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Background: While several attempts have been made to elucidate the pathophysiology of burnout, neural stress responses have not yet been investigated. Therefore, the aim of this study was to examine salivary cortisol and - for the first time - neural responses to acute psychosocial stress within a strictly specified sample consisting of individuals suffering from burnout (BO group) and a healthy comparison group (HC group)., Methods: After a multi-stage recruitment procedure based on burnout symptomatology and pathogenesis, 55 individuals suffering from burnout (25 women) and 61 individuals serving as HC group (31 women) out of an initial sample of 1022 volunteers were exposed to acute psychosocial stress during functional magnetic resonance imaging (fMRI) applying ScanSTRESS., Results: No differences were found between the BO and the HC group with respect to cortisol and mean neural stress responses. However, an exploratory comparison of neural stress responses of the first and second run of ScanSTRESS (exposure-time effect) revealed group-specific response patterns in one cluster peaking in the left dorsal anterior cingulate cortex (dACC). While the neural activation of the HC group was higher in the first compared to the second run of ScanSTRESS (i.e., decreasing activation), this pattern was reversed in the BO group (i.e., increasing activation)., Conclusions: Our analysis mainly did not provide evidence for altered acute cortisol and mean neural stress responses in burnout. However, the BO group was characterized by a limited capacity to show decreasing activation over stress exposure-time and exhibited instead increasing activation. Importantly, this group difference manifested in the left dACC which is both involved in neural stress processing and affected in individuals suffering from burnout. Given the present results, it seems promising to further examining temporal dynamics of neural stress responses in (sub-) clinical conditions such as burnout., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Genetic factors contribute significantly to interindividual differences in the susceptibility to stress-related disorders. As stress can also be conceptualized as environmental exposure, controlled gene-environment interaction (GxE) studies with an in-depth phenotyping may help to unravel mechanisms underlying the interplay between genetic factors and stress. In a prospective-longitudinal quasi-experimental study, we investigated whether polygenic scores (PGS) for depression (DEP-PGS) and neuroticism (NEU-PGS), respectively, were associated with responses to chronic stress in daily life. We examined law students (n = 432) over 13 months. Participants in the stress group experienced a long-lasting stress phase, namely the preparation for the first state examination for law students. The control group consisted of law students without particular stress exposure. In the present manuscript, we analyzed perceived stress levels assessed at high frequency and in an ecologically valid manner by ambulatory assessments as well as depression symptoms and two parameters of the cortisol awakening response. The latter was only assessed in a subsample (n = 196). No associations between the DEP-PGS and stress-related variables were found. However, for the NEU-PGS we found a significant GxE effect. Only in individuals experiencing academic stress a higher PGS for neuroticism predicted stronger increases of perceived stress levels until the exam. At baseline, a higher NEU-PGS was associated with higher perceived stress levels in both groups. Despite the small sample size, we provide preliminary evidence that the genetic disposition for neuroticism is associated with stress level increases in daily life during a long-lasting stress period., (© 2023 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)

The importance of amygdala, hippocampus, and medial prefrontal cortex (mPFC) for the integration of neural, endocrine, and affective stress processing was shown in healthy participants and patients with stress-related disorders. The present manuscript which reports on one study-arm of the LawSTRESS project, aimed at investigating the predictive value of acute stress responses in these regions for biopsychological consequences of chronic stress in daily life. The LawSTRESS project examined law students either in preparation for their first state examination (stress group [SG]) or in the mid-phase of their study program (control group [CG]) over 13 months. Ambulatory assessments comprising perceived stress measurements and the cortisol awakening response (CAR) were administered on six sampling points (t1 = - 1 year, t2 = - 3 months, t3 = - 1 week, t4 = exam, t5 =  + 1 week, t6 =  + 1 month). In a subsample of 124 participants (SG: 61; CG: 63), ScanSTRESS was applied at baseline. In the SG but not in the CG, amygdala, hippocampus, and (post-hoc analyzed) right mPFC activation changes during ScanSTRESS were significantly associated with the trajectory of perceived stress but not with the CAR. Consistent with our finding in the total LawSTRESS sample, a significant increase in perceived stress and a blunted CAR over time could be detected in the SG only. Our findings suggest that more pronounced activation decreases of amygdala, hippocampus, and mPFC in response to acute psychosocial stress at baseline were related to a more pronounced increase of stress in daily life over the following year., (© 2023. The Author(s).)

The investigation of the relationship between neural measures of limbic structures and hypothalamic pituitary adrenal axis responses to acute stress exposure in healthy young adults has so far focused in particular on task-based and resting state functional connectivity studies. Thus, the present study examined the association between limbic volume and thickness measures and acute cortisol responses to the psychosocial stress paradigm ScanSTRESS. Using Permutation Analysis of Linear Models controlling for sex, age and total brain volume, the associations between (sex-specific) cortisol increases and human connectome project style anatomical variables of limbic structures (i.e. volume and thickness) were investigated in 66 healthy and young (18-33 years) subjects (35 men, 31 women taking oral contraceptives). In addition, exploratory (sex-specific) bivariate correlations between cortisol increases and structural measures were conducted. The present data provide interesting new insights into the involvement of striato-limbic structures in psychosocial stress processing, suggesting that acute cortisol stress responses are also associated with mere structural measures of the human brain. Thus, our preliminary findings suggest that not only situation- and context-dependent reactions of the limbic system (i.e. blood oxygenation level-dependent reactions) are related to acute (sex-specific) cortisol stress responses but also basal and somewhat more constant structural measures. Our study hereby paves the way for further analyses in this context and highlights the relevance of the topic., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Burnout is characterized by feelings of exhaustion, depersonalization as well as reduced personal accomplishment and is linked to various negative health effects. Previous studies on biological correlates of burnout have focused on the hypothalamic-pituitary-adrenal (HPA) axis. However, especially studies on hair cortisol concentrations (HCC) were often based on cross-sectional data and yielded inconsistent results, probably due to the heterogeneity of the selected samples. Accordingly, the aim of the present study was to investigate cross-sectional as well as longitudinal associations between burnout and HCC within a sample consisting of a strictly specified group of individuals suffering from burnout (BO group) and a healthy comparison group (HC group)., Methods: After a multi-stage recruitment procedure based on burnout symptoms and pathogenesis, eligible subjects (out of an initial sample of 1022 volunteers) were assigned either to a BO (n = 55) or HC group (n = 59), as described in detail in Bärtl et al. (2022). Burnout symptoms as well as HCC (1 cm hair samples) were measured repeatedly at two sampling time points t1 (n = 114) and t2 (n = 100) with an interval of M = 7.20 months (SD = 1.16) between assessments., Results: In the total study sample, no cross-sectional associations between burnout and HCC were found either at t1 or at t2. When the analysis was restricted to the BO group, HCC was positively related to burnout symptomatology at t1 but not t2. In the longitudinal analysis, burnout symptoms at t1 were significant negative predictors of HCC at t2. However, the change in HCC from t1 to t2 was not associated with the change in burnout symptoms., Conclusions: In the present study, we investigated the association between HCC and burnout in a strictly defined sample of subjects suffering from burnout and healthy controls. Our findings mainly do not support our hypotheses. At least, the positive association between HCC and burnout symptoms only within the BO group supports the idea that HPA axis alterations in burnout might only become apparent once a certain threshold of burnout symptomatology has been exceeded, while the longitudinal data provide some empirical evidence for the potential long-term development of hypocortisolism in burnout. However, respective results remain relatively inconclusive., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The present post-hoc analysis of two independent studies conducted in different laboratories aimed at comparing reactions of stress activation systems in response to two different psychosocial stress induction paradigms. Both paradigms are based on the Trier Social Stress Test (TSST) and suited for neuroimaging environments. In an in-depth analysis, data from 67 participants (36 men, 31 women) from a functional magnetic resonance imaging study implementing ScanSTRESS were compared with data from a functional near-infrared spectroscopy (fNIRS) study implementing the so-called 'fNIRS-TSST' including 45 participants (8 men, 37 women). We tested the equivalence of correlation patterns between the stress response measures cortisol, heart rate, affect, and neural responses in the two samples. Moreover, direct comparisons of affective and neural responses were made. Similar correlation structures were identified for all stress activation systems, except for neural contrasts of paradigm conditions (stress vs. control) showing significant differences in association with cortisol, heart rate, and affective variables between the two samples. Furthermore, both stress paradigms elicited comparable affective and cortical stress responses. Apart from methodological differences (e.g., procedure, timing of the paradigms) the present analysis suggests that both paradigms are capable of inducing moderate acute psychosocial stress to a comparable extent with regard to affective and cortical stress responses. Moreover, similar association structures between different stress response systems were found in both studies. Thus, depending on the study objective and the respective advantages of each imaging approach, both paradigms have demonstrated their usefulness for future studies., Competing Interests: Conflict of interest We declare no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

