Hair cortisol predicts avoidance behavior and depressiveness after first-time and single-event trauma exposure in motor vehicle crash victims.

The role of cortisol as a premorbid vulnerability factor for trauma sequelae remains unclear. Furthermore, the onset of long-term endocrine changes in response to first-time trauma as a function of later psychopathology is not clarified yet. Thus the predictive value of pre- and post-traumatic hair cortisol concentrations (HCCs) for psychological trauma sequelae was investigated in response to motor vehicle crash (MVC). A total of N= 62 MVC survivors participated in this study (46 females, mean age (SD): 43.94(12.95)). Subsequent trauma sequelae were measured with a structured clinical interview and self-report questionnaires to evaluate psychological symptoms (pre-MVC and three months post-MVC). Hair strands were taken immediately after MVC and three months post-MVC, reflecting cumulative cortisol secretion over the three-month period before and after the MVC. A total of 22.6% of the participants developed a trauma sequela with an affective disorder (14.5%) and/or anxiety disorder (16.1%). We observed a significant main effect of group and diagnosis × time interaction with an increase of HCC in those individuals who presented a subsequent psychiatric disorder. Regression analyses revealed that post-MVC increased HCC were significantly predictive of higher levels of subsequent depressiveness, and that pre-MVC increased HCC were predictive of higher levels of subsequent avoidance behavior. Our findings demonstrate that individual differences in long-term cortisol secretion in response to a first-time traumatic event (MVC) contribute to subsequent psychopathology. Specifically, higher long-term cortisol secretion before and after first-time MVC was a risk factor for subsequent development of avoidance behavior and depressiveness, respectively.Lay summaryHigher cortisol secretion and stress experience before a motor vehicle crash was a risk factor for subsequent development of psychological symptoms.

Effects of Mental Stress Induction on Heart Rate Variability in Patients with Panic Disorder.

Reduced heart rate variability (HRV) constitutes a widely used marker of cardiac autonomic inflexibility which has been linked to disorders such as panic disorder (PD). To date, the pathophysiological mechanisms whereby panic leads to attenuated HRV are not fully elucidated. We aimed to investigate the hypothesis that PD patients show pathological reactivity both in response to interoceptive and psychosocial stress in comparison to healthy individuals. We performed a controlled study on 38 patients diagnosed with PD [20 males and 18 females aged 35.55 ± 10.12 years, mean ± standard deviation] and 23 age and gender matched healthy control participants. Distress was induced using the Trier Social Stress Test (TSST) and the dexamethasone-corticotropin-releasing-hormone (DEX-CRH) test. We assessed HRV prior to, during, and post-stress induction using the root mean square successive differences (RMSSD) as well as spectral analysis (high frequency; HF and low frequency; LF). Statistical analyses revealed significant main effects of time for mean heart rate (HR), HF, LF (solely DEX-CRH), LFHF-ratio (solely TSST) and the RMSSD. Significant interaction effects were observed with more pronounced increases in mean HR (TSST) and LFHF-ratio (DEX-CRH) in the healthy control participants. No significant main effects of group were observed. Overall, our results indicate "normal" HRV parameters in patients with PD. The HRV of PD patients is no worse than that of healthy control participants since the HRV profiles were similar between the study groups. The current study is one of rather rarely published studies which was unable to show an influence of PD on HRV. Implications for future studies are under discussion.

Stress-induced pro- and anti-inflammatory cytokine concentrations in panic disorder patients.

BACKGROUND: An attenuated responsivity of the hypothalamus-hypophysis-adrenal (HPA) axis upon challenge and an increased risk for cardiac events are relatively consistent findings in panic disorder (PD) patients. Due to cytokine-HPA interactions, an altered HPA-axis responsivity may be accompanied by altered cytokine concentrations. Immunological reactions under stress might be considered the missing link for explaining an increased cardiac risk. This study analyzed stress-induced cytokine levels in PD patients. METHODS: A total of n = 32 PD patients and n = 32 healthy control individuals performed the Trier Social Test (TSST). Blood sample collection accompanied the TSST for the collection of cortisol and pro- (IL-6, TNF-α) and anti-inflammatory cytokines (IL-10). Established self-report questionnaires were handed out for the clinical characterization and the assessment of subjective levels of distress during testing. Repeated measures ANCOVA were conducted to evaluate main effects of time or group and time x group interaction effects. Additional ANCOVAS with disease severity as between-subjects factor (healthy, borderline, mild, moderate, severe) took global panic severity into account. Pearson correlation analyses were carried out to test for an association of panic specific symptoms and peak cytokine release. RESULTS: The TSST resulted in a significantly increased secretion of cortisol, IL-6 and IL-10. The data analysis further revealed a significant time x group interaction effect for cortisol and IL-10. Compared to the healthy volunteers, the PD patients showed significantly higher baseline and challenged IL-10 concentrations but lower challenged cortisol concentrations. Mildly and moderately affected patients showed the highest levels of IL-10 compared to the healthy individuals. There were no differential secretion patterns of IL-6 and TNF-α between both groups in the course of the TSST. The peak IL-6 release was found to be significantly associated with global disease severity. CONCLUSION: We found evidence for altered levels of cytokines with primarily anti-inflammatory properties in PD patients under baseline and a psychosocial stress condition. The results provide tentative evidence for a low-grade inflammatory process in PD patients, possibly representing a missing link factor between PD diagnosis and the increased risk for cardiac disease.

