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Context Maternal obesity, hypertensive pregnancy disorders, and gestational diabetes (GDM) are linked to an increased risk of negative offspring health outcomes. This association may be mediated by maternal hypothalamic-pituitary-adrenal axis (HPA axis) activity, resulting in elevated maternal cortisol levels and fetal exposure, but evidence remains scarce. Objective We (1) examined maternal diurnal cortisol profiles longitudinally across gestation, and (2) explored associations with maternal cardiometabolic complications. Methods Women in the InTraUterine sampling in early pregnancy (ITU) study (n = 667) provided 7 salivary cortisol samples from awakening to bedtime up to 3 times during pregnancy (median gestational week 19.3, 25.7, and 38.1; n = 9356 samples). Changes in cortisol awakening response (CAR) and diurnal slope (indicative of HPA axis activity) and their associations with maternal body mass index (BMI), hypertensive pregnancy disorders and GDM were examined using linear mixed models. Results The CAR declined in 60% to 67% of women, and the diurnal slope attenuated from early to late pregnancy (b = 0.006; P =.001). Higher BMI was associated with less decline in CAR (b = 0.031; P =.0004) and less attenuation in diurnal slope from early to late pregnancy (b = −0.001; P =.006). Hypertensive pregnancy disorders and GDM were not significantly associated with diurnal cortisol profiles. Conclusion The attenuation in CAR and diurnal slope support HPA axis hyporesponsivity during pregnancy. Less attenuation of both markers in women with a higher BMI may indicate reduced adaption of the HPA axis to pregnancy, presenting a mechanistic link to offspring health outcomes. [ABSTRACT FROM AUTHOR]

Several autism‐related characteristics, such as social difficulties, may contribute to high perceived stress and increased exposure to stressful life events in some autistic individuals. Repeated exposure to stress might lead to the dysfunction of the hypothalamic–pituitary‐adrenocortical‐axis and be a vulnerability factor for developing mental health difficulties. Previous studies show contradictory findings on salivary cortisol in autism. In the current study, we investigated diurnal cortisol profiles in autistic adolescents and young adults, as well as their associations with social difficulties, stress exposure, and mental health symptoms. Autistic (n = 48, Mage = 17.6) and nonautistic (n = 51, Mage = 18.4) participants collected salivary cortisol at home six times a day for 2 days. Social difficulties, exposure to stressful life events/bullying, and mental health symptoms were assessed with questionnaires and clinical interviews. Similar diurnal cortisol slopes (DCS) and cortisol awakening responses were observed between the groups, but autistic participants showed higher total cortisol output (AUCG, area under the curve with respect to ground) during the day (b = 19.09, p = 0.009). In the autistic group, more severe social difficulties were associated with flatter DCS (b = 0.01, p = 0.007). Finally, cortisol alterations were associated with self‐reported mental health symptoms, especially in autistic females in analyses uncorrected for multiple comparisons. In conclusion, our results do not indicate autism‐related group‐level alterations in most diurnal cortisol measures, but autistic youth showed higher total cortisol (AUCG) compared with nonautistic peers. More detailed investigation of interindividual variability in cortisol profiles within autistic people might give us important insights into vulnerability to developing stress‐related mental health difficulties. Lay Summary: Cortisol is a glucocorticoid hormone the levels of which fluctuate following the body's daily rhythm over a 24‐hour cycle (i.e. circadian rhythm). Cortisol levels can also be altered due to perceived stress or other factors. We investigated whether daily cortisol rhythms differ in autistic and nonautistic adolescents and young adults. Most daily cortisol measures did not differ between the groups, but autistic youth showed higher cortisol levels than nonautistic youth. Moreover, in autistic participants, more severe social difficulties were associated with greater fluctuation in cortisol throughout the day. More detailed investigation of the observed variability in cortisol rhythms might help us to understand the vulnerability to stress‐related mental health difficulties. [ABSTRACT FROM AUTHOR]

Light influences circadian rhythms, including that of the stress hormone cortisol. Cortisol, in turn, has been observed to promote expression of the anti-inflammatory cytokine IL-10. It is thus of interest whether the cytokine IL-10 is also influenced by light, perhaps in accord with the diurnal variations in cortisol. Hence, this highly standardized preliminary sleep laboratory study in healthy adult men investigated a potential influence of different light exposure on IL-10 and cortisol concentrations in blood. In a between-subject design, N = 42 participants were exposed to either bright, dim, blue or red light after wake-up. Two mixed-model analyses with the factors of light condition and time (across eight IL-10 and cortisol sampling points) were conducted. Additionally, area under the curve measurements (AUCg and AUCi) were calculated for both cortisol and IL-10. Across all conditions, IL-10 and cortisol concentrations significantly changed over time. However, none of the light conditions exerted a greater influence on IL-10 or cortisol levels than others. For cortisol, there was greater total output (AUCg) in the blue-light condition in particular. Further research is needed to gain insight into whether or not types of light or cortisol levels have a hand in influencing natural IL-10 concentrations.

Light is essential in shaping human circadian rhythms, including that of the hormone cortisol. While cortisol is known to influence secretion of the cytokine IL-6, the influence of light itself on IL-6 remains unclear. Thus, this study investigated the effects of two light conditions – red and blue – on IL-6 concentrations and the cortisol awakening response in blood. The interplay between cortisol and IL-6 was explored as well. The between-subject experiment was conducted with 71 healthy adult men (aged Mred = 24.30, SD = 3.56; Mblue = 24.40, SD = 3.51) in a standardized sleep laboratory setting with 60-min light exposure post-awakening at 05:00 a.m. Two mixed models, with light condition and time across measurement points as factors, were calculated. In the one for cortisol, chronotype was introduced as a covariate. Mean cortisol concentrations did not differ between exposure to red vs. blue light (p = 0.443), but overall cortisol output (area under the curve with respect to ground; AUCG) and sensitivity (area under the curve with respect to increase; AUCI) were greater in the blue-light condition (p = 0.050 and p

Previous research suggests that affectionate touch such as hugs might downregulate stress systems such as the hypothalamic pituitary adrenal (HPA) axis. However, the current literature lacks in generalizability beyond the laboratory setting and outside the context of romantic relationships. The cortisol awakening response (CAR) is a measure of the HPA axis and is responsive to daily fluctuations in stress and social information. However, associations between affectionate touch and the CAR have never been assessed. This study used ecological momentary assessment (EMA) to measure daily hugging behaviors in 104 first-year college students and salivary cortisol to assess the CAR. Participants who reported more daily hugs in their social interactions had significantly smaller CARs the next morning compared to days they reported fewer hugs. This study contributes to the literature on social interactions and stress responsive systems and emphasizes the importance of assessing affectionate touch behaviors such as hugs that can be exchanged outside the context of romantic relationships.

