Child maltreatment and hypothalamic-pituitary-adrenal axis functioning: A systematic review and meta-analysis.

Alterations in hypothalamic-pituitary-adrenal (HPA) axis and its effector hormone cortisol have been proposed as one possible mechanism linking child maltreatment experiences to health disparities. In this series of meta-analyses, we aimed to quantify the existing evidence on the effect of child maltreatment on various measures of HPA axis activity. The systematic literature search yielded 1,858 records, of which 87 studies (k = 132) were included. Using random-effects models, we found evidence for blunted cortisol stress reactivity in individuals exposed to child maltreatment. In contrast, no overall differences were found in any of the other HPA axis activity measures (including measures of daily activity, cortisol assessed in the context of pharmacological challenges and cumulative measures of cortisol secretion). The impact of several moderators (e.g., sex, psychopathology, study quality), the role of methodological shortcomings of existing studies, as well as potential directions for future research are discussed.

Stress Hormone Dynamics Are Coupled to Brain Serotonin 4 Receptor Availability in Unmedicated Patients With Major Depressive Disorder: A NeuroPharm Study.

BACKGROUND: A prominent finding in major depressive disorder (MDD) is distorted stress hormone dynamics, which is regulated by serotonergic brain signaling. An interesting feature of the cerebral serotonin system is the serotonin 4 receptor (5-HT4R), which is lower in depressed relative to healthy individuals and also has been highlighted as a promising novel antidepressant target. Here, we test the novel hypothesis that brain 5-HT4R availability in untreated patients with MDD is correlated with cortisol dynamics, indexed by the cortisol awakening response (CAR). Further, we evaluate if CAR changes with antidepressant treatment, including a selective serotonin reuptake inhibitor, and if pretreatment CAR can predict treatment outcome. METHODS: Sixty-six patients (76% women) with a moderate to severe depressive episode underwent positron emission tomography imaging with [11C]SB207145 for quantification of brain 5-HT4R binding using BPND as outcome. Serial home sampling of saliva in the first hour from awakening was performed to assess CAR before and after 8 weeks of antidepressant treatment. Treatment outcome was measured by change in Hamilton Depression Rating Scale 6 items. RESULTS: In the unmedicated depressed state, prefrontal and anterior cingulate cortices 5-HT4R binding was positively associated with CAR. CAR remained unaltered after 8 weeks of antidepressant treatment, and pretreatment CAR did not significantly predict treatment outcome. CONCLUSIONS: Our findings highlight a link between serotonergic disturbances in MDD and cortisol dynamics, which likely is involved in disease and treatment mechanisms. Further, our data support 5-HT4R agonism as a promising precision target in patients with MDD and disturbed stress hormone dynamics.

Stress and the hypothalamic-pituitary-adrenal axis: How can the COVID-19 pandemic inform our understanding and treatment of acute insomnia?

Stress and sleep are very closely linked, and stressful life events can trigger acute insomnia. The ongoing COVID-19 pandemic is highly likely to represent one such stressful life event. Indeed, a wide range of cross-sectional studies demonstrate that the pandemic is associated with poor sleep and sleep disturbances. Given the high economic and health burden of insomnia disorder, strategies that can prevent and treat acute insomnia, and also prevent the transition from acute insomnia to insomnia disorder, are necessary. This narrative review outlines why the COVID-19 pandemic is a stressful life event, and why activation of the hypothalamic-pituitary-adrenal axis, as a biological marker of psychological stress, is likely to result in acute insomnia. Further, this review outlines how sleep disturbances might arise as a result of the COVID-19 pandemic, and why simultaneous hypothalamic-pituitary-adrenal axis measurement can inform the pathogenesis of acute insomnia. In particular, we focus on the cortisol awakening response as a marker of hypothalamic-pituitary-adrenal axis function, as cortisol is the end-product of the hypothalamic-pituitary-adrenal axis. From a research perspective, future opportunities include identifying individuals, or particular occupational or societal groups (e.g. frontline health staff), who are at high risk of developing acute insomnia, and intervening. From an acute insomnia treatment perspective, priorities include testing large-scale online behavioural interventions; examining if reducing the impact of stress is effective and, finally, assessing whether "sleep vaccination" can maintain good sleep health by preventing the occurrence of acute insomnia, by preventing the transition from acute insomnia to insomnia disorder.