Stress hormone response to the DEX-CRH test and its relation to psychotherapy outcome in panic disorder patients with and without agoraphobia.

This study tested whether the hormonal stress response to the DEX-CRH test may be predictive of the psychotherapy success for panic disorder (PD). Thirty-four patients diagnosed either with agoraphobia with PD or PD without agoraphobia were subjected to cognitive behavioural therapy (CBT). Patients (pre-therapy) and healthy volunteers were exposed to the DEX-CRH test. Blood samples were taken for cortisol and adrenocorticotropic hormone (ACTH) assessment. Established panic-specific questionnaires were handed out for the pre-therapy and post-therapy evaluation of disease severity (with reference to panic beliefs and agoraphobic cognitions, fear of bodily sensations, agoraphobic avoidance behaviour). Repeated measures ANCOVA were conducted for the analysis of the pre-therapy hormonal response, and Pearson's correlation analysis to test for associations with the psychotherapy outcome. Data analyses revealed large effect sizes for CBT in the clinical measures (η2 ≥ 0.321), main effects of time for cortisol and ACTH with no differences between both groups, and significant associations between cortisol release and agoraphobic cognitions for the patients. PD diagnosis had no impact on the hormonal response. However, those patients with higher cortisol release showed less improvement after CBT (significantly for agoraphobic cognitions). Clinical implications of these findings are the prediction of the therapy success from a potential endocrine correlate whose persistency (if assessed repeatedly) during the treatment may predict (non-)response to the current treatment, possibly representing a decision support for a change in treatment to avoid the continuation of an inefficient treatment.

Cortisol stress response in post-traumatic stress disorder, panic disorder, and major depressive disorder patients.

BACKGROUND: Previous research has focussed extensively on the distinction of HPA-axis functioning between patient groups and healthy volunteers, with relatively little emphasis on a direct comparison of patient groups. The current study's aim was to analyse differences in the cortisol stress response as a function of primary diagnosis of panic disorder (PD), post-traumatic stress disorder (PTSD), and major depressive disorder (MDD). METHODS: A total of n=30 PD (mean age±SD: 36.07±12.56), n=23 PTSD (41.22±10.17), n=18 MDD patients (39.00±14.93) and n=47 healthy control (HC) individuals (35.51±13.15) participated in this study. All the study participants were female. The Trier Social Stress Test (TSST) was used for reliable laboratory stress induction. Blood sampling accompanied the TSST for cortisol and ACTH assessment. Panic-related, PTSD-specific questionnaires and the Beck Depression Inventory II were handed out for the characterisation of the study groups. Repeated measure ANCOVAs were conducted to test for main effects of time or group and for interaction effects. Regression analyses were conducted to take comorbid depression into account. RESULTS: 26.7% of the PD patients, 43.5% of the PTSD patients, 72.2% of the MDD patients and 80.6% of the HC participants showed a cortisol stress response upon the TSST. ANCOVA revealed a cortisol hypo-responsiveness both in PD and PTSD patients, while no significant group differences were seen in the ACTH concentrations. Additional analyses showed no impact of comorbid depressiveness on the cortisol stress response. MDD patients did not differ in the hormonal stress response neither compared to the HC participants nor to the PD and PTSD patients. CONCLUSION: Our main findings provide evidence of a dissociation between the cortisol and ACTH concentrations in response to the TSST in PTSD and in PD patients, independent of comorbid depression. Our results further support overall research findings of a cortisol hypo-responsiveness in PD patients. A hypo-response pattern was also seen in the PTSD patients agreeing with previous finding on the cortisol stress reactivity following TSST stress induction in these patients. Patients with a primary MDD diagnosis showed descriptively higher cortisol concentrations compared to the anxiety patients, and lower cortisol concentrations as the healthy individuals. The limitations of the study and implications for future studies will be discussed.

Effects of the cortisol stress response on the psychotherapy outcome of panic disorder patients.

