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Objective: High-grade (HGOC) and low-grade ovarian carcinoma (LGOC) are distinct malignancies with different biological features, treatment paradigms, and life expectancies. However, differences in quality of life (QOL), sleep, and depressive symptoms have not been examined by grade, and neither have inflammatory profiles associated with these symptoms. We aim to characterize QOL and biomarkers by OC grade., Methods: Participants included patients with HGOC (N = 578) or LGOC (N = 85). Participants completed baseline assessments of psychosocial factors prior to primary surgery or neoadjuvant chemotherapy and contributed saliva for cortisol and blood for interleukin-6 (IL-6) quantification. Samples were collected intraoperatively to quantify tumor cortisol. General linear models were used to examine differences in biological and psychological variables by grade., Results: At baseline, patients with LGOC reported less depression (p = 0.018) and sleep disturbances (p = 0.014), but no significant difference in depressive mood (p = 0.11) or QOL (p = 0.51) compared to patients with HGOC, adjusting for age and disease stage. There were trends towards lower tumor cortisol levels (p = 0.078) in LGOC compared to HGOC. One-year post-diagnosis, we found a significant improvement in QOL and fatigue, and a decrease in vegetative depression and IL-6 levels irrespective of grade., Conclusions: We present the first characterization of psychosocial experiences of patients with LGOC. Despite having a better disease prognosis, patients with LGOC were just as likely to have mood disturbances as those with HGOC. There was a trend towards differences in tumor cortisol by grade. Our findings highlight the need to address well-being in patients with both low- and high-grade ovarian malignancies., Competing Interests: Declaration of competing interest Dr. Thaker has done consulting for Iovance Biotherapeutics, Imunon, Merck, Eisai, Agenus, Immunogen, R-Pharm, Astra Zeneca, Clovis Oncology. Aadi Biosciences, Glaxo Smith Kline, Relacorilant, Seagen, Mersana, Novocure, and Verastem. Merck and Glaxo Smith Kline have provided institutional research grants. Immunon has provided shares to Dr. Thaker. Dr. Sood has done consulting for Merck, GSK, ImmunoGen, Astra Zeneca, Kiyatec, Iylon, Onxeo and is a shareholder for BioPath. Dr. Lutgendorf is a shareholder for AbbVie., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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

Stress may contribute to the development of obesity through its effects on dysregulated eating, although this has not yet been examined among low-income, rural adolescents. We examined adolescents' stress-induced changes in eating an ad libitum meal, and after, in the absence of hunger (EAH), and the extent to which these varied by sex, race, and weight status. Participants included 260 adolescents, drawn from a sample of rural households experiencing poverty. Adolescents completed two home visits while salivary cortisol was measured; during the control (low stress) visit, they completed questionnaires and procedures thought to elicit low levels of stress and had BMI assessed. During the stress visit, adolescents completed a 20-min set of psychosocial stress challenges before eating. At each visit, adolescents consumed an ad-libitum meal after which they were additionally given large portions of snacks (EAH task). Results revealed that indeed cortisol was higher during the stress visit, across the sample. Boys showed stress-induced increases during ad-libitum meal intake (for calories, fat, and carbohydrates) whereas girls exhibited decreased intake. Further, adolescents with obesity showed stress-induced increases in fat intake, but only when hunger was satiated (EAH). There were no differences by race. These findings provide the first evidence of stress-induced alterations in food intake in a rural, low-income sample of adolescents and point to a strong vulnerability for stress-induced increases in eating in rural boys as well as stress-induced increases in fat intake when satiated as a possible contributor to obesity in youth., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this manuscript to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Children's exposure to chronic stress is associated with several health problems. Measuring hair cortisol concentration is particularly useful for studying chronic stress but much is unknown about hair cortisol determinants in children and adolescents, and previous research has often not considered the simultaneous exposure of multiple variables. This research is focused on investigating the relationship between environmental, social and individual factors with hair cortisol concentration in children., Methods: The data used in this study are from the INMA prospective epidemiological cohort study. The assessment of chronic stress was made on the basis of hair samples taken at the age of 11 years in the INMA-Gipuzkoa cohort (n = 346). A metamodel summarizing the hypothesized relationships among environmental, social and individual factors and hair cortisol concentration was constructed based on previous literature. Structural Equation