Search

Objectives. The incidence of occupational traumatic injuries caused by human error has been reported to occur at 11:00 and 8-9 h after commencing work. Impaired attention is closely related to the incidence of these accidents. Therefore, this study aimed to clarify the changes in blood glucose, fatigue and stress response hormone levels over time among workers in a secondary industry. Methods. The blood glucose and subjective fatigue levels of 26 male secondary-industry workers were measured on workdays. In addition, the cortisol and dehydroepiandrosterone levels in saliva were measured on one workday and one holiday. Results. Blood glucose levels at 11:00 and 17:30 on the workday were significantly lower than those at 09:30. Moreover, hypoglycemia was observed in some participants. A significant increase in subjective fatigue levels was observed during the workday. However, no significant differences in salivary cortisol levels were observed between the workday and the holiday at any time point. Conclusions. Blood glucose levels decreased and subjective fatigue levels increased at the time points that occupational accidents were reported to occur most frequently during work. These factors may contribute to human errors due to impaired attentional function.

Background: Frequent or prolonged exposure to stressors may jeopardize young children's health. The onset of the COVID-19 pandemic, coupled with disruptions in daily routines and social isolation resulting from public health preventive measures, have raised concerns about its potential impact on children' experienced stress, particularly for young children and vulnerable families. However, whether the pandemic was accompanied by changes in physiological stress remains unknown as perceived stress is not a good proxy of physiological stress. This study examined if preschoolers showed increasing hair steroid concentrations following the onset of the COVID-19 pandemic and whether family characteristics may have exacerbated or buffered these changes., Methods: 136 preschoolers (2-4 years) provided hair for steroid measurement (cortisol, dehydroepiandrosterone (DHEA), cortisone, cortisol-to-DHEA ratio, cortisol-to-cortisone ratio) in October-November 2019 (T0) and in July-August 2020 (T1). A 2-centimeter hair segment was analyzed, reflecting steroid production over the two months leading up to collection. Family income, conflict resolution and lack of cohesion, as well as parents' COVID-19 stress were reported by parents. Linear mixed models for repeated measures and Bayes factors were used., Results: No significant changes were noted from before to after the onset of the COVID-19 pandemic for most hair steroids. However, a moderating role of family conflict resolution was noted. Children living with parents with a better ability to resolve conflicts had lower levels of DHEA compared to those who had more difficulty managing conflicts. Additionally, lower levels of family cohesion and income were linked to some steroids, especially DHEA, suggesting that these factors may relate to children's physiological stress. Finally, boys had higher DHEA levels than girls., Conclusion: Our findings suggest that stress biomarkers were comparable from before to during the COVID-19 pandemic. This observation holds true despite the pandemic being perceived by many as a novel, unpredictable, and potentially threatening event. Findings further suggest that family characteristics are associated with hair steroid, especially DHEA, which deserves further investigation., 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. Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Advances in chromatography and mass spectrometry have allowed us to develop a novel technique for measuring intraprostatic hormone concentrations directly on prostate needle biopsies, rather than using traditional punch excision. This has significant clinical implications as intraprostatic dihydrotestosterone and testosterone levels could help monitor prostate growth, neoplasia and castration resistance., Methods: Patients undergoing radical cystoprostatectomy for bladder cancer were prospectively included. Each prostate specimen received one 90mg punch excision and six needle biopsies. Intraprostatic hormones were dosed through gas chromatography-mass spectrometry., Results: We included twenty patients, of which eleven were incidentally diagnosed with prostate cancer; four had ISUP 1 (20%) and seven had ISUP 2 (35%). The prostate biopsy technique was unable to obtain measures for testosterone, Delta-4-androsterone and androstenedione. Tissue concentrations of DHEA, DHT, E1 and E2 can be obtained with no significant difference from the reference established on a punch from a single biopsy core sample., Conclusions: Our study demonstrates that intraprostatic concentrations of DHEA, DHT, E1 and E2 can be measured without significant difference from the reference established on a single punch excision. This finding opens the way to research on the interactions between endocrinology and prostate oncogenesis and particularly on the mechanisms of resistance to hormone therapies in vivo., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Despite evidence that early life stress (ELS) can influence the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and increase maladaptive behaviors in adolescence, less attention has been paid to the role of the coordinated effects of the two primary adrenal hormones, cortisol and dehydroepiandrosterone (DHEA), in these associations., Methods: 138 typically developing adolescents (76 females) reported the stressful events experienced during childhood and early adolescence across 30 domains. Two years later we assessed levels of externalizing problems and obtained salivary levels of cortisol and DHEA. Using causal moderated mediation analyses, we examined whether the ratio of cortisol to DHEA (CD ratio) mediates the association between ELS and subsequent externalizing problems., Results: We found that ELS is associated with both a lower CD ratio and more externalizing problems. Importantly, a lower CD ratio mediated the association between ELS and externalizing problems in boys., Conclusions: An imbalance in adrenal hormones may be a mechanism through which ELS leads to an increase in externalizing problems in adolescent boys. These findings underscore the utility of using the CD ratio to index HPA-axis functioning., Competing Interests: Declaration of Competing Interest 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 © 2024 Elsevier Ltd. All rights reserved.)

Background: Past studies on schizophrenia (SCZ) and the stress-sensitive neuroendocrine systems have mostly focused on a single system and traditionally utilized acute biomarkers (e.g., biomarkers from blood, urine and saliva) that poorly match the chronic course of schizophrenia in time span. Using eight biomarkers in hair, this study aimed to explore the functional characteristics of SCZ patients in the hypothalamic-pituitary-adrenocortical (HPA) and hypothalamic-pituitary-gonadal (HPG) axes and the interaction between the two axes., Methods: Hair samples were taken from 137 SCZ patients and 73 controls. The SCZ patients were diagnosed by their attending physician according to the Diagnostic and Statistical Manual of Mental Disorders IV and were clinically stable after treatment. Gender, age, BMI, frequency of hair washing, marital status, education level, family history of mental illness and clozapine dosage were concurrently collected as covariates. The 10-item perceived stress scale (PSS-10) and the social readjustment rating scale were used to assess chronic stress status in SCZ patients. Eight hair biomarkers, cortisol, cortisone, dehydroepiandrosterone (DHEA), testosterone, progesterone, cortisol/cortisone, cortisol/DHEA and cortisol/testosterone, were measured by high performance liquid chromatography tandem mass spectrometer. Among them, cortisol, cortisone, DHEA and cortisol/DHEA reflected the functional activity of the HPA axis, and testosterone and progesterone reflected the functional activity of the HPG axis, and cortisol/cortisone reflected the activity of 11β-hydroxysteroid dehydrogenase types 2 (11β-HSD 2), and cortisol/testosterone reflected the HPA-HPG interaction., Results: SCZ patients showed significantly higher cortisone and cortisol/testosterone than controls (p<0.001, η² p =0.180 and p=0.015, η² p =0.031), lower testosterone (p=0.009, η² p =0.034), progesterone (p<0.001, η² p =0.069) and cortisol/cortisone (p=0.001, η² p =0.054). There were significant intergroup differences in male and female progesterone (p=0.003, η² p =0.088 and p=0.030, η² p =0.049) and female testosterone (p=0.028, η² p =0.051). In SCZ patients, cortisol, cortisol/cortisone, cortisol/DHEA and cortisol/testosterone were positively associated with PSS-10 score (ps<0.05, 0.212

Female adolescents have a greatly increased risk of depression starting at puberty, which continues throughout the reproductive lifespan. Sex hormone fluctuation has been highlighted as a key proximal precipitating factor in the development of mood disorders tied to reproductive events; however, hormone-induced affective state change is poorly understood in the pubertal transition. The present study investigated the impact of recent stressful life events on the relationship between sex hormone change and affective symptoms in peripubertal female participants. Thirty-five peripubertal participants (ages 11-14, premenarchal, or within 1 year of menarche) completed an assessment of stressful life events, and provided weekly salivary hormone collections [estrone, testosterone, dehydroepiandrosterone (DHEA)] and mood assessments for 8 weeks. Linear mixed models tested whether stressful life events provided a context in which within-person changes in hormones predicted weekly affective symptoms. Results indicated that exposure to stressful life events proximal to the pubertal transition influenced the directional effects of hormone change on affective symptoms. Specifically, greater affective symptoms were associated with increases in hormones in a high stress context and decreases in hormones in a low stress context. These findings provide support for stress-related hormone sensitivity as a diathesis for precipitating affective symptoms in the presence of pronounced peripubertal hormone flux.

