety disorders groups showed greater interference by diagnosis-related and negative stimuli, but not by positive stimuli. The age and sex had no significant impact on interference.ConclusionsThese findings highlight the importance of diagnosis-relevant information on attentional processing in all three clinical populations, posttraumatic stress disorder, major depressive disorder and anxiety disorders. Further, the impact of generally negative stimuli but not generally positive stimuli in major depressive disorder and anxiety disorders indicate impaired attentional bias for mood-congruent stimuli but not for general stimuli. Finally, it remains to be studied whether the influence of generally positive stimuli in posttraumatic stress disorder indicate that positive stimuli are perceived as PTSD related.

Project description:BACKGROUND:Repetitive transcranial magnetic stimulation (TMS) is clinically effective for major depressive disorder (MDD) and investigational for other conditions including posttraumatic stress disorder (PTSD). Understanding the mechanisms of TMS action and developing biomarkers predicting response remain important goals. We applied a combination of machine learning and electroencephalography (EEG), testing whether machine learning analysis of EEG coherence would (1) predict clinical outcomes in individuals with comorbid MDD and PTSD, and (2) determine whether an individual had received a TMS course. METHODS:We collected resting-state 8-channel EEG before and after TMS (5?Hz to the left dorsolateral prefrontal cortex). We used Lasso regression and Support Vector Machine (SVM) to test the hypothesis that baseline EEG coherence predicted the outcome and to assess if EEG coherence changed after TMS. RESULTS:In our sample, clinical response to TMS were predictable based on pretreatment EEG coherence (n?=?29). After treatment, 13/29 had more than 50% reduction in MDD self-report score 12/29 had more than 50% reduction in PTSD self-report score. For MDD, area under roc curve was for MDD was 0.83 (95% confidence interval 0.69-0.94) and for PTSD was 0.71 (95% confidence interval 0.54-0.87). SVM classifier was able to accurately assign EEG recordings to pre- and post-TMS treatment. The accuracy for Alpha, Beta, Theta and Delta bands was 75.4?±?1.5%, 77.4?±?1.4%, 73.8?±?1.5%, and 78.6?±?1.4%, respectively, all significantly better than chance (50%, p?<?0.001). LIMITATION:Limitations of this work include lack of sham condition, modest sample size, and a sparse electrode array. Despite these methodological limitations, we found validated and clinically meaningful results. CONCLUSIONS:Machine learning successfully predicted non-response to TMS with high specificity, and identified pre- and post-TMS status using EEG coherence. This approach may provide mechanistic insights and may also become a clinically useful screening tool for TMS candidates.

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

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