Modelling was performed to examine the relationships among the variables., Results: In the general model higher behavioural problems were associated with higher cortisol levels and an inverse relationship between environmental noise and cortisol levels was observed, explaining 5 % of the variance in HCC. Once stratified by sex these associations were only hold in boys, while no significant effect of any of the study variables was related with cortisol levels in girls. Importantly, maternal stress was positively related to behavioural difficulties in children. Finally, higher traffic-related air pollution and lower exposure to neighborhood greenness were related to higher environmental noise., Discussion: This study highlights that simultaneous exposure to different environmental, social and individual characteristics may determine the concentration of hair cortisol. More research is needed and future studies should include this complex view to better understanding of hair cortisol determinants in children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Under stress, parents tend to use more controlling feeding behaviors toward their children (Berge et al., 2017; Doan et al., 2022; Loth et al., 2016). However, the majority of prior work focuses on subjective reports of stress, and there is a dearth of research examining parental physiological stress and its impact on feeding behaviors. In the current study, we examined how parental physiological stress reactivity would influence their feeding behaviors under mild stress in a lab-based setting. Parents (n = 83, 50 % females) and their children (59% female, M age  = 42 months, SD = 4.48) participated. Stress was induced using the Trier Social Stress Test in the laboratory (Kirshbaum et al., 1993). Salivary samples were collected at 4 time points during the visit to index stress reactivity and later assayed for cortisol and DHEA. Parent-child interactions during the anticipatory period of the stress test were observationally coded for parent use of controlling feeding behaviors. To examine whether parent stress physiology predicts their feeding behaviors, we ran a Poisson regression using income, parent ethnicity, parent sex (mom/dad), time of day, and DHEA/cortisol ratio as predictors of controlling feeding behavior. Latinx parents used less controlling feeding behaviors, b = -0.323, p = 0.041 than non-Latinx parents. Parents with a higher DHEA/Cortisol ratio were less likely to use controlling feeding behaviors, b = -0.231, p = 0.008. To our knowledge, this is the first study to show that for both mothers and fathers, DHEA relative to cortisol has a protective role in controlling feeding practices, and lends support to the role of acute stress reactivity in predicting behavioral outcomes., Competing Interests: Declaration of competing interest We have no conflict of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Several internal and external factors can influence animals' hormonal activity. Cortisol level in hair and wool determines chronic stress, which is connected with the long-term HPA axis effect. Wool cortisol levels in alpacas have never been determined to this time. The study aimed to assess the influence of selected factors on wool cortisol concentration in alpacas. The study included 36 alpacas. Wool samples were collected during shearing in June 2021, cut with an electric clipper from the right shoulder and the rump. Wool samples were fragmented into proximal (winter-spring regrowth) and distal (summer-fall regrowth) segments. Alpacas' Heat Stress Index (HSI) for the summer of 2020 was 139.4, and 116 for the winter of 2021. The cortisol levels in the wool samples were determined with the General Cortisol ELISA Kit assay. The most significant differences in wool cortisol concentrations were caused by two factors: the wool segment (P < 0.001; η2 = 0.889) and the region on the body (P < 0.001; η2 = 0.876). Wool cortisol level was higher in the distal segment (referring to the summer-fall season) than in the proximal one (referring to the winter-spring season). It is suggested that alpacas can feel heat stress in summer (HSI = 139.4), which could influence higher cortisol levels in the distal segment. The wool cortisol level was higher in the rump samples than the shoulder ones. Therefore, it is essential in future studies that wool samples from all tested animals should be completed from the same body region. Differences among age and sex groups were also observed. Wool cortisol level was higher in older animals, as differences between age groups were observed in samples from the rump in the distal and proximal segments (distal, the rump younger*older: P < 0.001; η 2  = 0.321; proximal, the rump older*younger: P = 0.007; η 2  = 0.195). Males showed higher cortisol levels than females, as a difference between sexes was observed in samples from the rump in the proximal segment (P = 0.001, η 2  = 0.271). This study emphasizes that various factors may significantly influence wool cortisol levels, which can be helpful in alpacas' welfare estimation using this hormonal indicator as a noninvasive long-term stress assessment method., 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 Inc. All rights reserved.)