Objective: Anxiety is a prevalent comorbidity in lung cancer (LC) patients associated with a decline in quality of life. Dehydroepiandrosterone (DHEA), a neuroactive steroid, levels rise in response to stress. Prior research on the association between DHEA and anxiety has yielded contradictory results and no study has investigated this association in LC patients., Methods: A total of 213 patients with LC were recruited from a general hospital. Data on demographic and cancer-related variables were collected. Using the Chinese version of the Hospital Anxiety and Depression Scale (HADS), the degree of anxiety was determined. Cortisol, DHEA, and Dehydroepiandrosterone sulfate (DHEA-S) levels in saliva were measured. Adjusting for confounding variables, a multivariate regression analysis was conducted., Results: 147 men and 66 women comprised our group with an average age of 63.75 years. After accounting for demographic and treatment-related factors, anxiety levels were significantly correlated with, post-traumatic stress symptoms (PTSSs) (β = 0.332, p < 0.001) and fatigue (β = 0.247, p = 0.02). Association between anxiety and three factors, including DHEA, PTSSs, and fatigue, was observed in patients with advanced cancer stages (III and IV) (DHEA β = 0.319, p = 0.004; PTSS β = 0.396, p = 0.001; fatigue β = 0.289, p = 0.027) and those undergoing chemotherapy (DHEA β = 0.346, p = 0.001; PTSS β = 0.407, p = 0.001; fatigue β = 0.326, p = 0.011)., Conclusions: The association between anxiety and DHEA remained positive in advanced cancer stages and chemotherapy patients. Further study is necessary to determine whether DHEA is a potential biomarker of anxiety in LC patients., (© 2024. The Author(s).)

Stress is associated with activation of the hypothalamus-adrenal-axis (HPA). Cortisol, a product of the HPA, is thought to predict depression. However, to date, the majority of studies investigating the cortisol-depression relationship have been cross-sectional and results have been mixed. One possible reason for these mixed findings, may be that many studies fail to consider the moderating role of dehydroepiandosterone (DHEA), which is released alongside cortisol and is thought to serve opposing functions. Therefore, the present study investigated the main and interactive effects of cortisol and DHEA on depressive symptoms. Salivary cortisol and DHEA were measured from saliva throughout the Trier Social Stress task for N = 417 participants at baseline. Participants reported on their depressive symptoms using the Beck Depression Inventory - II at both baseline and follow up (ranging from 1-20 months post baseline; M = 11.60, SD = 5.80) as well as general demographics. The lavaan package in R (version 0.6.11; Rosseel, 2012) was used to conduct multiple regression analyses with FIML to explore the relationships between these variables. Results demonstrated no main effect of cortisol or DHEA, but did show a significant interaction with DHEA. The relations between cortisol and depressive symptoms depended on levels of DHEA such that the relationship was positive at low and negative at high levels of DHEA, with the overall interaction significant (β = -.22, p < .001, 95% CI = [-.333, -.115]). DHEA can act as a protective factor against depression when cortisol levels are high. This presents opportunities for future research on how to improve DHEA levels to potentially reduce depression., 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 Elsevier Ltd. All rights reserved.)

Puberty is linked to mental health problems during adolescence, and in particular, the timing of puberty is thought to be an important risk factor. This study developed a new measure of pubertal timing that was built upon multiple pubertal features and their nonlinear changes over time (i.e., with age), and investigated its association with mental health problems. Using the Adolescent Brain Cognitive Development (ABCD) cohort (N ~ 9900, aged 9-13 years), we employed three different models to assess pubertal timing. These models aimed to predict chronological age based on: (i) observed physical development, (ii) hormone levels (testosterone and dehydroepiandrosterone [DHEA]), and (iii) a combination of both physical development and hormones. To achieve this, we utilized a supervised machine learning approach, which allowed us to train the models using the available data and make age predictions based on the input pubertal features. The accuracy of these three models was evaluated, and their associations with mental health problems were examined. The new pubertal timing model performed better at capturing age variance compared to the more commonly used linear regression method. Further, the model based on physical features accounted for the most variance in mental health, such that earlier pubertal timing was associated with higher symptoms. This study demonstrates the utility of our new model of pubertal timing and suggests that, relative to hormonal measures, physical measures of pubertal maturation have a stronger association with mental health problems in early adolescence., (© 2023. The Author(s).)

Dehydroepiandrosterone (DHEA) and cortisol release appear to have contrasting effects on stress perception during stressful tasks. This study aimed to investigate anticipatory examination stress in college students by considering DHEA, cortisol, psycho-emotional aspects and examination performance. Seventy-six students (66 females, 10 males; age range 18-25 years) provided saliva samples and completed questionnaires in two sessions 48 hours apart. During the second session, the students performed the examination. The questionnaires used were the State-Trait Anxiety Inventory, the Positive and Negative Affect Scale, and the Brief-Coping Orientation to Problems Experienced Inventory. DHEA, cortisol, anxiety and negative affect showed an anticipatory rise before the examination (all p s < 0.001). This rise of DHEA and cortisol was associated with lower positive affect ( p  = 0.001 and p  = 0.043, respectively). However, only the DHEA anticipatory levels were linked to poorer examination marks ( p  = 0.020). Higher levels of the DHEA/cortisol ratio in anticipation of the examination were related to lower scores on the support-seeking strategy ( p  = 0.022). There was no association between DHEA and cortisol levels and anxiety, negative affect, active and avoidant coping strategies, or academic record. These results suggest that how DHEA and cortisol respond in anticipation of examination stress significantly impacts students' emotional well-being during examination periods and how they cope with stress. They also suggest that levels of DHEA in anticipation of an academic stressor have detrimental effects on stress management.

Although the link between androgens and depression is well established in adults, the effects of cofactors on this association are less clearly understood, particularly in youth. Epidemiological cohort study of adolescents in Dresden, Germany. Analyses comprised data of 985 individuals assessed at baseline and of 512 individuals at 1-year follow-up. We investigated multivariable regression models for cross-sectional and longitudinal associations of hair testosterone, dehydroepiandrosterone (DHEA), and their cortisol ratios with 12-month diagnoses of major depressive disorder (MDD) and MDD without any anxiety disorder assessed with standardized diagnostic interview (DIA-X-5), and with dimensional depression scores (PHQ-9, PROMIS), separately for males and females. The potential moderating effect of social support was determined. Cross-sectional analyses yielded inverse associations of testosterone and DHEA with MDD and MDD without any anxiety disorders in males. In cross-sectional and longitudinal analyses, baseline ratio cortisol/DHEA was significantly, inversely associated to PROMIS-depression in males. Only cross-sectional associations for ratio cortisol/DHEA and PROMIS-depression remained significant after Bonferroni-Holm correction. No robust associations were observed in female participants. Social support exerted no consistent moderating effect on the investigated association. The present observational cohort study showed no consistent association of hair androgen concentrations with depressive disorders in adolescents. However, findings provide some support for the association between the cortisol/DHEA ratio and depression in males. Longitudinal research designs in large samples are needed to understand the interplay between androgens, depression, and developmental and social factors in youth., (© 2022. The Author(s).)

Animal research suggests that the gut microbiota and the HPA axis communicate in a bidirectional manner. However, human data, especially on early childhood, remain limited. In this exploratory design, we investigated the connections between long-term HPA axis functioning, measured as cortisol, cortisone or dehydroepiandrosterone concentrations and their ratios from hair segments of three centimeters, and gut microbiota profiles, (measured as diversity and bacterial composition by 16 S rRNA sequencing) in healthy 2.5-year-old toddlers (n = 135) recruited from the FinnBrain Birth Cohort Study. The alpha diversity of the microbiota was studied by linear regression. Beta diversity analyses with weighted UniFrac or Bray-Curtis distances were performed using PERMANOVA. The bacterial core genus level analyses were conducted using DESeq2 and ALDEx2. These analyses suggested that hair sample concentrations of separate hormones, cortisol/cortisone and cortisol/dehydroepiandrosterone ratios were associated with various gut bacterial genera such as the Veillonella, the [Ruminococcus] torques group and [Eubacterium] hallii group, although multiple testing correction attenuated the p-values. Alpha or beta diversity was not linked with either steroid concentrations or ratios. These findings in toddlers suggest that long-term HPA axis activity may be related to genera abundancies but not to ecosystem-level measures in gut microbiota. The influence of these observed interrelations on later child health and development warrants further research., Competing Interests: Declaration of Competing Interest EM is currently a Medical Advisor in Biocodex Nordics. Other authors report no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: This study aimed to investigate the neuroendocrine responses based on cortisol, dehydroepiandrosterone (DHEA), cortisol/DHEA ratio, and chromogranin A levels, which reflect the activity of the hypothalamic-pituitary-adrenal axis, according to the presence or absence of psychological stress in patients with gingivitis and periodontitis compared to that in healthy controls., Methods: In total, 117 patients (60 women, mean age: 36.29 ± 19.03 years) participated in this case-control study, comprising 32 healthy controls, 49 patients with gingivitis, and 36 patients with periodontitis. We investigated the presence of psychological stress and salivary characteristics, and analyzed the stress-related biomarkers of cortisol, DHEA, cortisol/DHEA ratio, and chromogranin A in the stimulated saliva., Results: Salivary cortisol and chromogranin A levels increased with the severity of periodontal disease; their levels were the highest in the periodontitis group and were significantly higher in the following descending order: periodontitis, gingivitis, and healthy control groups (all values of p < 0.001). Additionally, the DHEA levels and cortisol/DHEA ratio were higher in the periodontitis group than those in the healthy control group (all values of p < 0.001). A multivariate logistic regression analysis revealed that the factors predicting above-average cortisol levels were periodontitis (odds ratio [OR] = 256.829; p < 0.001), women (OR = 6.365; p = 0.004), and psychological stress (OR = 6.036; p = 0.007); those predicting above-average cortisol/DHEA ratios were periodontitis (OR = 11.436; p < 0.001), psychological stress (OR = 3.977; p = 0.003), and women (OR = 2.890; p = 0.026). Thus, periodontitis and psychological stress were significant and strong predictors of above-average cortisol levels and cortisol/DHEA ratios. In the gingivitis group, salivary cortisol levels (r = 0.381, p = 0.007) and cortisol/DHEA ratios (r = 0.479, p < 0.001) were correlated with the presence of psychological stress. In the periodontitis group, increased cortisol/DHEA ratios (r = 0.412, p = 0.013) and lowered salivary buffer capacities (r = -0.334, p = 0.047) were correlated with the presence of psychological stress., Conclusion: Periodontitis is a multifactorial disease resulting in inflammatory tissue destruction, which differs from gingivitis and a healthy state. Differences in stress-related neuroendocrine markers were revealed based on the severity of periodontal disease. The biomarkers that could be classified according to disease severity were salivary cortisol and chromogranin A levels. Above-average cortisol levels and cortisol/DHEA ratios are significant predictors of psychological stress in patients with gingivitis and periodontitis., 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 © 2023 Lee, Suk, Shin and Hong.)