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., Competing Interests: Declaration of Competing Interest none., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The neuropeptide S (NPS) and its receptor (NPSR1) have been implicated in stress regulation and stress-related disorders. The present study aimed at investigating the association between overall genetic variability in the NPS/NPSR1 system and psychological and cortisol stress regulation in everyday life. Our study was conceptualized as a gene-environment-(quasi-) experiment, a design that facilitates the detection of true GxE interactions. As environmental variable, we used the preparation for the first state examination for law students. In the prospective and longitudinal LawSTRESS project, students were examined at six sampling points over a 13-months period. While students who prepared for the exam and experienced long-lasting and significant stress, formed the stress group, law students experiencing usual study-related workload were assigned to the control group. As phenotypes we assessed changes over time in the cortisol awakening response (CAR; n = 176), perceived stress levels (n = 401), and anxiety symptoms (n = 397). The CAR was assessed at each sampling point immediately upon awakening and 30 as well as 45 min later. Perceived stress levels in daily life were measured by repeated ambulatory assessments and anxiety symptoms were repeatedly assessed with the anxiety subscale of the Hospital Anxiety and Depression Scale. With gene-set analyses we examined the joint association of 936 NPS/NPSR1 single nucleotide polymorphisms with the phenotypes to overcome well known limitations of candidate gene studies. As previously reported, we found a blunted CAR during the exam as well as significant increases in perceived stress levels and anxiety symptoms until the exam in the stress group, compared to the control group. The gene-set analysis did not confirm associations between genetic variability in the NPS/NPSR1 system and changes in perceived stress levels and anxiety symptoms. Regarding the CAR, we found a significant GxE interaction for the area under the curve with respect to the ground (p = .050) and a trend towards a significant effect for the area under the curve with respect to the increase (p = .054). When the analysis was restricted to the SG, associations for both CAR parameters were significant (ps < .050). This finding suggests that the association between genetic variability in the NPS/NPSR1 system and the CAR becomes visible under the environmental condition 'chronic stress exposure'. We conclude that the present study complements findings from animal models and that it provides novel evidence for a modulatory influence of the NPS/NPSR1 system on cortisol regulation in humans., Competing Interests: Conflict of interest All authors report no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The externalizing spectrum describes a range of heterogeneous personality traits and behavioral patterns, primarily characterized by antisocial behavior, disinhibition, and substance (mis)use. In psychopathology, abnormalities in neural threat, reward responses and the impulse-control system may be responsible for these externalizing symptoms. Within the non-clinical range, mechanisms remain still unclear. In this fMRI-study, 61 healthy participants (31 men) from the higher versus lower range of the non-clinical variation in externalization (31 participants with high externalization) as assessed by the subscales disinhibition and meanness of the Triarchic-Psychopathy-Measure (TriPM) performed a monetary modified Taylor-Aggression-Paradigm (mTAP). This paradigm consisted of a mock competitive-reaction-time-task played against a fictional opponent with preprogrammed win- and lose-trials. In lose-trials, participants were provoked by subtraction of an amount of money between 0 and 90 cents. As a manipulation check, provocation induced a significant rise in behavioral aggression levels linked with an increased activation in the anterior cingulate cortex (ACC). High externalization predicted reduced ACC responses to provocation. However, high externalizing participants did not behave more aggressively than the low externalization group. Additionally, the high externalizing group showed a significantly lower positive affect while no group differences emerged for negative affect. In conclusion, high externalization in the non-clinical range was related to neural alterations in regions involved in affective decision-making as well as to changes in affect but did not lead to higher behavioral aggression levels in response to the mTAP. This is in line with previous findings suggesting that aberrations at multiple levels are essential for developing externalizing disorders., (© 2022. The Author(s).)

Background: Burnout and chronic work stress have been linked to various negative health outcomes. While the mechanisms underlying this interplay are still unclear, the allostatic load (AL) model was suggested to demonstrate a possible biological pathway. However, previous studies provided divergent results regarding the association between burnout and AL, probably also due to the heterogeneity of selected samples. Therefore, the aim of the present study was to examine differences in AL between a conceptually strictly specified group of individuals suffering from burnout (BO group) and a healthy comparison group (HC group)., Methods: After a multi-stage recruitment procedure with strict inclusion criteria based on burnout symptomatology and pathogenesis, the BO group (n = 56) was compared to the HC group (n = 65) regarding an index of AL. The AL-index included 14 parameters: high-sensitivity c-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), fibrinogen, d-dimer, plasminogen activator inhibitor 1 (PAI-1), glycosylated hemoglobin (HbA1c), high-density lipoprotein (HDL) cholesterol, total cholesterol to HDL cholesterol ratio (TC/HDL), dehydroepiandrosterone-sulphate (DHEA-S), systolic blood pressure (SBP), diastolic blood pressure (DBP), waist-hip ratio (WHR), and body fat percentage., Results: The BO group showed significantly higher AL-scores in comparison to the HC group. This effect remained significant after adjusting for sex, age, and smoking status. Additionally, burnout symptoms (assessed with the Maslach Burnout Inventory; MBI), MBI-subscales emotional exhaustion and depersonalization as well as chronic work stress (assessed with the effort-reward imbalance questionnaire) were significantly associated with higher AL-scores., Conclusions: Consistent with our hypothesis, we detected higher AL-scores in the BO compared to the HC group, indicating a greater cumulative physiological burden in individuals suffering from burnout. Given the high heterogeneity in individuals experiencing burnout symptoms, future studies may focus on well-specified subgroups, when examining the association between burnout and psychophysiological dysregulations., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The LawSTRESS project is a controlled prospective-longitudinal study on psychological, endocrine, central nervous and genetic predictors of responses to long-lasting academic stress in a homogenous cohort. In this first project report, we focused on the association between daily life stress and the cortisol awakening response (CAR). The CAR, a distinct cortisol rise in the first 30-45 min after morning awakening, is a well-established marker of cortisol regulation in psychoneuroendocrinology. Law students from Bavarian universities (total n = 452) have been studied over a 13-months period at six sampling points starting 12 months prior exam. The stress group (SG) consisted of students experiencing a long-lasting and significant stress period, namely the preparation for the first state examination for law students. Law students assigned to the control group (CG) were studied over an equally long period without particular and sustained stress exposure. To investigate stress related alterations in the CAR, we examined a subsample of the LawSTRESS project consisting of 204 students with 97 participants from the SG (69.1% female, mean age = 22.84 ± 1.82) and 107 from the CG (78.5% female, mean age = 20.95 ± 1.93). At each sampling point, saliva samples for cortisol assessment were collected immediately upon awakening and 30 as well as 45 min later. Perceived stress in daily life was measured by repeated ambulatory assessments (about 100 queries over six sampling points). The time course of perceived stress levels in the two groups differed significantly, with the SG showing an increase in perceived stress until the exam and a decrease thereafter. Stress levels in the CG were relatively stable. The CAR was not significantly different between groups at baseline. However, a blunted CAR in the SG compared to the baseline measure and to the CG developed over the measurement timepoints and reached significance during the exam. Remarkably, this effect was neither associated with the increase in perceived stress nor with anxiety and depression symptoms, test anxiety and chronic stress at baseline. The present study successfully assessed multidimensional stress trajectories over 13 months and it documented the significant burden, law students preparing for the first state examination are exposed to. This period was related to a blunted CAR with presumed physiological consequences (e.g., on energy metabolism and immune function). Mean psychological stress levels as well as the CAR returned to baseline levels after the exam, suggesting a fast recovery in the majority of the participants., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Stress is a major threat to well-being that manifests in a variety of physiological and mental symptoms. Utilising speech samples collected while the subject is undergoing an induced stress episode has recently shown promising results for the automatic characterisation of individual stress responses. In this work, we introduce new findings that shed light onto whether speech signals are suited to model physiological biomarkers, as obtained via cortisol measurements, or self-assessed appraisal and affect measurements. Our results show that different indicators impact acoustic features in a diverse way, but that their complimentary information can nevertheless be effectively harnessed by a multi-tasking architecture to improve prediction performance for all of them.