BACKGROUND: A proportion of patients with panic disorder (PD) fail to show a remission after psychotherapy. Biological correlates of psychotherapy non-response have rarely been described in the literature. The aim of the present study was to research the relationship between the cortisol stress response and the psychotherapy outcome in PD patients. METHODS: Twenty-eight PD patients (20 females, mean age±SD: 35.71±13.18) seeking psychological treatment for PD and n=32 age- and sex-matched healthy control participants (21 females, aged 34.66±12.07) participated in this study. The patients underwent five weeks of cognitive behavioural therapy (CBT). Within the first two weeks of the CBT, both study groups were confronted with the Trier Social Stress Test (TSST). Blood sampling for cortisol and adrenocorticotropic hormone (ACTH) evaluation as well as fear-rating (Visual Analogue Scale; Primary Appraisal and Secondary Appraisal Questionnaire, PASA) accompanied the TSST. The global severity of PD (Panic & Agoraphobia Scale; PAS), agoraphobic cognitions (Agoraphobic Cognitions Questionnaire; ACQ), fear of bodily sensations (Bodily Sensations Questionnaire; BSQ), agoraphobic avoidance (Mobility Inventory; MI), and depressiveness (Beck Depression Inventory; BDI) were assessed before and after the CBT (except the BDI). RESULTS: The statistical analysis revealed significant main effects of time for cortisol and the ACTH concentration in response to the TSST, independently of the study group. 42.9% of the PD patients and 65.6% of the healthy control participants showed a cortisol stress response to the TSST≥55.2nmol/l (descriptive finding). The data showed a significant inverse association of the TSST cortisol stress response with the MI total score when accompanied. Further, a significant association of the PASA subjective level of fear and the BSQ as well as a trend for an association of the PASA with the ACQ were observed. CONCLUSION: Consistent with prior research, we could replicate findings of decreased cortisol concentrations in the PD patients in comparison to the healthy control participants. Furthermore, our findings agree with previous data showing an association of the attenuated cortisol stress response with the psychotherapy non-response. In the present sample, those patients with the lowest cortisol concentrations showed the least improvement in agoraphobic avoidance after psychotherapy. The patients with the highest level of fear showed the most improvement in fear of bodily sensations. Study limitations as well as implications for future studies will be discussed.

Hair cortisol concentrations and cortisol stress reactivity in generalized anxiety disorder, major depression and their comorbidity.

Studies investigating cortisol secretion in patients with generalized anxiety disorder (GAD) have reported heterogeneous findings. Further, current knowledge on the specificity of endocrine changes for GAD and/or comorbid major depression (MD) is limited. Hence, the current study investigated long-term integrated cortisol secretion, as indexed by hair cortisol concentrations (HCC), and experimentally-induced cortisol stress reactivity in relation to GAD, MD and their comorbidity. Carefully characterized groups of 17 GAD patients including 8 with comorbid MD (GAD-MD), 12 MD patients and 21 healthy controls were recruited. Alongside psychometric data, HCC (N = 43) and salivary cortisol stress reactivity in response to the Trier Social Stress Test (N = 45) were determined. Findings revealed that MD patients exhibited lower HCC compared to controls and GAD patients, with no differences between the latter two groups. Interestingly, when the GAD group was separated into two groups based on MD comorbidity, lower HCC in MD patients were found compared to controls and GAD-noMD patients, but did not show differences when compared to GAD-MD patients. No HCC differences were seen between GAD-MD or GAD-noMD patients and healthy controls. No TSST group differences emerged. Our findings suggest MD to be related to long-term attenuation in cortisol secretion. While no group differences emerged between patients with GAD, neither with nor without MD, and controls, the current results provide tentative evidence that MD determines long-term endocrine changes, with pure GAD showing a distinct pattern. Future studies are needed to confirm our findings in larger samples of pure and comorbid groups.

Stress-related and basic determinants of hair cortisol in humans: A meta-analysis.

The analysis of hair cortisol concentrations (HCC) is a relatively new strategy to measure long-term cumulative cortisol levels, which is increasingly used in psychoneuroendocrinological research. Here, we conduct a first comprehensive meta-analysis of HCC research based on aggregated data from a total of 124 (sub)samples (66 independent studies; total N=10,289). We seek to answer two central questions: (i) Which covariates and basic features of HCC need to be considered in future research? (ii) What are the main determinants of HCC in terms of chronic stress exposure and mental health? Concerning basic characteristics, our findings identify several covariates to be considered (age, sex, hair washing frequency, hair treatment, oral contraceptive use), confirm a decline of HCC from the first to the second proximal 3cm hair segment, and show positive associations between HCC and short-term salivary cortisol measures. Regarding chronic stress, we show that stress-exposed groups on a whole exhibit 22% increased HCC. This long-term cortisol hypersecretion emerges particularly when stress is still ongoing at the time of study (+43% HCC) but is not present in conditions of past/absent stress (-9% HCC, n.s.). We also report evidence for 17%-reduced HCC in anxiety disorders, such as PTSD. Interestingly, no consistent associations with mood disorders and self-reports of perceived stress, depressiveness or social support are found. However, our findings reveal positive associations of HCC with stress-related anthropometric (body mass index, waist-to-hip ratio) and hemodynamic measures (systolic blood pressure). These meta-analytic results are discussed in the light of their practical implications and important areas for future inquiry are outlined.