Although research has shown that pets appear to provide certain types of social support to children, little is known about the physiological bases of these effects, especially in naturalistic contexts. In this study, we investigated the effect of free-form interactions between children (ages 8-10 years) and dogs on salivary cortisol concentrations in both species. We further investigated the role of the child-dog relationship by comparing interactions with the child's pet dog to interactions with an unfamiliar dog or a nonsocial control condition, and modeled associations between survey measures of the human-animal bond and children's physiological responses. In both children and dogs, salivary cortisol decreased from pre- to post-interaction; the effect was strongest for children interacting with an unfamiliar dog (compared to their pet dog) and for the pet dogs (compared to the unfamiliar dog). We found minimal evidence for associations between cortisol output and behaviors coded from video, but children scoring higher on survey measures of the human-animal bond exhibited the greatest reductions in cortisol when interacting with dogs. Self-reported loneliness was not related to cortisol or the human-animal bond, but measures of both loneliness and the human-animal bond were higher among children who participated after the onset of the COVID-19 pandemic, relative to those who participated before the pandemic. This study builds on previous work that investigated potential stress-buffering effects of human-animal interaction during explicit stressors and demonstrates important physiological correlates of naturalistic interactions between children and dogs, similar to those that occur in daily life., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The cumulative negative effects of prolonged Hypothalamic-Pituitary-Adrenal axis (HPA axis) activation are associated with several age-related diseases. Some psychological traits such as optimism and pessimism have been shown to be related to both health and the stress response, although their relationship with the HPA axis is inconclusive. More stable HPA axis biomarkers, such as hair samples of cortisol (HC) and dehydroepiandrosterone (HDHEA), would help to clarify the association between these psychological traits and HPA axis functioning. The main aim of this study was to test the relationships between optimism and pessimism and chronic stress biomarkers measured in hair (HC and HDHEA). Additionally, a secondary objective was to explore sex differences in HC and HDHEA levels and their relationship with these psychological traits. We measured optimism, pessimism, and their combination (dispositional optimism) using the Life Orientation Test Revised (LOT-R) and chronic stress biomarkers (HC and HDHEA) in 119 healthy participants (46 men and 73 women) between 56 and 81 years old who belonged to a university program. Regression analyses controlling for perceived stress and BMI indicated that higher dispositional optimism was related to lower HC and HC:HDHEA ratio (β = -0.256, p = .008 and β = -0.300, p = .002, respectively). More specifically, higher pessimism was related to higher HC (β = 0.235; p = .012) and HC:HDHEA ratio (β = 0.240; p = .011), whereas higher optimism was associated with a lower HC:HDHEA ratio (β = -0.205; p = .031). Moderation analyses showed no sex differences. To date, this is the first study to investigate the link between these traits and HC and HDHEA in older people. Our results confirm that positive and negative expectations about the future (i.e. optimism and pessimism) may play an important role in health due to their relationship with the HPA axis. They also strengthen the idea that the negative effects of pessimism have a greater weight than the protective effects of optimism in their relationship with HPA axis regulation., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Research incorporating the analysis of glucocorticoids, specifically cortisol, in hair samples has exploded over the past 10-15 years, yet factors contributing to the accumulation of cortisol in hair are not yet fully characterized. In particular, it is not clear whether cortisol accumulation in hair is dependent on hair growth rate, a possibility raised by prior rodent studies reporting glucocorticoid-mediated inhibition of hair growth. Using rhesus macaque monkeys (Macaca mulatta), an extensively studied nonhuman primate species, the present pilot study evaluated the hypothesis that hair cortisol accumulation is inversely related to hair growth rate (i.e., slower hair growth leading to elevated cortisol levels). Hair samples were collected from 19 adult female macaques and 17 infants (9 males) 3 months apart using a shave-reshave procedure from the same site below the posterior vertex of the scalp. The second hair samples were measured to the nearest millimeter (mm) for growth rate over the previous 3 months and assayed for hair cortisol concentrations (HCCs) using enzyme immunoassay. Because of the possibility of age-related differences in hair growth rate, correlational analyses were performed separately for adults and infants to determine whether HCC values were associated with growth rate in each age group. These analyses revealed that neither group displayed a significant correlation of HCCs with hair growth. The results additionally showed that overall, adults had a faster hair growth rate than infants and, as expected from previous studies, had lower HCCs than infants. Our results suggest that higher HCCs within the non-stress range do not result from cortisol-mediated inhibition of hair growth. Moreover, similarities between humans and macaque monkeys in both HPA axis regulation and hair growth rates argue that these findings are relevant for human hair cortisol studies. Extrapolation to other species in which the features of hair growth and the relevant regulatory mechanisms are less well understood should be done with caution., 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 © 2023 Elsevier Inc. All rights reserved.)