BackgroundCompared to their White counterparts, Latina breast cancer survivors have poorer survival rates and health-related quality of life, and higher rates of depression and anxiety which may be a result of chronic stress. Chronic stress impacts the hypothalamic-pituitary-adrenal (HPA) axis, resulting in cortisol dysregulation which may be associated with breast cancer survival. However, cortisol levels and cortisol profiles of Latina breast cancer survivors are poorly characterized due to their underrepresentation in biomedical research.ObjectiveThe objective of this study was to describe cortisol levels and patterns of cortisol secretions in rural Latina breast cancer survivors participating in an RCT study of Nuevo Amanecer-II, an evidence-based peer-delivered cognitive behavioral stress management intervention.MethodsParticipant-centered recruitment and collection strategies were used to obtain biospecimens for cortisol analysis. Nine saliva samples (3/day for 3 days) and a hair sample were obtained at baseline and 6-months (3-months post-intervention). We describe cortisol levels and profiles, explore correlations of biomarkers with self-report measures of stress and psychological distress, and compare women who received the intervention with a delayed intervention group on biomarkers of stress. Mean hair cortisol concentration (HCC) was used to assess chronic stress. Based on daily measures of cortisol (awakening, 30 min post-awakening, and bedtime), we calculated three summary measures of the dynamic nature of the cortisol awakening response (CAR): 1) the CAR slope, 2) whether CAR demonstrates a percent change ≥40, and 3) total daily cortisol output (AUCg). Linear and log-binomial regression, accounting for multiple samples per participant, were used to compare cortisol measures at 6-month follow-up by treatment arm.ResultsParticipants (n = 103) were from two rural California communities; 76 provided at least one saliva sample at baseline and follow-up and were included in the analysis. At baseline, mean age was 57 years, mean years since diagnosis was 2 years, 76% had a high school education or less, and 34% reported financial hardship. The overall median CAR slope was 0.10, and median cortisol AUCg (in thousands) was 11.34 (range = 0.93, 36.66). Mean hair cortisol concentration was 1751.6 pg/mg (SD = 1148.6). Forty-two percent of samples had a ≥40% change in CAR. We found no statistically significant correlations between the cortisol measures and self-reported measures of stress and psychological distress. At follow-up, no differences were seen in HCC (mean difference between intervention and control: -0.11, 95% CI -0.48, 0.25), CAR slope (0.001, 95% CI -0.005, 0.008), cortisol AUCg (-0.15, 95% CI -0.42, 0.13), or ≥40% change in CAR (prevalence ratio 0.87, 95% CI 0.42, 1.77) between treatment arms.ConclusionOur findings of flattened cortisol profiles among more than half of the sample suggest potential HPA-axis dysregulation among rural Spanish-speaking Latina breast cancer survivors that merits further study due to its implications for long-term survival.Trial registrationhttp://www.ClinicalTrials.gov identifier NCT02931552.

Cortisol awakening response (CAR) refers to the dynamic change of cortisol concentration within 1 h after awakening. Trait anxiety is a general risk marker of anxiety disorders. The present study aimed to investigate the effect of trait anxiety on CAR using R30 (change in cortisol level at 30 min after awakening) and AUCi (the area under the curve with respect to the increase) as indicators. 133 college students were divided into high trait anxiety (HTA) and low trait anxiety (LTA) group according to the median score of the trait version of State-Trait Anxiety Inventory. Saliva samples were collected immediately upon awakening, 30 min, 45 and 60 min on two consecutive mornings. The results showed that, (1) decreased CAR was found for the male than female participants. (2) Compared to the LTA group, the HTA group showed decreased R30 and AUCi. (3) Both R30 and AUCi were negatively correlated with trait anxiety scores. These results demonstrated that trait anxiety might weaken the CAR, and both R30 and AUCi can be used as CAR indicators in detecting trait anxiety. Future research on CAR should consider the moderating effect of trait anxiety. [ABSTRACT FROM AUTHOR]

This study investigated whether chronic academic stress could affect the directed forgetting (DF) process. Both the stress group (undergoing preparation for a major academic examination) and the control group performed a DF task. A forgetting cue was presented after a to-be-forgotten (TBF) word, whereas no cue appeared after a to-be-remembered (TBR) item in the study phase. An old/new recognition test was used in the test phase. The results showed that (1) the stress group showed a higher level of self-reported stress, state anxiety, negative affect, and decreased cortisol awakening response (CAR) compared with the control group, suggesting a higher level of stress for the stress group. (2) Both groups showed superior recognition performance of TBR than TBF items, suggesting a DF effect. (3) The stress group showed inferior recognition performance of TBF items and an enhanced DF effect compared with the control group. These results demonstrated that the intentional memory control process might be enhanced under chronic academic stress. [ABSTRACT FROM AUTHOR]

A dysregulated circadian rhythm is significantly associated with cancer risk, as is aging. Both aging and circadian dysregulation show suppressed pineal melatonin, which is indicated in many studies to be linked to cancer risk and progression. Another independently investigated aspect of the circadian rhythm is the cortisol awakening response (CAR), which is linked to stress-associated hypothalamus-pituitary-adrenal (HPA) axis activation. CAR and HPA axis activity are primarily mediated via activation of the glucocorticoid receptor (GR), which drives patterned gene expression via binding to the promotors of glucocorticoid response element (GRE)-expressing genes. Recent data shows that the GR can be prevented from nuclear translocation by the B cell lymphoma-2 (Bcl-2)-associated athanogene 1 (BAG-1), which translocates the GR to mitochondria, where it can have diverse effects. Melatonin also suppresses GR nuclear translocation by maintaining the GR in a complex with heat shock protein 90 (Hsp90). Melatonin, directly and/or epigenetically, can upregulate BAG-1, suggesting that the dramatic 10-fold decrease in pineal melatonin from adolescence to the ninth decade of life will attenuate the capacity of night-time melatonin to modulate the effects of the early morning CAR. The interactions of pineal melatonin/BAG-1/Hsp90 with the CAR are proposed to underpin how aging and circadian dysregulation are associated with cancer risk. This may be mediated via differential effects of melatonin/BAG-1/Hsp90/GR in different cells of microenvironments across the body, from which tumors emerge. This provides a model of cancer pathogenesis that better integrates previously disparate bodies of data, including how immune cells are regulated by cancer cells in the tumor microenvironment, at least partly via the cancer cell regulation of the tryptophan-melatonin pathway. This has a number of future research and treatment implications.

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. [ABSTRACT FROM AUTHOR]

Mental contrasting with implementation intentions (MCII) has been successfully applied to improve health-related behaviors (e.g. exercise). We explored its effectiveness to improve sleep outcomes beyond effects of sleep hygiene (SH) information, and investigated associations with stress. Eighty university employees (mean age: 29.6, SD = 4.5) were randomized to either a MCII + SH or a SH-only condition. During a baseline-week and a post-intervention week, sleep duration (Fitbit Alta and self-report), sleep quality, and stress were assessed daily and saliva was collected to assess the cortisol awakening response (CAR). In total, self-reported sleep quality and duration increased, but there was no meaningful condition*week interaction for sleep parameters or CAR. Higher average stress was associated with shorter sleep duration and lower sleep quality. Within-person, days with higher stress were followed by nights with lower sleep quality. Despite overall improvements, effects of MCII were not confirmed. MCII might be less effective to improve behaviors which are less controllable. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Anxiety and depression are some of the most common mental disorders associated with a dysregulation of the hypothalamic-pituitary-adrenal axis (HPA) and elevated cortisol levels in the saliva. The aim of this scoping review was to synthesize all of the current information about the relationship between salivary cortisol and depression as well as address some of the shortcomings in prior research to explore its potential applications in diagnosing depression. In late July 2022, records from 2012-2022 were identified using Web of Science, PubMed, and Scopus. Unique abstracts were screened using the following criteria: (1) depression and saliva; (2) anxiety and saliva; (3) age and salivary cortisol and depression; (4) sex and salivary cortisol and depression. 4,869 records were identified across all three databases; resulting in 90 unique abstracts. 11 articles met all inclusion criteria. On balance, most studies associated the dysregulation of the HPA with depression and anxiety disorders, with a cofactor being the cortisol awakening response. Several studies also presented sex and age-related differences in salivary cortisol measures. However, there were several inconsistencies with some studies showing no age and/or sex-related differences. Furthermore, several studies also emphasized the importance of testing morning salivary cortisol as an effective method to diagnose depression and anxiety disorders. The oral microbiome may play a role in mental health disorders through changes in inflammation and cortisol levels in saliva. Our review contributes to the existing literature on the topic, highlighting gaps and strategizing the next steps. [ABSTRACT FROM AUTHOR]

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.

