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Background: Women with premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) typically experience a range of psychological and physiological symptoms that negatively affect their quality of life. Disruption in biological rhythms, including alterations of the sleep-wake cycle, have been implicated in PMS/PMDD, though literature is still growing to substantiate these findings. The objective of this study is to systematically review the available literature on biological rhythms disruption in PMS/PMDD., Methods: A literature search was conducted on four databases (Pubmed, Embase, Medline, and Web of Science) on December 3rd, 2021. This search yielded a total of 575 articles that assessed the relationship between biological rhythms and PMS/PMDD/premenstrual symptoms., Results: After the exclusion of irrelevant articles and hand-searching references, 25 articles were included in this systematic review. Some studies showed that women with PMS/PMDD present lower melatonin levels, elevated nighttime core body temperature, and worse subjective perception of sleep quality when compared to women without PMS/PMDD. Other biological rhythms parameters showed either no differences between groups (wrist actimetry) or conflicting results (objective sleep parameters, cortisol, prolactin, and thyroid stimulating hormone)., Conclusion: Current research demonstrates that women with PMS/PMDD experience lower melatonin levels, higher body temperature, and worse subjective perception of sleep quality. This review outlines some possible mechanisms behind these findings and proposes recommendations for future research. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42020149921., (© 2024. The Author(s).)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Time of day can alter memory performance in general. Its influence on memory recognition performance for faces, which is important for daily encounters with new persons or testimonies, has not been investigated yet. Importantly, high levels of the stress hormone cortisol impair memory recognition, in particular for emotional material. However, some studies also reported high cortisol levels to enhance memory recognition. Since cortisol levels in the morning are usually higher than in the evening, time of day might also influence recognition performance. In this pre-registered study with a two-day design, 51 healthy men encoded pictures of male and female faces with distinct emotional expressions on day one around noon. Memory for the faces was retrieved two days later at two consecutive testing times either in the morning (high and moderately increased endogenous cortisol levels) or in the evening (low endogenous cortisol levels). Additionally, alertness as well as salivary cortisol levels at the different timepoints was assessed. Cortisol levels were significantly higher in the morning compared to the evening group as expected, while both groups did not differ in alertness. Familiarity ratings for female stimuli were significantly better when participants were tested during moderately increased endogenous cortisol levels in the morning than during low endogenous cortisol levels in the evening, a pattern which was previously also observed for stressed versus non-stressed participants. In addition, cortisol levels during that time in the morning were positively correlated with the recollection of face stimuli in general. Thus, recognition memory performance may depend on the time of day and as well as on stimulus type, such as the difference of male and female faces. Most importantly, the results suggest that cortisol may be meaningful and worth investigating when studying the effects of time of day on memory performance. This research offers both, insights into daily encounters as well as legally relevant domains as for instance testimonies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Serum total testosterone (T) decreases postprandially. Postprandial salivary testosterone (SalT) responses, however, have not been studied. We report on the effect of glucose ingestion on fasting SalT concentrations., Objective: To investigate the effect of oral glucose ingestion on fasting SalT., Methods: Salivary and blood samples were collected between 09.00 and 09.30 and 2 hours after a 75g oral glucose load in 32 men with mean (standard deviation) age of 52 (5.7) years and body mass index of 32.6 (5.56) kg/m 2 . Free T and bioavailable testosterone (BAT) were calculated using the Vermeulen equation., Results: Two hours following oral glucose, there was a decrease in fasting mean (standard deviation) SalT [178.2 (56.6) versus 146.0 (42.2) pmol/L; P = .0003], serum cortisol [332 (105.0) versus 239 (75.3) nmol/L; P = <0.0001], prolactin [193 (75.0) versus 127 (55.9) mIU/L; P = <0.0001] and TSH [1.60 (0.801) versus 1.16 (0.584) mIU/L; P = <0.0001]. Plasma glucose increased [6.2 (0.72) versus 8.1 (3.71) mmol/L; P = .0029]. Serum total T, SHBG, albumin, Free T, BAT, gonadotrophins and FT4 remained unchanged., Conclusions: SalT decreased postprandially. A concomitant decrease in serum cortisol, prolactin and TSH reflecting diurnal variation offers an alternative explanation for the decrease in SalT independent of food consumption. Further studies are required to determine whether morning temporal changes in SalT are related to food consumption or circadian rhythm or both., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Adolescence is a developmental period marked by significant social shifts accompanied by concurrent changes across biological, cognitive, and emotional domains. Within adolescence, the high school transition is a pivotal time for youth that is ripe with opportunities yet has the potential to disrupt functioning. An increasingly sophisticated understanding of health and developmental biology indicates that the hypothalamic-pituitary-adrenal (HPA) axis plays an important role in transducing social experiences into physiological changes that have long-term impacts on health and wellbeing. There is reason to believe that attentional biases to social threat could impact cortisol, a steroid hormone indexing activity of the HPA axis, during the high school transition. The present study examined associations between attentional biases to socially threatening stimuli, measured using the Affective Posner paradigm, and components of the diurnal cortisol rhythm among youth across the first two days of high school. Participants included 67 youth (N = 504 saliva samples) with a mean age of 12.86 years and a relatively equal split with regard to both sex assigned at birth and gender identity (54 % male; 54 % boys). Findings build upon and extend previous work by demonstrating that greater attentional engagement bias to socially threatening stimuli is associated with a pattern of greater diurnal HPA axis reactivity across the first two days of the high school transition, as evidenced by a steeper cortisol awakening response and a steeper diurnal cortisol slope. This work extends our understanding of the mechanisms through which stress relates to wellbeing in youth by embedding biological development in the life course. Clinically, this work has the potential to inform interventions to protect youth against the biological embedding of stress by identifying a theoretically driven, socio-contextually relevant risk factor to be attenuated - namely, attentional bias to threat., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Does the practice of yoga impact stress? Various studies have suggested that yoga may reduce both self-reported stress and stress biomarkers, but the evidence for such claims remains inconclusive, especially for yoga styles with a focus on physical postures. In a randomized controlled trial with 98 participants, we therefore examined whether an eight-week Hatha yoga intervention (60 min, 3×/week or more) led to reduced levels of diurnal salivary cortisol (sCort), salivary alpha-amylase (sAA), and subjective momentary stress as compared to a waitlist control group. To ensure the concomitant assessment of self-report and biological measures in an ecologically valid setting, and to capture the diurnal profile of cortisol and alpha-amylase, we employed an ecological momentary assessment approach. Five times per day, participants reported their momentary stress levels on a visual analogue scale and collected saliva samples for the assessment of salivary biomarkers. The intervention led to a significant reduction of subjective momentary stress but there was no change in diurnal sCort or sAA levels. There are several potential explanations for these findings: The intervention may have helped participants to cope better with stress while leaving diurnal levels of stress biomarkers unaffected, or the change may at least not have been reflected in sCort and sAA. Alternatively, there may have been a self-report bias, insofar as a favorable disposition towards yoga may have led participants to report reductions in stress in order to indicate positive effects of the intervention. Our findings contribute to a better understanding of the effects of distinct yoga interventions, demonstrating their potential to serve as low-risk stress relief tools., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Previous studies indicate a possible bidirectional stimulatory relationship between parathyroid hormone (PTH) and adrenocortical hormones, but the pattern of adrenocortical secretion in hypoparathyroidism is unknown. We aimed to characterize the adrenocortical secretion in patients with postsurgical hypoparathyroidism, and whether continuous subcutaneous PTH (1-34) infusion alters secretion patterns., Design: Crossover interventional study., Methods: We recruited 10 patients with postsurgical hypoparathyroidism with very low PTH levels on stable treatment with active vitamin D and calcium. Cortisol, cortisone, and aldosterone levels were measured in microdialysate from subcutaneous tissue over 24 h, before and during continuous subcutaneous PTH (1-34) infusion. Cortisol was also assayed in serum, saliva, and urine, and aldosterone and ACTH in serum and plasma, respectively. Ten patients with primary hyperparathyroidism and 10 healthy volunteers matched for sex and age served as controls., Results: Hypoparathyroid patients displayed both ultradian and circadian rhythmicity for tissue cortisol, cortisone, and aldosterone. Tissue aldosterone and cortisone levels were significantly lower in hypoparathyroid patients than in healthy controls, with no difference in tissue cortisol, but a higher cortisol to cortisone ratio. Treatment with PTH (1-34) increased tissue levels of aldosterone, cortisol, and cortisone and reduced the ratio of cortisol to cortisone., Conclusion: Adrenocortical hormone levels are reduced in postsurgical hypoparathyroidism, and partly restored by short-term continuous subcutaneous PTH (1-34) therapy., Clinical Trial Registration Number: NCT02986607., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Background: Cortisol typically peaks in the morning after waking up and declines throughout the day, reaching its lowest levels during nighttime sleep. Shift work can cause misalignment between cortisol levels and sleep-wake timing. We analyzed this misalignment in female shift workers focusing on the timing and extent of these changes., Methods: We conducted a cross-sectional study involving 68 shift workers (aged 37 ± 10 years) and 21 non-shift workers (aged 45 ± 10 years) from a hospital. Shift workers were monitored through two day shifts and three night shifts, whereas non-shift workers were monitored during two day shifts. Each participant collected six to eight saliva samples (depending on their shift type) and provided sleep timing information, which was recorded via polysomnography and sleep diaries. Generalized additive mixed models were used to estimate shift-specific differences in cortisol smooth curves. Summary measures calculated for the cortisol smooth curves included cortisol awakening response, peak-to-bed slope, and total output., Results: Between shift workers and non-shift workers, we observed similar diurnal cortisol profiles with a steep negative diurnal slope during day shifts. In shift workers on night shifts, a flattened U-shaped cortisol profile after the post-awakening maximum was observed, with a peak-to-bed slope close to zero. When comparing night to day shifts in the group of shift workers, mean cortisol levels were lower between 42 and 56 minutes and 1.8-11.9 hours after waking up, and higher between 14.9 and 22 hours after waking up., Conclusion: Our findings indicate altered cortisol profiles in female hospital employees on night shifts. Specifically, cortisol levels were lower at night when higher levels would typically be necessary for work activities, and higher at bedtime after a night shift, when levels should normally be low., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this study is to investigate circadian rhythms in independently living adults with obesity and mental disease, exploring the interplay between biological markers and lifestyle factors. Eighty participants divided equally into four groups; (i) people with obesity and schizophrenia; (ii) people with obesity and bipolar disorder; (iii) people with obesity without mental disease or sleep disorders, and (iv) people without obesity, mental disease or sleep disorders. Over two consecutive days, participants engage in repeated self-sampling of hair follicle and saliva; concurrently, data is collected on diet, body temperature, light exposure, sleep parameters, and physical activity by accelerometry. Hair follicles are analyzed for circadian gene expression, saliva samples for cortisol and melatonin concentrations. Circadian rhythms are investigated by cosinor analysis. The study employs a participant-tailored sampling schedule to minimize disruptions to daily routine and enhance ecological validity. The methodology aims to provide a comprehensive insight into the factors contributing to circadian disruptions in people with obesity, bipolar disorder and schizophrenia, potentially informing strategies for future management and mitigation. Trial registration: (ClinicalTrials.gov Identifier: NCT05413486)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kolind et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.)