Only two studies to date have considered the joint effects of testosterone and cortisol on direct measures of criminal behavior. The current study extends this earlier work by incorporating the direct and interactive effects of baseline hormone measures and hormone change scores in response to social stress. The current study also extends prior work by considering distinct measures of different criminal behavior types and sex differences. Analyses based on a large sample of undergraduates indicated that testosterone had a positive and statistically significant association with impulsive and violent criminal behavior. The interaction of testosterone with cortisol had a negative association with income generating crime. Simple slopes analyses of this interaction indicated testosterone had a positive association with income generating crime when cortisol was low (-1 SD). Associations between hormones and criminal behavior were not moderated by sex., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Measurement of steroids in wild pinnipeds can facilitate assessment of breeding, nutritional and stress status, and is useful in understanding behavioral responses. Even in young animals, sex steroids may be important in behavioral interactions and immune modulation. Use of saliva can avoid the large fluctuations seen in some steroids in plasma, and can negate the need for venipuncture, making it a potentially useful matrix in the wildlife. However, its utility in estimating steroid levels in wild young pinnipeds has not been evaluated. Here, we investigated the suitability of saliva for steroid hormone analysis in wild grey seal pups during their suckling and post-weaning fast periods. We collected saliva (n = 38) and plasma (n = 71) samples during the breeding season on the Isle of May, Scotland, 2012. We investigated success of sample collection, ease of preparation, accuracy and precision of analysis, and, where possible, comparability of measurements (n = 27) from saliva and plasma. Plasma sampling was rapid, whereas sampling saliva took up to five times longer. Analytical performance criteria (parallelism, accuracy, and precision (intra and inter assay co-efficient of variation (% CV)) of commercial ELISA kits to measure estradiol, testosterone and cortisol in both matrices were assessed. Estradiol and cortisol assays performed well and can be used in plasma and saliva. However, we could not confidently validate testosterone for either matrix. Saliva estradiol correlated with levels in plasma. Saliva sample preparation was faster and simpler than plasma preparation because it did not require extraction. However, given the additional time taken to obtain saliva in the wild, the possibility of blood contamination from oral damage and the lower success rate in obtaining sufficient sample for analysis, we recommend that this matrix only be used as an alternative to plasma sampling measurement in pinnipeds when animals are anaesthetized, tolerate mouth swabbing, or have been trained to accept saliva sampling in captivity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Differential HPA axis function has been proposed to underlie sex-differences in mental disorders; however, the impact of fluctuating sex hormones across the menstrual cycle on HPA axis activity is still unclear. This meta-analysis investigated basal cortisol concentrations as a marker for HPA axis activity across the menstrual cycle. Through a systematic literature search of five databases, 121 longitudinal studies were included, summarizing data of 2641 healthy, cycling participants between the ages of 18 and 45. The meta-analysis showed higher cortisol concentrations in the follicular vs. luteal phase (d SMC  = 0.12, p =.004, [0.04 - 0.20]). Comparisons between more precise cycle phases were mostly insignificant, aside from higher concentrations in the menstrual vs. premenstrual phase (d SMC  = 0.17, [0.02 - 0.33], p =.03). In all included studies, nine samples used established cortisol parameters to indicate HPA axis function, specifically diurnal profiles (k = 4) and the cortisol awakening response (CAR) (k = 5). Therefore, the meta-analysis highlights the need for more rigorous investigation of HPA axis activity and menstrual cycle phase., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In various mammalian species, there has been an increase in the use of hair cortisol analysis to evaluate long-term stress. This trend is because of some advantages relative to the standard tools, such as hormone analysis using blood, urine, or feces. Here, I carried out assay validation and adrenocorticotrophic hormone (ACTH) challenge to measure long-term stress in Pallas's squirrel Callosciurus erythraeus. In addition, I investigated the effects of sex, body condition, season, and reproductive conditions on hair cortisol concentrations (HCC) in free-living individuals. The assay validation was reported in this study. Hair cortisol concentrations in squirrels given repeated ACTH injections were significantly higher than those that received a single-ACTH injection and a saline injection. I found a negative effect of body condition on adult HCC. In contrast, body condition had a positive effect on HCC in juveniles. I found no effects of other factors in either adult or juvenile squirrels. Furthermore, although I investigated whether reproductive conditions, such as pregnancy, lactation, and non-breeding in females or testis size in males, affected HCC, I found that there were no effects of reproductive conditions. This study validated the assay and utility of hair cortisol analysis to assess long-term stress, and continuous investigation of the relationship between HCC and fitness is important for determining whether hair cortisol analysis is a reliable method for estimating population health in Pallas's squirrels., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Social rank in a structured society has been linked to basal levels of glucocorticoids in various species, with dominant individuals generally presenting lower levels than subordinates. The biotic and abiotic factors influencing glucocorticoids levels across social ranks are still, however, unclear in fishes. We