To better understand how health risk processes are linked to adrenarche, measures of adrenarcheal timing and tempo are needed. Our objective was to describe and classify adrenal trajectories, in terms of timing and tempo, in a population of children transitioning to adolescence with repeated measurements of salivary dehydroepiandrosterone (DHEA), DHEA-sulphate, and testosterone. We analysed data from the Childhood to Adolescence Transition Study (CATS), a longitudinal study of 1239 participants, recruited at 8-9 years old and followed up annually. Saliva samples were assayed for adrenal hormones. Linear mixed-effect models with subject-specific random intercepts and slopes were used to model longitudinal hormone trajectories by sex and derive measures of adrenarcheal timing and tempo. The median values for all hormones were higher at each consecutive study wave for both sexes, and higher for females than males. For all hormones, between-individual variation in hormone levels at age 9 (timing) was moderately large and similar for females and males. Between-individual variation in hormone progression over time (tempo) was of moderate magnitude compared with the population average age-slope, which itself was small compared with overall hormone level at each age. This suggests that between-individual variation in tempo was less important for modelling hormone trajectories. Between-individual variation in timing was more important for determining relative adrenal hormonal level in childhood than tempo. This finding suggests that adrenal hormonal levels at age 8-9 years can be used to predict relative levels in early adolescence (up to 13 years)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Dashti 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.)

Background: Predicting viral suppression early is crucial to improving treatment outcomes among people living with HIV/AIDS (PLWH) in clinics. Viral suppression is affected by stress, making stress indicators a potential predictive factor. Most of previous studies used the self-report questionnaire as stress indicators, but there were great drawbacks due to its subjective. In contrast, end products of neuroendocrine systems such as hypothalamic-pituitaryadrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes and endogenous cannabinoid system (ECS) that involved in regulating stress as objective stress indicators are urgently needed to predict viral suppression. Therefore, this study aimed to investigate whether neuroendocrine indictors can strongly predict viral suppression among PLWH in China., Methods: This cross-sectional study recruited 1198 PLWH on antiretroviral therapy (ART) in Guangxi, China. The concentrations of steroids (i.e., cortisol, cortisone, dehydroepiandrosterone, testosterone and progesterone) and endocannabinoids (i.e., N-arachidonoyl-ethanolamine and 1-arachidonyl glycerol) in hair were quantitated using the LC-APCI + -MS/MS method. To screen biomarkers that were used to predict viral suppression, association between hair biomarkers and viral suppression was examined by Mann-Whitney U test and partial correlation analyses. Receiver operating characteristic (ROC) curves and binary logistic regression based on the optimal classification threshold determined with ROC curves were used to estimate the prediction effects of the screened biomarkers on viral suppression (HIV-1 RNA < 200 copies/mL)., Results: Hair levels of dehydroepiandrosterone (DHEA), and N-arachidonoyl-ethanolamine (AEA), and the cortisol to DHEA ratio exhibited significant intergroup differences (ps < 0.05) and were correlated with HIV viral load (ps < 0.05). Hair DHEA concentrations strongly predicted viral suppression, showing good classification performance (area under the ROC curve = 0.651, p < 0.01) and strong predictive utility (adjusted odd ratio = 2.324, 95 % confidence interval = 1.211-4.899, p < 0.05) with an optimal threshold of 10.5 pg/mg. A hair AEA concentration of 2.4 pg/mg was the optimal threshold for predicting viral suppression based on good classification performance (area under the ROC curve = 0.598, p < 0.05) and predictive power (adjusted odd ratio = 2.124, 95 % confidence interval = 1.045-4.244, p < 0.05). In hair levels of cortisol to DHEA, viral suppression was observed to be highly predictive, with a threshold of 10.5 pg/mg being optimal for classification (area under the ROC curve = 0.624, p < 0.05) and prediction (adjusted odd ratio = 0.421, 95 % confidence interval = 0.201-0.785, p < 0.05)., Conclusion: Hair levels of DHEA, and AEA and the cortisol to DHEA ratio were screened and verified to have significant predictive power with optimal thresholds for predicting viral suppression in a large-scale cohort. The data may provide new insights into predictors of successful virological outcomes and inform public health intervention and clinical practice to assist PLWH in achieving and sustaining viral suppression., 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 © 2022 Elsevier B.V. All rights reserved.)

