Repressive and vigilant coping styles in stress and relaxation: evidence for physiological and subjective differences at baseline, but not for differential stress or relaxation responses.

Introduction: Previous research suggested differential stress reactivity depending on individuals' coping style, e.g., as classified by the model of coping modes. Specifically, stronger physiological reactivity and weaker subjective stress ratings were found for repressors than for sensitizers. However, it remains to be investigated (i) whether these findings, which are largely based on social stress induction protocols, also generalize to other stressors, (ii) whether repressors vs. sensitizers also exhibit differential stress recovery following the application of a relaxation method, and (iii) which stress reactivity and recovery patterns are seen for the two remaining coping styles, i.e., fluctuating, and non-defensive copers. The current study thus examines stress reactivity in physiology and subjective ratings to a non-social stressor and the subsequent ability to relax for the four coping groups of repressors, sensitizers, fluctuating, and non-defensive copers. Methods: A total of 96 healthy participants took part in a stress induction (Mannheim Multicomponent Stress Test) and a subsequent relaxation intervention. Subjective ratings of stress and relaxation, heart rate (HR), heart rate variability (HRV), and blood pressure were assessed during the experiment. HR and blood pressure are markers of the sympathetic stress response that can be regulated by relaxation, while HRV should increase with relaxation. To investigate long-term relaxation effects, subjective ratings were also assessed on the evening of testing. Results: Despite successful stress induction, no differential responses (baseline to stress, stress to relaxation) were observed between the different coping groups on any of the measures. In contrast, a strong baseline effect was observed that persisted throughout the experiment: In general, fluctuating copers showed lower HR and higher HRV than non-defensive copers, whereas repressors reported lower subjective stress levels and higher levels of relaxation during all study phases. No differences in subjective ratings were observed in the evening of testing. Conclusion: Contrary to previous research, no differential stress reactivity pattern was observed between coping groups, which could be due to the non-social type of stressor employed in this study. The novel finding of physiological baseline differences between fluctuating and non-defensive individuals is of interest and should be further investigated in other stressor types in future research.

Associations between hair cortisol and subjective stress measures in a large occupational sample.

BACKGROUND: Hair cortisol concentrations (HCC) are commonly used to capture long-term cumulative cortisol secretion in stress research. However, data on associations between HCC and subjective stress measures have been inconsistent. This may partly be due to bias introduced by smaller-sized academic samples. Here, we investigate associations between HCC and (work-) stress-related measures in a large occupational, predominantly male, sample. METHODS: Demographic, anthropometric, and self-reported data were collected as part of an occupational health assessment for employees of an airplane manufacturing company (N = 1258). Hair samples (3 cm) were obtained and glucocorticoid concentrations (HCC and hair cortisone, HairE) were analyzed using liquid chromatography-tandem mass spectrometry. RESULTS: HCC and HairE were unrelated to self-report measures of perceived stress, work-related stress (effort-reward imbalance, overcommitment), and other stress-related constructs. Group-based analyses concerning associations with job strain revealed a small effect of individuals with high job strain (n = 281) exhibiting higher HCC than the remaining sample (n = 811). CONCLUSIONS: Our data replicate previous findings of no consistent associations between hair glucocorticoids and subjective stress-related questionnaire data, besides evidence for elevated HCC in a high job strain group. Further research addressing open methodological questions regarding HCC by means of advanced stress assessment methods is needed.

Pupil dilation tracks divergent learning processes in aware versus unaware Pavlovian conditioning.