Anxiety and depression are some of the most common mental disorders associated with a dysregulation of the hypothalamic-pituitary-adrenal axis (HPA) and elevated cortisol levels in the saliva. The aim of this scoping review was to synthesize all of the current information about the relationship between salivary cortisol and depression as well as address some of the shortcomings in prior research to explore its potential applications in diagnosing depression. In late July 2022, records from 2012-2022 were identified using Web of Science, PubMed, and Scopus. Unique abstracts were screened using the following criteria: (1) depression and saliva; (2) anxiety and saliva; (3) age and salivary cortisol and depression; (4) sex and salivary cortisol and depression. 4,869 records were identified across all three databases; resulting in 90 unique abstracts. 11 articles met all inclusion criteria. On balance, most studies associated the dysregulation of the HPA with depression and anxiety disorders, with a cofactor being the cortisol awakening response. Several studies also presented sex and age-related differences in salivary cortisol measures. However, there were several inconsistencies with some studies showing no age and/or sex-related differences. Furthermore, several studies also emphasized the importance of testing morning salivary cortisol as an effective method to diagnose depression and anxiety disorders. The oral microbiome may play a role in mental health disorders through changes in inflammation and cortisol levels in saliva. Our review contributes to the existing literature on the topic, highlighting gaps and strategizing the next steps.

Background and objective: According to the diathesis-stress model, disturbances of the hypothalamic-pituitary-adrenal (HPA) axis are thought to play a role in the development, onset, and progression of psychosis. The aim of this paper is to present the available body of evidence on the abnormalities of the cortisol awakening response (CAR) in psychotic disorders and at-risk states. Methods: Review of literature from the years 2011-2022 available across three databases (Scopus, Pub-Med and Google Scholar) was performed. With an aim to: i) ensure that the review covers a wide range of research related to psychotic presentations as manifested in a broad range of clinical populations (from CHR/UHR to full-blown psychosis), and ii) identify the neurobiological background thereof, the following combination of search terms was applied: "chr" OR "uhr" OR "arms" OR "first-episode schizophrenia" OR "psychosis" AND "cortisol" OR "HPA axis" OR "CAR" OR "cortisol awakening response". Results and conclusion: Research suggests that abnormalities of the HPA axis (in this case, disturbances of the CAR) appear to be an important factor in the pathogenesis of psychotic disorders. The cortisol awakening response was blunted in patients with first-episode psychosis or schizophrenia. On the other hand, in subjects with at-risk states, the results were inconclusive. These findings, however, are based on a small number of studies; therefore, more research in this area is required. [ABSTRACT FROM AUTHOR]

Objectives: Psychosocial stress is an inherent part of modern lifestyle, and many suffer from chronic stress exposure and the subsequent development of stress-related diseases. In searching for efficient low-cost interventions to reduce stress, we investigated the effects of regular contemplative mental practice on diurnal cortisol activity as an indicator of the basal, everyday stress load. Method: Data were collected in the context of the ReSource Project, an open-label efficacy trial comprising three distinct 3-month training modules targeting attention and interoception (Presence Module), socio-affective (Affect Module) or socio-cognitive abilities (Perspective Module) through dyadic exercises and secularized meditation practices. Diurnal cortisol activity was assayed at four time points: pre-training and after 3, 6, and 9 months. As outcome measures, the cortisol awakening response (CAR), cortisol slope over the course of the day, and total daily cortisol output were computed. Results: Analyses revealed a stable reduction in CAR specifically after the compassion- and care-based Affect Module, contrasted by a CAR increase following the attention- and interoception-based Presence training. Cortisol slope over the day and total daily cortisol output were unaffected by any of the mental trainings. Conclusions: These findings emphasize the necessity for a more granular approach in the investigation of contemplative mental training effects. Not all types of training can be expected to equally beneficial for all types of hardship. Specifically, with regard to the CAR, which represents the anticipatory stress response to the upcoming day, compassion- and care-based qualities rather than bare attention or meta-cognitive skills seem to drive stress reduction. Preregistration: This study is not preregistered. [ABSTRACT FROM AUTHOR]

Sleep restriction is likely to affect the activities of stress axes, namely the hypothalamic-pituitary-adrenal axis (HPA) and the autonomic nervous system (ANS). Sleep restriction is likely to be experienced by everybody, yet the number of studies on that subject is very scarce. The current study aimed to examine the effects of sleep restriction on cortisol awakening response (CAR) as an indicator of HPA and heart rate variability (HRV) as an indicator of ANS activity. Participants (second-year medical students) were divided into two groups as sleep restricting group (n=27, sleeping at 02:00 p.m., waking up at 06:30 a.m.) and normal sleep duration group (n=25, sleeping at 11:00 p.m., waking up at 06:30 a.m.). The participants who filled in sleep dairies provided salivary samples (taken at 0, 15, 30, and 60 min post-awakening) for measurement of CAR and had an electrocardiogram recording (for 5 min) for determination of HRV. Mann-Whitney U test was used for statistical analyses. Sleep restriction reduced cortisol concentrations 15 and 30 minutes following awakening (p0.05). Sleep diaries showed that awakening problem scores were higher but daily disturbed sleep score was lower in the restricted sleep group (p [Med-Science 2022; 11(2.000): 682-9]

The cortisol awakening response (CAR) has been hypothesized to prepare the body for anticipated demands of the upcoming day. This pilot study investigates the influence of anticipated stress on the upcoming day on the CAR, using an intensive longitudinal design with ecological momentary assessments. Over a 30-day period, three healthy participants collected saliva samples each morning at three time points after awakening to measure cortisol levels and completed a questionnaire each evening on the anticipated stress for the following day. Additionally, they wore a smart headband to objectively determine the time point of awakening. There was high variability in the CAR magnitude within participants over time. A multi-level model was estimated to investigate the influence of anticipated stress on the CAR. Results indicated that anticipated stress is predictive of the CAR on the following morning, with higher anticipated stress being associated with increased cortisol levels at the post-awakening time points. These findings underscore the role of stress anticipation in modulating the CAR and highlight the importance of considering within-person variation and temporally lagged effects in biopsychological research. • Anticipated stress was found to predict the next-day cortisol awakening response. • Higher anticipated stress was linked to an increased cortisol awakening response. • There was no effect of anticipated stress on the awakening cortisol levels. [ABSTRACT FROM AUTHOR]

Recent studies suggest a therapeutic effect of psychiatric service dogs for military veterans with posttraumatic stress disorder (PTSD), but are limited by self-report biases. The current study assessed the effect of PTSD service dogs on the salivary cortisol awakening response (CAR) and arousal-related functioning in a population of military veterans with PTSD. Participants included 73 post-9/11 military veterans with PTSD including 45 with a service dog and 28 on the waitlist to receive one. Saliva samples were collected on two consecutive weekday mornings at awakening and 30 min later to quantify the cortisol awakening response (CAR) and its area under the curve (AUCi) in addition to standardized survey measures of anxiety, anger, sleep quality and disturbance, and alcohol abuse. There was a significant main effect of having a service dog on both the CAR and the AUCi, with individuals with a service dog exhibiting a higher CAR and AUCi compared to those on the waitlist. Results also revealed that those with a service dog reported significantly lower anxiety, anger, and sleep disturbance as well as less alcohol abuse compared to those on the waitlist, with medium to large effect sizes. Although those with a service dog reported significantly less PTSD symptom severity, CAR was not significantly associated with PTSD symptoms within or across group. In conclusion, results indicate that the placement of a PTSD service dog may have a significant positive influence on both physiological and psychosocial indicators of wellbeing in military veterans with PTSD. Although clinical significance cannot be confirmed, a higher CAR/AUCi among those with a service dog may indicate better health and wellbeing in this population. Future within-subject, longitudinal research will be necessary to determine potential clinical significance and impact of individual differences.