Introduction: Bariatric surgery (BS) is the most effective therapy for morbid obesity. Cortisol and DHEA are steroid hormones with opposing effects, thus using Cortisol/DHEA ratio (C/D) rather than the use of either hormone alone has been found to predict health outcomes more reliably. It was interesting to study C/D as an indicator of favorable metabolic and cardiovascular outcomes after BS., Objective: To assess C/D in morbidly obese patients before and after BS in relation to metabolic parameters and cardiovascular performance., Patients and Methods: Forty morbidly obese patients were followed prospectively for 1 year after BS. Fasting blood glucose (FBG), fasting insulin (FI), C/D, lipid profile, high-sensitive CRP (hs-CRP), and echocardiography were done before BS and at 3 months and 1 year post BS., Results: A total of 40 morbidly obese patients undergone sleeve gastrectomy. Blood pressure, FBG, FI, hs-CRP, C/D were significantly decreased after BS (p < 0.001). At 1 year post BS; significant reduction in left ventricular posterior wall thickness (LVPW) (p < 0.001), left ventricular mass (LVM) (p = 0.003), relative wall thickness (RWT) (p < 0.001) with a significant improvement in early diastolic velocity (E) (p < 0.001), early diastolic velocity/late diastolic velocity (E/A) (p = 0.01). After BS; C/D significantly positively correlated with FBG (p = 0.019), hs-CRP (p = 0.008), interventricular septum thickness (IVS) (p = 0.028), LVPW (p = 0.028), relative wall thickness (RWT) (p = 0.022), early diastolic velocity /early diastolic velocity (E') measured by pulsed tissue Doppler imaging (E/E') (p = 0.001), and significantly negatively correlated with E' (p = 0.032). C/D was the single significant independent variable affecting E' and E/E' post BS., Conclusion: C/D can be used as a surrogate marker of the improved FBG and the resolution of inflammation post BS. C/D is an independent predictor of diastolic function improvement post BS., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The goal of the current study was to create reference intervals and values for several common and one potential novel physiological indicators of animal welfare for four species of cetaceans. The subjects included 189 bottlenose dolphins (Tursiops truncatus), 27 Indo-Pacific bottlenose dolphins (Tursiops aduncus), eight Pacific white-sided dolphins (Lagenorhynchus obliquidens), and 13 beluga whales (Delphinapterus leucas) at Alliance of Marine Mammal Parks and Aquariums and/or Association of Zoos and Aquariums accredited facilities. During two sampling time periods between July and November of 2018 and between January and April of 2019, fecal samples were collected weekly for five weeks from all animals. Samples were processed and analyzed using enzyme immunoassay for fecal cortisol, aldosterone, and dehydroepiandrosterone (DHEA) metabolites. Linear mixed models were used to examine demographic and time factors impacting hormone metabolite concentrations. Age, sex, and time of year were all significant predictors for some of the models (p < 0.01). An iOS mobile application ZooPhysioTrak was created for easy access to species-specific reference intervals and values accounting for significant predictors. For facilities without access to this application, additional reference intervals and values were constructed without accounting for significant predictors. Information gained from this study and the use of the application can provide reference intervals and values to make informed management decisions for cetaceans in zoological facilities., Competing Interests: The authors have read the journal’s policy, and the authors of the study have the following competing interests to declare: LJM and LKL are affiliated with the Chicago Zoological Society – Brookfield Zoo (an AZA and AMMPA accredited zoo), and Chicago Zoological Society provides a salary for LJM. Before the study, JDM was previously affiliated with Disney’s Animal Kingdom (an AZA accredited zoo). The Seas® Epcot® Walt Disney World® Resort, Dolphin Island – Resorts World Sentosa, and Loro Parque and Loro Parque Fundación provided funding to the Chicago Zoological Society for this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been increasingly used to measure steroids in human saliva. We studied the performance of a conventional LC-MS/MS for measuring dehydroepiandrosterone (DHEA), testosterone and progesterone in human saliva. These three steroids were co-extracted by liquid-liquid extraction and derivatized. Derivatives were resolved on a C18 column and quantified using an LC-MS/MS (AB Sciex API 2000) instrument. The assay's limits of quantification were 0.03 ng/mL for all three steroids. Inter-assay coefficients of variation were 16.6-18.8% (DHEA), 12.0-15.8% (testosterone), and 12.7-19.3% (progesterone). Assay linearity analysis showed R 2 of 0.9926, 0.9750 and 0.9949 for DHEA, testosterone and progesterone, respectively. No carry-over between samplings was observed. An ion-enhancement effect of 11.6% for DHEA determination and ion-suppression effects of 13.9% and 20.7% for analysis of progesterone and testosterone, respectively, were determined. No interferences by 9 steroid analogs were detected. Spiked recoveries were 85.5% (DHEA), 86.5% (testosterone), and 92.6% (progesterone). Comparison with laboratory developed test (LDT)-LC-MS/MS methods by other New York State Department of Health certified laboratories revealed R 2  = 0.9425 (DHEA, LC-MS/MS = 1.0267 LDT + 21.989), R 2  = 0.9849 (testosterone, LC-MS/MS = 0.9447 LDT + 9.8037), and R 2  = 0.9736 (progesterone, LC-MS/MS = 1.1196 LDT + 0.0985). Reference intervals for the 3 steroids in saliva for young males and females were estimated. Results of intra-individual salivary progesterone analysis indicated that caution should be exercised when using progesterone concentrations in predicting ovulation for females who are under treatment with birth control pills/devices or has body a weight of > 90 kg., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Many studies investigating pubertal development use Tanner staging to assess maturation. Endocrine markers in urine and saliva may provide an objective, sensitive, and non-invasive method for assessing development., Objective: Our objective was to examine whether changes in endocrine levels can indicate the onset of pubertal development prior to changes in self-rated Tanner stage., Methods: Thirty-five girls and 42 boys aged 7 to 15 years were enrolled in the Growth and Puberty (GAP) study, a longitudinal pilot study conducted from 2007-2009 involving children of women enrolled in the Agricultural Health Study (AHS) in Iowa. We collected saliva and urine samples and assessed pubertal development by self-rated Tanner staging (pubic hair, breast development (girls), genital development (boys)) at three visits over six months. We measured dehydroepiandrosterone (DHEA) in saliva and creatinine-adjusted luteinizing hormone (LH), testosterone, follicle stimulating hormone (FSH), estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) concentrations in first morning urine. We evaluated the relationships over time between Tanner stage and each biomarker using repeated measures analysis., Results: Among girls still reporting Tanner breast stage 1 at the final visit, FSH levels increased over the 6-month follow-up period and were no longer lower than higher stage girls at the end of follow-up. We observed a similar pattern for testosterone in boys. By visit 3, boys still reporting Tanner genital stage 1 or pubic hair stage 1 had attained DHEA levels that were comparable to those among boys reporting Tanner stages 2 or 3., Conclusions: Increasing concentrations of FSH in girls and DHEA and testosterone in boys over a 6-month period revealed the start of the pubertal process prior to changes in self-rated Tanner stage. Repeated, non-invasive endocrine measures may complement the more subjective assessment of physical markers in studies determining pubertal onset., Competing Interests: MG, LMK, JWM, JSK, MM, CM and DPS declare no competing interests exist. AJCJ, JAM, CB-C and DSC are employed by a commercial company, Social & Scientific Systems, Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The widespread abuse of anabolic androgenic steroids by healthy people leads to the risk of major mood disorders and heart failure; thus, the determination of anabolic androgenic steroids is vital. In this study, 17 anabolic androgenic steroids in dietary supplements and external drugs were identified, and their concentration was determined. For this purpose, polyaniline-coated magnetic nanoparticles were prepared and then subjected to magnetic solid-phase extraction combined with high-performance liquid chromatography-tandem mass spectrometry. The experimental parameters of magnetic solid-phase extraction were studied in detail, and the optimal conditions were established. Under the optimal conditions, the limits of detection were in the range of 0.001-0.02 μg/L, with relative standard deviations of 5.52-11.6% (n = 7) for all the steroids, and the enrichment factors were in the range of 20.0-24.8. The developed method was then successfully applied for the determination of 17 anabolic androgenic steroids in real samples, and dehydroepiandrosterone (prasterone) was detected in a commercially available external drug., (© 2021 Wiley-VCH GmbH.)

The traditional gold-nanoparticle-based lateral flow immunoassay (LFIA) cannot satisfy the requirements for the sensitive detection of dehydroepiandrosterone (DHEA) in human urine. To enhance the sensitivity of the LFIA, platinum-iridium nanocubes (Pt-Ir NCs) with high catalytic efficiency and stability were synthesized and labelled with polyclonal antibody (pAb) to form a pAb-Pt-Ir probe. For the detection of DHEA, a novel LFIA with Pt-Ir NCs as an optical label and an enhanced LFIA in which the peroxidase-like activity of the Pt-Ir NCs was triggered by the introduction of the chromogenic substrate 3-amino-9-ethyl-carbazole (AEC) were developed and compared with a LFIA with platinum nanocubes (PtNCs) as an optical label. The visual limit of detection was 0.5 ng mL-1 for Pt-Ir-LFIA and 0.05 ng mL-1 for AEC-enhanced Pt-Ir-LFIA, in comparison to 100 ng mL-1 for PtNCs-LFIA and 50 ng mL-1 for AEC-enhanced PtNCs-LFIA. The average recoveries from spiked urine samples ranged from 90.8% to 110.4%, with a coefficient of variation below 12.6%, suggesting the accuracy and reliability of our developed immunoassay. Achieving excellent sensitivity, specificity, and reproducibility, Pt-Ir-LFIA provided a promising platform for monitoring DHEA.

BNN27 is a novel 17-spiroepoxy derivative of the neurosteroid Dehydroepiandrosterone with neuroprotective properties. The purpose of this study was the detection and quantification of BNN27 after single intraperitoneal administration, in the serum and retina of normal rodents. Forty-two C57BL/6 mice and 48 Sprague-Dawley rats were used for the quantification of BNN27 in the blood serum and retina, respectively. BNN27 was injected intraperitoneally (i.p.) at concentrations of 100 and 30 mg/kg of body weight (b.w.), respectively. The blood was collected with retro-orbital bleeding and the retina was isolated after enucleation at various time points. The molecule concentrations were measured with Liquid chromatography-mass spectrometry (LC-MS). Non-compartmental analysis was used to determine pharmacokinetic parameters. BNN27 was found to have an elimination constant k el  = 0.465 h -1 and mean residence time (MRT) 2.154 h in the mouse serum. The maximum concentration (C max ) in the retina was detected at 2 h ( t C max ) after intraperitoneal administration and was equal to 1100 ng/g. BNN27 is rapidly eliminated from both blood and retina. In the retina specifically, it is undetectable 6 h after injection. BNN27 shows a rapid systemic elimination as anticipated by its small size and lipophilicity. It is measurable in small peripheral tissues such as the rat retina, after one single i.p. injection, using a simple method such as LC-MS. Its detection in the retina corroborates the existing biological data that the molecule crosses the blood-retinal barrier, highlighting it as a potential neuroprotective agent for retinal disease., (© 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Aim: To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics., Methods: Cross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study-a multi-site sample of 9-10 year-olds (n = 11,875)-and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels., Results: PDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child's weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample., Conclusions: Sociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes., Competing Interests: In the interest of full disclosure, DG is founder and chief scientific and strategy advisor at Salimetrics LLC and Salivabio LLC (Carlsbad, CA) and these relationships are managed by the policies of the committee’s on conflict of interest at Johns Hopkins University School of Medicine and the University of California at Irvine. ND and DF have a financial interest in Nous Imaging Inc. and may financially benefit if the company is successful in marketing FIRMM software products. DF is a patent holder on the Framewise Integrated Real-Time Motion Monitoring (FIRMM) software and is a co-founder of Nous Imaging Inc. KG provides consultation to Pfizer, Inc. MP is an advisor to Spring Care, Inc., a behavioral startup and has received royalties for an article about methamphetamine in Uptodate. Authors AG and FB were employed by the company SRI International. SW has stock ownership in GE and Merck. All other 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 Herting, Uban, Gonzalez, Baker, Kan, Thompson, Granger, Albaugh, Anokhin, Bagot, Banich, Barch, Baskin-Sommers, Breslin, Casey, Chaarani, Chang, Clark, Cloak, Constable, Cottler, Dagher, Dapretto, Dick, Dosenbach, Dowling, Dumas, Edwards, Ernst, Fair, Feldstein-Ewing, Freedman, Fuemmeler, Garavan, Gee, Giedd, Glaser, Goldstone, Gray, Hawes, Heath, Heitzeg, Hewitt, Heyser, Hoffman, Huber, Huestis, Hyde, Infante, Ivanova, Jacobus, Jernigan, Karcher, Laird, LeBlanc, Lisdahl, Luciana, Luna, Maes, Marshall, Mason, McGlade, Morris, Nagel, Neigh, Palmer, Paulus, Potter, Puttler, Rajapakse, Rapuano, Reeves, Renshaw, Schirda, Sher, Sheth, Shilling, Squeglia, Sutherland, Tapert, Tomko, Yurgelun-Todd, Wade, Weiss, Zucker and Sowell.)