The cortisol awakening response and the late positive potentials evoked by unpleasant emotional pictures in healthy adults.

The cortisol awakening response (CAR) refers to a sharp rise in cortisol concentrations within the 45 min following morning awakening. Alterations in CAR have been associated with various internalizing symptoms and brain function. The current study aimed to investigate the association between CAR and neural activity in response to unpleasant emotional pictures. A total of 46 healthy adults (22.55 years ± 1.69) collected saliva samples at 0, 30, and 45 min post-awakening on two days to assess the CAR. In the afternoon after CAR measurement on the first day, electroencephalograms were recorded when the participants completed a passive viewing task. The results showed that a greater CAR was associated with a decreased late positive potential difference score between unpleasant and neutral stimuli. This finding indicates that a larger CAR may be associated with decreased attentional engagement to unpleasant emotional information in healthy adults.

Cortisol awakening response and testosterone jointly affect adolescents' theory of mind.

Adolescence is a critical period for the maturation of neurobiological processes and hormone secretion. Recent studies on the dual-hormone hypothesis have indicated that basal cortisol and testosterone jointly affect dominant and aggressive behavior among adolescents and adults. Whether this hypothesis applies to prosocial-related understanding of others' mental states remains unclear. The present study investigated associations between basal testosterone, basal cortisol (and cortisol awakening response [CAR]), and the cognitive/affective theory of mind (ToM) in 243 adolescents (67.9 % male, aged 14 to 17 years, Mage = 16.09, standard deviation = 0.62). Cognitive ToM (cToM) and affective ToM (aToM) were assessed with a cartoon story reasoning task: In the cToM condition, participants viewed a comic strip story and needed to predict what would happen based on a character's intentions, and in the aToM condition, they viewed a comic strip of two characters interacting and needed to think about what would make the protagonist feel better. The results showed that basal testosterone and basal cortisol did not interact with each other to affect the performance of ToM, either in terms of ToM accuracy or response speed. However, under the condition of low CAR, testosterone is associated with the fast performance of cToM, although the interaction of testosterone and CAR occurred only in female adolescents. Overall, our data provide new evidence for the dual-hormone hypothesis and further extend the hypothesis to social understanding.

Unique and interactive associations of proactive and reactive aggression with cortisol secretion.

The association between aggressive behaviors and diurnal cortisol levels has been debated over the past two decades, as some studies found a negative link between the two, whereas others reported no or a positive association. One possible explanation for these contradictory results is that past studies failed to distinguish between proactive (PROA) and reactive (REA) aggression. The present study examined the unique and joint associations of PROA and REA with three diurnal cortisol indicators: awakening levels, awakening response, and diurnal change. Participants were 542 youths (55.4% girls) followed longitudinally. Teachers evaluated aggressive behaviors when participants were in Grades 4 and 6. In Grade 8, participants provided four saliva samples (i.e., awakening, 30 min thereafter, late afternoon, and bedtime) on four collection days. Controlling for several confounders, multilevel regression analyses revealed an inverse relation between PROA and the CAR in boys who displayed lower or moderate levels of REA, but not in those who exhibited higher levels of REA. No associations emerged with other cortisol indicators. These results are consistent with reports of lower physiological activity in individuals with PROA and underscore the confounding influence of REA in the association between the CAR and proactive aggression.

Dissociable hormonal profiles for psychopathology and stress in anorexia and bulimia nervosa.