investigated the influences of group size, fish size, sex, age, and reproduction type, plus water salinity and temperature, on the basal levels of cortisol, the major stress hormone in fishes. A phylogenetically controlled meta-analysis was performed on data from 72 studies over 22 species of fishes. As expected, dominants generally exhibited lower levels of cortisol than subordinates. More importantly, the strength of the correlation between cortisol and rank was modulated by three main factors, group size, environmental temperature, and fish size. Differences in basal cortisol between dominants and subordinates were significantly greater in small groups (dyadic contexts) when compared to larger groups. Differences between dominants and subordinates were also greater in temperate regions when compared to the tropics, and in species with larger body size. These results provide valuable insights into the links among hierarchy, stress and metabolism in fishes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Analysis of hair cortisol concentrations (HCCs) is a promising method for monitoring long-term stress in mammals. However, previous measurements of HCCs in polar bears (Ursus maritimus) have yielded highly variable results, which are likely due to different methodological approaches. In this study, hair samples of zoo-housed polar bears were analyzed for cortisol with two independent immunoassays [an enzyme-linked immunoassay (EIA) and a chemiluminescence assay (CLIA)] and liquid chromatography-tandem mass spectrometry (LC-MS/MS). HCC measurements depended significantly on assay type applied, sample processing (cutting vs. powdering hair) and their interaction. Best agreement was observed between LC-MS/MS and CLIA (R 2  = 0.81 for powdered hair) and sample processing had a minor, albeit significant, effect on obtained HCC measurements in these assays (R 2  > 0.9). EIA measurements were consistently higher than with the other assays. HCC measurement was validated biologically for CLIA and LC-MS/MS in one male polar bear that experienced considerable stress for a prolonged period of time (> 18 weeks). Subsequently, by using the validated LC-MS/MS the measurement of cortisol could be complemented by the analysis of other steroids including cortisone, testosterone and progesterone levels from hair samples collected over a 9-month period (5-13 months) from six zoo-housed polar bears (five males, one female). No seasonal steroid variation was observed except in male progesterone levels. For all steroids except cortisone, a strong body region effect (neck or paw) was observed. Cortisol and cortisone, as well as progesterone and testosterone, concentrations were positively correlated. We show that hair steroid concentrations can be used to longitudinally measure stress and reproductive hormone axes in polar bears. The data established herein provide important basic information regarding methodology and study design for assessing hair steroid hormones., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Providing negative feedback can be demanding, as it typically requires dealing with multiple negative emotions. The first aim of this study was to transfer this work-related task to a new laboratory protocol and to investigate short-term hormonal changes among feedback providers. The second aim was to test if such hormonal stress responses can be attenuated through a priori instructions on how to regulate emotions. Each of 150 participants (51% women) provided eight saliva samples before, during, and after anticipating and conducting a negative feedback conversation with a professional actor who displayed negative emotional reactions. Participants were divided into four conditions regarding the way they were instructed to regulate their emotions: expressive suppression (keeping a neutral expression); cognitive reappraisal (staying task-oriented and emotionally distanced); affect utilization (moving towards and using emotions); or control condition. By means of three-phase spline growth models, latent growth factors during baseline, stress response, and recovery were specified. Providing negative feedback was followed by significant temporary testosterone decreases as well as cortisol increases. Testosterone (but not cortisol) responses were attenuated when feedback providers had been instructed to either follow a cognitive reappraisal or affect utilization strategy. This study provides evidence that a typical managerial task, that is, having to provide negative feedback, is a testosterone- and cortisol-relevant experience. Down-regulation of an individual's emotional involvement through reappraisal, as well as the newly introduced technique of moving towards and making use of the interaction partner's emotions (affect utilization), revealed consequences in terms of attenuating the testosterone response to stress., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Pangolins are 'keystone species' driven towards extinction due to a lack of profound awareness and illegal trade. The drivers urge for immediate development in the understanding of demographics and reproductive dynamics of this species. In this study, we developed and validated a quantitative method to measure pangolin fecal extracts using the electrospray (ESI-MS/MS) interface in positive ionization mode. The method aids in the measurement of hormones from the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis, making it a possibly appropriate technique to understand the cross-talk between the axes. The study aims to measure the relative abundance of adrenal and gonadal hormones such as corticosterone, cortisol, estrone, estradiol-17β, progesterone, testosterone, and a number of its metabolites. From the dried fecal extract, the principal metabolite identified from the estrogen family was estradiol-17β, whereas the gestagen family revealed that the pregnane series is predominated in 5α-configuration. On the other hand, epiandrosterone was seen as the dominant form in the male fecal extracts. Additionally, the glucocorticoids are excreted majorly as corticosterone, but traces of cortisol are also present in both the male and female fecal samples. The physiological validation