Dioscorea polystachya, named Chinese yam, is widely cultivated as a functional food and natural medicine in China. There is currently little information about the chemical characteristics of Dioscorea polystachya in different organs (tuber cortex and tuber flesh) and at various ages. In this study, an ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was used to profile chemical compounds in Dioscorea polystachya. As a result, thirty-eight compounds were detected in yam tuber cortex and tuber flesh. More compounds were detected in yam tuber cortex than in tuber flesh. Compounds such as dehydroepiandrosterone, allantoin and flavonoids were selected as biomarker candidates. Dehydroepiandrosterone was found more abundant in tuber flesh, while allantoin and flavonoids showed higher levels in tuber cortex. Furthermore, the levels of dioscin, malvalic acid and sucrose differed significantly among age groups and were highest in the tubers at 2 years. While the levels of allantoin, adenosine and glutamine increased with the growing years and were highest at 4 years. Thus, 2-year old Dioscorea polystachya tubers could be harvested to prepare dioscin, malvalic acid and sucrose supplements. The 4-year-old Dioscorea polystachya tubers would be the best choice for obtaining a large amount of allantoin and adenosine in industrial production., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Introduction: Measurement of immunoglobulin free light chains (FLCs) in saliva can serve as a non-invasive biomarker in health and behavioural research. FLCs have been explored in relation to physiological stress but FLC responses to psychological stress and their relationship with infections remain unknown. This study aimed to investigate the impact of exam period stress on salivary FLCs alongside other established biomarkers of stress and whether FLCs relate to symptoms of infection., Methods: 58 healthy adults studying at university completed saliva samples and questionnaires in a period without exams (baseline), and again prior to the start of an exam period. Saliva samples were assessed for FLCs, IgA, cortisol and dehydroepiandrosterone (DHEA). Measures of life events stress, perceived stress, anxiety and depression were completed. Students also reported incidence and severity of symptoms of infection and rated general well-being at baseline, prior to, during and after the exam period. Exercise, sleep and alcohol consumption were also assessed at both timepoints., Results: FLCs secretion rates were significantly lower at the exam period compared to baseline (p < .01), with reductions of 26% and 25% for κ FLC and λ FLC, respectively. In agreement, salivary IgA secretion rate was lower at exams (non-significant trend, p = .07). Cortisol concentration significantly increased at exams (p < .05) while DHEA did not change, leading to an increase in the cortisol:DHEA ratio (p = .06). Depression (p < .05) and anxiety increased from baseline to exams and life stress reported in the build up to the exam period was higher compared with baseline (p < .001). Well-being significantly decreased from baseline to exams (p < .01). The proportion of participants reporting infection symptoms (70%) was unchanged between baseline and prior to exams. No significant relationships were found between FLCs or other saliva parameters and infection symptoms, well-being or stress/psychological measures. Changes in saliva parameters between timepoints were independent of health behaviours., Conclusions: Salivary FLCs are responsive to life events stress and corroborate with IgA. This preliminary study highlights the potential utility of FLCs as a new salivary biomarker in stress research., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Enhanced production of dehydroepiandrosterone (DHEA) by the foetal hypothalamic-pituitary-adrenal (HPA) axis enables maturational events critical for labour induction and neonatal adaptation. Despite knowledge of the interconnected nature of maternal and foetal physiology and dramatic changes in DHEA production after birth, few studies have examined DHEA levels in newborns and none have examined DHEA's response to acute stress. Understanding normative patterns of early DHEA activity is needed to accurately assess functioning of the biological stress system with relevance for health and development. The present study analysed DHEA concentrations and change after stress among 93 newborns and associations with pregnancy, delivery and demographic risk factors. Three saliva samples, collected prior to and following a blood draw stressor, were used to determine baseline and stress reactive DHEA levels. Mothers self-reported on health behaviours during pregnancy. Data on obstetric factors were obtained from medical records. DHEA levels declined from pre- to post-stressor assessments. Results also showed that post-stressor DHEA change was significantly associated with administration of medications used to treat pain and accelerate labour. However, there was no significant variation in DHEA pre-stress levels or change after stress as a function of time after birth. By capturing DHEA levels after birth, the present study provides a window into prenatal health of the HPA system. The study also advances knowledge of DHEA in newborns by providing data on reference levels and important covariates. This information on basic adrenal physiology provides a foundation that can be expanded on to enhance understanding of early hypothalamic-pituitary-adrenal axis activity., (© 2020 British Society for Neuroendocrinology.)

As a period of heightened plasticity, puberty may provide a window of opportunity for recalibration of the hypothalamic-pituitary-adrenal (HPA) axis to current conditions. Our group has recently documented evidence for pubertal recalibration of HPA axis reactivity among children internationally adopted as infants from institutions into supportive, well-resourced homes. As a first step at examining potential mechanisms by which puberty may facilitate recalibration of the HPA axis, the current study assessed whether previously-institutionalized (PI) children differed from non-adopted (NA) comparison children in levels of the adrenal steroid hormone dehydroepiandrosterone (DHEA) and in its intra-individual covariation (coupling) with cortisol by adrenal pubertal stage. In an accelerated longitudinal design, 7- to 15-year-olds completed up to 3 annual assessments, which included nurse-conducted pubertal staging and the Modified Trier Social Stress Test for Children (TSST-M). Adrenal (pubic hair) rather than gonadal pubertal stage scores were used in the analysis. Paired salivary cortisol-DHEA samples were available at 60-80 min post-TSST-M. NA and PI children did not differ in DHEA levels, which were higher among children at more advanced pubertal stages (averaged across the sessions) for both groups. For NA children, post-stressor cortisol and DHEA were positively coupled across sessions at all average adrenal pubertal stages. For PI children who were, on average, at earlier adrenal pubertal stages, post-stressor cortisol and DHEA were not coupled, but PI children who were at later pubertal stages demonstrated positive cortisol-DHEA coupling similar to that of the NA children. We suggest that these findings provide insights into processes which may underlie pubertal recalibration of the HPA axis., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The cortisol response in patients with obsessive-compulsive disorder (OCD) during exposure with response prevention (ERP), a stressful but very effective psychotherapeutic treatment, has shown contradictory findings in three prior studies with low sample sizes. In a larger cohort of 51 patients with OCD we repeatedly measured subjective units of distress (SUD) and the adrenocortical stress hormones cortisol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) in saliva during the very first session of ERP and on the day before. Expectedly, SUD were increased on the ERP day before the session and further rose during ERP, but salivary cortisol and DHEA were statistically indistinguishable from the comparison condition. Interestingly, DHEA-S was significantly elevated throughout the ERP versus the comparison day, but did not further increase in acute response to ERP. According to an explorative analysis in a subsample, hormone levels on the comparison or the ERP day did not predict anti-OCD treatment response one month later. These results corroborate our prior findings of cortisol non-response despite considerable subjective stress in ERP. The role of DHEA-S in anticipatory anxiety and the effects of augmentative cortisol therapy in ERP need further study., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The pubertal period is a time of rapid increase in the incidence of anxiety disorders, and thus, pubertal hormones may play a role in the precipitation of anxious psychopathology. DHEA, a steroid hormone that surges in adolescence, has been previously linked to anxiety, although the direction of this effect has been mixed. Using a cross-sectional design in a sample of 286 adolescent girls, the present study examined associations between salivary DHEA concentrations and self-report and interview-based measures of anxiety while controlling for pubertal status, menarche status, assessment time of day, and other hormones including testosterone, estradiol, and progesterone. Increased salivary DHEA concentrations were associated with more self-reported anxiety symptoms, increased anxiety symptom counts based on clinical interview, and increased probability of an anxiety disorder. Out of all anxiety symptom domains examined, generalized anxiety disorder symptoms were the best predictor of salivary DHEA concentrations after controlling for pubertal development. Collectively, our findings suggest relevance for DHEA in the development of anxiety in the pubertal period, as well as a robust relationship between DHEA and emerging symptoms of pathological worry during adolescence. The present study underscores the importance of examining associations between DHEA concentrations and anxiety in longitudinal designs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This research examines resilience from both cognitive and physiological perspectives and the relative importance of resilience for progression within an extremely physical training environment for 116 individuals. Our study provides a unique contribution as an examination of the combined effects of psychological and physiological resilience in the success of individuals in the first phase of a military special operations training course, the Navy's Basic Underwater Demolition/SEAL (BUD/S) course. Our study used the Connor-Davidson Resilience Scale (CD-RISC) for the psychological assessment and a blood sample to measure the concentrations of cortisol, DHEA and BDNF, each associated with stress adaptation and neuronal integrity. Our contributions include: heeding the call for more extensive research for resilience, examining physiological markers as predictors in training situations, combining psychological and physiological resilience into a single metric to assess resilience, and providing empirical support for the vital role of resilience in both stamina and persistence in training. Our findings indicate that both psychological and physiological resilience can be important predictors of persistence individually, but combining the measures provides a more holistic view to predict the success of an individual in this intensive training program. The present study has implications not only for the military community, but also for those individuals seeking elite performance in a broad array of fields, like professional athletes, CEO's, and emergency response workers.