Recent studies suggest a therapeutic effect of psychiatric service dogs for military veterans with posttraumatic stress disorder (PTSD), but are limited by self-report biases. The current study assessed the effect of PTSD service dogs on the salivary cortisol awakening response (CAR) and arousal-related functioning in a population of military veterans with PTSD. Participants included 73 post-9/11 military veterans with PTSD including 45 with a service dog and 28 on the waitlist to receive one. Saliva samples were collected on two consecutive weekday mornings at awakening and 30 min later to quantify the cortisol awakening response (CAR) and its area under the curve (AUCi) in addition to standardized survey measures of anxiety, anger, sleep quality and disturbance, and alcohol abuse. There was a significant main effect of having a service dog on both the CAR and the AUCi, with individuals with a service dog exhibiting a higher CAR and AUCi compared to those on the waitlist. Results also revealed that those with a service dog reported significantly lower anxiety, anger, and sleep disturbance as well as less alcohol abuse compared to those on the waitlist, with medium to large effect sizes. Although those with a service dog reported significantly less PTSD symptom severity, CAR was not significantly associated with PTSD symptoms within or across group. In conclusion, results indicate that the placement of a PTSD service dog may have a significant positive influence on both physiological and psychosocial indicators of wellbeing in military veterans with PTSD. Although clinical significance cannot be confirmed, a higher CAR/AUCi among those with a service dog may indicate better health and wellbeing in this population. Future within-subject, longitudinal research will be necessary to determine potential clinical significance and impact of individual differences.

The cortisol awakening response (CAR) is a non-invasive biomarker for hypothalamic-pituitary-adrenal axis (HPA) dysregulation, reflecting accumulated stress over time. In a previous study we reported that a blunted CAR before an inpatient treatment predicted self-reported depressive symptoms six weeks and six months after discharge [Eikeseth, F. F., Denninghaus, S., Cropley, M., Witthöft, M., Pawelzik, M., & Sütterlin, S. (2019). The cortisol awakening response at admission to hospital predicts depression severity after discharge in major depressive disorder (MDD) patients. Journal of Psychiatric Research, 111, 44-50)]. This replication study adopted an improved overall methodology with more stringent assessment protocols and monitoring. The longitudinal design included 122 inpatients from a psychosomatic hospital with a diagnosis of MDD displaying symptoms of moderate to severe major depression (n = 80 females). The CAR was measured at intake. Depression severity was assessed as Beck Depression Inventory II scores at intake, discharge, 6 weeks and 6 months following discharge. Results from the original study were replicated in terms of effect size but did not reach statistical significance (correlation between BDI-II 6 months after discharge and AUCg: r = -0.213; p = 0.054). The replication study yielded nearly identical correlation coefficients as in the original study (BDI-II 6 months and CAR, r = -0.223, p < 0.05). The replication of previously reported effect sizes with a concurrent lack of statistical significance in the more restrictive, larger and better controlled replication study may well inform research on psycho-endocrinological predictors for treatment success, but suggests a rather limited practical relevance for cortisol awakening response measures in this clinical context. [ABSTRACT FROM AUTHOR]

Light influences circadian rhythms, including that of the stress hormone cortisol. Cortisol, in turn, has been observed to promote expression of the anti-inflammatory cytokine IL-10. It is thus of interest whether the cytokine IL-10 is also influenced by light, perhaps in accord with the diurnal variations in cortisol. Hence, this highly standardized preliminary sleep laboratory study in healthy adult men investigated a potential influence of different light exposure on IL-10 and cortisol concentrations in blood. In a between-subject design, N  = 42 participants were exposed to either bright, dim, blue or red light after wake-up. Two mixed-model analyses with the factors of light condition and time (across eight IL-10 and cortisol sampling points) were conducted. Additionally, area under the curve measurements (AUCg and AUCi) were calculated for both cortisol and IL-10. Across all conditions, IL-10 and cortisol concentrations significantly changed over time. However, none of the light conditions exerted a greater influence on IL-10 or cortisol levels than others. For cortisol, there was greater total output (AUCg) in the blue-light condition in particular. Further research is needed to gain insight into whether or not types of light or cortisol levels have a hand in influencing natural IL-10 concentrations., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Katja Petrowski reports financial support was provided by 10.13039/501100002347Federal Ministry of Education and Research Bonn Office Library. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The cortisol awakening response (CAR) is a non-invasive biomarker for hypothalamic-pituitary-adrenal axis (HPA) dysregulation, reflecting accumulated stress over time. In a previous study we reported that a blunted CAR before an inpatient treatment predicted self-reported depressive symptoms six weeks and six months after discharge [Eikeseth, F. F., Denninghaus, S., Cropley, M., Witthöft, M., Pawelzik, M., & Sütterlin, S. (2019). The cortisol awakening response at admission to hospital predicts depression severity after discharge in major depressive disorder (MDD) patients. Journal of Psychiatric Research, 111, 44-50)]. This replication study adopted an improved overall methodology with more stringent assessment protocols and monitoring. The longitudinal design included 122 inpatients from a psychosomatic hospital with a diagnosis of MDD displaying symptoms of moderate to severe major depression (n = 80 females). The CAR was measured at intake. Depression severity was assessed as Beck Depression Inventory II scores at intake, discharge, 6 weeks and 6 months following discharge. Results from the original study were replicated in terms of effect size but did not reach statistical significance (correlation between BDI-II 6 months after discharge and AUCg: r = −0.213; p = 0.054). The replication study yielded nearly identical correlation coefficients as in the original study (BDI-II 6 months and CAR, r = −0.223, p < 0.05). The replication of previously reported effect sizes with a concurrent lack of statistical significance in the more restrictive, larger and better controlled replication study may well inform research on psycho-endocrinological predictors for treatment success, but suggests a rather limited practical relevance for cortisol awakening response measures in this clinical context.

Background: Stress and cortisol dysregulation are linked to NCDs. Moreover, stress favours unhealthy lifestyle patterns, which increase the risk for NCDs. The role of the Cortisol Awakening Response (CAR) and the effect of lifestyle interventions on the same remain unclear. Methods: The impact of the intensive 8-week phase of the Healthy Lifestyle Community Programme (HLCP, cohort 1) on parameters of the CAR, ie cortisol values 0 (sample [S]1), 30), 45 and 60 minutes post-awakening, average peak, S1-peak delta and area under the increase curve (AUCI), and perceived stress levels (PSL) was evaluated in a non-randomized, controlled trial. Covariates of the CAR (eg sleep measures) and irregularities in sampling were assessed. The intervention focussed on stress management, a healthy diet, regular exercise, and social support. Participants were recruited from the general population. Multiple linear regression analyses were conducted. Results: 97 participants (age: 56 ± 10 years; 71% female), with 68 in the intervention group (IG; age: 55 ± 8, 77% female) and 29 participants in the control group (CG; age: 59 ± 12, 59% female), were included in the analysis. The baseline characteristics of both groups were comparable, except participants of IG were younger. On average, the PSL at baseline was low in both groups (IG: 9.7 ± 5.4 points; CG: 8.5 ± 6.9 points; p =.165), but 22% (n = 15) in the IG and 20% (n = 6) in the CG reported a high PSL. Most participants reported irregularities in CAR sampling, eg interruption of sleep (IG: 80% CG: 81%). After 8 weeks, most CAR parameters and the PSL decreased in the IG and CG, resulting in no differences of change between the groups. In the IG only, a decrease of PSL was linked to an increase of CAR parameters, eg AUCI (correlation coefficient = −0.307; p =.017). Conclusion: The HLCP may potentially reduce PSL and change the CAR, but results cannot be clearly attributed to the programme. Methodological challenges and multiple confounders, limit suitability of the CAR in the context of lifestyle interventions. Other measures (eg hair-cortisol) may give further insights. Trial registration : German Clinical Trials Register (DRKS); DRKS00018821; www.drks.de [ABSTRACT FROM AUTHOR]