Evidence regarding unaware differential fear conditioning in humans is mixed and even less is known about the effects of contingency awareness on appetitive conditioning. Phasic pupil dilation responses (PDR) might be more sensitive for capturing implicit learning than other measures, such as skin conductance responses (SCR). Here, we report data from two delay conditioning experiments utilizing PDR (alongside SCR and subjective assessments) to investigate the role of contingency awareness in aversive and appetitive conditioning. In both experiments, valence of unconditioned stimuli (UCS) was varied within participants by administering aversive (mild electric shocks) and appetitive UCSs (monetary rewards). Preceding visual stimuli (CSs) predicted either the reward, the shock (65% reinforcement), or neither UCS. In Exp. 1, participants were fully instructed about CS-UCS contingencies, whereas in Exp. 2, no such information was given. PDR and SCR demonstrated successful differential conditioning in Exp. 1 and in (learned) aware participants in Exp. 2. In non-instructed participants who remained fully unaware of contingencies (Exp. 2), differential modulation of early PDR (immediately after CS onset) by appetitive cues emerged. Associations with model-derived learning parameters further suggest that early PDR in unaware participants mainly reflect implicit learning of expected outcome value, whereas early PDR in aware (instructed/learned-aware) participants presumably index attentional processes (related to uncertainty/prediction error processing). Similar, but less clear results emerged for later PDR (preceding UCS onset). Our data argue in favor of a dual-process account of associative learning, suggesting that value-related processing can take place irrespective of mechanisms involved in conscious memory formation.

Evaluation and update of the expert consensus guidelines for the assessment of the cortisol awakening response (CAR).

The cortisol awakening response (CAR) is frequently assessed in psychobiological (stress) research. Obtaining reliable CAR data, however, requires careful attention to methodological detail. To promote best practice, expert consensus guidelines on the assessment of the CAR were published (Stalder et al., 2016, PNEC). However, it is unclear whether these highly cited guidelines have resulted in actual methodological improvements. To explore this, the PNEC editorial board invited the present authors to conduct a critical evaluation and update of current CAR methodology, which is reported here. (i) A quantitative evaluation of methodological quality of CAR research published in PNEC before and after the guidelines (2013-2015 vs. 2018-2020) was conducted. Disappointingly, results reveal little improvement in the implementation of central recommendations (especially objective time verification) in recent research. (ii) To enable an update of guidelines, evidence on recent developments in CAR assessment is reviewed, which mostly confirms the accuracy of the majority of the original guidelines. Moreover, recent technological advances, particularly regarding methods for the verification of awakening and sampling times, have emerged and may help to reduce costs in future research. (iii) To aid researchers and increase accessibility, an updated and streamlined version of the CAR consensus guidelines is presented. (iv) Finally, the response of the PNEC editorial board to the present results is described: potential authors of future CAR research to be published in PNEC will be required to submit a methodological checklist (based on the current guidelines) alongside their article. This will increase transparency and enable reviewers to readily assess the quality of the respective CAR data. Combined, it is hoped that these steps will assist researchers and reviewers in assuring higher quality CAR assessments in future research, thus yielding more reliable and reproducible results and helping to further advance this field of study.

Hair cortisol, glucocorticoid gene receptor polymorphisms, stress, and testicular function.

OBJECTIVE: Self-reported psychological stress has been associated with decreased semen quality. Cortisol levels in scalp hair (hair cortisol concentration, HCC) has emerged as a potential objective marker of psychological stress. Thus, we investigated if HCC was associated with markers of testicular function. Furthermore, we examined whether three common single nucleotide polymorphisms in the glucocorticoid-receptor gene (NR3C1, chromosome 5), potentially affecting receptor sensitivity, were associated with HCC and could influence the studied association between HCC and testicular function. DESIGN: Cross-sectional study. METHODS: We analysed HCC, serum-levels of reproductive hormones, semen parameters, and the three NR3C1-polymorphisms; BclI (rs41423247), Tth111I (rs10052957), and 9ß (rs6198), in a population of 696 men from the general population. RESULTS: HCC was not associated with testicular function, and adjustment for the three NR3C1-polymorphisms did not alter the results. However, HCC increased significantly with the number of Tth111I minor-alleles (T) and decreased significantly with the number of 9ß minor-alleles (G). CONCLUSION: Given previously shown associations between stress and semen quality, and that no association between HCC and self-reported stress was observed in the current study, we speculate that negative reproductive effects of stress may not be mediated directly by cortisol. This study demonstrates associations between HCC and glucocorticoid receptor gene variants indicating that these SNPs may influence systemic glucocorticoid levels, but the potential health effects of such alterations are yet unknown.