confirmed that the ESI-MS/MS technique is suitable to determine physiologically caused differences in the fecal steroid concentrations. Physiologically, the age structure in pangolin is not responsible for causing differences within gender. However, the results revealed that glucocorticoids might vary between the sexes, i.e., males have a higher relative abundance of glucocorticoids over females. Therefore, our studies show that some of the main adrenal and gonadal metabolites can be predicted by exploiting MS/MS, which can steer research to potentially assess the reproductive status of captive and free-ranging pangolin species., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In sport, testosterone has been positioned as a substrate for motivation with both directional and time dependencies. However, evidence is scarce when considering the complexities of competitive sport and no work has explicitly modeled these dependencies. To address these gaps, we investigated the bidirectional and time-dependent interrelationships between testosterone and training motivation in an elite rugby environment. Thirty-six male athletes were monitored across training weeks before and after eight international rugby matches. Pre-breakfast measures of salivary testosterone and training motivation (1-10 rating) were taken on training, competition, and recovery days (up to 40 tests). Using a continuous-time (CT) model, within-person estimates of autoregressive effects (persistence) and cross-lagged effects (relationships) were derived. A stronger, more persistent temporal association was identified for testosterone than for motivation. Cross-lagged effects verified that training motivation was positively related to testosterone at latter time points (p < 0.001). Discrete-time analyses revealed a non-linear association; increasing in strength from a zero-time lag to peak after 2.83 days (standardized effect = 0.25), before dissipation over longer lagged intervals. The testosterone relationship with ensuing training motivation was also positive, but non-significant. Match effects also appeared (p < 0.001) with a predicted decline in training motivation, but a rise in testosterone, at match onset. In summary, a positive association emerged between within-person fluctuations in self-appraised motivation to train and testosterone concentration in an elite rugby environment. The lagged, non-linear nature of this relationship and match predictions on both outcomes support, and extend, theoretical models linking testosterone and competitive behaviors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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 dynamic relationship between glucocorticoids and behavior are not well understood in wild mammals. We investigated how weather, body condition, and reproduction interact to affect cortisol levels and activity patterns in a free-living population of arctic ground squirrels (Urocitellus parryii). As a proxy for foraging and escape behaviors, collar-mounted accelerometers and light loggers were used to measure above-ground activity levels and the amount of time squirrels spent below the surface, respectively. Fecal cortisol metabolites (FCMs) were quantified to assess glucocorticoid secretion in squirrels. Male and female squirrels differed in above-ground activity levels and time spent below-ground across the active season, with males being most active during mating and females most active during lactation. We also found that female, but not male, squirrels exhibited seasonal variation in FCM levels, with concentrations highest during mid-lactation and lowest after the lactation period. In female squirrels, the seasonal relationships between breeding stage, activity, and FCM levels were also consistent with changes in maternal investment and the preparative role that glucocorticoids are hypothesized to play in energy mobilization. Body condition was not associated with FCM levels in squirrels. As predicted, deteriorating weather also influenced FCM levels and activity patterns in squirrels. FCM concentrations were affected by an interaction between temperature and wind speed when seasonal temperatures were lowest. In addition, above-ground activity, but not time spent below-ground, positively correlated with FCM levels. These results suggest that, although ground squirrels avoid inclement weather by remaining below-ground, activation of the stress axis may stimulate foraging activity., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Physical exercise can improve cognitive functions and promote learning and memory, especially when performed in close temporal proximity to the encoding of information. This benefit may occur due to circulating stress hormones released in response to acute exercise. When administered after encoding, acute stress typically enhances the consolidation of emotional stimuli. However, whether acute exercise also selectively modulates emotional memories remains to be explored. Likewise, the potential role of sex in moderating these effects has not been addressed so far. Here, we tested whether a single bout of aerobic exercise after learning boosts the consolidation and thus long-term memory for emotional versus neutral visuospatial stimuli. Healthy men and women learned an object-location task and subsequently were exposed to a vigorous-treadmill running task or control intervention. Memory was assessed 24 h later. Acute exercise significantly increased heart rate and salivary cortisol in both sexes and selectively facilitated the consolidation of emotional stimuli. In particular, we found improved memory for negative items in women and better recall of positive items in men following exercise exposure. This memory benefit was positively related to the increase in heart rate and cortisol in both men and women, suggesting that the favorable effects of acute exercise on emotional memory may be mediated via a co-activation of the sympathetic nervous system and the hypothalamus-pituitary-adrenocortical axis. Our findings thereby provide first evidence for the improvement of emotional memory consolidation by acute physical exercise that appears to rely on similar neuroendocrine