BACKGROUND: Anorexia nervosa (AN) and bulimia nervosa (BN) are complex psychiatric conditions, in which both psychological and metabolic factors have been implicated. Critically, the experience of stress can precipitate loss-of-control eating in both conditions, suggesting an interplay between mental state and metabolic signaling. However, associations between psychological states, symptoms and metabolic processes in AN and BN have not been examined. METHODS: Eighty-five women (n = 22 AN binge/purge subtype, n = 33 BN, n = 30 controls) underwent remote salivary cortisol sampling and a 2-day, inpatient study session to examine the effect of stress on cortisol, gut hormones [acyl-ghrelin, peptide tyrosine tyrosine (PYY) and glucagon-like peptide-1] and food consumption. Participants were randomized to either an acute stress induction or control task on each day, and plasma hormones were serially measured before a naturalistic, ad libitum meal. RESULTS: Cortisol-awakening response was augmented in AN but not in BN relative to controls, with body mass index explaining the most variance in post-awakening cortisol (36%). Acute stress increased acyl-ghrelin and PYY in AN compared to controls; however, stress did not alter gut hormone profiles in BN. Instead, a group-by-stress interaction showed nominally reduced cortisol reactivity in BN, but not in AN, compared to controls. Ad libitum consumption was lower in both patient groups and unaffected by stress. CONCLUSIONS: Findings extend previous reports of metabolic dysfunction in binge-eating disorders, identifying unique associations across disorders and under stress. Moreover, we observed disrupted homeostatic signaling in AN following psychological stress, which may explain, in part, the maintenance of dysregulated eating in this serious illness.

Associations between age and cortisol awakening response in patients with borderline personality disorder.

Patients with borderline personality disorder (BPD) often display increased stress vulnerability, which may be linked to altered hypothalamus-pituitary-adrenal (HPA) axis functioning. Corresponding deviations of the cortisol awakening response (CAR) are presumed to mirror maladaptive neuroendocrine processes, which may explain why CARs are increased compared to healthy controls (HC). Prior research speculated that these alterations may be caused by early life stress and/or chronic stress related to the ongoing burden of the disorder. Yet, it remains to be investigated how BPD influences CAR in the course of development. Therefore, the current study examined CAR in female adolescents and adults with BPD compared to HC with a particular focus on associations with age. These potential associations were especially focused, as it was hypothesized that the CAR would be even more elevated (i.e., higher) in older individuals with BPD. CAR was assessed in 54 female individuals with BPD (aged 15-40 years) and 54 sex-, age-, and intelligence-matched HC (aged 15-48 years). Group differences were investigated and analyses of covariance using age as continuous predictor were performed to analyze potential developmental associations with CAR alongside BPD-specific effects. Pearson's correlations were calculated to examine associations between CAR and age. Analyses were repeated with potential confounders as control factors. Results not only demonstrated increased CARs in female individuals with BPD compared to HC but demonstrated elevated CARs with increasing age in BPD individuals exclusively. Effects remained stable after controlling for potential confounders. Thereby, findings suggest that endocrine alterations in BPD may reinforce with increasing age and BPD chronicity.

Pubertal transition with current life stress and support alters longitudinal diurnal cortisol patterns in adolescents exposed to early life adversity.

Current and early life stress (ELS) are associated with diurnal cortisol patterns, which themselves are associated with mental and physical health. The pubertal recalibration hypothesis suggests that the social environment can impact dysregulated cortisol patterns for previously ELS-exposed youth as they transition through puberty. This study examined longitudinal change in cortisol awakening response (CAR) and diurnal slope (DS) across puberty as a function of ELS in infancy, current stress, and social support (N = 290, 7-17 years). The CAR and DS were examined thrice annually with an accelerated longitudinal design with nurse-assessed puberty to assess associations between diurnal cortisol and pubertal recalibration with ELS and the current social environment. Exposure to ELS was associated with less steep DS but not changes in CAR, and no evidence of pubertal calibration was found. The DS became less steep for youth in later pubertal stages and as youth progressed through puberty. The CAR was steeper for youth in later pubertal stages. Across the cohort, current life stress and support were associated with changes in the DS and the CAR through the pubertal transition. The pubertal stage and the peripubertal and pubertal social environment may have important implications for adrenocortical functioning with or without exposure to ELS.