Open and reproducible science practices in psychoneuroendocrinology: Opportunities to foster scientific progress.

This perspective article was written by invitation of the editors in chief as a summary and extension of the symposium entitled Psychoneuroendocrine Research in the Era of the Replication Crisis which was held at the virtual meeting of the International Society of Psychoneuroendocrinology 2021. It highlights the opportunities presented by the application of open and reproducible scientific practices in psychoneuroendocrinology (PNE), an interdisciplinary field at the intersection of psychology, endocrinology, immunology, neurology, and psychiatry. It conveys an introduction to the topics preregistration, registered reports, quantifying the impact of equally-well justifiable analysis decisions, and open data and scripts, while emphasizing 'selfish' reasons to adopt such practices as individual researcher. Complementary to the call for adoption of open science practices, we highlight the need for methodological best practice guidelines in the field of PNE, which could further contribute to enhancing replicability of results. We propose concrete steps for future actions and provide links to additional resources for those interested in adopting open and reproducible science practices in future studies.

Facilitating relaxation and stress reduction in healthy participants through a virtual reality intervention: study protocol for a non-inferiority randomized controlled trial.

BACKGROUND: Repeated or chronic stress is considered a major source of disease, in terms of both somatic and mental illnesses. The prevention of stress-related disease by interventions for relaxation has thus increased societal relevance. In this randomized controlled non-inferiority trial, we will compare a newly developed virtual reality (VR) environment for relaxation to an active control group applying a freely chosen relaxation method. To test if our VR environment supports relaxation in a situation of acute stress, a standardized stress induction protocol will precede the relaxation phase. METHODS: One hundred healthy participants will be recruited from the University of Siegen and randomly assigned to the VR or the active control group that will be free to choose their own relaxation strategy. The multi-sensory VR includes visual, acoustic, and haptic features to induce a strong feeling of presence. The laboratory testing will comprise a baseline measurement, a stress induction, a relaxation intervention, and a recovery measurement. The primary outcomes are self-reported stress and relaxation measured with a visual analog scale (VAS) at pre- and post-baseline, at the start, middle, and end of the stress induction, at pre- and post-relaxation, at pre- and post-recovery, and in the evening of testing. Secondary outcomes are the physiological parameters, namely heart rate and heart rate variability, tonic skin conductance level as well as the number of non-specific skin conductance responses, systolic and diastolic blood pressure and respiratory rate recorded during the four experimental phases as well as state mood, and state rumination assessed at four time points (pre- and post-stress, post-relaxation, and in the evening of testing). Finally, post-event processing will be assessed after relaxation and in the evening of testing. Repeated measures ANOVAs will be performed to test for statistical effects of group, time, and group × time interaction. DISCUSSION: The newly developed, multi-sensory VR offers an intervention for relaxation without prior training. Its immersive character might increase efficacy compared to other relaxation methods, especially in situations of acute stress. Future directions could be the development of a mobile version of the VR to enhance accessibility for users. To achieve a transfer of training effects to real life, VR components should successively be eliminated until relaxation is practiced without guidance by the VR. TRIAL REGISTRATION: ISRCTN Registry ISRCTN11162338 . Retrospectively registered on January 22, 2021.

Hair cortisol levels in schizophrenia and metabolic syndrome.