mechanisms as psychosocial stressors. Given that exercise is healthy, cost-effective and practical in nature, it constitutes an ideal behavioral intervention strategy for boosting memory in clinical and educational settings alike., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The prefrontal cortex, and especially the Dorsolateral Prefrontal Cortex (DLPFC), plays an inhibitory role in the regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis under stressful situations. Moreover, recent evidence suggests that a sustained DLPFC activation is associated with adaptive stress regulation in anticipation of a stressful event, leading to a reduced stress-induced amygdala response, and facilitating the confrontation with the stressor. However, studies using experimental manipulation of the activity of the DLPFC before a stressor are scarce, and more research is needed to understand the specific role of this brain area in the stress-induced physiological response. This pre-registered study investigated the effect on stress regulation of a single excitatory high frequency (versus sham) repetitive transcranial magnetic stimulation (HF-rTMS) session over the left DLPFC applied before the Trier Social Stress Test in 75 healthy young women (M = 21.05, SD = 2.60). Heart rate variability (HRV) and salivary cortisol were assessed throughout the experimental protocol. The active HF-rTMS and the sham group showed a similar cognitive appraisal of the stress task. No differences in HRV were observed during both the anticipation and the actual confrontation with the stress task and therefore, our results did not reflect DLPFC-related adaptive anticipatory adjustments. Importantly, participants in the active HF-rTMS group showed a lower cortisol response to stress. The effect of left prefrontal HF-rTMS on the stress system provides further critical experimental evidence for the inhibitory role played by the DLPFC in the regulation of the HPA axis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Dietary intake of polyunsaturated fatty acids (PUFAs) or saturated fatty acids (SFAs) differently modulates neurophysiological and behavioral functions in response to altered hypothalamic-pituitary-adrenal (HPA)-axis activity and an individual's development. In this context, an individual's social environment, including social interactions and social hierarchies, is closely related to hormone concentrations and possibly interacts with dietary fatty acid effects. We investigated if dietary supplementation with walnut oil (high in PUFAs) and coconut fat (high in SFAs), compared to a control group, affects body mass gain, cortisol and testosterone concentrations, plasma fatty acids, and social behavior in male domestic guinea pigs from adolescence to adulthood. For analyses of cortisol and testosterone concentrations, social interactions were included as covariates in order to consider effects of social behavior on hormone concentrations. Our results revealed that SFAs increased escalated conflicts like fights and stimulated cortisol and testosterone concentrations, which limited body mass gain and first-year survival. PUFAs did not remarkably affect social behavior and hormone concentrations, but enabled the strongest body mass gain, which probably resulted from an energetic advantage. Neither sociopositive nor agonistic behaviors explained age-specific differences in hormone concentrations between groups. However, a high number of subdominant individuals and lower testosterone concentrations were related to increased cortisol concentrations in adult PUFA males. Our findings demonstrate the importance of dietary fatty acids regarding behavioral and endocrine developmental processes and adaptations to the social environment by modulating HPA-axis function and body homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Millions of women worldwide use oral contraceptives (i.e., birth control pill; OCs), often starting during puberty/adolescence; however, it is unknown how OC use during this critical period of development affects the brain, especially with regard to emotional working memory. Here, we examined stress reactivity, and brain structure and function in OC users using the Trier Social Stress Test and structural and functional magnetic resonance imaging (MRI). Our results show that OC use during puberty/adolescence gives rise to a blunted stress response and alters brain activation during working memory processing. OC use, in general, is also linked to increased prefrontal brain activation during working memory processing for negatively arousing stimuli. OC use is also related to significant structural changes in brain regions implicated in memory and emotional processing. Together, these findings highlight that OC use induces changes to brain structure and function and alters stress reactivity. These findings may provide a mechanistic insight for the increased vulnerability to mood-related mental illness in women after OC use., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The extraction of cortisol from fingernails represents a recent advancement in the retrospective, long-term assessment of hypothalamic-pituitaryadrenal (HPA) axis activity: Fingernail cortisol has the potential to overcome some of the major disadvantages of established HPA axis markers. However, the introduction of any novel methodology also raises certain caveats. This review provides a comprehensive summary of the current state of research on fingernail cortisol. It identifies a number of strengths of his novel methodology (e.g., its high feasibility), while also pointing out open questions which currently challenge the interpretability of fingernail findings, in particular regarding the time period of cortisol secretion reflected in fingernail samples, as well as regarding potential determinants or confounders of fingernail cortisol (e.g. sociodemographic, lifestyle, or health characteristics). Clarification of these issues in the context of further methodological studies is necessary to validate the use of fingernail cortisol as a retrospective marker of HPA axis activity., 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 © 2020 Elsevier Inc. All rights reserved.)