Objectives: There is a growing interest in the relevance of salivary cortisol and cortisone concentrations in stress-related research. To correctly attribute the magnitude of salivary cortisol and cortisone variation as an effect of a stressful event, a coherent understanding of the day-to-day intra-individual and inter-individual variability across the diurnal cycle of the two steroids is required. However, such information is currently lacking., Methods: This study aimed to overcome these existing limitations by performing an investigation of the biological variation (BV) of salivary cortisol and cortisone within one day and between five days using an LC-MS/MS method. Saliva samples were collected from 20 healthy volunteers immediately after waking up, at 8:00, 12:00, 15:00, 19:00 and 23:00 on each day over five days. All samples were analyzed in duplicate in one run. Nested ANOVA was used to calculate the sums of squares for analytical and biological components of variation., Results: The within-subject BV of salivary cortisol and cortisone (CV I ) ranged from a minimum of 29.3 and 19.0 % to a maximum of 56.5 and 49.1 %, respectively, while the between-subject biological variation (CV G ) ranged from 29.7 and 29.0 % to 51.6 and 43.6 %. The reference change values (RCVs) ranged from 96 to 245 % for cortisol and from 55 to 194 % for cortisone. A medium index of individuality was observed for both compounds at all time points., Conclusions: This study provides updated BV estimates and RCVs for different times of day that can be used to assess the magnitude of change in biomarkers in future stress-related research., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

The transition to college is a time of increased opportunity and stress spanning multiple domains. Adolescents who encounter significant stress during this transition may be vulnerable to adverse outcomes due to a "wear and tear" of the hypothalamic pituitary adrenal (HPA) axis. Latino/a students may be particularly at-risk for heightened stress exposure due to experiences of both minority-specific and general life stress. Despite this, little is known regarding the cumulative impact of multiple stressors on Latino/a students' HPA axis functioning. The present study employed a "multi-risk model" approach to examine additive, common, and cumulative effects of multiple stress forms (general, academic, social, financial, bicultural, ethnic/racial discrimination) on diurnal cortisol in a sample of first-year Latino/a college students ( N = 196; 64.4% female; M age = 18.95). Results indicated that no stress forms were additively associated with the cortisol awakening response (CAR), but general stress was associated with a flatter diurnal cortisol slope (DCS) and bicultural stress was linked with a steeper DCS. A college stress latent factor was associated with a lower CAR, whereas a latent factor of discrimination was not associated with diurnal cortisol. Cumulative risk was linked with a lower CAR. Findings highlight the physiological correlates of various stressors experienced by Latino/a college students.

