PTSD psychotherapy improves blood pressure but leaves HPA axis feedback sensitivity stable and unaffected: First evidence from a pre-post treatment study.

Although key to development of tailored drugs for augmentation treatment of psychotherapy for posttraumatic stress disorder (PTSD), the biological correlates of PTSD remission are still unknown, probably because pre-post treatment studies searching for them are rare. Not even the feedback sensitivity of the otherwise well-studied hypothalamic-pituitary-adrenal (HPA) axis nor arterial blood pressure (BP), which was previously reported to be elevated in PTSD patients, have so far been analyzed during PTSD treatment. To narrow this knowledge gap, we first performed an overnight dexamethasone suppression test (DST) in a mixed-sex cohort of 25 patients with severe PTSD vs. 20 non-traumatized healthy controls (nt-HC). In addition to hormones, BP and heart rate (HR) were measured at each of the four assessment points (APs). Second, the same parameters were assessed again in 16 of these patients after 12 sessions of integrative trauma-focused cognitive behavioral therapy (iTF-CBT). In relation to nt-HC, PTSD patients showed a significant elevation in HR and diastolic BP while their systolic BP, DST outcomes and basal serum cortisol levels (BSCL) were not significantly altered. In response to iTF-CBT, PTSD symptoms and dysfunctional stress coping strategies improved significantly in PTSD patients. Most important, also their systolic and diastolic BP levels ameliorated at distinct APs while their DST outcomes and BSCL remained unchanged. To our knowledge, this is the first pre-post treatment study assessing the stability of the DST outcome and BP levels during PTSD treatment. Our results provide first evidence for a non-involvement of HPA axis feedback sensitivity in PTSD symptom improvement and, furthermore, suggest a possible role for BP-regulating pathways such as the sympathetic nervous system in PTSD remission. Limitations arise from the small sample size, the lack of an untreated patient group and drug treatment of patients.

Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients.

Analysis of the function of the hypothalamic-pituitary-adrenal (HPA)-axis in patients suffering from posttraumatic stress disorder (PTSD) has hitherto produced inconsistent findings, inter alia in the Trier Social Stress Test (TSST). To address these inconsistencies, we compared a sample of 23 female PTSD patients with either early life trauma (ELT) or adult trauma (AT) or combined ELT and AT to 18 age-matched non-traumatized female healthy controls in the TSST which was preceded by intensive baseline assessments. During the TSST, we determined a variety of clinical, psychological, endocrine and cardiovascular parameters as well as expression levels of four HPA-axis related genes. Using a previously reported definition of HPA-axis responsive versus non-responsive phenotypes, we identified for the first time two clinically and biologically distinct HPA-axis reactivity subgroups of PTSD. One subgroup ("non-responders") showed a blunted HPA-axis response and distinct clinical and biological characteristics such as a higher prevalence of trauma-related dissociative symptoms and of combined AT and ELT as well as alterations in the expression kinetics of the genes encoding for the mineralocorticoid receptor (MR) and for FK506 binding protein 51 (FKBP51). Interestingly, this non-responder subgroup largely drove the relatively diminished HPA axis response of the total cohort of PTSD patients. These findings are limited by the facts that the majority of patients was medicated, by the lack of traumatized controls and by the relatively small sample size. The here for the first time identified and characterized HPA-axis reactivity endophenotypes offer an explanation for the inconsistent reports on HPA-axis function in PTSD and, moreover, suggest that most likely other factors than HPA-axis reactivity play a decisive role in determination of PTSD core symptom severity.