Fear is a phasic state of apprehension to an imminent threat, whereas anxiety is a more sustained state of expecting a potential threat leading to tension and worry. The NPU-threat test is a laboratory startle paradigm allowing a reliable and valid assessment of both, fear- and anxiety-potentiated reactions. It is suggested to differentiate between anxiety disorders, but little is known on associations with everyday life experiences of cognitive-emotional processes regarding anxiety in non-clinical samples. In the present project, the NPU-threat test was applied in three studies with (1) unselected healthy individuals, (2) participants with extreme manifestations of trait anxiety (low vs. high) and (3) individuals preparing for a high-stakes exam. Self-reported states of emotionality and worry were assessed during a four-day ambulatory assessment (AA). Overall, NPU-threat test measures did not significantly differ between studies, while the AA dependent measures were sufficiently sensitive to capture differences between groups. However, there was no significant association between psychophysiological measures of the NPU-threat test and AA state measures across participants. In participants recruited for low vs. high trait anxiety we found an association with AA worry and emotionality, but no interaction with potentiated startle. The present findings do not support the idea of a link between our laboratory biomarker and adaptive regulation of cognitive-emotional states in everyday life in healthy individuals. We speculate that an association between laboratory physiological measures and everyday experience of anxious states may be detectable in clinical samples., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The externalizing spectrum is characterized by disinhibition, impulsivity, antisocial-aggressive behavior as well as substance (mis)use. Studies in forensic samples and mentally impaired children suggested that higher rates of externalization are linked to lower cortisol stress responses and altered affect-related neural activation. In this fMRI-study, we investigated whether externalizing behavior in healthy participants is likewise associated with altered cortisol responses and neural activity to stress. Following a quasi-experimental approach, we tested healthy participants (N = 61, 31 males) from the higher versus lower range of the non-clinical variation in externalization (31 participants with high externalization) as assessed by the subscales disinhibition and meanness of the Triarchic-Psychopathy-Measure. All participants were exposed to ScanSTRESS, a standardized psychosocial stress paradigm for scanner environments. In both groups, ScanSTRESS induced a significant rise in cortisol levels with the high externalization group showing significantly lower cortisol responses to stress than the low externalization group. This was mainly driven by males. Further, individual increases in cortisol predicted neural response differences between externalization groups, indicating more activation in the dorsal striatum in low externalization. This was primarily driven by females. In contrast, post-hoc analysis showed that hypothalamic-pituitary-adrenal axis hyporeactivity in males was associated with prefrontal and hippocampal activation. Our data substantiate that individuals from the general population high on externalization, show reduced cortisol stress responses. Furthermore, dorsal striatum activity as part of the mesolimbic system, known to be sensitive to environmental adversity, seems to play a role in externalization-specific cortisol stress responses. Beyond that, a modulating influence of gender was disclosed., (© 2021 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Although women and men differ in psychological and endocrine stress responses as well as in the prevalence rates of stress-related disorders, knowledge on sex differences regarding stress regulation in the brain is scarce. Therefore, we performed an in-depth analysis of data from 67 healthy participants (31 women, taking oral contraceptives), who were exposed to the ScanSTRESS paradigm in a functional magnetic resonance imaging study. Changes in cortisol, affect, heart rate and neural activation in response to psychosocial stress were examined in women and men as well as potential sex-specific interactions between stress response domains. Stress exposure led to significant cortisol increases, with men exhibiting higher levels than women. Depending on sex, cortisol elevations were differently associated with stress-related responses in striato-limbic structures: higher increases were associated with activations in men but with deactivations in women. Regarding affect or heart rate responses, no sex differences emerged. Although women and men differ in their overall stress reactivity, our findings do not support the idea of distinct neural networks as the base of this difference. Instead, we found differential stress reactions for women and men in identical structures. We propose considering quantitative predictors such as sex-specific cortisol increases when exploring neural response differences of women and men., (© The Author(s) 2021. Published by Oxford University Press.)

There is increasing empirical evidence that social distance and timing affect prosocial behavior after acute stress exposure. The present study focused on everyday moral decision-making after acute psychosocial stress and how it is influenced by effects of social closeness and timing. We exposed 40 young healthy men to the Trier Social Stress Test (TSST, n  = 20) or its non-stressful placebo version (PTSST, n  = 20). Moral decision-making was assessed early (+10 until +30 min) and late (+75 until +95 min) after (P)TSST exposure by the Everyday Moral Conflict Situations (EMCS) Scale. The EMCS Scale requests altruistic versus egoistic responses to everyday moral conflict situations with varying closeness of target persons. Results revealed significantly higher total percentages of altruistic decisions in the stress than in the control condition and for scenarios involving socially close (e.g., mother) versus socially distant (e.g., stranger) protagonists, while the main effect of timing was nonsignificant. Only secondary analyses showed increased altruistic decision-making after acute stress exposure toward socially close but not toward distant protagonists at the early but not at the late point of measurement. Moreover, psychological stress responses and personality traits were significantly associated with EMCS scores. Positive correlations between cortisol levels and altruistic decision-making were descriptively observable, but did not reach statistical significance. In sum, our findings suggest increased altruistic decision-making toward socially close compared to socially distant protagonists and provide further evidence that acute stress influences decision-making in everyday moral conflict scenarios in a prosocial manner.Lay summaryIn order to investigate the effects of acute stress on everyday moral decision-making, 40 young healthy men were exposed to moderate psychosocial stress by the use of the Trier Social Stress Test (TSST) or its non-stressful placebo version and then completed a hypothetical everyday moral decision-making paradigm. Our findings provide evidence that acute stress exposure influences decision-making in everyday moral conflict situations in a prosocial manner. Furthermore, participants decided more altruistically in scenarios involving socially close (e.g., mother) versus socially distant (e.g., stranger) protagonists.