In the equestrian world, two different types of management can be distinguished: traditional management and natural boarding. The aim of this research was to compare hormonal, hematological and immunological parameters of 47 horses kept in these two different managements. Blood and horsehair of the horses were sampled to determine DHEA (dehydroepiandrosterone) and cortisol concentration through RIA. Moreover, blood count was conducted, and flow cytometry was employed to phenotype lymphocyte subpopulations. Results showed that, in horsehair, DHEA concentration was significantly higher in natural horses, whereas cortisol concentration and cortisol/DEHA ratio significantly lower. These hormonal parameters are used to assess the stress condition and the welfare of animals. The most favorable endocrine framework found in horses kept in natural boarding suggests that this management conveys most with ethological and physiological needs of the species. The research underlines the need of a modification of horses' husbandry systems. For the first time, this study validates the assay of DHEA in horsehair.

Background: Person and environment-related childhood adverse events have been demonstrated to increase the risk of impaired mental health in later life differently for boys and girls. Altered hypothalamic pituitary adrenal (HPA)-axis functioning has been suggested as a key mechanism underlying this association. Cortisol and dehydroepiandrosterone (DHEA) are both output hormones of the HPA-axis. DHEA may have a protective function against long-term exposure to increased levels of cortisol, but has been little investigated in relation to childhood adversity., Objective: We aimed to test the associations between person-, and environment-related childhood adversity and levels of cortisol, DHEA and cortisol/DHEA ratio in adolescent boys and girls., Methods: A total of 215 Dutch adolescents participated in the study and filled out the 27-item Adverse Life Events Questionnaire for the assessment of childhood adversity, which was split up in separate scores for person-related and environment-related events. Cortisol and DHEA concentrations and cortisol/DHEA ratio were determined in proximal 3 cm long hair segments. Additionally, saliva samples were collected immediately and 30 minutes after waking up, at noon and at 8 pm. Multiple linear regression analyses were used to test associations between childhood adversity and cortisol and DHEA concentrations, for boys and girls separately, with age, BMI and pubertal development as covariates., Results: Data were available for 74 boys and 116 girls with a mean age of 15.7 years (SD = 2.0). Higher levels of person-related childhood adversity were associated with higher hair DHEA levels in girls and with higher hair cortisol levels in boys. A trend towards a significant association was observed between higher levels of environment-related childhood adversity and higher DHEA levels in boys. Neither person- nor environment related childhood adversity was associated with cortisol/DHEA ratio. A trend was observed for environment-related childhood adversity and lower daily cortisol output in boys., Conclusion: We found differential associations between childhood adversity and cortisol and DHEA levels in girls and boys, for respectively person-related and environment-related childhood adversity. Our findings suggest that different types of childhood adversity are not only linked to levels of cortisol, but also to DHEA concentrations, in a sex-specific manner, with possible future implications for mental health., Competing Interests: The authors have declared that no competing interests exist.

Chronobiology is defined as the temporal fluctuations occurring in the human physiology due to the circadian cycle. These fluctuations are good indicators of the functioning of the Hypothalamic-Pituitary-Adrenal axis (HPA axis) and can be tracked by using biomarkers: cortisol and DHEA. Low volume tracking systems will be beneficial for patients exposed to chronic stress, patients suffering from endocrine conditions manifested by circadian disruption and act as a lifestyle monitoring tool. The sensor system demonstrated in this work was an affinity-based system, characterized using EIS (Electrochemical Impedance Spectroscopy).The sensor can detect cortisol and DHEA in the physiologically relevant ranges i.e. 8-200 ng ml-1 and 2-131 ng ml-1 respectively. Thus, the senor is a non-invasive, label free, cost-effective solution for tracking chronobiology for circadian diagnostics.

Recent studies have found elevated dioxin levels inside some former US military air bases in Vietnam, known as hotspots. The aim of the present study was to evaluate the association of dioxin exposure and steroid hormone in preschool children in Vietnam. In 2010, 2011, 52 primiparae mother-infant pairs in the hotspot and 52 pairs in a non-exposure region were enrolled. For the final analysis, 26 vs 26 pairs were selected, who participated at all three surveys. Univariable and multivariable linear regressions were used to evaluate associations between hormone and dioxin congeners. Geometric mean total TEQ of PCDD/DFs in the hotspot were significantly higher than in the non-exposure region, 8.7 and 3.4 pg TEQ/g lipid, respectively. In the hotspot, salivary dehydroepiandrosterone (DHEA) was significantly higher in 1-year-old children (Boys = 123 pg/mL, Girls = 120 pg/mL) than in the non-exposure region (Boys = 28 pg/mL, Girls = 27 pg/mL). In contrast, DHEA was significantly lower in 5-year-old children (Boys = 70 pg/mL, Girls = 106 pg/mL) in the hotspot than in the non-exposure region (Boys = 496 pg/mL, Girls = 654 pg/mL). Salivary testosterone was significantly lower in the hotspot (Boys = 1.9 pg/mL, Girls = 1.9 pg/m; Boys = 1.0 pg/mL, Girls = 1.1 pg/mL, respectively) than in the non-exposure region (Boys = 3.7 pg/mL, Girls = 3.8 pg/m; Boys = 5.7 pg/mL, Girls = 7.0 pg/mL, respectively) at 3 years and 5 years of age. Higher levels of highly chlorinated dioxins in breast milk were associated with higher DHEA in 1-year-old and lower DHEA and testosterone levels in 5-year-old children. Our findings indicated that dioxins were associated with changes of DHEA and testosterone levels in preschool Vietnamese children., (Copyright © 2019. Published by Elsevier Ltd.)

BACKGROUND The aim of this study was to investigate factors affecting the sex lives of middle-aged women, and whether surgical menopause affects sexual function differently from natural menopause, by comparing effects on sexual performance of women with similar demographic features. MATERIAL AND METHODS The study included 151 women with surgical menopause (SM), 357 women with natural menopause (NM), and 186 perimenopausal women (PM). The women were asked to complete a 6-question survey of sexual performance parameters. The relationship between the demographic and clinical features and hormone levels of the groups and sexual function parameters were evaluated. We also compared these parameters between the 3 study groups, and paired comparisons were made between the SM group and the NM group. RESULTS Demographic features, serum DHEA-S, total testosterone, and FSH levels were found to have statistically significant effects on sexual performance of women (p<0.05). The sexual function scores for the frequency of sexual desire, coitus, and orgasm were significantly higher in the PM group, whereas vaginal lubrication scores were lower compared to the NM and SM group (p<0.05). In paired comparison of NM and SM, the scores for the frequency of coitus, orgasm, and vaginal lubrication were significantly higher in the SM group, while sexual desire frequency scores were higher in the NM group (p<0.05). CONCLUSIONS Our study approached to this topic in an extended manner and found significant relationships between several demographic-clinical and hormonal factors. SM was found to not affect female sexual performance, except for sexual desire, more than NM.

Non-invasive measures of stress are crucial for captive and conservation management programs. The adrenal hormone dehydroepiandrosterone-sulfate (DHEAS) has recently been adopted as a stress marker, but there is little investigation of its relationship to glucocorticoids (GC), well-known indicators of stress. This study examined the influence of age, reproductive state and environment on GC and DHEAS levels in orangutans, to test whether the GC/DHEAS ratio can provide an index of stress response in primates. We measured fecal GC (fGC) and fecal DHEAS (fDHEAS) concentrations in 7 captive orangutans from zoological parks in Japan and 22 wild orangutans from Danum Valley Conservation Area, Malaysia. We found that in a stressful condition (transportation), fDHEAS levels increased 2 days after the fGC response, which occurred 1 day after the stressor. One pregnant female had elevated levels of both hormones, and a higher fGC/fDHEAS ratio than baseline. Females in the first year of lactation had fGC levels and the fGC/fDHEAS ratio significantly higher than both baseline and females in the second and subsequent years of lactation. There was no effect of age on fGC levels, but the fGC/fDHEAS ratio was higher in infants than adults and adolescents. fDHEAS concentrations were lower in infants than juveniles, adolescents and adults, a phenomenon known as adrenarche, shared with humans and other great apes. We suggest that changes in DHEAS during orangutan life history are associated with changes in the dynamics of maintaining homeostasis that vary with age and reproductive state. The GC/DHEAS ratio index is useful to evaluate age-related abilities of responding to stressful challenges.