Probiotics can alter brain function via the gut–brain axis. We investigated the effect of a probiotic mixture containing Bifidobacterium longum, Lactobacillus helveticus and Lactiplantibacillus plantarum. In a randomized, placebo-controlled, double-blinded crossover design, 22 healthy subjects (6 m/16 f; 24.2 ± 3.4 years) underwent four-week intervention periods with probiotics and placebo, separated by a four-week washout period. Voxel-based morphometry indicated that the probiotic intervention affected the gray matter volume of a cluster covering the left supramarginal gyrus and superior parietal lobule (p < 0.0001), two regions that were also among those with an altered resting state functional connectivity. Probiotic intervention resulted in significant (FDR < 0.05) functional connectivity changes between regions within the default mode, salience, frontoparietal as well as the language network and several regions located outside these networks. Psychological symptoms trended towards improvement after probiotic intervention, i.e., the total score of the Hospital Anxiety and Depression Scale (p = 0.056) and its depression sub-score (p = 0.093), as well as sleep patterns (p = 0.058). The probiotic intervention evoked distinct changes in brain morphology and resting state brain function alongside slight improvements of psycho(bio)logical markers of the gut–brain axis. The combination of those parameters may provide new insights into the modes of action by which gut microbiota can affect gut–brain communication and hence brain function. [ABSTRACT FROM AUTHOR]

The home environment of offspring of parents with bipolar disorder (OBD) has been characterized by high levels of stress and disorganization, which may impact development of the hypothalamic-pituitary-adrenal (HPA) axis and their subsequent risk for affective disorders. The present study examined the effects of a family-based preventative intervention on the OBD's HPA axis functioning and whether intervention-related changes in the home environment might have driven change in the HPA axis. Fifty-five children (6–11 years) were recruited from families having a parent with bipolar disorder (n=26) or families having two parents with no current mental disorders (n=29). Only those families with a parent having bipolar disorder participated in the preventative intervention. Both groups completed assessments at baseline, post-prevention, 3-, and 6-months post-prevention. At each assessment, family organization, control, cohesion, conflict, and expressiveness, in addition to childhood internalizing problems, were measured, and offspring saliva samples were collected across two consecutive days. Hierarchical Linear Modelling found no significant differences in HPA axis functioning between groups at baseline or across time. Improvements in family organization, however, were associated with elevations in participants' cortisol awakening response (CAR; p =.004) and total daily output (p =.023), and a steepening of their diurnal slope (p =.003) across time. Similar findings were obtained for family cohesion with respect to CAR (p <.001) and, to a lesser degree, diurnal slope (p =.064). HPA axis functioning did not differ between the OBD and healthy controls at baseline or in response to the preventative intervention. However, intervention-related improvements in family organization and, to a lesser degree, cohesion, were associated with adaptive changes in HPA functioning over time. • The study examined the effects of a prevention program on hypothalamic-pituitary-adrenal (HPA) axis function in children. • Offspring of parents with bipolar disorder (OBD) participated in a 12-week program aimed at improving the family environment. • OBD and controls provided saliva samples to assess cortisol at baseline, post-prevention, and at 3- and 6-month follow-ups. • No significant differences in diurnal cortisol between the OBD and controls were found at baseline or across time. • Prevention-related improvements in family organization were associated with adaptive changes in HPA axis function in the OBD. [ABSTRACT FROM AUTHOR]

ObjectiveThe aim of the study was to investigate hypothalamic-pituitary-adrenal axis (HPA axis) functioning as a neurobiological risk factor for depressive symptoms in an ongoing longitudinal, observational study of women undergoing treatment and recovery from breast cancer. Many women with breast cancer experience depressive symptoms that interfere with their treatment, recovery, and quality of life. Psychosocial risk factors for depression among patients with cancer and survivors have been identified, yet neurobiological risk factors in this population remain largely unexamined.MethodsWomen recently diagnosed with early-stage breast cancer (N = 135) were enrolled before starting neoadjuvant/adjuvant treatment (radiation, chemotherapy, endocrine therapy). At baseline, participants collected saliva samples to measure diurnal HPA axis functioning for 3 days: at waking, 30 minutes after waking, 8 hours after waking, and bedtime. Participants also completed a standardized measure of depressive symptoms (Center for Epidemiological Studies-Depression Scale) at baseline and 6 months after completion of primary treatment. Multivariate regression was used to predict continuous depressive symptoms at 6-month posttreatment from continuous depressive symptoms at baseline, cortisol awakening response (CAR), and other measures of diurnal HPA axis functioning.ResultsThe magnitude of CAR predicted changes in depressive symptoms over time, such that women with a higher CAR showed a greater increase from baseline to 6-month posttreatment (b = 5.67, p = .023). Diurnal slope and total cortisol output were not associated with concurrent depressive symptoms or their change over time.ConclusionsElevated CAR may be a neurobiological risk factor for increases in depressive symptoms in the months after breast cancer treatment and warrants further investigation.

Background: Compared to their White counterparts, Latina breast cancer survivors have poorer survival rates and health-related quality of life, and higher rates of depression and anxiety which may be a result of chronic stress. Chronic stress impacts the hypothalamic-pituitary-adrenal (HPA) axis, resulting in cortisol dysregulation which may be associated with breast cancer survival. However, cortisol levels and cortisol profiles of Latina breast cancer survivors are poorly characterized due to their underrepresentation in biomedical research. Objective: The objective of this study was to describe cortisol levels and patterns of cortisol secretions in rural Latina breast cancer survivors participating in an RCT study of Nuevo Amanecer-II, an evidence-based peer-delivered cognitive behavioral stress management intervention. Methods: Participant-centered recruitment and collection strategies were used to obtain biospecimens for cortisol analysis. Nine saliva samples (3/day for 3 days) and a hair sample were obtained at baseline and 6-months (3-months post-intervention). We describe cortisol levels and profiles, explore correlations of biomarkers with self-report measures of stress and psychological distress, and compare women who received the intervention with a delayed intervention group on biomarkers of stress. Mean hair cortisol concentration (HCC) was used to assess chronic stress. Based on daily measures of cortisol (awakening, 30 min post-awakening, and bedtime), we calculated three summary measures of the dynamic nature of the cortisol awakening response (CAR): 1) the CAR slope, 2) whether CAR demonstrates a percent change ≥40, and 3) total daily cortisol output (AUCg). Linear and log-binomial regression, accounting for multiple samples per participant, were used to compare cortisol measures at 6-month follow-up by treatment arm. Results: Participants (n = 103) were from two rural California communities; 76 provided at least one saliva sample at baseline and follow-up and were included in the analysis. At baseline, mean age was 57 years, mean years since diagnosis was 2 years, 76% had a high school education or less, and 34% reported financial hardship. The overall median CAR slope was 0.10, and median cortisol AUCg (in thousands) was 11.34 (range = 0.93, 36.66). Mean hair cortisol concentration was 1751.6 pg/mg (SD = 1148.6). Forty-two percent of samples had a ≥40% change in CAR. We found no statistically significant correlations between the cortisol measures and self-reported measures of stress and psychological distress. At follow-up, no differences were seen in HCC (mean difference between intervention and control: −0.11, 95% CI -0.48, 0.25), CAR slope (0.001, 95% CI -0.005, 0.008), cortisol AUCg (−0.15, 95% CI -0.42, 0.13), or ≥40% change in CAR (prevalence ratio 0.87, 95% CI 0.42, 1.77) between treatment arms. Conclusion: Our findings of flattened cortisol profiles among more than half of the sample suggest potential HPA-axis dysregulation among rural Spanish-speaking Latina breast cancer survivors that merits further study due to its implications for long-term survival. Trial registration: http://www.ClinicalTrials.gov identifier NCT02931552.