AIM: Individuals with schizophrenia demonstrate higher rates of metabolic syndrome (MetS) than the general population. Hair cortisol concentrations (HCC) reflect longer-term cortisol secretion and can provide additional insights into the role of the hypothalamic pituitary adrenal (HPA) axis in schizophrenia and co-occurring MetS. METHODS: In a case-control study of 16 patients with schizophrenia (11 first episode psychosis [FEP] and 5 chronic) and 21 controls hair samples, representing a 3-month retrospective window of cortisol, were collected and analysed utilizing liquid chromatography tandem mass spectrometry. We investigated whether schizophrenia and MetS co-occurrence were associated with HCC utilizing multivariate regression models. We also explored the longitudinal trajectory of HCC in FEP patients by conducting a mixed models analysis. RESULTS: At baseline HCC were significantly lower (Cohen's d = 0.88) in patients with schizophrenia than in controls (p = .014). HCC increased from baseline to month-12 in FEP patients compared to controls, demonstrating a trend towards significance (p = .097). MetS was not associated with HCC at baseline, but HCC increased significantly from baseline to month-12 in relation to MetS (p = .037). CONCLUSIONS: In a subgroup of schizophrenia patients, psychosis may be associated with a blunted HPA axis with lower long-term cortisol output. MetS was associated with an increase in HCC and elevated cortisol levels observed in schizophrenia may be related to increased rates of MetS in schizophrenia patients.

Cross-sectional relation of long-term glucocorticoids in hair with anthropometric measurements and their possible determinants: A systematic review and meta-analysis.

BACKGROUND: Long-term glucocorticoids (HairGC) measured in scalp hair have been associated with body mass index (BMI), waist circumference (WC), and waist-hip-ratio (WHR) in several cross-sectional studies. We aimed to investigate the magnitude, strength, and clinical relevance of these relations across all ages. METHODS: We performed a systematic review and meta-analysis (PROSPERO registration CRD42020205187) searching for articles relating HairGC to measures of obesity. Main outcomes were bivariate correlation coefficients and unadjusted simple linear regression coefficients relating hair cortisol (HairF) and hair cortisone (HairE) to BMI, WC, and WHR. RESULTS: We included k = 146 cohorts (n = 34,342 individuals). HairGC were positively related to all anthropometric measurements. The strongest correlation and largest effect size were seen for HairE-WC: pooled correlation 0.18 (95%CI 0.11-0.24; k = 7; n = 3,158; I2  = 45.7%) and pooled regression coefficient 11.0 cm increase in WC per point increase in 10-log-transformed HairE (pg/mg) on liquid-chromatography-(tandem) mass spectrometry (LC-MS) (95%CI 10.1-11.9 cm; k = 6; n = 3,102). Pooled correlation for HairF-BMI was 0.10 (95%CI 0.08-0.13; k = 122; n = 26,527; I2  = 51.2%) and pooled regression coefficient 0.049 kg/m2 per point increase in 10-log-transformed HairF (pg/mg) on LC-MS (95%CI 0.045-0.054 kg/m2 ; k = 26; n = 11,635). DISCUSSION: There is a consistent positive association between HairGC and BMI, WC, and WHR, most prominently and clinically relevant for HairE-WC. These findings overall suggest an altered setpoint of the hypothalamic-pituitary-adrenal axis with increasing central adiposity.

Ylide-Stabilized Phosphenium Cations: Impact of the Substitution Pattern on the Coordination Chemistry.

Although N-heterocyclic phosphenium (NHP) cations have received considerable research interest due to their application in organocatalysis, including asymmetric synthesis, phosphenium cations with other substitution patterns have hardly been explored. Herein, the preparation of a series of ylide-substituted cations of type [YPR]+ (with Y=Ph3 PC(Ph), R=Ph, Cy or Y) and their structural and coordination properties are reported. Although the diylide-substituted cation forms spontaneous from the chlorophosphine precursor, the monoylidylphosphenium ions required the addition of a halide-abstraction reagent. The molecular structures of the cations reflected the different degrees of electron donation from the ylide to the phosphorus center depending on the second substituent. Molecular orbital analysis confirmed the stronger donor properties of the ylide systems compared to NHPs with the mono-ylide substituted cations featuring a more pronounced electrophilicity. This was mirrored by the reaction of the cations towards gold chloride, in which only the diylide-substituted cation [Y2 P]+ formed the expected LAuCl]+ complex, while the monoylide-substituted compounds reacted to the chlorophosphine ligands by transfer of the chloride from gold to the phosphorus center. These results demonstrate the tunability of ylide-functionalized phosphorus cations, which should allow for further applications in coordination chemistry in the future.