A Brief Mindfulness-Based Intervention (bMBI) to Reduce Teacher Stress and Burnout.

Teacher stress and burnout contribute to attrition and stress-related health concerns. Despite some positive effects, previous mindfulness-based interventions (MBI) have failed to incorporate key elements of methodological rigor and have included large dosages despite research suggesting that such dosages are iatrogenic. The current study demonstrates the efficacy of a brief MBI (bMBI; four sessions, six total hours) to reduce self-reported stress, burnout, and depression, and suggests the bMBI can protect against deleterious impacts to physiological functioning. The study informs the design and implementation of future MBIs, including strategies for reducing intervention dosages, in order to improve effectiveness and maximize cost-effectiveness.

Sleep problems in adolescence are prospectively linked to later depressive symptoms via the cortisol awakening response.

Sleep disturbance is a symptom of and a well-known risk factor for depression. Further, atypical functioning of the HPA axis has been linked to the pathogenesis of depression. The purpose of this study was to examine the role of adolescent HPA axis functioning in the link between adolescent sleep problems and later depressive symptoms. Methods: A sample of 157 17-18 year old adolescents (61.8% female) completed the Pittsburgh Sleep Quality Inventory (PSQI) and provided salivary cortisol samples throughout the day for three consecutive days. Two years later, adolescents reported their depressive symptoms via the Center for Epidemiological Studies Depression Scale (CES-D). Results: Individuals (age 17-18) with greater sleep disturbance reported greater depressive symptoms two years later (age 19-20). This association occurred through the indirect effect of sleep disturbance on the cortisol awakening response (CAR) (indirect effect = 0.14, 95%CI [.02 -.39]). Conclusions: One pathway through which sleep problems may lead to depressive symptoms is by up-regulating components of the body's physiological stress response system that can be measured through the cortisol awakening response. Behavioral interventions that target sleep disturbance in adolescents may mitigate this neurobiological pathway to depression during this high-risk developmental phase.

Cortisol Awakening Response, Self-Reported Affect and Exam Performance in Female Students.

The purpose of the study was to find whether there were differences in cortisol awakening response (CAR) between a neutral day and an exam day in a group of female students and to explore possible relationships between CAR, self-reported affect, and exam performance. A group of 25 female students took samples of their saliva using Salivettes at the moment of waking and after 30 min. They then described their affect using the PANAS scale. Measures were taken twice: three days before an examination and on the day of the examination. The level of free cortisol in saliva samples was determined using enzyme immunoassay. The integrated volume of cortisol (CARauc) was significantly higher on the day of the exam than on the neutral day. There were also significant differences in affect, with negative higher and positive lower on the exam day, but correlations between cortisol measures and self-reported affect were low and not significant. A negative relationship between integrated volume of cortisol (CARauc) and exam performance was also found. Anticipated exam stress caused a significant increase in CAR in female study participants when compared to a neutral day, but only in the case of integrated volume of cortisol over the waking period (CARauc). The negative relationship between this measure and exam performance can be explained by attributing CARauc to negative expectations concerning the anticipated exam.

Depression, violence and cortisol awakening response: a 3-year longitudinal study in adolescents.

BACKGROUND: Despite evidence of links between depression and violent outcomes, potential moderators of this association remain unknown. The current study tested whether a biological marker, cortisol, moderated this association in a longitudinal sample of adolescents. METHODS: Participants were 358 Dutch adolescents (205 boys) with a mean age of 15 years at the first measurement. Depressive symptoms, the cortisol awakening response (CAR) and violent outcomes were measured annually across 3 years. The CAR was assessed by two measures: waking cortisol activity (CAR area under the curve ground) and waking cortisol reactivity (CAR area under the curve increase). Within-individual regression models were adopted to test the interaction effects between depressive symptoms and CAR on violent outcomes, which accounted for all time-invariant factors such as genetic factors and early environments. We additionally adjusted for time-varying factors including alcohol drinking, substance use and stressful life events. RESULTS: In this community sample, 24% of adolescents perpetrated violent behaviours over 3 years. We found that CAR moderated the effects of depressive symptoms on adolescent violent outcomes (ßs ranged from -0.12 to -0.28). In particular, when the CAR was low, depressive symptoms were positively associated with violent outcomes in within-individual models, whereas the associations were reversed when the CAR was high. CONCLUSIONS: Our findings suggest that the CAR should be investigated further as a potential biological marker for violence in adolescents with high levels of depressive symptoms.