Exposure to acute psychosocial stress has been shown to affect moral decision-making, though little is known about potential gender differences or effects of personality. In two within-subjects design studies, 179 healthy men and women (N = 99 in Study 1, N = 80 in Study 2) were exposed to the Trier Social Stress Test (TSST) and a non-stress control condition (resting period) on two testing days in random order. After stress/resting, moral decision-making was assessed by the Everyday Moral Conflict Situations (EMCS) Scale (Singer et al., 2019), which requests altruistic versus egoistic responses to everyday moral conflict scenarios with varying closeness of target persons. We investigated effects of acute stress, social closeness, participants' gender, and the a priori selected personality traits agreeableness, empathy, and social desirability on everyday moral decision-making. Despite high statistical power, we could neither confirm the hypothesized effects of acute stress nor social closeness on EMCS scores in both samples. However, our data revealed a prosocial impact of acute stress on everyday moral decisions rather in females than males as well as effects of agreeableness and social desirability. Salivary alpha-amylase (sAA) levels in Study 1 and cortisol levels in females in Study 2 were significantly correlated with higher EMCS scores after acute stress exposure. Additionally, lower anticipatory subjective stress responses were associated with more altruistic decisions. Moreover, we found positive relationships between hypothetical moral decision-making and real prosocial behavior (opportunity for a charitable donation). In sum, due to methodological differences compared to previous between-subjects design studies, it might not be justified to rule out effects of acute stress on everyday moral decision-making based on the current within-subjects results. Nevertheless, the present data suggest that specific personality traits like agreeableness might have a stronger impact on everyday moral decision-making than short term-exposure to acute stress., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Understanding the interplay between central nervous system and hypothalamic-pituitary-adrenal axis responses to stress in humans is assumed to be essential to contribute to the central question of stress research, namely how stress can increase disease risk. Therefore, the present study used a neuroimaging stress paradigm to investigate the interplay of 3 stress response domains. Furthermore, we asked if the brain's stress response changes over exposure time., Methods: In a functional magnetic resonance imaging study, changes in brain activation, cortisol levels, affect, and heart rate in response to an improved ScanSTRESS protocol were assessed in 67 young, healthy participants (31 females)., Results: Stress exposure led to significant increases in cortisol levels, heart rate, and negative affect ratings as well as to activations and deactivations in (pre)limbic regions. When cortisol increase was used as a covariate, stronger responses in the hippocampus, amygdala, medial prefrontal cortex, and cingulate gyrus were observed. Responses within the same regions predicted negative affect ratings. Remarkably, an increasing deactivation over the two ScanSTRESS runs was found, again, in the same structures. A reanalysis of an independent sample confirmed this finding., Conclusions: For the first time, reactions in a cluster of (pre)limbic structures was consistently found to be associated with changes in cortisol and negative affect. The same neural structures showed increasing deactivations over stress exposure time. We speculate that investigating possible associations between exposure-time effects in neural stress responses and stress-related interindividual differences (e.g., chronic stress) might be a promising new avenue in stress research., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Sugar administration prior acute psychosocial stress exposure was shown to enhance subsequent salivary cortisol responses. However, this finding is based on studies that have administered high doses of glucose to male subjects after long fasting periods. Therefore, in the present study, we investigated the effect of different sugar-containing drinks on acute cortisol stress responses under experimental conditions that are commonplace in stress research and our sample included females and males. Our primary aim was to derive feasible recommendations for a standardized sugar administration in future studies. Of the 103 healthy young participants (49 females, 54 males), 72 were confronted with the Trier Social Stress Test after being randomly assigned to one of three sugar conditions (200 ml of grape juice, a 75 g glucose or a 75 g maltodextrin drink); 31 subjects served as control sample and were exposed to the TSST without sugar administration. Cortisol stress responses were significantly enhanced in the grape juice as well as the glucose group as compared to the control group. Post hoc analysis revealed that this effect seemed to be more pronounced in males than in females. We did not find a significant effect of maltodextrin. Cortisol responder rates in all three experimental groups were higher than in the control group. Our results suggest that, at least in males, the administration of 200 ml of grape juice is sufficient to facilitate HPA axis reactivity and to minimize confounding effects due to interindividual differences in energy availability while being exposed to a laboratory stress paradigm. The unexpected gender-specific effect is of potential relevance and should be scrutinized in future studies., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Stress is an ubiquitous phenomenon with significant impact on human physiology when it lasts too long, when it is too intense, or when it hits vulnerable individuals. Examining the mechanisms linking stress exposure with health and disease is an important endeavor in psychoneuroendocrine research. Empirical evidence so far revealed large intra- as well as inter-individual variability in hypothalamic-pituitary-adrenal (HPA) axis responses to acute psychosocial stress, showing that the HPA axis is a highly adaptive system. Thus, the characterization of intra- und inter-individual patterns of HPA axis reactivity is of high scientific interest and forms the basis on which mechanistic links between stress response (dys)regulation and health impairments can be examined. To date, basic knowledge has been, and still is, accumulated on demographic, biological (including genetic and epigenetic) factors, lifestyle behavioral variables, consumption of substances and medication, psychological and personality factors, as well as on methodological aspects. Besides this, there is also very recent progress in respect to the development of laboratory stress paradigms that can be applied in virtual reality or inside an MRI-scanner. In sum, the present review updates our current knowledge on moderating and intervening factors as sources of intra- und inter-individual variability in human cortisol stress responses and offers recommendations for future research designs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In everyday life, we are often confronted with morally conflicting social interaction situations. Therefore, the main objective of the present set of studies was the development and validation of a new measure to assess decision-making in everyday moral conflict situations. All vignettes required a decision between an altruistic versus an egoistic behavioral response alternative. In three independent surveys (N = 200), we developed a 40-items measure with preferable mean rates of altruistic decisions (Study 1), clear representation of altruistic and egoistic response classes (Study 2), unambiguousness of social closeness classifications (socially close vs. socially distant protagonists; Studies 1 and 2), and high similarity to reality ratings (Studies 1 and 2). Additionally, we developed two parallelized item sets for future use in within-subjects design studies and investigated the measurement properties of our new scale (Studies 1 and 3). Results of Rasch model analyses and classical test theory fit indices showed unidimensionality and confirmed the appropriateness of the fragmentation into two parallelized item sets. Notably, in our data, there were neither effects of social closeness nor gender on the percentage of altruistic decisions. In sum, we propose the Everyday Moral Conflict Situations (EMCS) Scale as a promising new measurement tool that may facilitate further research in different research areas due to its broad applicability., Competing Interests: The authors have declared that no competing interests exist.

Even though chronic stress is a pervasive problem in contemporary societies and is known to potentially precede both adverse psychological as well as physiological conditions, its effects on decision making have not been systematically investigated. In this paper, we focus on the relation between self-reported chronic stress and self-reported as well as behaviorally shown social preferences. We measured chronic stress with the Trier Inventory for Chronic Stress. To determine social preferences, participants played a double anonymous dictator game. In order to control for the robustness of social preferences we employed a 2x2x2x2 design where we manipulated four variables: the frame (Give to Recipient vs. Take from Recipient), the decision maker's gender (Female vs. Male), the recipient's gender (Female vs. Male), and the nature of the reward (Real vs. Hypothetical). Results show that perceived chronic stress is not significantly related to social preferences in monetarily rewarded dictator decisions for either gender. However, women's displayed preferences for hypothetical rewards are negatively correlated to chronic stress levels. This indicates that higher chronic stress in women is associated with lower hypothetical transfers but not with altered actual behavior as compared to non-stressed women. For men, we do not observe such effects. Our findings suggest that, while chronic stress leaves social preferences unaffected in an incentive compatible task, it might foster what could be interpreted as a decrease in self-image promotion in women. Thus, we conclude that in a thoroughly controlled behavioral task differences in reported chronic stress do not entail differences in social preferences, but relate to variation in hypothetical decisions for women., Competing Interests: The authors have declared that no competing interests exist.

In a randomized controlled trial, we investigated the effects of karate versus a mindfulness-based stress reduction (MBSR) intervention on well-being and cognitive functioning in older adults. Fifty-five adults (52-81 years old) participated in twice-weekly karate versus MBSR sessions or no training for 8 weeks. In pre- and postassessments, subjective well-being, health, cognitive functioning, and chronic stress were measured. Preassessment hair cortisol served as physiological stress marker. The results showed an improvement for the karate group, but not the MBSR and control group, in subjective mental health and anxiety as well as cognitive processing speed. The MBSR group showed by trend as a decrease in stress. No significant correlation between preassessment hair cortisol and postassessment outcomes could be established. But the higher the level of baseline self-reported perceived stress, the higher the increase in depression, anxiety, and chronic stress. Generally, it can be assumed that karate and MBSR showed only small training effects concerning the assessed emotional and cognitive parameters.