Constant availability, overtime and feeling overwhelmed by work can impact employees' wellbeing and their biological stress responses. Especially working parents often struggle to balance the demands of their work and family life and were found to be distracted from their work due to family responsibilities. The Family-to-Work Conflict (FWC) indicates the extent to which participating in work is made difficult by family demands. Recent studies have found associations between FWC and biological outcomes such as the Cortisol Awakening Response (CAR), a measure of an individual's Hypothalamic-Pituitary-Adrenal (HPA)-axis activity. This diary study investigates the effect of parental work demands on next day's cortisol response as well as the moderating role of FWC and the mediating role of fatigue. Over the course of five consecutive days (from Monday to Friday), 168 observations were made on a total of 42 parents. Participants had at least one child and worked a minimum of 20 hours per week. Salivary cortisol samples were obtained immediately, 15 and 30 minutes after awakening each day. Work demands, FWC and fatigue were assessed using standardized questionnaires. Within-person effects were examined using multilevel modeling and mediation analyses. Our results indicate that there are no main effects of work demands on next day's cortisol response. The multilevel analysis revealed that FWC predicts lower wakening cortisol levels and confirmed FWC as an increasing moderator between work demands and next day's HPA-axis activity. Further, work overload was found to increase fatigue, which in turn leads to higher CAR on the following day. This indicates that fatigue mediates the relationship between work demands and CAR. Our findings add to a growing body of research demonstrating further predictors for HPA-axis activity and emphasise the importance of considering family related demands when investigating biological outcomes for working parents. • Parental work demands had no main effect on next day's cortisol levels. • Parental family-to-work conflict moderates the effects between work demands and next day's wakening cortisol. • Fatigue was identified as a mediator, as work overload increases fatigue, which in turn increased next day's CAR. [ABSTRACT FROM AUTHOR]

Mild traumatic brain injury (mTBI) is the most common form of TBI, with more than 2.5 million TBI cases in the United States annually. Identification of easily obtainable biomarkers that track strongly with mTBI symptoms may improve our understanding of biological factors that contribute to mTBI symptom profiles and long-term outcomes. Notably, some individuals with mTBI exhibit circadian disruptions and elevated stress sensitivity, which in other clinical groups often correlate with disrupted secretion of cortisol, a glucocorticoid hormone that coordinates circadian and stress physiology. Here, we examined whether cortisol profiles could serve as a biomarker to complement the assessment of neurobehavioral sequelae after mTBI. We partnered with our on-campus health clinic to recruit college students seeking medical care after mTBI (n = 46) and compared this population to a well-matched non-injured student control group (n = 44). We collected data at an initial visit (shortly after injury in mTBI subjects) and one week later. At each visit, we evaluated neurobehavioral function using the Automated Neuropsychological Assessment Metric (ANAM). The subjects also provided cortisol samples through at-home saliva collection. We observed strong coherence between ANAM subjective and objective measures, indicating significant multi-dimensional impairment in subjects with mTBI. Further, female mTBI subjects exhibited diminished neurobehavioral function compared with males. Regardless of sex, decreased amplitude of diurnal cortisol and a blunted cortisol awakening response were associated with mTBI symptom severity and neurobehavioral impairment. Taken together, these findings suggest that salivary cortisol profiles may be a sensitive biomarker for studying underlying biological factors that impact mTBI symptoms and outcomes. [ABSTRACT FROM AUTHOR]

Sleep restriction is likely to affect the activities of stress axes, namely the hypothalamic-pituitary-adrenal axis (HPA) and the autonomic nervous system (ANS). Sleep restriction is likely to be experienced by everybody, yet the number of studies on that subject is very scarce. The current study aimed to examine the effects of sleep restriction on cortisol awakening response (CAR) as an indicator of HPA and heart rate variability (HRV) as an indicator of ANS activity. Participants (second-year medical students) were divided into two groups as sleep restricting group (n=27, sleeping at 02:00 p.m., waking up at 06:30 a.m.) and normal sleep duration group (n=25, sleeping at 11:00 p.m., waking up at 06:30 a.m.). The participants who filled in sleep dairies provided salivary samples (taken at 0, 15, 30, and 60 min post-awakening) for measurement of CAR and had an electrocardiogram recording (for 5 min) for determination of HRV. Mann-Whitney U test was used for statistical analyses. Sleep restriction reduced cortisol concentrations 15 and 30 minutes following awakening (p<0.05) but it did not affect time- and frequency-domain parameters of HRV (p>0.05). Sleep diaries showed that awakening problem scores were higher but daily disturbed sleep score was lower in the restricted sleep group (p<0.05). Results of the current study suggest that sleep restriction suppresses HPA and causes awakening problems. On the other hand, ANS activity, as assessed by HRV, is not affected by sleep restriction. [ABSTRACT FROM AUTHOR]

Sunlight controls endogen hormone balances and numerous health effects. Therefore, it is important to provide building users, such as schoolchildren, with sufficient daylight. Too much of it, however, leads to overheating, which is why shading systems are used. Consequently, these systems improve energy balance, but might not have positive effects on present people's health. Within this study, shading systems were installed in classrooms of a middle school: common shading in two rooms, while two others were equipped with shading blades "Schlotterer RETROLux 80D" in an innovative design, reflecting more daylight indoors. The participating classes were divided between rooms with ordinary daylighting (n = 43) and advanced daylighting (n = 42). They spent, on average, 5 days weekly and 5–8 h daily in these classrooms. Saliva samples were collected during three semesters to detect hormonal changes. Questionnaires were collected to obtain more information about the mental alterations and, furthermore, to support the physiological results. A significant reduction in cortisol levels between 6:30 AM and 11:30 AM (p < 0.001) was observed within the group that had advanced daylighting. Questionnaires show that both groups sleep less as study duration increases (p < 0.001 time effect), but only the control group has a concurrent increase in daytime sleepiness according to relative treatment effects. The results show that increased daylight supply indoors leads to a significant greater reduction in cortisol levels of children and that those positive outcomes can be achieved by using innovative technologies for buildings. [ABSTRACT FROM AUTHOR]

Abstract Objective The Cortisol Awakening Response (CAR) measured as the transient increase in cortisol levels following morning awakening appears to be a distinct feature of the HPA axis. Patients with bipolar disorder (BD) experience daily stress, mood instability (MI) and studies have shown disrupted HPA-axis dynamics. Aims: to evaluate (1) patient-evaluated stress against the CAR, (2) associations between the CAR and mood symptoms, and (3) the effect of smartphone-based treatment on the CAR. Methods Patients with BD (n = 67) were randomized to the use of daily smartphone-based monitoring (the intervention group) or to the control group for six months. Clinically rated symptoms according to the Hamilton Depression Rating Scale 17-items (HDRS), the Young Mania Rating Scale (YMRS), patient-evaluated perceived stress using Cohen’s Perceived Stress Scale (PSS) and salivary awakening cortisol samples used for measuring the CAR were collected at baseline, after three and six months. In the intervention group, smartphone-based data on stress and MI were rated daily during the entire study period. Results Smartphone-based patient-evaluated stress (B: 134.14, 95% CI: 1.35; 266.92, p = 0.048) and MI (B: 430.23, 95% CI: 52.41; 808.04, p = 0.026) mapped onto increased CAR. No statistically significant associations between the CAR and patient-evaluated PSS or the HDRS and the YMRS, respectively were found. There was no statistically significant effect of smartphone-based treatment on the CAR. Conclusion Our data, of preliminary character, found smartphone-based patient-evaluations of stress and mood instability as read outs that reflect CAR dynamics. Smartphone-supported clinical care did not in itself appear to disturb CAR dynamics.