Maternal circadian cortisol mediates the link between prenatal distress and breastfeeding.

Breastfeeding is associated with positive maternal and infant outcomes. It is recommended that women exclusively breastfeed for the first 6 months postpartum; however, these recommendations are not met in the majority of women. Psychological distress in pregnancy is associated with lower rates of breastfeeding initiation and duration in the postpartum period. The mechanisms linking maternal distress to breastfeeding are not understood. In this study we examined maternal circadian cortisol as a mechanism linking distress in pregnancy to breastfeeding. This study is a secondary data analysis of 197 pregnant women with singleton pregnancies who were part of a larger study of the effects of maternal mood on fetal and infant development. About 34% of women reported exclusively breastfeeding, 18% reported exclusively formula feeding, and 48% reported mixed feeding. Participants reported on perceived stress, perinatal anxiety and depression, and socioeconomic status during pregnancy. They provided salivary cortisol samples at three times a day for 3 days at 24, 30, and 36 weeks' gestation. Participants who reported lower socioeconomic status in pregnancy were less likely to breastfeed, and lower maternal cortisol awakening responses mediated this association. This area of research may identify foci in the prenatal period that could serve as targets for interventions to increase rates of breastfeeding. Lay summary Pregnant women who reported lower socioeconomic status in pregnancy were less likely to breastfeed. This association was mediated by lower cortisol awakening responses, but not evening cortisol levels, over pregnancy.

Premenstrual syndrome is associated with altered cortisol awakening response.

Previous studies have revealed stress-induced dysregulation of hypothalamic-pituitary-adrenal (HPA) axis in women with premenstrual syndrome (PMS). So far, however, the results about the relationship between HPA axis dysregulation and PMS are mixed. To this end, it is necessary to investigate the basal activity of the HPA axis in women with PMS instead of only assessing a certain stressor. Therefore, this study evaluated the relationship between the cortisol awakening response (CAR) and PMS. Thirty-two women with PMS (mean age 22.47 ± 2.20 years) and 36 healthy controls (mean age 22.28 ± 2.43 years) were included in this study. Saliva samples of our participants were collected successively at 0, 30, 45, and 60 min after awakening to assess CAR during each of two phases of the menstrual cycle (the mid-follicular phase and the late luteal phase). The results showed a significantly attenuated CAR in women with PMS compared with the healthy controls, especially at 45 and 60 min after awakening, regardless of the menstrual cycle phases. Furthermore, there was a significant negative correlation between PMS severity as measured by PMS scale and AUCi (i.e. the Area Under the Curve with respect to increase) in the mid-follicular phase. Our findings suggested that an attenuated CAR activity profile may be an important risk factor for the development of PMS.

Interdependent self-construal modulates the adrenocortical stress response in the socially evaluated cold-pressor test.

Previous studies suggested that the Trier social stress test (TSST) induced a higher cortisol stress response in individuals with high interdependent self-construal (InterSC) as compared to those with low InterSC, and that participants' perception of social evaluative threat mediated the association between InterSC and cortisol stress response. To further examine if individuals with high InterSC exhibit a strong psychological stress response independent of the stress paradigm, the current study investigated the stress response of individuals with high InterSC in a socially evaluated cold-pressor test (SECPT) paradigm, which has also been shown to reliably increase hypothalamus-pituitary-adrenal (HPA) activity with a social evaluative element. Fifty-five healthy participants (29 females; mean age = 20.55 years) completed the Self-Construal Scale and their salivary cortisol samples were collected at 0, 30, 45, and 60 minutes after waking up on a weekday morning. Participants' cardiovascular and adrenocortical stress responses in the SECPT were also measured while they immersed their hand in ice water, and they were observed by the experimenter and videotaped during this task. Our results indicated that participants with high InterSC showed a higher level of cortisol awakening response (CAR). Additionally, they perceived higher levels of social evaluative threat and exhibited higher saliva cortisol response to the SECPT. Taken together, the present findings and those obtained from previous studies suggest a significant and reliable role of InterSC in regulating biological and psychological stress responses.