The association between hair cortisol levels, inflammation and cognitive functioning in females.

Glucocorticoids and inflammatory markers can influence cognitive function. Hair cortisol concentrations (HCC) reflect longer-term hypothalamic pituitary adrenal (HPA) axis function and combined with immune markers can provide insights into how HPA-axis and immune pathways interact to influence cognition. We examined the association between HCC and high sensitivity c-reactive protein (hsCRP) levels, as well as the interaction between HCC and hsCRP, and cognitive function in a sample of 153 females, aged between 18 and 79 years, from a cross-sectional case-control study (SHARED ROOTS), conducted in Cape Town, South Africa from May 2014 until June 2017. We examined whether HCC and hsCRP levels were associated with performance on neurocognitive tests in both unadjusted and adjusted linear regression models. HCC demonstrated a significant inverse association with verbal working memory in both unadjusted (p = 0.010) and adjusted (p = 0.016) analyses. There were significant interactions between HCC and hsCRP on verbal intelligence (p = 0.016), language (p = 0.023) and executive function (p = 0.008) scores, such that at low HCC hsCRP levels were positively associated with language (p = 0.020) and executive function (p = 0.006) scores and at high HCC hsCRP levels were inversely associated with verbal intelligence (p = 0.034) scores. Though the results did not survive correction for multiple comparisons, they suggest stress-related neuroendocrine effects on working memory impairment. Furthermore, under physiological conditions and low long-term HCC, there may be positive effects of peripheral inflammatory markers on cognitive performance, whereas there may be detrimental effects when the HPA-axis is dysregulated as reflected by high long-term cortisol output.

Pupil dilation as an index of Pavlovian conditioning. A systematic review and meta-analysis.

The use of pupillometry to track emotional learning processes in humans is generating an increasing interest. Here, we provide a first systematic review and meta-analysis on the value of pupil dilation as a marker of Pavlovian conditioning, focusing on the roles of UCS valence (aversive vs. appetitive), the time course across trials and response intervals within trials. Based on data from 39 independent samples (total n = 1303), our results revealed strong evidence for the overall validity of conditioned pupil responses, with a trend for larger effects in aversive (average g = 0.73) vs. appetitive conditioning (g = 0.39). Response differentiation increased over the course of acquisition. Substantial differentiation effects were found in both early and late response windows. Moderator analyses revealed a consistent influence of UCS modality on differential conditioning, while evidence for moderation by contingency instructions and length of acquisition phase was mixed. The results highlight pupil dilation as a sensitive and reliable index of Pavlovian conditioning across valence categories and stimulus modalities. Important implications regarding methodological considerations and research goals are discussed.

Contemplative Mental Training Reduces Hair Glucocorticoid Levels in a Randomized Clinical Trial.