The quantification of salivary oxytocin (OXT) concentrations emerges as a helpful tool to assess peripheral OXT secretion at baseline and after various challenges in healthy and clinical populations. Both positive social interactions and stress are known to induce OXT secretion, but the relative influence of either of these triggers is not well delineated. Choir singing is an activity known to improve mood and to induce feelings of social closeness, and may therefore be used to investigate the effects of positive social experiences on OXT system activity. We quantified mood and salivary OXT and cortisol (CORT) concentrations before, during, and after both choir and solo singing performed in a randomized order in the same participants (repeated measures). Happiness was increased, and worry and sadness as well as salivary CORT concentrations were reduced, after both choir and solo singing. Surprisingly, salivary OXT concentrations were significantly reduced after choir singing, but did not change in response to solo singing. Salivary OXT concentrations showed high intra-individual stability, whereas salivary CORT concentrations fluctuated between days within participants. The present data indicate that the social experience of choir singing does not induce peripheral OXT secretion, as indicated by unchanged salivary OXT levels. Rather, the reduction of stress/arousal experienced during choir singing may lead to an inhibition of peripheral OXT secretion. These data are important for the interpretation of future reports on salivary OXT concentrations, and emphasize the need to strictly control for stress/arousal when designing similar experiments.

In everyday life, moral decisions must frequently be made under acute stress. Although there is increasing evidence that both stress and cortisol affect moral judgment and behavior as well as decision-making in various domains unrelated to morality, surprisingly few attempts have been made to explore the effects of stress on everyday moral decision-making. Therefore, in the present study, we exposed 50 young healthy men to the Trier Social Stress Test (TSST) or its non-stressful placebo version (PTSST). We investigated the impact of acute stress exposure and stress-related cortisol levels on decision-making, decision certainty, and emotions in 28 everyday moral conflict situations with altruistic versus egoistic response alternatives. Results showed that the TSST-exposed group made more altruistic decisions than the non-stress control group, while groups did not differ in decision certainty and emotion ratings. Moreover, in correlational as well as regression analyses, additionally controlling for confounding variables, we observed significant positive associations between cortisol levels and altruistic decision-making. Further analyses revealed that altruistic decisions came along with significantly higher decision certainty and significantly more positive emotion ratings than egoistic decisions. Notably, our data also raise the idea that the personality trait agreeableness plays an important role in everyday moral decision-making. In sum, our findings provide initial evidence that both acute stress exposure and cortisol levels have prosocial effects on everyday moral decision-making in young healthy men., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The Trier Social Stress Test (TSST) is the most widely used laboratory stress protocol in psychoneuroendocrinology. Despite its popularity, surprisingly few attempts have been made to explore the ecological validity of the TSST. In the present study, 31 young healthy subjects (24 females) were exposed to the TSST about 4 weeks before completing an oral exam on a separate day. Salivary cortisol levels increased significantly in response to both stimuli (TSST: F(2.21, 66.33)=5.73, p=0.004; oral exam: F(1.98, 59.28)=4.38, p=0.017) with similar mean response curves and significant correlations between cortisol increases and areas under the response curves (increase: r=0.67; AUC: r=0.56; both p≤0.01). Correspondingly, changes in positive and negative affect did also show significant correlations between conditions (increase: positive affect: r=0.36; negative affect: r=0.50; both: p≤0.05; AUC: positive affect: r=0.81; negative affect: r=0.70; both p≤0.01) while mean time course dynamics were significantly different (positive affect: F(2.55, 76.60)=10.15, p=0.001; negative affect: F(1.56, 46.82)=23.32, p=0.001), indicating that the oral exam had a more pronounced impact on affect than the TSST. Our findings provide new evidence for the view that cortisol as well as subjective stress responses to the TSST are indeed significantly associated with acute stress responses in real life., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Chronic stress is a public health problem that affects a significant part of the population. While the physiological damage it causes is under ongoing scrutiny, its behavioral effects have been overlooked. This is one of the first studies to examine the relation between chronic stress and decision-making, using a standard lottery paradigm. We measured risk taking in the gain domain through binary choices between financially incentivized lotteries. We then measured self-reported chronic stress with the Trier Inventory for the Assessment of Chronic Stress (TICS). We additionally collected hair samples in a subsample of volunteers, in order to quantify accumulation of the stress hormone cortisol. We discovered a significant positive, though modest, correlation between self-reported chronic stress and risk taking that is stronger for women than for men. This confirms part of the findings in acute stress research that show a connection between higher stress and increased risk taking. However, unlike the biologically-based results from acute stress research, we did not identify a significant relation between hair cortisol and behavior. In line with previous literature, we found a clear gender difference in risk taking and self-reports: women generally take less risk and report slightly higher stress levels than men. We conclude that perceived chronic stress can impact behavior in risky situations.

The cortisol awakening response (CAR), the marked increase in cortisol secretion over the first 30-45 min after morning awakening, has been related to a wide range of psychosocial, physical and mental health parameters, making it a key variable for psychoneuroendocrinological research. The CAR is typically assessed from self-collection of saliva samples within the domestic setting. While this confers ecological validity, it lacks direct researcher oversight which can be problematic as the validity of CAR measurement critically relies on participants closely following a timed sampling schedule, beginning with the moment of awakening. Researchers assessing the CAR thus need to take important steps to maximize and monitor saliva sampling accuracy as well as consider a range of other relevant methodological factors. To promote best practice of future research in this field, the International Society of Psychoneuroendocrinology initiated an expert panel charged with (i) summarizing relevant evidence and collective experience on methodological factors affecting CAR assessment and (ii) formulating clear consensus guidelines for future research. The present report summarizes the results of this undertaking. Consensus guidelines are presented on central aspects of CAR assessment, including objective control of sampling accuracy/adherence, participant instructions, covariate accounting, sampling protocols, quantification strategies as well as reporting and interpreting of CAR data. Meeting these methodological standards in future research will create more powerful research designs, thus yielding more reliable and reproducible results and helping to further advance understanding in this evolving field of research., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The consistent gender differences favoring males in some spatial abilities like mental rotation have raised the question of whether testosterone or other gonadal hormones contribute to these differences--especially because such gender differences seem to appear mainly from the age of puberty on. Studies generally suggest that spatial ability is facilitated by moderately high testosterone levels (i.e., levels that are relatively high for females and relatively low for males). However, the role of sex steroids for mental-rotation performance of (pre-) pubertal children has not been the focus of research, yet. In our study, the relationships between different aspects of mental-rotation performance (accuracy, reaction time, rotation speed) and salivary testosterone and estradiol levels were investigated. Subjects were 109 children (51 boys and 58 girls) aged between 9 and 14 years (M = 11.41, SD = 1.74). They performed a chronometric mental-rotations test, in which the stimuli consisted of three-dimensional drawings of Shepard and Metzler cube figures. In addition, saliva samples were gathered for the analysis of free testosterone and estradiol levels. Results showed a significant gender difference in reaction time and rotational speed in favor of boys, and a significant age, but no gender difference in testosterone and estradiol levels. We found no significant relationships between hormonal levels and any measure of mental-rotation performance., (© 2015 Wiley Periodicals, Inc.)

Background: Prior research indicates that blacks and Hispanics/Latinos have flatter diurnal cortisol declines across the day, a profile associated with poorer health. The stability of racial and ethnic differences in cortisol levels over time is not well understood, and additional research is needed to establish racial and ethnic differences in psychosocial stress levels as related to changes in cortisol levels., Methods: With data from a community-based study of 152 adults (mean age = 58 years; 53% women; 34% black, 26% Hispanic/Latino), we examined the magnitude of racial and ethnic differences over a 5-year period. Salivary cortisol samples were obtained 3 times per day for 3 days in Years 1, 3, 4, and 5. Life events and chronic stress were assessed by questionnaires in which participants reported on whether they had experienced specific types of events or stress within the past year. Depressive symptoms scales (Center for Epidemiologic Studies of Depression Scale) were also administered annually. Daily cortisol slopes were calculated by subtracting wakeup cortisol from bedtime levels and dividing by hours awake., Results: Increases in psychosocial stress were associated with flatter cortisol slopes among blacks (β = 0.010) and Hispanics/Latinos (β = 0.014), although including cardiovascular disease risk factors attenuates associations in blacks (β = 0.007; p = .125). Higher income predicts a steepening of cortisol rhythms across the study (β = -0.003; p = .019)., Conclusions: Racial and ethnic differences in diurnal cortisol rhythms are stable over time. However, the magnitude of changes in cortisol levels associated with chronic stress levels may vary by racial and ethnic subgroups.