Hypothalamic pituitary adrenal gland (HPA) axis functioning has been linked with daily demands during adolescence. A ubiquitous, yet understudied daily demand in the lives of youth is the commute to school, which may be associated with the diurnal rhythm of cortisol as demonstrated in prior research among adults. The current study hypothesized that longer school commute times would be associated with altered HPA axis functioning as demonstrated by a heightened cortisol awakening response (CAR) and flatter diurnal slope. Additionally, given that the HPA axis follows a diurnal rhythm and adolescence is marked by changes in the circadian rhythm, adolescents with a more evening chronotype were hypothesized to evince even more altered HPA axis functioning in the face of long school commute times. A total of 269 adolescents (M = 16.38 years, SD = 0.74) provided saliva samples at wake, 15-min. post-wake, and 30-min. post-wake for the calculation of CAR and at dinnertime and bedtime for the calculation of diurnal slope, completed up to 8 nights of sleep actigraphy, and self-reported school commute time. Results suggest that more evening chronotype youth with longer school commute times evince a higher CAR, but not an altered diurnal slope. The present findings may have implications for adolescent mental health as higher CAR has been associated poor mental health and heightened stress., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The positive direct relation between stress and the development of cardiovascular disease has increasingly been recognized. However, the link between hypothalamic-pituitary-adrenal (HPA) dysregulation and subclinical cardiovascular disease has not been studied longitudinally. We investigated the relation of diurnal salivary cortisol, as a biological marker of stress levels, with progression of aortic stiffness over five years., Methods: A total of 3281 people (mean age 65.5) in the Whitehall II prospective study provided six saliva samples on a single weekday. We assessed the diurnal salivary cortisol using the daytime slope and bedtime level. Aortic stiffness was measured by carotid-femoral pulse wave velocity (PWV) at baseline (2007-2009) and five years later (2012-2013). Linear mixed models were used to estimate the association of diurnal salivary cortisol with baseline PWV and five-year longitudinal changes., Results: Diurnal salivary cortisol were not associated with PWV at baseline. Among women but not men, a 1-SD shallower salivary cortisol slope at baseline was associated with a five-year increase in PWV (β = 0.199; 95% CI = 0.040, 0.358 m/s) and higher bedtime cortisol level (β = 0.208, 95% CI = 0.062, 0.354 m/s)., Conclusions: Dysregulation of the HPA axis measured using salivary cortisol (shallower slope, higher bedtime level) predicted the rate of progression of aortic stiffness among women., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Loneliness is associated with multiple forms of psychopathology in youth. However, we do not yet know how loneliness gets "under the skin" in ways that may impact the long-term health and development of early adolescents. In particular, loneliness may influence youths' patterns of diurnal cortisol, an index of hypothalamic-pituitary-adrenal (HPA) axis functioning and a central predictor of health across the lifespan. The current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, or COVID-19) pandemic represents a salient period in which to study the consequences of loneliness, as recent work has provided evidence that the physical-distancing measures put in place to contain the virus have resulted in greater loneliness, particularly among youth. Thus, the current study aimed to examine the prospective association between loneliness during the COVID-19 pandemic and diurnal cortisol in early adolescents. We found that greater loneliness was associated with higher levels of cortisol at waking and a blunted cortisol awakening response (CAR). These results held even when controlling for covariates that can influence diurnal trajectories of cortisol. Critically, this pattern of HPA-axis functioning increases risk for adverse mental and physical health outcomes across adolescence and into adulthood. This study is the first to examine the prospective association between loneliness and diurnal cortisol in early adolescence, and the first to identify mechanisms that contribute to biological markers of distress during the COVID-19 pandemic. Findings underscore the importance of developing and distributing strategies to mitigate feelings of loneliness among youth., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Previous research has used cortisol, the major hormonal byproduct of the hypothalamic pituitary adrenal (HPA) axis system, to explore how environmental stressors influence daily physiological functioning. Most of the research focused on diurnal cortisol has examined specific cortisol markers, with little consideration of how different components of the diurnal pattern may co-occur. Morning level, cortisol awakening response (CAR), bedtime level, as well as the diurnal slope and total cortisol exposure throughout the day (area under the curve; AUC), are five common parameters of diurnal HPA axis functioning that have been individually linked to physical and mental health outcomes, with mixed results. The current study introduces a novel approach to capture heterogeneity in HPA axis activity by using latent profile analysis to generate empirically-derived, theoretically supported diurnal cortisol profiles based on all five indicators. We analyzed salivary cortisol data from 278 young adults during a time of heightened sociopolitical stress - the 2016 U.S. presidential election - and examined whether profiles differentially predicted mental health trajectories across six months. Findings suggest that a specific combination of cortisol parameters (i.e., flat slope, high AUC, and high CAR) may predict worse mental health risk over time. Overall, this work suggests that diurnal cortisol profiles likely reflect distinct physiological underpinnings with unique health consequences that may not be observed by studying individual cortisol parameters., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Chronic stress is often accompanied by alterations in the diurnal rhythm of hypothalamus-pituitary-adrenal activity. However, there are limited data on the diurnal rhythmicity of breast milk glucocorticoids (GCs) among women with psychological distress. We compared mothers who sought consultation at an expertise center for pregnant women with an increased risk of psychological distress with control mothers for GC diurnal rhythmicity in milk and saliva obtained at the same time., Methods: We included 19 mothers who sought consultation at the psychiatry-obstetric-pediatric (POP) outpatient clinic and 44 control mothers. One month postpartum, mothers collected on average eight paired milk and saliva samples during a 24 h period. GC levels were measured using liquid chromatography-tandem mass spectrometry. GC rhythmicity parameters were determined with specialized software., Results: For both milk and saliva, no group differences regarding GC rhythms were found. Milk cortisol area under the curve with respect to the ground was lower in the POP group than in the control group ( p = 0.02). GC levels in human milk and saliva were highly correlated within each group ( p < 0.001)., Conclusion: Although there were no differences between groups in GC rhythmicity, the total amount of milk cortisol was lower in the POP group. Long-term follow-up is needed to address the impact of vertical transmission of breast milk GCs.

Background: Obstructive sleep apnea syndrome (OSAS) may be associated with an increase in hypothalamic-pituitary-adrenocortical axis activity (HPA AA). We reviewed research comparing morning salivary and blood (serum and plasma) cortisol concentrations of individuals with OSAS to those of healthy controls., Methods: We made a systematic search without any restrictions of the PubMed/Medline, Scopus, Cochrane Library, and Web of Science databases for relevant articles published up to August 25, 2019., Results: Sixteen studies were analyzed in this meta-analysis; five studies compared morning salivary concentrations, five compared serum concentrations, four compared plasma cortisol concentrations, and two compared both salivary and plasma concentrations. In pediatric samples, compared to healthy controls, those with OSAS had significantly lower saliva morning cortisol concentrations (MD = -0.13 µg/dl; 95% CI: 0.21, -0.04; P = 0.003). In contrast, no significant differences were observed for serum cortisol concentrations, plasma cortisol concentrations, or salivary morning cortisol concentrations between adults with and without OSAS ( p = 0.61, p = 0.17, p = 0.17)., Conclusion: Cortisol concentrations did not differ between adults with OSAS and healthy controls. In contrast, morning salivary cortisol concentrations were lower in children with OSAS, compared to healthy controls. Given that a reduced HPA AA is observed among individuals with chronic stress, it is conceivable that children with OSAS are experiencing chronic psychophysiological stress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Imani, Sadeghi, Khazaie, Sanjabi, Brand, Brühl and Sadeghi Bahmani.)

