Associations between cortisol stress responses and limbic volume and thickness in young adults: An exploratory study.

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.

Dissociation of behavioral and neural responses to provocation during reactive aggression in healthy adults with high versus low externalization.

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.

Everyday moral decision-making after acute stress exposure: do social closeness and timing matter?

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.

Acute psychosocial stress and everyday moral decision-making in young healthy men: The impact of cortisol.

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.

Is there a relationship between the performance in a chronometric mental-rotations test and salivary testosterone and estradiol levels in children aged 9-14 years?

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.

Racial and ethnic differences in diurnal cortisol rhythms: are they consistent over time?

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 (ß = 0.010) and Hispanics/Latinos (ß = 0.014), although including cardiovascular disease risk factors attenuates associations in blacks (ß = 0.007; p = .125). Higher income predicts a steepening of cortisol rhythms across the study (ß = -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.

Neural and cortisol responses to acute psychosocial stress in work-related burnout: The Regensburg Burnout Project.

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.

Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers.

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.

Investigation of cross-sectional and longitudinal associations between work-related burnout and hair cortisol: The Regensburg Burnout Project.

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.

Comparing two psychosocial stress paradigms for imaging environments - ScanSTRESS and fNIRS-TSST: Correlation structures between stress responses.

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.

Neural responses to acute stress predict chronic stress perception in daily life over 13 months.

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.

Association of polygenic scores for depression and neuroticism with perceived stress in daily life during a long-lasting stress period.

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.

Salivary cortisol in ambulatory assessment--some dos, some don'ts, and some open questions.

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.

Physical and mental health of different types of orchestra musicians compared to other professions.

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.

Sustained threat and phasic fear in the laboratory and cognitive-emotional processes of anxiety in everyday life - An ambulatory assessment study.

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.

Insights on Modelling Physiological, Appraisal, and Affective Indicators of Stress using Audio Features.

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.

Higher allostatic load in work-related burnout: The Regensburg Burnout Project.

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.

The association between genetic variability in the NPS/NPSR1 system and chronic stress responses: A gene-environment-(quasi-) experiment.

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.

Daily life stress and the cortisol awakening response over a 13-months stress period - Findings from the LawSTRESS project.

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.

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.