Economic decisions are often made in stressful situations (e.g., at the trading floor), but the effects of stress on economic decision making have not been systematically investigated so far. The present study examines how acute stress influences economic decision making under uncertainty (risk and ambiguity) using financially incentivized lotteries. We varied the domain of decision making as well as the expected value of the risky prospect. Importantly, no feedback was provided to investigate risk taking and ambiguity aversion independent from learning processes. In a sample of 75 healthy young participants, 55 of whom underwent a stress induction protocol (Trier Social Stress Test for Groups), we observed more risk seeking for gains. This effect was restricted to a subgroup of participants that showed a robust cortisol response to acute stress (n = 26). Gambling under ambiguity, in contrast to gambling under risk, was not influenced by the cortisol response to stress. These results show that acute psychosocial stress affects economic decision making under risk, independent of learning processes. Our results further point to the importance of cortisol as a mediator of this effect.

We investigate how emotional exhaustion (EE), the core component of burnout, relates to cognitive performance, job performance and health. Cognitive performance was assessed by self-rated cognitive stress symptoms, self-rated and peer-rated cognitive impairments in everyday tasks and a neuropsychological test of learning and memory (LGT-3); job performance and physical health were gauged by self-reports. Cross-sectional linear regression analyses in a sample of 100 teachers confirm that EE is negatively related to cognitive performance as assessed by self-rating and peer-rating as well as neuropsychological testing (all p < .05). Longitudinal linear regression analyses confirm similar trends (p < .10) for self-rated and peer-rated cognitive performance. Executive control deficits might explain impaired cognitive performance in EE. In longitudinal analyses, EE also significantly predicts physical health. Contrary to our expectations, EE does not affect job performance. When reversed causation is tested, none of the outcome variables at Time 1 predict EE at Time 2. This speaks against cognitive dysfunctioning serving as a vulnerability factor for exhaustion. In sum, results underpin the negative consequences of EE for cognitive performance and health, which are relevant for individuals and organizations alike. In this way, findings might contribute to the understanding of the burnout syndrome., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: We investigated how matching and non-matching demands and resources are related to emotional exhaustion (EE) in teachers. Theoretically, we draw on the Demand-Induced Strain Compensation (DISC) model that proposes that demands, resources, and strains are multidimensional and comprise emotional, cognitive, and physical components. We first tested whether resources compensate aversive effects of demands. Second, as proposed by the triple-match principle, we tested whether interaction effects between job demands and resources are most likely if demands, resources, and outcomes relate to the same dimension., Methods: We retrieved data from 177 school teachers; a subsample was re-examined after a time lag of about 21 month (N = 56)., Results: Linear regression analyses reveal concurrent and longitudinal main and interaction effects of teacher-specific emotional and cognitive job demands and resources on EE., Conclusion: Results support the compensation principle and triple-match principle. Therefore, the DISC model seems to provide a valuable framework for the study of interaction effects in job stress research and, in particular, for interventions to reduce job strain in teachers., (© 2013 The Authors. Applied Psychology: Health and Well-Being © 2013 The International Association of Applied Psychology.)

Ambulatory assessments of hypothalamus-pituitary-adrenal axis responses to acute natural stressors yield evidence on stress regulation with high ecological validity. Sampling of salivary cortisol is a standard technique in this field. In 21 healthy student teachers, we assessed cortisol responses to a demonstration lesson. On a control day, sampling was repeated at analogous times. Additionally, the cortisol awakening response (CAR) was assessed on both days. Participants were also exposed to a laboratory stressor, the Trier Social Stress Test, and rated their individual levels of chronic work stress. In pre-to-post-stress assessment, cortisol levels declined after the lesson. However, post-stress cortisol levels were significantly higher compared with those on the control day. Also, the Trier Social Stress Test yielded higher cortisol responses when using the control day as reference baseline. Associations between the CAR and chronic stress measures were observed solely on the control day. There were no significant associations between cortisol responses to the natural and laboratory stressors. Our results indicate that a control day might be an important complement in laboratory but especially in ambulatory stress research. Furthermore, associations between chronic stress measures and the CAR might be obscured by acute stress exposure. Finally, responses to the laboratory stressor do not seem to mirror natural stress responses., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: According to the effort-reward-imbalance (ERI) model, a lack of reciprocity between costs and gains at work increases the risk for adverse health outcomes. Inflammation has been shown to play a crucial role in a variety of stress-related diseases and alterations in immune system glucocorticoid sensitivity may help to explain the increased risk for cardiovascular disease (CVD) and depression related to chronic work stress., Methods: Changes in lipopolysaccharide (LPS)-induced interleukin (IL)-6 production and inhibition of IL-6 production by dexamethasone in reaction to the Trier Social Stress Test (TSST) were assessed in forty-six healthy school teachers to test whether chronic work stress is accompanied by alterations in inflammatory activity and glucocorticoid sensitivity of the innate immune system., Results: High ERI was associated with an increase in pro-inflammatory potential, reflected in elevated IL-6 production before and after stress and with a lower capacity of dexamethasone to suppress IL-6 production in vitro over all measurement time points. ERI was not associated with stress-related changes in GC sensitivity., Conclusion: The present findings suggest a less effective anti-inflammatory regulation by glucocorticoids in teachers suffering from chronic work stress., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus-pituitary-adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30-64 years): a low-dose adrenocorticotrophic hormone (ACTH(1-24), Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone-corticotropin releasing hormone (DEX-CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at - 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort-reward-imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX-CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis.

Background: One of the most widely studied genetic polymorphisms regarding cognitive and emotional phenotypes is the COMT Val158Met polymorphism that influences dopamine availability in the prefrontal cortex (PFC). The PFC is the key brain structure for higher cognitive functions such as working memory, as well as an important regulatory site and target of the psychoendocrine stress response. Dopamine is thought to influence PFC functions in an inverted u-shaped manner. Thus, a stress-related increase in prefrontal dopamine is hypothesized to exert differential effects on working memory performance depending on the genetically determined baseline dopamine level in the PFC., Method: Thirty-three healthy young subjects homozygous for the COMT Val158Met polymorphism were selected from a larger pre-genotyped sample. They performed an n-back working memory task after exposure to a laboratory psychosocial stress induction paradigm (The Trier Social Stress Test for Groups; TSST-G)., Results: Under stress, working memory performance of Met homozygotes was significantly worse than working memory performance of Val homozygotes. Importantly, this genotype effect was restricted to the medium difficulty level of the n-back task., Conclusion: Our results demonstrate that working memory performance under stress is influenced by genetic variation in prefrontal dopamine levels. More generally, our results point to the importance of considering the complex interaction of genes, environment, and task variables., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The impact of stress on health and disease is an important research topic in psychosomatic medicine. Because research on hypothalamic-pituitary-adrenal (HPA) axis regulation under controlled laboratory studies lacks ecological validity, it needs to be complemented by a research program that includes momentary ambulatory assessment. The measurement of salivary cortisol offers the possibility to trace the free steroid hormone concentrations in ambulant settings. Therefore, in this article, we first discuss the role of salivary cortisol in ambulatory monitoring. We start with a brief description of HPA axis regulation, and we then consider cortisol assessments in other organic materials, followed by a presentation of common salivary markers of HPA axis regulation suitable for ambulatory assessment. We further provide an overview on assessment designs and sources of variability within and between subjects (intervening variables), acknowledge the issue of (non)compliance, and address statistical aspects. We further give an overview of associations with psychosocial and health-related variables relevant for ambulatory assessment. Finally, we deal with preanalytical aspects of laboratory salivary cortisol analysis. The relative simplicity of salivary cortisol assessment protocols may lead to an overoptimistic view of the robustness of this method. We thus discuss several important issues related to the collection and storage of saliva samples and present empirical data on the stability of salivary cortisol measurements over time.