Context: Cortisol in blood has a robust circadian rhythm and exerts potent effects on energy balance that are mediated in part by central mechanisms. These interactions involve orexigenic agouti-related protein (AgRP) neurons that are stimulated by glucocorticoids. However, diurnal changes in brain or cerebrospinal fluid (CSF) cortisol and cortisone, which are interconverted by 11ß-HSD1, have not been characterized in humans., Objective: To conduct a secondary analysis of existing samples to characterize diurnal changes in cortisol and cortisone in CSF and examine their relationships to changes in AgRP., Methods: Stored CSF and plasma samples were obtained from 8 healthy subjects who served as controls for a sleep study. CSF was collected every 2h for 36h via indwelling lumbar catheter; plasma was collected every 2h., Results: There was a diurnal rhythm for cortisol and cortisone in CSF that closely followed the plasma rhythm by 2 h with peak and nadir levels at 0900h and 0100h. The ratio of cortisol (active) to cortisone (inactive) in CSF was 48% higher at the peak versus nadir. There was a diurnal rhythm for AgRP in plasma that was out of phase with the cortisol rhythm. There was a less distinct diurnal rhythm for AgRP in CSF that oscillated with a similar phase as cortisol., Conclusions: There is a robust diurnal rhythm for cortisol and cortisone in CSF. Diurnal changes were noted for AgRP that are related to the cortisol changes. It remains to be determined if AgRP mediates adverse metabolic effects associated with disruption of the cortisol circadian rhythm., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Circadian rhythm plays an important role as our internal body's clock that synchronizes behavior and physiology according to the external 24-h light-dark cycle. Past studies have associated disrupted circadian rhythm with higher risk of miscarriages, preterm birth and low birth weights. This paper described the protocol of a prospective cohort study which aims to determine the circadian rhythm in pregnant women, identify its association with maternal factors during pregnancy, gestational weight gain, birth and infant outcomes., Methods: Ten government maternal and child health clinics in Kuala Lumpur, Malaysia will be randomly selected. Sample size of 438 first-trimester pregnant women will be followed-up until the birth of their infant. Salivary melatonin and cortisol concentration among subsample will be determined using enzyme-linked immunosorbent assay. Data on sleep quality, psychological distress and morningness/eveningness chronotype of pregnant women will be collected using validated questionnaires. Pedometer will be used to measure 5-day physical activity data. Total gestational weight gain will be determined at the end of pregnancy. Utilization of 3-day food record is to capture meal timing and nutrient intake. All measurements will be done in 2nd and 3rd trimester. Birth outcomes will be collected through clinic records and Centers for Disease Control and Prevention (CDC) Neonatal questionnaire. Infants will be followed-up at 6 and 12 months old to obtain anthropometric measurements., Discussion: There is a growing recognition of the role of maternal circadian rhythm, which entrains fetal circadian rhythms that may subsequently have long-term health consequences. The present study will identify the effect of circadian rhythm on pregnancy outcomes and infant growth in the first year of life.

Data were drawn from an ongoing study of preschoolers (N = 221). Mothers self-reported experiences of intimate partner violence (IPV) and parenting practices, and collected three saliva samples (waking, midday, and bedtime) on themselves and their child on 2 consecutive days. Saliva samples were later assayed for cortisol. Bootstrapped mediation analyses revealed IPV to indirectly impact child diurnal cortisol through positive parenting. Specifically, greater exposure to IPV was associated with reduced positive parenting and subsequently heightened child waking cortisol levels. IPV did not indirectly impact child diurnal cortisol via autonomy supporting parenting or maternal diurnal cortisol. These findings suggest a possible pathway by which mother's experience of IPV indirectly influences child physiological regulation via maternal positive parenting., (© 2020 International Society for Developmental Neuroscience.)

Context: The pituitary-adrenal axis had historically been considered a representative model for circadian rhythms. A recently developed portable collection device has provided the opportunity to evaluate free cortisol profiles using the microdialysis approach in individuals free to conduct their day-to-day activities in their own surroundings., Methods: Two separate experiments were conducted in healthy male volunteers. The total and subcutaneous (SC) free cortisol levels were measured at 10-minute intervals for a 24-hour period in one experiment, and the SC free cortisol levels were measured at 20-minute interval for 72 consecutive hours in free-living individuals in the second experiment., Results: The characteristic circadian rhythm was evident in both serum total and SC free cortisol, with the lowest levels achieved and maintained in the hours surrounding sleep onset and the peak levels occurring in every individual around waking. In all free-living individuals, the circadian rhythm was consistent across the 72-hour period, despite a wide range of activities. All the participants also showed increased cortisol after the consumption of lunch. The lowest levels during all 24-hour periods were observed during the hours after lights off, at the onset of sleep., Conclusions: To the best of our knowledge, the present study is the first to report up to three consecutive 24-hour measurements of SC free cortisol in healthy individuals. We believe our study is a landmark study that paves the way for ambulatory monitoring of free cortisol profiles continuously for a period of 72 hours in free-living individuals performing their day-to-day activities whether healthy or with diseases involving the hypothalamic-pituitary-adrenal axis., (Copyright © 2019 Endocrine Society.)

Background: It is assumed that the expression of the cortisol awakening response (CAR) is modulated by light exposure during the peri-awakening period. While initial evidence supports this principal effect, the specific role of the spectral composition of light (brightness and wavelength) is still incompletely understood., Method: Two counterbalanced within-subject experiments were conducted in a standardized sleep laboratory setting to investigate the effect of light intensity (study I; two days: dim vs. bright light) and spectral composition (study II; three days: red vs. blue vs. green light) on the CAR. Across studies, light exposure was conducted for one-hour post-awakening and the accuracy of CAR assessments (based on eight saliva samples) was well-controlled in line with recent guidelines., Results: The two studies revealed consistent effects of light exposure on the CAR. Specifically, an increased CAR was found after exposure to bright (vs. dim) light (study I; (F (3.7, 106.4)  = 11.93, p < .001, η² p  = .29) and following blue and green (vs. red) light exposure (study II; F (4.9, 194.6)  = 2.49, p = .037, η² p  = .10)., Conclusion: Our findings illustrate the crucial role of light intensity and wavelength for expression of the CAR, in line with current theoretical knowledge of underlying neurobiological mechanisms., (Copyright © 2019. Published by Elsevier Ltd.)

Background: There is conflict between living according to our endogenous biological rhythms and our external environment, with disruptions resulting in negative consequences to health and performance. This is often documented in shift work and jet lag, but 'societal norms' (eg, typical working hours) can create profound issues for 'night owls', people whose internal biological timing predisposes them to follow an unusually late sleep-wake cycle. Night owls have also been associated with health issues, mood disturbances, poorer performance and increased mortality rates., Methods: This study used a randomized control trial design aimed to shift the late timing of night owls to an earlier time (phase advance), using non-pharmacological, practical interventions in a real-world setting. These interventions targeted light exposure (through earlier wake up/sleep times), fixed meals times, caffeine intake and exercise., Results: Overall, participants demonstrated a significant advance of ∼2 h in sleep/wake timings as measured by actigraphy and circadian phase markers (dim light melatonin onset and peak time of the cortisol awakening response), whilst having no adverse effect on sleep duration. Notably, the phase advance was accompanied by significant improvements to self-reported depression and stress, as well as improved cognitive (reaction time) and physical (grip strength) performance measures during the typical 'suboptimal' morning hours., Conclusions: Our findings propose a novel strategy for shifting clock timing towards a pattern that is more aligned to societal demands that could significantly improve elements of performance, mental health and sleep timing in the real world., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Young children living in institutional settings often show a range of deficits in social, physical, and cognitive functioning. Whereas the diurnal production of cortisol has been examined among post-institutionalized children in a number of investigations, studies of children continuing to live in institutions are limited. In this study, we assessed wake-up and bedtime cortisol among 73 children living in Russia, with 52 institutionally-reared (n = 31 at time 2), and 21 family-reared (n = 18 at time 2). Institutionally-reared children showed a blunter wake-up to bedtime slope than family-reared children at both time 1 and time 2, with significantly higher cortisol levels at bedtime. These findings highlight the deleterious effects of institutional care on children's developing neuroendocrine regulation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Women have smaller cortisol responses to psychological stress than men do, and women taking hormonal contraceptives (HC+) have smaller responses than HC- women. Cortisol secretion undergoes substantial diurnal variation, with elevated levels in the morning and lower levels in the afternoon, and these variations are accompanied by differences in response to acute stress. However, the impact of HC use on these diurnal relationships has not been examined. We tested saliva cortisol values in 744 healthy young adults, 351 men and 393 women, 254 HC- and 139 HC+, who were assigned to morning (9:00 am) or afternoon (1:00 pm) test sessions that were held both on a rest day and on a stress day that included public speaking and mental arithmetic challenges. Saliva cortisol responses to stress were largest in men and progressively smaller in HC- and in HC+ women (F = 23.26, p < .0001). In the morning test sessions, HC+ women had significantly elevated rest day cortisol levels (t = 5.99, p ≪ .0001, Cohen's d = 0.95) along with a complete absence of response on the stress day. In the afternoon sessions, both HC+ and HC- women had normal rest-day cortisol levels and normal responses to the stressors. Heart rates at rest and during stress did not vary by time of day or HC status. Cortisol stress responses in HC+ women are absent in the morning and normal in size by early afternoon. Studies of stress reactivity should account for time of day in evaluating cortisol responses in women using hormonal contraceptives.