OBJECTIVE: This study aimed to investigate the effect of regular contemplative mental training on endocrine and psychological indices of long-term stress. METHODS: An open-label efficacy trial that comprised three distinct 3-month long modules targeting attention and interoception, socioaffective, or sociocognitive abilities through dyadic exercises and secularized meditation practices was conducted with healthy adults. Participants underwent the training for 3 or 9 months, or were assigned to a retest control cohort. Chronic stress indices were assayed at four time points: pretraining and after 3, 6, and 9 months. The main outcome measures were cortisol (HC) and cortisone (HE) concentration in hair and self-reported long-term stress. RESULTS: Of 362 initially randomized individuals, 30 dropped out before study initiation (n = 332; mean [SD] age = 40.7 [9.2] years; 197 women). Hair-based glucocorticoid assays were available from n = 227, and questionnaire data from n = 326. Results from three separate training cohorts (TC1-3) revealed consistent decreases in HC and HE levels over the first three (TC3) to 6 months (TC1 and TC2) of training, with no further reduction at the final 9-month mark (baseline to end of training differences, HC, TC1: t(355) = 2.59, p = .010, contrast estimate (est.) [SE] = 0.35 [0.14]; HC, TC2: t(363) = 4.06, p < .001, est. = 0.48 [0.12]; HC, TC3: t(368) = 3.18, p = .002, est. = 0.41 [0.13]; HE, TC1: t(435) = 3.23, p = .001, est. = 0.45 [0.14]; HE, TC2: t(442) = 2.60, p = .010, est. = 0.33 [0.13]; HE, TC3: t(446) = 4.18, p < .001, est. = 0.57 [0.14]). Training effects on HC increased with individual compliance (practice frequency), and effects on both HC and HE were independent of training content and unrelated to change in self-reported chronic stress. Self-reported stress, and cortisol-to-dehydroepiandrosterone ratios as an exploratory endpoint, were also reduced, albeit less consistently. CONCLUSIONS: Our results point to the reduction of long-term cortisol exposure as a mechanism through which meditation-based mental training may exert positive effects on practitioners' health.Trial Registration: ClinicalTrials.gov identifier: NCT01833104.

Lifetime Trauma History and Cognitive Functioning in Major Depression and Their Role for Cognitive-Behavioral Therapy Outcome.

Background: While cognitive-behavioral therapy (CBT) is the gold-standard psychological treatment for major depression (MD), non-response and lacking stability of treatment gains are persistent issues. Potential factors influencing treatment outcome might be lifetime trauma history and possibly associated primarily prefrontal-cortex- and hippocampus-dependent cognitive alterations. Method: We investigated MD and healthy control participants with (MD+T+, n = 37; MD-T+, n = 39) and without lifetime trauma history (MD+T-, n = 26; MD-T-, n = 45) regarding working memory, interference susceptibility, conflict adaptation, and autobiographical memory specificity. Further, MD+T+ (n = 21) and MD+T- groups (n = 16) were re-examined after 25 CBT sessions, with MD-T- individuals (n = 34) invited in parallel in order to explore the stability of cognitive alterations and the predictive value of lifetime trauma history, cognitive functioning, and their interaction for treatment outcome. Results: On a cross-sectional level, MD+T+ showed the highest conflict adaptation, but MD+T- the lowest autobiographical memory specificity, while no group differences emerged for working memory and interference susceptibility. Clinical improvement did not differ between groups and cognitive functioning remained stable over CBT. Further, only a singular predictive association of forward digit span, but no other facets of baseline cognitive functioning, lifetime trauma history, or their interaction with treatment outcome emerged. Discussion: These results indicate differential roles of lifetime trauma history and psychopathology for cognitive functioning in MD, and add to the emerging literature on considering cognitive, next to clinical remission as a relevant treatment outcome.

Cognitive functioning in posttraumatic stress disorder before and after cognitive-behavioral therapy.