Salivary cortisol profiles of on-call from home fire and emergency service personnel.

Working on-call with a night call resulted in a depressed (lower) cortisol awakening response (CAR) peak and post-awakening cortisol area under the curve with respect to ground (AUCG) the following day compared to when off-call. This may be due to exposure to noise, physical exertion, and stressful events during night callouts. There was no anticipatory effect to working on-call in any of the cortisol measures examined. This study, of male fire and emergency service workers who operate on-call from home, had two aims: (1) examine CAR and diurnal cortisol profile following a night on-call with a call, on-call without a call, and off-call; and, (2) explore whether there is an anticipatory effect of working on-call from home on diurnal cortisol profiles. Participants wore activity monitors, completed sleep and work diaries and collected seven saliva samples a day (0 min, 30 min, 60 min, 3 h, 6 h, 9 h, and 12 h after final awakening) for one week. CAR peak, reactivity and area under the curve with respect to increase (AUCI), post-awakening cortisol AUCG, diurnal cortisol slope and AUCG, and mean 12-h cortisol concentrations were calculated. The final analysis included 26 participants for Aim 1 (22 off-call nights, 68 nights on-call without a call, and 20 nights on-call with a call) and 14 participants for Aim 2 (25 days leading up to a night off-call and 92 days leading up to a night on-call). Generalized estimating equations models were constructed for each variable of interest. Aim 1: CAR peak and post-awakening cortisol AUCG were 8.2 ± 3.4 nmol/L and 5.7 ± 2.4 units lower, respectively, following a night on-call with a call compared to an off-call night. Aim 2: the day before a night on-call was not a significant predictor in any model. The lower CAR peak and post-awakening cortisol AUCG following a night on-call with a call compared to following an off-call night may be due to exposure to noise, physical exertion, and stressful events during night callouts. The lack of difference between the day before a night on-call and the day before an off-call night suggests there may not be an anticipatory effect on cortisol when on-call from home.

Cortisol awakening response and additive serotonergic genetic risk interactively predict depression in two samples: The 2019 Donald F. Klein Early Career Investigator Award Paper.

BACKGROUND: The serotonin system and hypothalamic pituitary-adrenal (HPA)-axis are each implicated in the pathway to depression; human and animal research support these systems' cross-talk. Our work implicates a 5-variant additive serotoninergic multilocus genetic profile score (MGPS) and separately the cortisol awakening response (CAR) in the prospective prediction of depression; other work has shown that the serotonin transporter polymorphism 5HTTLPR predicts CAR and interacts with the CAR to predict depression. METHODS: We tested the hypothesis that a 6-variant MGPS (original plus 5HTTLPR) would interact with CAR to predict prospective depressive episode onsets in 201 emerging adults using four annual follow-up interviews. We also tested whether MGPS predicted CAR. We attempted replication of significant findings in a sample of 77 early adolescents predicting depression symptoms. RESULTS: In sample 1, MGPS did not significantly predict CAR. MGPS interacted with CAR to predict depressive episodes; CAR slopes for depression steepened as MGPS increased, for risk or protection. No single variant accounted for results, though CAR's interactions with 5HTTLPR and the original MGPS were both significant. In sample 2, the 6-variant MGPS significantly interacted with CAR to predict depression symptoms. CONCLUSIONS: Higher serotonergic MGPS appears to sensitize individuals to CAR level-for better and worse-in predicting depression.

Stress load of emergency service: effects on the CAR and HRV of HEMS emergency physicians on different working days (N = 20).