Literature suggests that women experience ovulatory shifts in risk-taking behaviours across different domains, which might be partly attributed to changes in testosterone (T). Thus, we investigated associations between menstrual variability in T concentrations and economic risk-related decisions among athletic women. Thirty-five women were monitored across three consecutive menstrual cycles. Testing occurred on day seven (D7), 14 (D14) and 21 (D21) following the onset of menses. The morning (7 to 8 am) assessment of salivary T (sal-T) and cortisol (sal-C) was followed by the economic Hawk-Dove game (11 am to 12 pm) played in pairs, where hawk decisions were used to index risk. Morning sal-T concentration increased from D7 to D14, before decreasing on D21 (p < 0.001), representing moderate effect size (ES) changes of 0.6 to 0.8. Morning sal-C did not vary over time. Hawk choices paralleled the sal-T results, being elevated on D14 (p < 0.001) with large ES changes of 1.8. Regression analyses revealed that morning sal-T concentration was positively related (p ≤ 0.01) to the number of hawks chosen between- (beta = 0.47) and within-participants (beta = 0.10) when controlling for training hours and menstrual day. In summary, the risk-related choices of athletic women during a dyadic contest covaried with morning sal-T concentrations across the menstrual cycle. Both outcomes were positively correlated on a within- and between-person level. Confirming the major sources of T variation across the menstrual cycle, whilst discerning its relationship with other risk-related behaviours, would be worthwhile avenues for research., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Working atypical schedules leads to temporal misalignments between a worker's rest-activity cycle and their endogenous circadian system. Several studies have reported disturbed centrally controlled rhythms, but little is known on shift workers' peripheral clocks. Here, we assessed central clock markers, urinary 6-sulfatoxymelatonin and salivary cortisol, and clock gene expression in 2 peripheral clocks, oral mucosa cells and peripheral blood mononuclear cells (PBMCs), in 11 police officers. Before working 7 consecutive nights, officers' centrally controlled rhythms were aligned to a day-oriented schedule. These rhythms were partially realigned to the shifted schedule and dampened after a week working nights. For peripheral clocks at baseline, Period ( PER)1-3 and nuclear receptor subfamily 1, group D, member 1 ( REV-ERBα ) in oral mucosa cells had a significant mRNA peak in the afternoon, whereas in PBMCs, higher PER1-3 expression was observed at 10:00 compared with 19:30. After a week working nights, PER1-3 and REV-ERBα expression in oral mucosa cells lost rhythmicity, and in PBMCs, the morning/evening difference observed at baseline was lost. To our knowledge, this is the first study to demonstrate the disruption of several peripheral clocks in real shift workers. Molecular circadian disturbances are believed to have important clinical implications for the occurrence of shift work-associated medical disorders.-Koshy, A., Cuesta, M., Boudreau, P., Cermakian, N., Boivin, D. B. Disruption of central and peripheral circadian clocks in police officers working at night.

Purpose The current study investigated diurnal cortisol dynamics in adults with and without aphasia, along with subjective reports of stress and measures of language production. Dysregulation of cortisol, a common biomarker of stress, is associated with cognitive dysfunction in different clinical populations. However, little is known about the consequences of stress-induced cortisol disturbances for stroke survivors, including those with aphasia. Method Nineteen participants with aphasia and 14 age-matched neurotypical adults were tested. Saliva samples were collected from participants to assess the cortisol awakening response, a marker of the integrity of the hypothalamic-pituitary-adrenal (HPA) axis. Participants also completed 2 subjective stress questionnaires. Language was evaluated using 3 short, picture description narratives, analyzed for discourse (dys)fluency and productivity markers. Results In contrast to neurotypical participants, adults with aphasia did not show the predictable cortisol awakening response. Participants with aphasia also showed an unusual heightened level of cortisol upon awakening. Additionally, neurotypical participants demonstrated an association between intact language performance and the cortisol awakening response, whereas the participants with aphasia did not, although they did perceive the language tasks as stressful. Conclusion This study indicates that the functionality of the HPA axis, as indexed by cortisol, contributes to optimal language performance in healthy adults. The absence of an awakening response among participants with aphasia suggests that stroke leads to dysregulation of the HPA axis, although the degree to which this impairment affects language deficits in this population requires further investigation.

Psychological symptoms that arise in early childhood can follow a multitude of patterns into adolescence, including homotypic continuity (i.e., similar symptoms over time) and heterotypic continuity (i.e., a shift in symptoms over time). However, we know very little about the factors that distinguish homotypic vs. heterotypic continuity of early internalizing and externalizing symptoms over development. In a separate line of research, diurnal cortisol has been shown to predict later internalizing and externalizing problems. In the current study, we tested whether diurnal cortisol patterns moderated the course of internalizing and externalizing symptoms from preschool to early adolescence. 554 children (54% male) and parents participated in a longitudinal study. Parents reported on their children's internalizing and externalizing symptoms at ages 3 and 12, and children collected diurnal saliva samples at age 9. Results showed that a steeper cortisol decline at age 9 combined with high internalizing or externalizing problems at age 3 predicted higher internalizing problems at age 12. A more blunted cortisol decline combined with early internalizing or externalizing problems predicted higher externalizing problems in early adolescence. These results illustrate the moderating role of stress system functioning in homotypic and heterotypic patterns of psychopathology from preschool to early adolescence.