Depressive and anxiety disorders substantially contribute to the global burden of disease, particularly in poor countries. Higher prevalence rates for both disorders among women indicate sex hormones may be integrated in the pathophysiology of these disorders. The Kshetriya Gramin Financial Services study surveyed a random sample of 4160 households across 876 villages in rural Tamil Nadu, India. An interviewer-administered questionnaire was conducted to quantify depressive (K6-D) and anxiety (K6-A) symptoms. Alongside, hair samples for sex hormone profiling were collected from a subsample of 2105 women aged 18-85 years. Importantly, 5.9%, 14.8%, and 46.3% of samples contained non-detectable hormone levels for dehydroepiandrosterone, progesterone, and testosterone, respectively. Our primary analysis imputes values for the non-detectable sample and we check robustness of results when non-detectable values are dropped. In this cohort of women from rural India, higher depressive symptomatology is associated with lower levels of dehydroepiandrosterone and higher depressive and anxiety symptoms are associated with higher levels of testosterone. Progesterone shows no clear association with either depressive or anxiety symptoms. These results support a potential protective effect of higher endogenous dehydroepiandrosterone levels. An important caveat on the potential negative effect of hair testosterone levels on women's mental health is that the testosterone analysis is sensitive to how non-detectable values are treated., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Steroid hormones and their respective nuclear receptors are essential mediators in numerous physiologic and pathophysiologic processes, ranging from regulation of metabolism, immune function, and reproductive processes to the development of hormone-dependent cancers such as those of the breast and prostate. Because steroids must enter cells before activating nuclear receptors, understanding the mechanisms by which cellular uptake occurs is critical, yet a clear understanding of these mechanisms has been elusive. It is generally assumed that diffusion-driven uptake is similar across various steroids whereas an elevated cellular concentration is thought to reflect active uptake, but these assumptions have not been directly tested. Here we show that intact cells rapidly accumulate free steroids to markedly elevated concentrations. This effect varies widely depending on steroid structure; more lipophilic steroids reach more elevated concentrations. Strong preferences exist for 3β-OH, Δ5-steroids vs. 3-keto, Δ4-structural features and for progestogens vs. androgens. Surprisingly, steroid-structure-specific preferences do not require cell viability, implying a passive mechanism, and occur across cells derived from multiple tissue types. Physiologic relevance is suggested by structure-specific preferences in human prostate tissue compared with serum. On the other hand, the presence of serum proteins in vitro blocks much, but not all, of the passive accumulation, while still permitting a substantial amount of active accumulation for certain steroids. Our findings suggest that both passive and active uptake mechanisms make important contributions to the cellular steroid uptake process. The role of passive, lipophilicity-driven accumulation has previously been largely unappreciated, and its existence provides important context to studies on steroid transport and action both in vitro and in vivo., Competing Interests: The authors have declared that no competing interests exist

Interoception describes the ability to perceive internal bodily signals. Previous research found a relationship between interoceptive accuracy (IAcc) and cardiovascular outcomes during or after acute stress. So far, the association between IAcc and long-term stress has not been investigated, although this would be important to identify a starting point to prevent long-term stress. To address this idea in the current study, we examined the relationship between IAcc and long-term stress, which was assessed with different questionnaires and biological markers, including cortisol and dehydroepiandrosterone (DHEA). Furthermore, we investigated self-regulation as a mechanism linking IAcc to long-term stress. The sample consisted of 98 participants. To measure IAcc, participants completed the heartbeat perception task. Perceived long-term stress and self-regulation were assessed via an online questionnaire. Moreover, hair samples were taken from 65 participants to determine long-term stress with cortisol and DHEA as well as the ratio of both. Results showed that IAcc was positively related to DHEA and weakly negatively related to the other indicators of long-term stress, except for the nonsignificant relationships to the indicators cortisol and stress experiences due to negative events. Furthermore, these relationships were mediated by participants' enhanced self-regulation. Thus, our results suggest that enhanced self-regulation could be a mechanism explaining why IAcc is associated with long-term stress., (© 2019 Society for Psychophysiological Research.)

Chronotype describes preferences for functioning at different times of the day. At the onset of puberty, a sharp shift towards eveningness starts, reaching its peak at the end of adolescence, followed by a steady shift towards morningness as the ageing process occurs. Puberty is also the time when sex differences appear, with men being more inclined to eveningness than women, which diminishes around menopause; the described pattern of changes in chronotype leads to the hypothesis that reproductive hormones may be the driving factor behind this conversion. In the present study, we aimed to verify this hypothesis by analysing participants' testosterone, progesterone and dehydroepiandrosterone (DHEA) levels in the three months, as indicated by assays in 3-cm hair strands from the scalp. Participants (n = 239) of both sexes also completed the Munich Chronotype Questionnaire. The results showed that in men higher testosterone levels were related to eveningness and less sleep loss, whereas greater sleep loss was associated with lower levels of DHEA. In women, no associations between chronotype and levels of the analysed hormones were found. The results support the hypothesis that testosterone levels play a role in shaping eveningness. We further hypothesised that a possible cause of the higher secretion level of testosterone in men with the evening chronotype is a mechanism to offset the negative consequences of sleep loss., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Low birth weight in term-born individuals correlates with adverse cardiometabolic outcomes; excess glucocorticoid exposure has been linked to these relationships. We hypothesized that cortisol and adrenal androgens would correlate inversely with birthweight and directly with markers of cardiometabolic risk in school-aged children born extremely preterm; further, preterm-born would have increased cortisol and adrenal androgens compared to term-born children., Methods: Saliva samples were obtained at age 6 from 219 preterm-born children followed since birth and 40 term-born children and analyzed for dehydroepiandrosterone (DHEA) and cortisol. Cortisol was also measured at home (awakening, 30' later, evening)., Results: For preterm-born children, cortisol and DHEA correlated inversely with weight and length Z-scores at 36 weeks PMA and positively with systolic BP. DHEA was higher in preterm-born than term-born children (boys p < 0.01; girls p = 0.04). Cortisol was similar between preterm-born and term-born at study visit; however, preterm-born children showed a blunted morning cortisol. In term-born children, DHEA correlated with BMI (p = 0.04), subscapular, and abdominal skinfold thicknesses (both p < 0.01)., Conclusion: Cortisol and DHEA correlated inversely with early postnatal growth and directly with systolic BP in extremely preterm-born children, suggesting perinatal programming. Blunted morning cortisol may reflect NICU stress, as seen after other adverse childhood experiences (ACEs).

Objective: To determine whether prenatal sex hormones from maternal saliva are associated with birth-weight-for-gestational age., Study Design: We measured salivary progesterone, testosterone, estradiol, dehydroepiandrosterone (DHEA), and cortisone in 504 pregnant women in a Mexico City cohort. We performed linear and modified Poisson regression to examine associations of log-transformed hormones with birth-weight-for-gestational age z-scores and the risk of small-for-gestational age (SGA) and large-for-gestational age (LGA) adjusting for maternal age, sex, BMI, parity, smoking, education, and socioeconomic status., Results: In total, 15% of infants were SGA and 2% were LGA. Each interquartile range increment in testosterone/estradiol ratio was associated with a 0.12 decrement in birth-weight-for-gestational age z-score (95% CI: -0.27 to -0.02) and a 50% higher risk of SGA versus appropriate-for-gestational age (AGA) (95% CI: 1.13-1.99)., Conclusion: Higher salivary testosterone/estradiol ratios may affect fetal growth, and identifying the predictors of hormone levels may be important to optimizing fetal growth.