Menstrual symptoms include some rhythmical changes and stress perception but women differ in duration and severity of these symptoms. It is not known whether these differences are associated with cortisol awakening response (CAR). The aim of the current study was to follow young women daily for the CAR and menstrual parameters throughout the whole menstrual cycle. Healthy and regularly cycling young women (n = 16, 17 to 31‐year‐old) participated in the current study. The daily records of severity of problems (DRSP) was filled in daily by the participants. CAR was also assessed daily form the salivary samples collected at a 0‐, 15‐, 30‐ and 60‐min post‐awakening. In terms of daily awakening cortisol profiles, women had either 2–20 (n = 3), or 20–200 (n = 8) or 200–2000 (n = 5) ng/ml cortisol according to the median levels throughout their cycle. CAR was weakly and negatively correlated with DRSP scores but strongly and positively with oestradiol (R2 = 0.300; p = 0.000) and progesterone (R2 = 0.490; p = 0.000) concentrations. Individuals with higher oestradiol and progesterone concentrations did not have high DRSP scores. In conclusion, CAR had a very high between‐subject difference but had a low within‐subject difference throughout the days of menstrual cycle, suggesting that CAR is a relatively stable personal trait. Moreover, the interplay between cortisol, progesterone and oestradiol appears to be important for the severity of menstrual symptoms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Mindfulness-based Stress Reduction (MBSR) has shown good efficacy for improving wellbeing in employees experiencing occupational stress. However, comparisons with other interventions, longer-term follow-up, and data from varying sociocultural contexts are lacking. This three-arm, parallel randomised controlled trial (RCT) examined the effects of MBSR on psychological distress in non-physician health workers in direct contact with patients. 105 participants were randomly allocated to either: (1) MBSR (N = 35), (2) Stress Management Course (SMC; N = 34) or (3) wait-list (N = 36). Participants and those assessing outcomes were blinded to group assignment. Participants completed questionnaires pre- and post-intervention and four months after the intervention. Psychological distress was measured using the General Health Questionnaire (GHQ-12) and Outcome Questionnaire (OQ-45). Secondary outcomes included perceived stress, job satisfaction, mindfulness skills and changes in salivary cortisol. 77 participants completed measures post-intervention and 52 at 4-month follow-up. MBSR showed a post-intervention effect in reducing GHQ-12 (ß = −0.80 [SE = 1.58] p < 0.01) and OQ-45 (ß = −0.72, [SE = 5.87] p < 0.05) psychological distress, compared to SMC and in reducing GHQ-12 (ß = −1.30 [SE = 1.38] p < 0.001) and OQ-45 (ß = −0.71, [SE = 5.58] p < 0.01) psychological distress compared to wait-list condition. In our secondary outcome, only MBSR was associated with a decrease in the cortisol awaking response by 23% (p < 0.05). At follow-up, only effects of MBSR on the psychological distress 'social role' subscale (ß = −0.76 [SE = 1.31] p < 0.05) remained significant, compared to SMC. In conclusion, MBSR appears useful in reducing short-term psychological distress in healthcare workers, but these effects were not maintained at follow-up. Trial registration: ISRCTN12039804. • Three-arm randomised controlled trial from Chile targeting occupational stress. • Mindfulness-based stress reduction reduces psychological distress in health workers. • Reduction in psychological distress not found in psychoeducation or waitlist groups. • Mindfulness intervention only associated with reductions in salivary cortisol. • Weak effects at follow-up suggests crucial to target maintenance of benefits. [ABSTRACT FROM AUTHOR]

Background Depressive disorders are common mental health problems during adolescence. Many adolescents with depression describe difficulties with sleeping. Findings of previous studies regarding changes in objective sleep quality in adolescents with depressive disorders are heterogeneous. Aims This study aims to investigate differences in objective and subjective sleep quality between adolescents with depressive disorders and healthy peers, and to evaluate if potential changes in sleep occur concurrently with changes in the release of cortisol and alpha-amylase after awakening. Method This non-interventional parallel study examines correlations between depressive disorders, sleep quality and release of stress hormones. Sleep quality in the past 2 weeks, severity of depressive symptoms, psychiatric comorbidities and stress response of 30 adolescents with depressive disorders and 30 healthy controls (N = 60) are assessed via questionnaires. In participants’ home environments, the objective sleep quality of seven consecutive nights is measured by sleep accelerometry. After awakening, participants answer sleep questionnaires to examine the subjective sleep quality of those nights. Furthermore, salivary cortisol and alpha-amylase are measured three times after awakening (+0 min, +30 min and +45 min after awakening). Conclusions Sleep is an important factor for prognosis and well-being in adolescents with depression. The results of this study can be highly valuable to integrate a more detailed examination of sleep quality and sleeping impairments in the treatment of adolescent depressive disorders.

Globally, the COVID-19 (coronavirus disease 2019) pandemic has resulted in abrupt shifts in ecological and social environments, including school contexts, which became predominately virtual. This study (1) examines the role of the COVID-19 pandemic (transitioning to college prior to vs. during the COVID-19 pandemic) on cortisol awakening response (CAR) – a biological marker of chronic psychosocial stress – and university belonging among Latinx and Black first-year college students; and (2) explores whether university belonging serves as a mediator in the relationship between the COVID-19 pandemic and CAR. Latinx and Black students who were in their first semester at a four-year public university in Los Angeles County – one of the United States' hot spots for COVID-19, were recruited for this study. Across two separate cohorts (fall 2019, fall 2020), participants (N = 136) completed an online survey and provided salivary samples to assess for morning cortisol levels. Findings revealed that students who transitioned to college during the COVID-19 pandemic exhibited a flatter CAR and lower levels of belonging than students who transitioned to college prior to the COVID-19 pandemic. Implications for intervention, programs and policies aimed at fostering positive transitions to college during the COVID-19 pandemic and beyond are discussed.

Light is essential in shaping human circadian rhythms, including that of the hormone cortisol. While cortisol is known to influence secretion of the cytokine IL-6, the influence of light itself on IL-6 remains unclear. Thus, this study investigated the effects of two light conditions - red and blue - on IL-6 concentrations and the cortisol awakening response in blood. The interplay between cortisol and IL-6 was explored as well. The between-subject experiment was conducted with 71 healthy adult men (aged M red  = 24.30, SD  = 3.56; M blue  = 24.40, SD  = 3.51) in a standardized sleep laboratory setting with 60-min light exposure post-awakening at 05:00 a.m. Two mixed models, with light condition and time across measurement points as factors, were calculated. In the one for cortisol, chronotype was introduced as a covariate. Mean cortisol concentrations did not differ between exposure to red vs. blue light ( p  = 0.443), but overall cortisol output (area under the curve with respect to ground; AUC G ) and sensitivity (area under the curve with respect to increase; AUC I ) were greater in the blue-light condition ( p  = 0.050 and p  < 0.001, respectively). Additionally, chronotype significantly influenced cortisol concentrations ( p  = 0.035). As for IL-6, a main effect of time was obtained, with increasing concentrations over time ( p  = 0.002). Total IL-6 secretion was greater under blue-light exposure ( p <. 001), but mean IL-6 concentrations ( p  = 0.230) and IL-6 sensitivity ( p  = 0.777) did not differ between the red- and blue-light condition. Mean and total cortisol and IL-6 concentrations were significantly negatively correlated ( p  = 0.021 and p  < 0.001, respectively) during the red-light exposure. In the blue-light condition, cortisol sensitivity was significantly negatively correlated with IL-6 sensitivity ( p  = 0.034). Overall, blue light seemed to have exerted a greater influence on cortisol and IL-6. For cortisol, this effect might be moderated by chronotype. Additionally, cortisol and IL-6 seem to interact under light exposure. However, these effects were mixed and could not be found consistently across mean secretion, AUCg and AUCi., Competing Interests: This research received funding from the 10.13039/501100002347Federal Ministry of Education and Research (BMBF), Germany. This study was conducted in the subproject: “Einfluss von Licht auf die hormonelle Stressverarbeitung” [influence of light on hormonal stress management] as part of the joint project: “Nicht-visuelle Lichtwirkungen” [non-visual effects of light] (Funding code: 13N13397)., (© 2024 The Authors.)