Evidence from both preclinical and clinical studies suggests aerobic exercise may dampen age-related decline in cognitive performance. Alterations in hypothalamic-pituitary-adrenal (HPA) axis function and reactivity may be a mechanism by which aerobic exercise benefits cognitive performance, and reduces perceived stress. This investigation was completed as an ancillary investigation of the Brain in Motion (BIM) study, a 6-month supervised aerobic exercise intervention. Participants were generally healthy and screened for inclusion/exclusion criteria for the parent study. Thirty-eight participants were recruited (Mean age = 65.0 [SD = 5.1]; 60% female) and the final longitudinal sample was 32 participants. Participants provided a passive drool sample at: waking, 15, 30, and 45 min post-waking to assess the cortisol awakening response (CAR) and 3, 6, 9, and 12 h post-waking to assess daily area under the curve for cortisol. Salivary cortisol was quantified by liquid chromatography coupled to tandem mass spectrometry. The exercise intervention increased CAR but no differences were observed in daily AUC. In addition, larger increases in CAR were positively associated with greater decreases in subjective stress. Thus, aerobic exercise improved the CAR in otherwise healthy, but sedentary older adults and greater improvements in CAR were associated with greater reductions in perceived stress., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: To investigate ocular and systemic diurnal rhythms in emmetropic and myopic adults and examine relationships with light exposure., Methods: Adult subjects (n = 42, 22-41 years) underwent measurements every 4 hours for 24 hours, including blood pressure, heart rate, body temperature, intraocular pressure (IOP), ocular biometry, and optical coherence tomography imaging. Mean ocular perfusion pressure (MOPP) was calculated. Saliva was collected for melatonin and cortisol analysis. Acrophase and amplitude for each parameter were compared between refractive error groups. Subjects wore a light, sleep, and activity monitor for 1 week before measurements., Results: All parameters exhibited significant diurnal rhythm (ANOVA, P < 0.05 for all). Choroidal thickness peaked at 2.42 hours, with a diurnal variation of 25.8 ± 13.44 μm. Axial length peaked at 12.96 hours, with a variation of 35.71 ± 6.6 μm. Melatonin peaked at 3.19 hours during the dark period, while cortisol peaked after light onset at 8.86 hours. IOP peaked at 11.24 hours, with a variation of 4.92 ± 1.57 mm Hg, in antiphase with MOPP, which peaked at 22.02 hours. Amplitudes of daily variations were not correlated with light exposure, and rhythms were not significantly different between emmetropes and myopes, except for body temperature and MOPP., Conclusions: Diurnal variations in ocular and systemic parameters were observed in young adults; however, these variations were not associated with habitual light exposure. Emmetropic and myopic refractive error groups showed small but significant differences in body temperature and MOPP, while other ocular and systemic patterns were similar.

Major life stress often produces a flat diurnal cortisol slope, an indicator of potential long-term health problems. Exposure to stress early in childhood or the accumulation of stress across the life span may be responsible for this pattern. However, the relative impact of life stress at different life stages on diurnal cortisol is unknown. Using a longitudinal sample of adults followed from birth, we examined three models of the effect of stress exposure on diurnal cortisol: the cumulative model, the biological-embedding model, and the sensitization model. As its name implies, the cumulative model focuses on cumulative life stress. In contrast, the biological-embedding model implicates early childhood stress, and the sensitization model posits that current life stress interacts with early life stress to produce flat diurnal cortisol slopes. Our analyses are consistent with the sensitization model, as they indicate that the combination of high stress exposure early in life and high current stress predict flat diurnal cortisol slopes. These novel findings advance understanding of diurnal cortisol patterns and point to avenues for intervention.

Objective: This study aimed to examine associations between sleep duration, BMI, and cortisol levels across childhood., Methods: Participants included 361 children adopted domestically in the United States. Random-intercept cross-lagged panel models tested for between-person and bidirectional within-person associations of sleep duration, BMI, and morning and evening cortisol at age 4.5 to 9 years., Results: Sleep duration and BMI were stable during childhood, inversely associated at the between-person level, and unrelated to morning or evening cortisol. BMI at age 6 years predicted longer sleep duration and lower evening cortisol at age 7 years, and lower morning cortisol at age 7 years predicted higher BMI at age 9 years within individuals., Conclusions: The association between sleep and BMI is more likely a stable between-person phenomenon rather than a unidirectional association that develops within individuals over time., (© 2019 The Obesity Society.)

Background & Aims: Assessment of circadian health is confined to adults. However, understanding circadian status of school-aged children is necessary due to its health implications. The aim was to develop 1) a protocol to assess circadian function in school-aged children by combining the best non-invasive tools previously validated in adults; 2) a score to capture circadian function in children including food timing. This protocol will allow to explore gender differences and to compare the circadian function of school-aged children with adults from the same Mediterranean area., Methods: Healthy children (8-12 y) from 3 schools in a Mediterranean area of Spain were recruited (n = 248; 125 males and 123 females). Several non-invasive tools were used: a) 7-day-diaries of food timing and food intake, physical-activity and sleep, b) Munich-chronotype-self-reported-questionnaire; c) cortisol and melatonin saliva determinations; d) 7-day-rhythms of wrist temperature (T), activity (A), position (P) and the integrative variable TAP e) 7-day-light exposure., Results: We have constructed the first school-aged children population for the assessment of circadian function (ONTIME-Jr) and a new circadian score has been developed. Among circadian-related measures, TAP was the most suitable and reliable to determine circadian system characteristics. Circadian function was better in girls than in boys [circadian score (AU) Mean ± SD (girls, 1216 ± 153 vs. 1159 ± 173 boys, P = 0.012)], and also in school-aged children than in adults from the same Mediterranean area (Circadian-Function-Index: children 0.47 ± 0.06 vs. adults 0.45 ± 0.06 P = 0.001)., Conclusions: A new protocol, including TAP and food timing, demonstrated to be reliable in assessing circadian function in children. These non-invasive techniques provide the wherewithal for paediatricians to assess circadian function in clinical practice., Trial Registration: Chronobiology and childhood obesity (ONTIME-Jr: Obesity, Nutrigenetics, Timing and Mediterranean, Junior). ClinicalTrials.gov ID: NCT02895282, October 2014., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: To assess the diurnal melatonin, cortisol, and activity/rest levels, as well as sleep quality, in patients with and without nonproliferative diabetic retinopathy (DR)., Methods: We included 25 diabetic patients with DR and 29 without DR. A total of 21 healthy subjects constituted the control group. We assessed the circadian rhythm by actigraphy and diurnal salivary melatonin and cortisol measurements. Sleep quality was evaluated by actigraphy and the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaires. Light exposure was quantified by actigraphy. The primary outcome was peak salivary melatonin level. Secondary outcomes were mean melatonin and cortisol levels during dark hours, activity-rest rhythm, sleep quality, as well as level of white, red, green, and blue light exposure., Results: Peak melatonin concentration at 04:00 and mean nocturnal melatonin level were significantly reduced in all diabetic patients, regardless of retinopathy stage (p < 0.001). Levels of light exposures during dark hours were not significantly different in patients with and without DR and healthy controls. Only patients with DR showed increased intradaily variability in their activity-rest interval, indicating circadian misalignment (p = 0.04). Neither the objective actigraphic sleep quality parameters nor the subjective PSQI or ESS scores were significantly different between healthy controls and diabetic patients., Conclusions: Reduced nocturnal melatonin concentration and increased fragmentation of activity-rest intervals revealed circadian rhythm disturbance in diabetic patients with DR., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Glucocorticoids (GCs) in breastmilk follow the maternal hypothalamus⁻pituitary⁻adrenal axis activity and may affect the offspring's growth and neurodevelopment. There is some evidence suggesting that macronutrients in breastmilk also fluctuate throughout the day. We aimed to research whether GCs and macronutrients are correlated in multiple breastmilk samples obtained over a 24-h period., Methods: A total of 10 mothers provided 45 breastmilk samples collected over a 24-h period. Cortisol and cortisone levels were determined by LC⁻MS/MS, and macronutrients were measured with mid-infrared spectroscopy. Correlations between breastmilk GCs and macronutrients were assessed with Pearson correlations and linear mixed models., Results: No associations were found between breastmilk GCs and macronutrients (cortisol: β-0.1 (95% confidence interval: -1.0 to 0.7), -4.9 (-12.9 to 3.1) for fat, protein, and carbohydrates, respectively; and -0.3 (-5.6 to 5.0) and cortisone: 0.0 (-2.5 to 2.5), -17.4 (-39.8 to 5.0), and -2.7 (-17.7 to 12.3)) for fat, protein, and carbohydrates, respectively. Adjusting for the time of collection to account for GC rhythmicity did not change the results., Conclusion: We found no associations between GCs and macronutrients in human breastmilk. The excretion of GCs in breastmilk and the effects of breastmilk GCs on offspring are, therefore, likely independent of the excretion and effects of the macronutrients.