PURPOSE: The occupation of the emergency physicians (EPs) of helicopter emergency medical services (HEMS) can be characterized as a high-strain occupation (Karasek in Adm Sci Q 24(2):285-308. https://doi.org/10.2307/2392498 , 1979). Therefore, the aim of this study was to measure and compare the stress load of the EPs of HEMS on duty on air ambulance workdays and on 2 control days. METHODS: In this field study (within-subjects design), hormonal, physiological, and self-perceived stress levels of 20 EPs [3 females, 17 males; mean age (M) = 44.95 years, SD = 4.80, 95% confidence interval (CI) (42.71, 47.19)] of HEMS, were recorded on different test days. Measurements of the cortisol awakening response (CAR) and the heart rate variability (HRV) were performed while on duty on the air ambulance and during workdays at the outpatient clinic as well as at home on days of rest. RESULTS: There were significant differences in the CAR (area under the curve with respect to ground F(2,38) = 12.81, p < 0.001) between the 3 test days with the highest values on the workday at the outpatient clinic [M = 81.24; 98.75% CI (61.24, 101.24)] and not on the air ambulance day [M = 61.82; 98.75% CI (45.18, 78.46)] or on the day of rest [M = 52.96; 98.75% CI (38.17, 67.76)]. In addition, the HRV parameter SDNN [F(2,38) = 6.369; p = 0.004] presented significant differences between the 3 test days with lower levels on the day at the outpatient clinic [M = 101.44; 98.75% CI (83.50, 119.38)] in contrast to the air ambulance day [M = 120.16; 98.75% CI (100.02, 140.30)] and to the resting day [M = 123.79; 98.75% CI (106.49, 141.10)]. Furthermore, there were significant differences in the HRV parameter LF/HF [F(2,38) = 6.215; p = 0.005] between the 3 testing days with the highest values on the workday at the outpatient clinic [M = 8.69; 98.75% CI (6.29, 11.09)] compared to the air ambulance day [M = 6.54; 98.75% CI (4.50, 8.57)] and the day of rest [M = 6.43; 98.75% CI (4.57, 8.29)]. CONCLUSIONS: Compared with the standard values and previous studies, EPs of HEMS have an increase in hormonal reactivity in the morning and a lack of recovery of the ANS. It can be concluded that-with respect to the psychobiological stress model by McEwen and Lasley (The end of stress as we know it, National Academic Press, Washington, 2003)-work-related stressors persist too long or the stress response is exaggerated (allostatic load) due to chronic stress induction and lack of recovery.

Weak Associations of Morningness-Eveningness and Stability with Skin Temperature and Cortisol Levels.

Differences in daytime preferences can be described on the dimension of morningness-eveningness (continuous) or circadian typology (categorical) and are associated with our physiological functioning, which is reflected in body temperature and cortisol levels in the morning. The purpose of the present study was to explore the relationship between morningness-eveningness, stability and physiological markers (body temperature and cortisol) based on a three-dimensional conceptualization of morningness-eveningness using the Morningness-Eveningness-Stability Scale improved (MESSi). In contrast to previously used unidimensional measures, the MESSi determines circadian typology and its amplitude in three dimensions: Morning affect (MA), Eveningness (EV) and Stability/Distinctness (DI). Furthermore, the differences of the cortisol levels between weekday and weekend were examined. The sample (N = 42) consisted of extreme chronotypes (age 18-54 years; M = 24.8 years, SD = 5.83; 22 morning types [5 men and 17 women] and 20 evening types [8 men and 12 women]). The participants were asked to measure their skin temperature for one week and sample four saliva probes for cortisol determination. Morning types showed a better fit in the actual temperature data to the approximating data as compared to Evening types and showed a higher overall temperature. The Stability/Distinctness (DI) component of the MESSi was negatively correlated with the nadir. Morning types also showed higher cortisol levels than Evening types immediately after awakening. The cortisol levels were higher on a weekday compared to the weekend. To conclude, the present findings demonstrate that the skin temperature is weakly associated with morningness-eveningness and the stability of the circadian phase.