Early timing of puberty (i.e., advanced pubertal maturation relative to same-age peers) has been associated with depressive symptoms during adolescence. To date, research on this relationship has focused on gonadarche, the second phase of puberty, while less is known about the first phase of puberty, adrenarche. Increasing evidence suggests that androgens that rise during adrenarche, most notably dehyrdoepiandrosterone (DHEA) and testosterone, may be involved both in the development of the hippocampus, and risk for depression. The current study investigated whether hippocampal volumes mediated the relationship between adrenarcheal timing (based on relative levels of adrenarcheal hormones) and depressive symptoms in children. Data were collected from a cross-sectional sample of 88 children (46 female) selected to have relatively increased variance in these androgens. Participants completed brain MRI structural scans, provided saliva samples for hormones, and completed the Children's Depression Inventory (CDI). Contrary to predictions, larger right hippocampi significantly partially mediated the positive relationship between early timing of testosterone exposure (i.e., relatively high levels of testosterone for one's age) and depressive symptoms in girls. No other evidence of significant mediation effects was obtained, however DHEA and testosterone exposure showed unique effects on hippocampal volumes in males and females, and larger hippocampal volumes predicted higher depressive symptoms in the entire sample. These results suggest that adrenarcheal timing may be related to hippocampal development and depressive symptoms, extending current knowledge of pubertal risk processes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Research with predominantly male samples supports primary and secondary developmental pathways to psychopathy that are phenotypically indistinguishable on aggressive and antisocial behavior. The aim of this study was to examine whether female variants of psychopathy show divergent endocrine (i.e., cortisol, dehydroepiandrosterone [DHEA], testosterone, and their ratios) and psychophysiological (i.e., heart rate variability [HRV]) reactivity to social provocation. We also tested whether variants differed on reactive aggression when performing a competitive reaction time task against the fictitious participant who previously insulted them. Latent profile analyses on 101 undergraduate women oversampled for high psychopathic traits identified a high-anxious, maltreated secondary variant (n=64) and a low-anxious primary variant (n=37). Although variants did not differ on aggression, secondary variants showed higher cortisol, testosterone, cortisol-to-DHEA ratios, and HRV following social provocation relative to primary variants. Findings suggest that the neurobiological mechanisms underpinning aggression in psychopathy may differ between women on primary versus secondary developmental pathways., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Previous research has found lower serum levels of dehydroepiandrosterone (DHEA) or its sulfated form, DHEA-S, in women diagnosed with Hypoactive Sexual Desire Disorder (HSDD). Given that DHEA and DHEA-S have multiple direct actions on the brain as well as anti-glucocorticoid properties, it is possible that lower levels of DHEA directly impact women's sexual functioning. To date, the significance of the lower DHEA levels remains unclear. To our knowledge, there has been no empirical study of stress hormones as markers of HPA dysregulation in women with HSDD. To attend to this gap, the present study utilized several measures of HPA axis function - morning and evening cortisol and DHEA, the cortisol awakening response (CAR), diurnal cortisol slope, and cortisol:DHEA ratio - and examined their relationship with sexual functioning in N = 275 women with (n = 137) and without (n = 138) HSDD. Results demonstrated multiple hormonal markers of HPA dysregulation in women diagnosed with HSDD compared to control participants, specifically, lower AM cortisol and AM DHEA levels, a flatter diurnal cortisol slope, and a lower CAR. Overall, results of the present study indicate that persistently low sexual desire in women is associated with HPA axis dysregulation, with both cortisol and DHEA alterations potentially detrimental to sexual desire., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and objectives: Intrauterine growth restriction is thought to be implicated in long-term programming of hypothalamic-pituitary-adrenal axis activity. We investigated adrenal function in adolescents born small for gestational age (SGA) in relation to their postnatal growth and cardiovascular parameters. Materials and Methods: Anthropometric parameters, blood pressure, heart rate, dehydroepiandrosterone sulfate (DHEAS), and cortisol levels were assessed in 102 adolescents aged 11-14 years followed from birth (47 SGA and 55 born appropriate for gestational age (AGA)). Results: Mean DHEAS levels were higher in SGA adolescents with catch-up growth (SGA CU+ ), compared with AGA. Second-year height velocity and body mass index (BMI) gain during preschool years were positively related to DHEAS levels. Morning cortisol levels and systolic and diastolic blood pressure were higher in SGA adolescents without catch-up growth (SGA CU - ) compared with AGA. Second-year BMI gain was inversely, and 2-12 years increase in subscapular skinfold thickness was directly associated with cortisol levels. Size at birth and postnatal growth explained 47.8% and 38.2% of variation in DHEAS and cortisol levels, respectively. Conclusion: Adrenal function in adolescence is affected by prenatal and postnatal growth: small size at birth with postnatal catch-up growth is related to higher DHEAS secretion, whereas increased cortisol levels and blood pressure are higher in short SGA adolescents., Competing Interests: All authors have no financial or other conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: Research suggests that it may be more stressful for children to grow up in an urban area than in a rural area. Urbanicity may affect physiological stress system functioning as well as the timing of sexual maturation. The purpose of the current study was to investigate whether moderate urbanicity (current and childhood, ranging from rural areas to small cities) was associated with indices of long-term hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axis functioning (cortisol, cortisone, dehydroepiandrosterone and progesterone levels) and whether sex moderated any associations., Method: Children (N = 92) were all 10 years old and from the Dutch general population. Hair samples were collected and single segments (the three cm most proximal to the scalp) were assayed for concentrations of steroid hormones (LCMS/MS method). Neighborhood-level urbanicity and socioeconomic status were measured from birth through age ten years. Analyses were controlled for neighborhood- and family socioeconomic status, body mass index and season of sampling., Results: The results from multivariate analyses of variance showed no associations between current or childhood moderate urbanicity and hair steroid hormone concentrations. Interaction terms between moderate urbanicity and sex were not statistically significant., Conclusions: Associations between urbanicity and steroid hormone levels may only be detectable in highly urban areas and/or during later stages of adolescence. Alternatively, our findings may have been due to most children being from families with a higher socioeconomic status., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Affective neuroscience research suggests that maturational changes in reward circuitry during adolescence present opportunities for new learning, but likely also contribute to increases in vulnerability for psychiatric disorders such as depression and substance abuse. Basic research in animal models and human neuroimaging has made progress in understanding the normal development of reward circuitry in adolescence, yet, few functional neuroimaging studies have examined puberty-related influences on the functioning of this circuitry. The goal of this study was to address this gap by examining the extent to which striatal activation and cortico-striatal functional connectivity to cues predicting upcoming rewards would be positively associated with pubertal status and levels of pubertal hormones (dehydroepiandrosterone, testosterone, estradiol). Participants included 79 adolescents (10-13 year olds; 47 girls) varying in pubertal status who performed a novel reward cue processing task during fMRI. Pubertal maturation was assessed using sex-specific standardized composite measures based on Tanner staging (self-report and clinical assessment) and scores from the Pubertal Development Scale. These composite measures were computed to index overall pubertal maturation as well as maturation of the adrenal and gonadal axes separately for boys and girls. Basal levels of circulating pubertal hormones were measured using immunoassays from three samples collected weekly upon awakening across a three-week period. Results indicated greater striatal activation and functional connectivity between nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC) to reward cue (vs. no reward cue) on this task. Also, girls with higher levels of estradiol showed reduced activation in left and right caudate and greater NAcc-putamen connectivity. Girls with higher levels of testosterone showed greater NAcc connectivity with the anterior cingulate cortex and the insula. There were no significant associations in boys. Findings suggest that patterns of activation and connectivity in cortico-striatal regions are associated with reward cue processing, particularly in girls. Longitudinal follow-up neuroimaging studies are needed to fully characterize puberty-specific effects on the development of these neural regions and how such changes may contribute to pathways of risk or resilience in adolescence., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Allopregnanolone and pregnanolone (together termed allo + pregnan) are neurosteroid metabolites of progesterone that equipotently facilitate the action of gamma-amino-butyric acid (GABA) at GABA A receptors. The adrenal steroid dehydroepiandrosterone (DHEA) allosterically antagonizes GABA A receptors and facilitates N-methyl-D-aspartate (NMDA) receptor function. In prior research, premenopausal women with posttraumatic stress disorder (PTSD) displayed low cerebrospinal fluid (CSF) levels of allo + pregnan [undifferentiated by the gas chromatography-mass spectrometry (GC-MS) method used] that correlated strongly and negatively with PTSD reexperiencing and negative mood symptoms. A PTSD-related decrease in the ratio of allo + pregnan to 5α-dihydroprogesterone (5α-DHP: immediate precursor for allopregnanolone) suggested a block in synthesis of these neurosteroids at 3α-hydroxysteroid dehydrogenase (3α-HSD). In the current study, CSF was collected from unmedicated, tobacco-free men with PTSD (n = 13) and trauma-exposed healthy controls (n = 17) after an overnight fast. Individual CSF steroids were quantified separately by GC-MS. In the men with PTSD, allo + pregnan correlated negatively with Clinician-Administered PTSD Scale (CAPS-IV) total (ρ=-0.74, p = 0.006) and CAPS-IV derived Simms dysphoria cluster (ρ=-0.71, p = 0.01) scores. The allo+pregnan to DHEA ratio also was negatively correlated with total CAPS (ρ=-0.74, p = 0.006) and dysphoria cluster (ρ=-0.79, p = 0.002) scores. A PTSD-related decrease in the 5α-DHP to progesterone ratio indicated a block in allopregnanolone synthesis at 5α-reductase. This study suggests that CSF allo + pregnan levels correlate negatively with PTSD and negative mood symptoms in both men and women, but that the enzyme blocks in synthesis of these neurosteroids may be sex-specific. Consideration of sex, PTSD severity, and function of 5α-reductase and 3α-HSD thus may enable better targeting of neurosteroid-based PTSD treatments., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose: Puberty influences biological and psychological development during adolescence. This includes a shift toward an evening circadian preference, which is characterized by greater physical and mental activity at night compared to the morning. This study examines how pubertal hormones are related to risk across key health domains among adolescents with an evening circadian preference., Methods: Participants were adolescents with an evening circadian preference (n = 165, 96 female and 69 male, mean age = 14.8) from an NICHD-funded study. Hormones included testosterone, dehydroepiandrosterone (DHEA), and estradiol (females only). Sleep measures included weeknight total sleep time and weeknight bedtime. Circadian preference was assessed with the Children's Morningness-Eveningness Preferences Scale. Health domains included emotional, cognitive, behavioral, social, and physical health., Results: For female adolescents, estradiol was related to higher risk in the emotional domain. Among female adolescents with later bedtimes, higher estradiol was associated with higher behavioral domain risk (specifically alcohol and substance use). For male adolescents with a more extreme evening circadian preference, higher DHEA and testosterone were associated with higher behavioral domain risk, specifically greater alcohol and substance use or sensation seeking (DHEA only). Among female adolescents with a more extreme evening circadian preference, higher DHEA was associated with greater physical health risk., Conclusions: Pubertal hormones may be associated with heightened risk across select health domains. Specifically, higher levels of hormones may contribute to increased risk for alcohol and substance use as well as sensation seeking in the context of an evening circadian preference., (Copyright © 2018. Published by Elsevier Inc.)