Study Objectives: The aim of this study was to investigate circadian rhythm and sleep complaints in individuals with spinal cord injury (SCI) as determined by diurnal saliva melatonin and cortisol as well as activity measurements and subjective sleep quality., Methods: Fourteen patients with cervical SCI (cSCI), six patients with thoracic SCI (tSCI) and eight able-bodied controls all underwent two consecutive weeks wearing a wrist actigraph in addition to filling out a sleep diary. During one 24-h period, cortisol and melatonin were measured at 4-h intervals. Furthermore, participants' sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and their overall daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS)., Results: The cSCI group demonstrated lower melatonin levels compared with the tSCI group and the controls at the 24:00 and 04:00 time points. Moreover, at one time point the tSCI group had a higher cortisol level than the cSCI group and the controls. In addition, baseline systolic blood pressure and oxygen saturation were significantly lower in the cSCI group. No differences were found in activity measurements or self-reported sleep quality., Conclusions: Individuals with cSCI demonstrate reduced melatonin secretion compared with tSCI individuals, but not in other circadian measures. This supports an involvement of melatonergic cervical fibers associated with the cervical lesion., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Cortisol plays a key role in initiating and maintaining different sleep stages. Patients with Addison's disease (AD) frequently report disrupted sleep, and their hydrocortisone medication regimes do not restore the natural diurnal rhythm of cortisol. However, few studies have investigated relations between sleep quality, especially as measured by polysomnographic equipment, and night-time cortisol concentrations in patients with AD., Methods: We used sleep-adapted EEG to monitor a full night of sleep in 7 patients with AD and 7 healthy controls. We sampled salivary cortisol before bedtime, at midnight, upon awakening, and at 30-minutes post-waking., Results: Controls had lower cortisol concentrations than patients before bedtime and at midnight. During the second half of the night, patient cortisol concentrations declined steeply, while control concentrations increased steadily. Whereas most controls experienced a positive cortisol awakening response, all patients experienced a decrease in cortisol concentrations from waking to 30-minutes post-waking (P = .003). Patients experienced significantly lower proportions of slow-wave sleep (SWS; P = .001), which was associated with elevated night-time cortisol concentrations., Conclusion: Overall, these results suggest that patients with AD demonstrate different patterns of night-time cortisol concentrations to healthy controls, and that relatively elevated concentrations are associated with a reduction of SWS. These hormonal and sleep architectural aberrations may disrupt the routine sleep-dependent processes of memory consolidation, and hence may explain, at least partially, the memory impairments often experienced by patients with AD., (© 2018 European Society of Endocrinology)

Objective: Results from experimental studies suggest that psychosis and psychosis liability are associated with increased cortisol levels and blunted cortisol reactivity, and that use of antipsychotics may reduce these aberrations. Here, we report on overall cortisol, diurnal slope, and cortisol stress reactivity in everyday life in psychosis and psychosis liability using the experience sampling method (ESM)., Methods: Our sample consisted of individuals diagnosed with psychotic disorder currently on (MPD; n = 53) or off antipsychotic medication (NMPD; n = 20), first-degree relatives of psychotic patients (REL; n = 47), and healthy volunteers (HV; n = 67). Saliva samples were collected throughout the day on six consecutive days and analyzed for cortisol levels. Simultaneously, stressfulness of the current activity was assessed with ESM questionnaires., Results: We found no group differences in overall cortisol level between groups, but REL had a steeper diurnal slope than HV; in MPD a trend was found in the same direction. Regarding reactivity to stressful activities, results indicated attenuation of the cortisol response in both patient groups compared to HV., Conclusion: These results do not confirm reports of increased cortisol levels in psychosis, but provide evidence of stress-related cortisol alterations in everyday life., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To examine cortisol diurnal rhythms over the transition from the critical care setting to home for fathers and mothers of very low-birth-weight infants, including how cortisol is associated with psychosocial stress and parenting sense of competence. This cohort study in a level III neonatal intensive care unit and the general community had 86 parents complete salivary collection and self-reported psychosocial measures. Salivary samples were collected 3 times a day on the day before discharge, and on 3 subsequent days at home. Self-report measures included the Perceived Stress Scale and the Parenting Sense of Competence Scale, which measure parenting satisfaction. Fathers showed increased physiologic stress over the transition home, reflected by flattening of slopes, lower wakeup, and higher bedtime cortisol. Mothers reporting increases in perceived stress over the transition home had higher bedtime cortisol, suggesting a link between higher perceived stress and higher physiologic stress. Results were significant after controlling for breastfeeding, insurance status, and gestational age. This study examined a physiologic marker of stress in parents with very low-birth-weight infants, finding sex disparities in diurnal cortisol patterns during the transition from neonatal intensive care unit to the community. Fathers may be especially susceptible to stressors during this transition.

Poor sleep in pregnancy is related to adverse neonatal health. Elevated maternal cortisol has been proposed as a pathway, yet the association in pregnancy is not well understood. The goals of the current study were to examine associations between (a) sleep and cortisol, (b) sleep, cortisol, and neonatal outcomes, and (c) variables that could explain these associations. Two hundred pregnant women completed the Pittsburgh Sleep Quality Index (PSQI; Buysse, Reynolds, Monk, Berman, & Kupfer, 1989) and provided diurnal salivary cortisol samples at two times over pregnancy. Poor sleep quality was associated with greater evening cortisol concentrations at 36 weeks' gestation. This association was mediated by anxiety symptoms. Higher evening cortisol at 36 weeks' gestation was associated with shorter gestation.

The majority of preschool children (aged 3-5 years) no longer habitually nap, yet in childcare settings daily mandated naptimes in which children lie down without alternative activity remains a common practice. Mandated naptimes are associated with observed reductions in emotional climate and increased incidence of distress. While intended to be restful, mandatory naptimes may induce stress in those children unable to sleep. To examine this possibility, we applied a 2 (mandated/flexible practice) × 2 (nap/no-nap) design to test group difference in stress responses of children (N = 43, mean age 56.3 months). Salivary cortisol level was measured at 4 time-points (waking, pre-naptime, post-naptime, and bedtime) across two days at childcare. Overall our results show a significant decline in cortisol level from wake to pre-naptime and from post-naptime to bedtime. No significant change in cortisol level was observed from pre- to post- naptime. Significant group differences in cortisol patterns were observed. Notably, children under mandatory naptime conditions who did not nap showed no significant reduction in cortisol level from post-naptime to bedtime. While cortisol measurement suggests naptime is neither stressful nor restful for children in any group, implications for bedtime arousal are raised for those unable to sleep under conditions of mandated naptimes.