Several autism-related characteristics, such as social difficulties, may contribute to high perceived stress and increased exposure to stressful life events in some autistic individuals. Repeated exposure to stress might lead to the dysfunction of the hypothalamic-pituitary-adrenocortical-axis and be a vulnerability factor for developing mental health difficulties. Previous studies show contradictory findings on salivary cortisol in autism. In the current study, we investigated diurnal cortisol profiles in autistic adolescents and young adults, as well as their associations with social difficulties, stress exposure, and mental health symptoms. Autistic (n = 48, M age  = 17.6) and nonautistic (n = 51, M age  = 18.4) participants collected salivary cortisol at home six times a day for 2 days. Social difficulties, exposure to stressful life events/bullying, and mental health symptoms were assessed with questionnaires and clinical interviews. Similar diurnal cortisol slopes (DCS) and cortisol awakening responses were observed between the groups, but autistic participants showed higher total cortisol output (AUC G , area under the curve with respect to ground) during the day (b = 19.09, p = 0.009). In the autistic group, more severe social difficulties were associated with flatter DCS (b = 0.01, p = 0.007). Finally, cortisol alterations were associated with self-reported mental health symptoms, especially in autistic females in analyses uncorrected for multiple comparisons. In conclusion, our results do not indicate autism-related group-level alterations in most diurnal cortisol measures, but autistic youth showed higher total cortisol (AUC G ) compared with nonautistic peers. More detailed investigation of interindividual variability in cortisol profiles within autistic people might give us important insights into vulnerability to developing stress-related mental health difficulties., (© 2024 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Introduction: The dynamic capacity of the hypothalamic-pituitary-adrenal (HPA) axis supports healthy adaptions to stress and play a key role in maintaining mental health. Perinatal adaptations in the HPA-axis dynamics in terms of the Cortisol Awakening Response (CAR), may be involved in dysregulation of perinatal mental health. We aimed to determine if CAR and absolute evening cortisol early postpartum differed from non-perinatal women and evaluate the association between the CAR and maternal mental well-being., Methods: The CAR was computed as the area under the curve with respect to increase from baseline from serial home-sampling of saliva across 0-60 minutes from awakening. We evaluated differences in CAR and absolute evening cortisol between postpartum women (N=50, mean postpartum days: 38, SD: ±11) and non-perinatal women (N=91) in a multiple linear regression model. We also evaluated the association between CAR and maternal mental well-being in a multiple linear regression model., Results: We found that healthy postpartum women had a blunted CAR (p<0.001) corresponding to 84% reduction and 80% lower absolute evening cortisol (p<0.001) relative to non-perinatal healthy women. In the postpartum group, there was a trend-level association between lower CAR and higher scores on the WHO Well-Being Index (WHO-5) (p=0.048) and lower Edinburgh Postnatal Depression Scale (EPDS) scores (p=0.04)., Conclusion: Our data emphasize the unique hormonal landscape during the postpartum period in terms of blunted CAR and lower absolute evening cortisol in healthy women early postpartum compared to non-perinatal. Our findings show a potential association between a reduced CAR and improved mental well-being during early motherhood, which suggests that reduced CAR might reflect healthy adjustment to early motherhood., Competing Interests: Declaration of Competing Interest VGF discloses that she has received honoraria in the form of consulting fees from SAGE Therapeutics, Lundbeck Pharma A/S, Janssen Cilag A/S, and Gedeon-Richter A/S. All other authors have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Women who use oral contraceptives (OCs) may have a higher risk of developing a depression, which is associated with both vulnerability to stress and cognitive dysfunction. OCs disrupt the hypothalamic-pituitary-gonadal (HPG) axis by suppressing endogenous sex steroid production including estradiol. The HPG axis and the hypothalamic-pituitary-adrenal (HPA) axis are known to interact, possibly through modulations driven by estradiol. OCs may affect HPA regulation capacity, i.e., disturb cortisol dynamics such as the cortisol awakening response (CAR), and influence cognition such as working memory (WM). We hypothesize that OC use is associated with blunted cortisol dynamics and impaired WM performance relative to non-users. Methods: Data from 78 healthy women in the reproductive age were available from the CIMBI database. We evaluated if CAR and WM differed between OC users (n=25) and non-users (n=53) and if the level of estradiol modulated the OC use effect on CAR or WM in generalized least square models. Results: We found that OC users had a blunted CAR (p= 0.006) corresponding to a 61% reduction relative to non-users; however, no estradiol-BY-OC use interaction effect was observed on CAR. Also, OC users had higher cortisol levels at awakening compared to non-users (p = 0.03). We observed no effect of OC use or an estradiol-BY-OC use interaction effect on WM. Also, within the OC user group, neither CAR nor WM was associated with suppressed estradiol. CAR was not associated with WM. Conclusion: Healthy women who use OCs have blunted cortisol dynamics relative to non-users. However, we could not detect OC use effects on working memory in our sample size. We speculate that disrupted cortisol dynamics may be important for the emergence of depressive symptoms in OC users. [ABSTRACT FROM AUTHOR]

Suicide is a global health issue. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, has been identified as one potential risk factor. Evidence is emerging to suggest that different psychological factors may be associated with increased resilience and vulnerability in this context. The current study investigated whether trait resilience, social support, socially prescribed perfectionism, trait worry and trait impulsivity influenced the cortisol awakening response (CAR) over a 7-day study in individuals vulnerable to suicide. 142 participants with a history of suicidal attempt or ideation (suicide vulnerability group; n = 95) and with no suicide risk history (control group; n = 47) were recruited. Participants completed baseline questionnaires before commencing a 7-day study where they provided cortisol samples immediately upon waking, at 15 min, 30 min and 45 min on 7 consecutive days. Higher worry, socially prescribed perfectionism and impulsivity, lower resilience and social support were found in the suicide vulnerability group compared to the control group. Lower levels of resilience, higher levels of socially prescribed perfectionism, worry and impulsivity were associated with significantly lower total CAR. Suicide group membership was also found to have an indirect effect on total CAR via trait worry. The current findings show for the first time, that these well-known psychological risk factors for suicide are associated with smaller total cortisol awakening responses. Researchers ought to elucidate the precise causal mechanisms linking these traits, CAR and suicide risk in order to develop interventions to help build resilience in vulnerable populations. • Lower levels of trait resilience were associated with significantly lower total cortisol awakening responses over 7 days. • Higher levels of socially prescribed perfectionism, trait worry and impulsivity were associated with significantly lower total cortisol awakening responses over 7 days. • Suicide group membership has an indirect effect on total CAR via trait worry [ABSTRACT FROM AUTHOR]