Unlabelled: OBEJECTS: This study examined the physical and mental health of orchestra musicians of different types of orchestras compared to a reference sample of the general population and of two other professions., Methods: Professional musicians (n = 429) from nine opera and/or concert orchestras were surveyed with the Short Form-12 general health questionnaire (SF-12). Data were compared with a reference sample (n = 2805) with a sample of physicians (n = 549) and aircraft manufacturers (n = 822)., Results: Compared to the reference sample and the two other professional groups, the musicians had a higher physical health score: 53.07 (SD 5.89) vs 49.03 (SD 9.35) reference, 51.26 (SD 7.53) physicians, and 49.31 (SD 7.99) aircraft manufacturers. The musicians' mental health score was lower compared to the reference sample but did not differ from the other professional groups: 48.33 (SD 9.52) for musicians vs 52.24 (SD 8.10) reference, 48.26 (SD 10.06) physicians, and 48.54 (SD 9.59) aircraft manufacturers. Physical health but not mental health decreased with age in all groups. In physical and mental health, women scored lower than men. There was no significant difference in physical and mental health scores between musicians of concert and opera orchestras. Age and gender accounted for 3.6% of the variance of the physical health score, but none of the demographic characteristics or orchestral roles and functions was predictive for mental health scores., Conclusions: Musicians report better physical but poorer mental health than the general population, but they did not differ in mental health scores from physicians or aircraft manufacturers.

The cortisol awakening response (CAR) has been established as a useful marker of hypothalamus-pituitary-adrenal (HPA) axis activity and has become a standard tool for stress research in ambulatory settings. Although much knowledge has been accumulated on a variety of factors modulating the CAR, the impact of the female menstrual cycle, especially during ovulation, still remains unclear. To the best of our knowledge, this is the first study that measured the CAR during menses, the follicular phase, ovulation and the luteal phase in a repeated measurement design. For this purpose, a final sample of 29 naturally cycling, healthy, non-smoking, and medication-free women collected saliva samples directly after awakening as well as 30, 45, and 60 min later during each of the four different phases. To determine the timing of ovulation, an ambulatory chromatographic ovulation test kit was applied. A repeated measurements ANOVA resulted in a significant interaction effect sample × cycle phase (p=0.04), with the highest awakening response during ovulation. While awakening cortisol levels were comparable across the four cycle phases (p=n.s.), the net increase was significantly elevated during ovulation (p=0.05). Our data also confirmed earlier cross-sectional results reporting no differences in the CAR between the follicular and luteal phase. Finally, a concurrent assessment of mood applying the POMS (Profile of Mood States) yielded no differences across the four cycle phases (all p=n.s.). In sum, the present data points to the idea that the CAR is elevated during ovulation, an effect which is presumably mediated by elevated sex steroid levels during the ovulation period., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in secretion of corticosteroids which facilitate behavioural adaptation. These effects exerted by corticosteroids are mediated by two brain corticosteroid receptor types, the mineralocorticoid receptor (MR), with a high affinity already occupied under basal conditions and the glucocorticoid receptor (GR), with a low affinity only activated during stress. Here, we studied MR gene haplotypes constituted by the two single nucleotide polymorphisms MR-2G/C (rs2070951) and MRI180V (rs5522). The haplotypes showed differences in cortisol-induced gene transcription and protein expression while the structural variant MRI180V did not affect ligand binding. Moreover, in a well characterized cohort of 166 school teachers these haplotypes have been associated with perceived chronic stress (Trier Inventory for the Assessment of Chronic Stress, TICS) and, in a subgroup of 47 subjects, with ACTH, cortisol and heart rate responses to acute psychosocial stress (Trier Social Stress Test, TSST). MR haplotypes were significantly associated with the TICS scales "excessive demands at work" and "social overload". Subjects homozygous for haplotype MR-2C/MRI180, which in vitro showed highest expression and transactivational activity, displayed the highest salivary cortisol (p<0.001), plasma cortisol (p=0.010), plasma ACTH (p=0.003) and heart rate (p=0.018) responses. It is concluded that the investigated MR haplotypes modulate cortisol-induced gene transcription in vitro. Moreover, these haplotypes may contribute to individual differences in perceived chronic stress as well as neuroendocrine and cardiovascular stress responses., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

To test whether chronic work stress is accompanied by altered immune functioning, changes in lymphocyte subsets and in lymphocyte production of cytokines were examined in reaction to acute psychosocial stress. Work stress was measured according to Siegrist's effort-reward-imbalance (ERI) model. ERI reflects stress due to a lack of reciprocity between costs and gains at work. Overcommitment (OC) is conceptualized as a dysfunctional coping pattern mainly characterized by the inability to withdraw from work obligations. Fifty-five healthy teachers (34 women, 21 men, mean age 50.0 ± 8.47 years) were exposed to a standardized laboratory stressor (Trier Social Stress Test). Lymphocyte subset counts and lymphocyte production of tumor-necrosis-factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, -4, -6 and -10 were measured before and after challenge. High levels of ERI and OC were associated with lower natural killer (NK) cell (CD16+/56+) numbers whereas high levels of OC were related to a lower increase in T-helper cells (CD4+) after stress. Furthermore, subjects with higher ERI showed an overall increased pro-inflammatory activity, with higher TNF-α production at both time points and elevated pre-stress IL-6 production. IL-10 production decreased with higher ERI after stress. The ratios of TNF-α/IL-10 and IL-6/IL-10 were significantly increased in subjects high on ERI. Finally, OC was associated with higher IL-2 production post-stress. The present findings suggest a dampened innate immune defence, reflected in lower NK cell numbers together with an increased pro-inflammatory activity in teachers high on ERI and OC. Such pathways could partly be responsible for the increased vulnerability for stress-related diseases in individuals suffering from chronic work stress., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We investigated if 12 min of high-intensity exercise performed within a regular school break lead to an increase in cortisol levels in primary school students. 53 students of a 4th grade (9-10 years of age) were randomly assigned to an experimental (EG) and a control group (CG). Saliva collection took place after a normal school lesson (pre-test) and after 12 min of intensive exercise in a defined heart rate (HR) interval (EG, n=32) and control condition (movie watching) (CG, n=21), respectively (post-test). Saliva was analyzed for cortisol. We observed a significant group by test interaction indicating a different pre-to-post-test development for EG as compared to CG. The interaction effect, however, was caused by an attenuated cortisol concentration in the control group. We argue that the control condition, in which the students watched a joyful movie, acted as a distractor, which led to a reduction of general school stress., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: Everyday stressors elicit adaptive changes in the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system. Data on the relationship between these two systems under real-life conditions are sparse. We, therefore, sought to examine the association between HRV and salivary cortisol, which were recorded simultaneously in a stress-exposed, prospective, occupational cohort., Methods: The study population comprised 88 nurses. We recorded heart rate (HR) and HRV during 301 working shifts. Participants provided salivary cortisol samples at the beginning of their work shift and every 2 hours thereafter. Samples were collected during three investigation periods spread over 9 months. Change scores for cortisol were calculated as deviations from the expected circadian baseline. Change scores from the grand diurnal mean in the time domain-based root mean square of successive differences served to index alterations in HRV. To account for the temporal delay between changes in HR/HRV and changes in salivary cortisol, the latter were compared with the changes in HR/HRV observed 15 minutes to 45 minutes before the cortisol sampling., Results: During periods of high stress as indexed by high cortisol levels, we found significant associations between cortisol levels and HR (r = .48, p < .001) and HRV (r = -.28, p = .05). However, during low stress periods, these associations were attenuated and became nonsignificant., Conclusions: These data suggest a relative independence in the regulation of the HPA axis and the autonomic nervous system in response to everyday stressors but synchrony of both systems in highly stressful situations.