Background and Aim: Impaired cortisol rhythm is a characteristic feature of Cushing's Syndrome, nevertheless late night salivary cortisol (LNSC) is not suitable to detect subclinical hypercortisolism in patients with adrenal incidentaloma (AI). We studied daily salivary cortisol (F) and cortisone (E) rhythm in patients with AI., Materials and Methods: Six saliva samples were collected from awakening to night in 106 patients with AI and 40 controls. F and E were measured with LC-MS/MS and daily F exposure was calculated with the area under the curve (AUC)., Results: Patients with serum cortisol after dexamethasone suppression test (DST) > 50 nmol/L showed higher morning F (15.5 ± 14.5 vs. 8.6 ± 5.5 nmol/L, p = 0.001), suppressed corticotropin levels (76 vs. 35%, p < 0.001) and increased daily F exposure (3795 ± 1716 vs. 2898 ± 1478, p = 0.012), especially in the morning (2035 ± 1267 vs. 1365 ± 777, p = 0.003), otherwise LNSC levels were similar. Salivary E and AUC levels were higher in patients with DST > 50 nmol/L. AUC was not correlated with urinary cortisol levels or adenoma size. F and E levels were similar among patients with unilateral or bilateral adenoma, or considering the presence of hypertension, dyslipidemia, diabetes, or cardiovascular events., Conclusion: Daily cortisol exposure, evaluated with AUC from multiple saliva collections, is increased in AI patients with serum cortisol > 50 nmol/L after DST, especially in the morning, leading to reduced corticotropin levels. Cortisol rhythm is preserved in patients with AI, remarking that LNSC is not a screening test for subclinical hypercortisolism.

The hypothalamic-pituitary-adrenal (HPA) axis represents an important and evolutionarily ancient biological pathway linking physical and psychological stressors with human health. Despite considerable research exploring the physiological stress response among developed populations, few studies have examined HPA activity in non-industrialized contexts, restricting understanding of variation in human stress reactivity across global socio-ecological diversity. The present study addresses this shortcoming by investigating diurnal cortisol rhythms among Garisakang forager-horticulturalists of remote, lowland Papua New Guinea. Using a large sample of repeated salivary cortisol measurements from 169 participants (age 4-70 years), multilevel growth curve models were constructed to assess Garisakang waking cortisol concentrations and diurnal cortisol slopes. As predicted, results demonstrate identifiable but substantially diminished diurnal cortisol rhythms relative to those of industrialized populations. Sample-wide, Garisakang cortisol concentrations are highest upon waking (mean = 4.86 nmol/L) and decrease throughout the day at a mean rate of only -0.18 nmol/L/h or -6.20%/h. Age and sex significantly predict evaluated cortisol parameters in ways not consistently reported among industrialized populations, suggesting that Garisakang diurnal cortisol rhythms are defined by distinct ontogenetic trajectories across the lifespan. These findings highlight cross-cultural diversity in HPA activity and have important implications for understanding basic mechanisms of the physiological stress response in contexts of chronic physical stressors such as limited nutrition, heavy burden of infectious disease, and high levels of physical activity.

Objective: To evaluate the diagnostic efficacy of various screening tests for the diagnosis of Cushing syndrome (CS)., Methods: Thirty-five patients with CS and 16 patients of pseudo-CS were enrolled. Assessment of 24-h urinary free cortisol (UFC), late-night salivary cortisol (LNSC), overnight dexamethasone suppression test (ONDST), late-night plasma cortisol (LNPC), and adrenocorticotropic hormone (ACTH) on outpatient basis, and during sleep as well as in awake state after 48 hours of hospital admission., Results: We found that 24-h UFC performed the best among the screening tests with sensitivity, specificity and areas under the curve (AUCs) of 96.0%, 99%, and 0.988, respectively, at a cut-off of 144.6 μg/24 h. A cut-off of 10.5 nmol/L for LNSC had sensitivity 85.7%, specificity 88.2%, and an AUC of 0.897. A cut-off of 412.4 nmol/L for LNPC on outpatient basis had sensitivity 88.2%, specificity 91.2%, and an AUC of 0.957. Cut-offs of 215 and 243.3 nmol/L for LNPC during sleep and awake states after acclimatization had sensitivity, specificity, and an AUC of 94.1%, 88.2%, and 0.958, respectively. An ONDST cut-off of 94.6 nmol/L provided sensitivity, specificity, and an AUC of 96.0%, 99.03% and 0.995, respectively. A cut-off of 30.3 pg/mL for late-night ACTH on outpatient basis had sensitivity 67.6%, specificity 99.9%, and an AUC 0.796.A cut-off of 22.6 pg/mL for ACTH during sleep state after acclimatization had sensitivity, specificity, and an AUC of 73.5%, 99.2%, and 0.827, respectively., Conclusion: UFC is the best screening test for CS. Furthermore, single measurements of LNPC and ACTH help to establish the diagnosis and ACTH dependency of CS in the majority of patients with CS., Abbreviations: ACTH = adrenocorticotropic hormone AUC = area under the curve CRH = corticotropin-releasing hormone CS = Cushing syndrome ECLIA = electrochemiluminescence immuno-assay LDDST = low-dose dexamethasone suppression test LNPC = late-night plasma cortisol LNSC = late-night salivary cortisol ONDST = overnight dexamethasone suppression test RIA = radio-immuno assay UFC = urinary free cortisol.

This study examined state-trait models of diurnal cortisol (morning level and diurnal slope), and whether income, cumulative risk and parenting behaviors predicted variance in trait and state levels of cortisol. The sample of 306 mothers and their preschool children included 29% families at or near poverty, 27% families below the median income, and the remaining families at middle and upper income. Diurnal cortisol, income, cumulative risk, and parenting were measured at 4 time points, once every 9months, starting when children were 36-40months. State-trait models fit the data, suggesting significant state but not trait variance in cortisol. Low income and cumulative risk were related to trait levels of diurnal cortisol with little evidence of time-varying or state effects. Stable levels of parenting predicted trait levels of diurnal cortisol and time-varying levels of parenting predicted time-varying state levels of diurnal cortisol. Findings highlight the allostatic process of adaptation to risk as well as time-specific reactivity to variability in experience., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The aim of present study was to test the diathesis-stress model of depression using baseline cortisol, prospective assessment of depression symptoms, and stressful life events., Methods: The sample consisted of 527 adolescent girls aged 13.5-15.5 years without major depressive disorder. At baseline, saliva samples were collected at waking, 30 minutes after waking, and 8 p.m. on 3 consecutive days. Diurnal cortisol was indexed by cortisol awakening response (CAR) and area under the curve with respect to ground (AUCg). Stressful events during the preceding interval and current depressive symptoms were assessed 18 months following baseline., Results: Stressful events and the interaction of CAR or AUCg with stressful events predicted depressive symptoms at 18 months, even after controlling for baseline depressive symptoms. Specifically, in the face of high levels of stress, baseline blunted CAR or smaller AUCg were associated with future depressive symptoms. This was more apparent for CAR than AUCg. The effect was reversed at low levels of stress, with heightened CAR associated with more severe depressive symptoms., Conclusions: Blunted CAR and less daily cortisol output at baseline appear to accentuate the depressogenic effects of stressful events after 18 months, consistent with the diathesis-stress model of hypothalamic-pituitary-adrenal axis function in depression., (Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)