Although substantial evidence suggests altered executive functioning and autobiographical memory in posttraumatic stress disorder (PTSD), the clinical significance of these findings remains unclear. Here, we investigated the effects of cognitive-behavioral therapy (CBT) on different aspects of cognitive functioning (working memory, interference susceptibility, conflict adaptation, autobiographical memory) in PTSD patients in a pre-post control group design with a nested cross-sectional element. Cross-sectional analyses at baseline were conducted on 58 PTSD patients, 39 traumatized (TC), and 45 non-traumatized controls (NTC). Intervention effects were investigated before and after 25 CBT sessions in 25 PTSD and 34 untreated NTC individuals assessed in parallel. At baseline, PTSD patients showed higher conflict adaptation than the NTC group and less autobiographical memory specificity than both control groups, suggesting particularly the latter to be a correlate of PTSD. No consistent evidence for treatment-induced improvements in cognitive functioning emerged on the group level or from associations between intra-individual clinical and cognitive changes. Analyses on the role of cognitive functioning on subsequent treatment effects revealed a predictive effect of backward digit span on CBT-induced reductions of depressiveness, but no other significant effects. Our findings highlight the need for further research to identify more relevant predictors of differential treatment response.

No association between FKBP5 gene methylation and acute and long-term cortisol output.

Prior studies identified DNA methylation (DNAM) changes in a regulatory region within the FK506 binding protein 5 (FKBP5) gene as a crucial mediator of long-term negative health outcomes following early adversity. A critical mechanism underlying this link, in turn, has been suggested to be epigenetically induced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The purpose of this study was thus to investigate associations of FKBP5 DNAM with both acute and chronic cortisol output. Two hundred adults with differential exposure to childhood trauma (CT) were underwent a laboratory stressor (Trier Social Stress Test) and provided salivary samples for the analysis of acute cortisol stress responses. In addition, hair cortisol concentrations were determined as a valid measure of integrated long-term cortisol levels. Whole blood samples were drawn for DNAM analyses of FKBP5 intron 7 via bisulfite pyrosequencing. In contrast to most prior work, only healthy participants were included in order to disentangle the effects of trauma exposure per se from those related to mental disorders. First, our findings did not reveal strong evidence for a robust effect of CT on FKBP5 intron 7 DNAM status, even if genetic predisposition (rs1360780 genotype) was taken into account. Second, FKBP5 DNAM levels were found to be unrelated to acute cortisol stress reactivity and long-term cortisol concentration in hair. The failure to demonstrate a significant association between CT and FKBP5 DNAM in an exclusively healthy sample could be interpreted as suggesting that individuals' mental health status may be a critical modulator of previously observed effects.

Hair glucocorticoid levels in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) and metabolic syndrome (MetS) share certain pathophysiological pathways, including hypothalamic pituitary adrenal (HPA) axis dysfunction. Hair glucocorticoid (GC) levels reflect longer-term HPA-axis function and can provide additional insights into the role of a dysregulated HPA-axis in PD and co-occurring cardiovascular disease (CVD) risk. OBJECTIVES: In a case-control study we examined the association of PD diagnosis, clinical features and PD-CVD risk (as defined by the MetS) co-occurrence with hair GC (cortisol and cortisone) levels. METHODS: Hair samples, representing a three-month retrospective window of GC levels, were collected and analysed utilizing liquid chromatography tandem mass spectrometry in 56 females (25 PD patients and 31 controls) of mixed ancestry, aged between 45 and 78 years (PD patients, M = 64.5, SD = 8.4; controls, M = 55.7, SD = 6.9). Multivariate regression models were constructed with PD diagnostic status, clinical features and MetS comorbidity regressed on hair GC levels, adjusting for potential confounders. RESULTS: The prevalence of MetS was 56.0 % in PD patients and 25.8 % in controls. Hair cortisone (adj B = 5.44, 95 % CI 2.05; 8.83, p =  0.002), but not hair cortisol levels (adj B = 0.05, 95 % CI -0.12; 0.22, p =  0.539), were significantly higher (Cohen's d = 0.87) in PD patients than in controls. Non-motor symptoms of PD (e.g., mood and anxiety) were significantly associated with hair cortisone levels (adj B = 0.29, 95 % CI 0.07; 0.51, p =  0.014). MetS was not associated with hair GC levels and there were no significant interactions between PD and MetS on hair GC levels. CONCLUSIONS: This study is the first study reporting on hair GC levels in PD. We found chronically increased cortisone, but not cortisol, levels in PD patients compared to controls. Furthermore, hair cortisone levels were significantly positively associated with PD symptoms related to mood, anhedonia, and anxiety. Hair GC levels were not associated with PD-MetS comorbidity in this sample. Hair cortisone levels may provide additional insights into HPA-axis dysfunction in PD.