Stress is one of the most significant health problems in modern societies and the 21st century. This explains a pressing need for investigations into the biological pathways linking stress and health. Besides the locus coeruleus-noradrenaline/autonomic (sympathetic) nervous system ( Chrousos and Gold 1992 ), the hypothalamus-pituitary-adrenal (HPA) axis is the major physiological stress response system in the body. Since alterations in HPA axis regulation under basal conditions and in response to acute stress appear to be a close correlate or even a determining factor of the onset of different diseases or disease progression ( Holsboer 1989 ; Chrousos and Gold 1992 ; Tsigos and Chrousos 1994, 2002 ; Stratakis and Chrousos 1995 ; McEwen 1998 ; Heim et al. 2000a ; Raison and Miller 2003 ), the characterization of an individual's HPA axis activity as well as reactivity pattern to psychosocial stress appears to be of major interest. It is obvious that such a research agenda substantially depends on the availability of appropriate measures. However, since the HPA axis is a highly adaptive system which is characterized by marked inter- and intraindividual variability ( Mason 1968 ; Hellhammer et al. 2009 ), the development of such markers of HPA axis regulation in humans was-and still is-a rather challenging task. In this brief review, we focus on findings on two HPA axis measures, namely the cortisol-awakening response (CAR) to assess HPA axis basal activity and the Trier social stress test (TSST) to investigate HPA axis stress reactivity.

Objective: Vital exhaustion and depression are psychosocial risk factors of coronary artery disease. A hypercoagulable state in response to acute psychosocial stress contributes to atherothrombotic events. We aimed to investigate the hypothesis that vital exhaustion and depression correlate with stress-induced changes in the hypercoagulability marker D-dimer., Methods: Thirty-eight healthy and nonsmoking school teachers (mean age 50+/-8 years, 55% women) completed the nine-item Maastricht Vital Exhaustion Questionnaire and the seven-item depression subscale of the Hospital Anxiety and Depression Scale. Within 1 week, subjects twice underwent the Trier Social Stress Test (i.e., preparation phase, mock job interview, and mental arithmetic that totaled 13 min). Plasma D-dimer levels were determined at five time points during the protocol., Results: Vital exhaustion (P=.022; eta(2)=.080) and depressive symptoms (P=.011; eta(2)=.090) were associated with stress-induced changes in D-dimer levels over time controlling for sex and age. Elevated levels of vital exhaustion (r=-.46, P=.005) and of depression (r=-.51, P=.002) correlated with reduced D-dimer increase from pre-stress to immediately post-stress. Also, elevated vital exhaustion (r=.34, P=.044) and depression (r=.41, P=.013) were associated with increase (i.e., attenuated recovery) of D-dimer levels between 20 and 45 min post-stress. Controlling for stress hormone and blood pressure reactivity did not substantially alter these results., Conclusion: The findings suggest an attenuated immediate D-dimer stress response and delayed recovery of D-dimer levels post-stress with elevated vital exhaustion and depressive symptoms. In particular, the prolonged hypercoagulability after stress cessation might contribute to the atherothrombotic risk previously observed with vital exhaustion and depression, even at subclinical levels.

Depression and anxiety previously predicted coronary artery disease (CAD) risk. Inflammation contributes to CAD and shows an association with depression. We followed 57 teachers (mean 49+/-8 years) over 21 months and investigated whether changes in depressive and anxiety symptoms relate to those in the CAD risk and inflammation marker fibrinogen and vice versa. Increase in depressive symptoms and in fibrinogen levels were significantly correlated. While controlling for baseline depression rendered the association between changes in depression and fibrinogen nonsignificant, taking into account baseline fibrinogen levels maintained the predictive value of fibrinogen change for depression change. Anxiety and fibrinogen changes were not significantly correlated. This dynamic relationship between depression and the inflammatory biomarker fibrinogen might advance our knowledge about psychobiological mechanisms underlying both CAD and sickness behavior.

Background: Circulating progenitor cells have been implicated with maintaining vascular integrity. Low counts are found in adults with high cardiovascular risk and are associated with impaired endothelial function. It remains unknown whether psychosocial risk factors are independently related to counts of circulating progenitor cells., Methods: We investigated a random sample of 468 adult industrial employees (mean age 41.2 years, 89% men) of Caucasian origin. Cardiovascular risk factors (blood pressure, LDL, HDL and C-reactive protein), health behavior (smoking, alcohol and physical exercise), psychological variables (effort-reward imbalance social support, negative affectivity) and interaction terms served as predictors of circulating progenitor cells (CD34+ CD31dim) as enumerated by flow-cytometry., Findings: Psychosocial variables were independently associated with progenitor cell counts. The association with risk factors increased with age (explained variance in 18-36 year olds R(2)=0.17, p=0.55; age 36.1-46 R(2)=0.32, p=0.001; age>46 R(2)=0.27, p<0.001). Data revealed a shift from a larger association between behavioral and psychosocial variables and cell counts to a stronger association between biological variables and cell counts in older individuals. A significant interaction was observed between smoking and effort-reward imbalance in middle-aged subjects, those with both risk factors present had lower cell counts. In older employees, the interaction between biological risk factors and smoking was related to lower cell counts., Interpretation: In working middle-aged and older men, psychosocial risk factors were related to circulating counts of progenitor cells. Smoking interacted negatively with psychosocial risk factors (middle-aged men) or with biological risk factors (older employees).

Introduction: Acute psychosocial stress accelerates blood coagulation and elicits hemoconcentration which mechanisms are implicated in acute coronary thrombotic events. We investigated the extent to which the change in prothrombotic measures with acute stress reflects hemoconcentration and genuine activation of coagulation., Material and Methods: Twenty-one middle-aged healthy men underwent three sessions of a combined speech and mental arithmetic task with one-week intervals. Coagulation and plasma volume were assessed at baseline, immediately post-stress, and 45 min post-stress at sessions one and three. Measures of both visits were aggregated to enhance robustness of individual biological stress responses. Changes in eight coagulation measures with and without adjustment for simultaneous plasma volume shift were compared., Results: From baseline to immediately post-stress, unadjusted levels of fibrinogen (p=0.028), clotting factor VII activity (FVII:C) (p=0.001), FVIII:C (p<0.001), FXII:C (p<0.001), and von Willebrand factor (VWF) (p=0.008) all increased. Taking into account hemoconcentration, fibrinogen (p=0.020) and FVII:C levels (p=0.001) decreased, activated partial prothrombin time (APPT) shortened (p<0.001) and prothrombin time (PT) was prolonged (p<0.001). Between baseline and 45 min post-stress, unadjusted (p=0.050) and adjusted (p=0.001) FVIII:C levels increased, adjusted APTT was prolonged (p=0.017), and adjusted PT was shortened (p=0.033). D-dimer levels did not significantly change over time., Conclusions: Adjustment for stress-hemoconcentration altered the course of unadjusted levels of several prothrombotic factors. After adjustment for hemoconcentration, APPT was shortened immediately post-stress, whereas 45 min post-stress, FVIII:C was increased and PT was shortened. Procoagulant changes to acute stress may reflect both hemoconcentration and genuine activation of coagulation molecules and pathways.

Salivary cortisol is frequently used as a biomarker of psychological stress. However, psychobiological mechanisms, which trigger the hypothalamus-pituitary-adrenal axis (HPAA) can only indirectly be assessed by salivary cortisol measures. The different instances that control HPAA reactivity (hippocampus, hypothalamus, pituitary, adrenals) and their respective modulators, receptors, or binding proteins, may all affect salivary cortisol measures. Thus, a linear relationship with measures of plasma ACTH and cortisol in blood or urine does not necessarily exist. This is particularly true under response conditions. The present paper addresses several psychological and biological variables, which may account for such dissociations, and aims to help researchers to rate the validity and psychobiological significance of salivary cortisol as an HPAA biomarker of stress in their experiments.