Endocannabinoid concentrations in hair and mental health of unaccompanied refugee minors.

Altered activity of the endocannabinoid (EC) system has been linked to dysregulated stress-reactivity and the development of trauma-related psychopathology. The EC system, with its main components anandamide (AEA), 2-arachidonoyl-glycerol (2-AG) and other N-acyl-ethanolamides, is considered to be a buffer system that protects against the negative effects of traumatic experiences on mental health. Recently, the use of hair analyses, a method to gain information on long-term cumulative system activity, has been introduced to the study of ECs. Here, we seek to extend current knowledge on the potential use of hair EC concentrations as a marker of trauma-related psychological symptoms as well as psychological resources. Ninety-one male URM from Syria and Afghanistan (mean age = 17.4 years) living in group homes of the Child Protection Services in Leipzig, Germany, completed assessments on traumatic life events (TLE), PTSD symptoms, depression, anxiety and somatic symptoms as well as on self-efficacy and prosocial behavior. Scalp-near 3 cm hair segments were obtained and EC concentrations quantified using liquid chromatography tandem mass spectrometry. Analyses revealed relatively week and inconsistent associations of hair ECs and psychological symptoms, with only a positive correlation between 2-AG and depression. Concerning prosocial behavior and self-efficacy positive relationships were found with oleoylethanolamide (OEA), stearoylethanolamide (SEA), and palmitoylethanolamide (PEA). Our findings add data concerning the utility of hair EC analyses for PNE research but on a whole fail to reveal a clear association pattern between hair ECs and mental health in URM.

Hair cortisol levels in posttraumatic stress disorder and metabolic syndrome.

Individuals with post-traumatic stress disorder (PTSD) evidence increased rates of metabolic syndrome (MetS), and both PTSD and MetS are associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis function. Few investigations have examined the possible role of HPA-axis dysfunction in the co-occurrence of PTSD and MetS. In a case-control study, we aimed to determine whether hair cortisol concentrations (HCC) were associated with (i) PTSD caseness and severity and (ii) PTSD and MetS co-occurrence. We used the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) to determine PTSD diagnoses and severity scores in 216 females of mixed ancestry aged between 20 and 79 years (M = 43.8, SD =13.3). Hair samples, representing a three-month retrospective window of cortisol levels, were obtained and analyzed utilizing liquid chromatography-tandem mass spectrometry. We constructed multivariate linear regression models to evaluate whether PTSD diagnosis, PTSD severity, and MetS comorbidity were associated with HCC, controlling for potential confounders. HCC were significantly higher (adj ß = 0.154, p = .033; Cohen's d = 0.44) in PTSD patients (n = 110) than trauma-exposed controls (n = 106) and CAPS severity scores (adj ß = 0.207, p = .005) were significantly associated with HCC. MetS was not associated with HCC and there were no significant interactions between PTSD and MetS on HCC. This study provides evidence of a chronically dysregulated neuroendocrine mediated stress response in PTSD, with a clear dose-response relationship. HCC do not, however, appear to have specificity for the comorbidity of PTSD and MetS in this sample.LAY SUMMARYWe found that levels of the stress hormone, cortisol, measured in hair samples were significantly higher in South African women with post-traumatic stress disorder (PTSD) than in women who had also experienced trauma but did not have PTSD. Hair cortisol levels were, however, not associated with metabolic syndrome, a cluster of risk factors for heart disease, in the women studied. We thus show that South African women with PTSD have elevated long-term stress hormone levels and that this effect is related to PTSD and not solely due to trauma exposure.