Externalizing and internalizing behavior problems can have deleterious psychosocial consequences for youth. Both sympathetic nervous system (SNS) and hypothalamic-pituitary adrenal (HPA) axis activity and reactivity may contribute to behavior problems but have largely been studied separately, with inconsistent findings. Because the SNS and HPA axis interact to carry out physiological processes (e.g., responding to stressors), considering SNS and HPA axis activity jointly may elucidate disparate findings. This review discusses studies that simultaneously assessed SNS and HPA axis (re)activity and youth behavior problems using measures of salivary alpha amylase (sAA) and salivary cortisol. Multiple patterns of SNS and HPA axis coordination were associated with problem behaviors, especially when considering individual differences and youth's psychosocial context. Importantly, many study findings may be artifacts of widespread methodological differences. The reviewed studies lay the foundation for future research on neuroendocrine coordination as a contributing factor to youth problem behaviors and some recommendations for future research are discussed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In many social species, hierarchical status within the group is associated with differences in basal adrenocortical activity. We examined this relationship in naked mole-rats (Heterocephalus glaber), eusocial rodents with arguably the most extreme social hierarchies of all mammals. This species lives in colonies where breeding is restricted to one socially dominant 'queen' and her male consorts, and all other individuals are reproductively suppressed 'subordinates'. The relationship between cortisol and social status in naked mole-rats has not fully been elucidated, as prior results on this topic have been contradictory. We used non-invasive feces sampling to measure baseline cortisol levels in eight laboratory colonies of naked mole-rats, to either replicate or reject rank differences. First, we successfully validated an assay to measure fecal cortisol metabolites (FCMs). Removal from the colony for the validation experiment, either alone or with an opposite sex conspecific, induced prolonged elevation of FCM levels on a scale of days to weeks. This increase in cortisol did not prevent the removed animals from sexually maturing. In colony-housed animals, we found no relationship between rank in the social hierarchy and FCM levels. Further, queens, breeding males, and reproductively suppressed subordinates all had equivalent FCM levels. We conclude that this species shows little evidence of the 'stress of dominance' or 'stress of subordination' and that reproductive suppression in naked mole-rats is not driven by elevated cortisol levels., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cultural mismatch theory suggests that a poor fit between the cultural values endorsed by individuals and the institutions to which they belong results in emotional distress and activation of physiological stress processes, particularly for underrepresented groups. To test a novel paradigm for reducing perceptions of this cultural mismatch, the current experiment evaluated whether reminding first-year Latino university students (N = 84; M age  = 18.56; SD = 0.35; 63.1% female; 85.7% Mexican descent; 65.5% first-generation college students) about institutional support for cultural diversity and inclusion would reduce neuroendocrine and affective responses to psychosocial stress. Prior to completing a modified version of the Trier Social Stress Test, participants were randomly assigned to view either a video conveying university commitment to cultural diversity and inclusion (n = 45) or a control video (n = 39) depicting a campus tour. Five saliva samples assayed for cortisol and corresponding negative affect measures were collected to assess stress reactivity and recovery patterns (pre-task baseline, post-task +30 min, +45 min, +60 min, +75 min). Repeated measures data were analyzed using bilinear spline growth models. Viewing the culture video (compared to control) significantly reduced cortisol reactivity to the TSST and post-task negative affect levels, specifically for students endorsing higher Latino cultural values (e.g., familism, respect). Post-task cortisol levels were also reduced for students endorsing higher U.S. mainstream cultural values (e.g., self-reliance, competition). Results provide novel evidence for cultural diversity in stress responsivity and individual variation in approaches to reduce perceived cultural mismatch., (Copyright © 2020 Elsevier Inc. All rights reserved.)

During the last two decades, hair cortisol concentration (HCC) has proven to be a promising marker for the evaluation of increased hypothalamic-pituitary-adrenal axis activity caused by repeated or long-term stressful conditions. A minimally invasive sampling procedure, simple storage and the retrospective characteristic of one hair sample are reasons why HCC is increasingly used not only in human medicine but also in animal welfare research. However, before applying HCC as a reliable indicator for stress, it is important to investigate potential influencing factors in addition to stressors in the species of interest. Thus, the aim of our study was to elucidate the impact of age, sex, hair color, body region, age of hair segments and season of hair sampling on HCC in pigs and cattle. Hair samples were taken by electric clippers and analyzed by ELISA after extraction. Our results show similar effects of influencing factors in both species. Significantly increased HCCs were found in young animals after birth compared with older age groups. In addition, HCCs were significantly higher in samples obtained from the tail tip in comparison with samples from the shoulder, neck and back regions, in black hair compared with white hair and in distal hair segments. Season had an impact on HCC only in cattle, which exhibited higher levels in winter than in summer. In conclusion, age, body region, hair color, hair segment and season affect hair cortisol concentrations and should be considered and controlled for when HCC is applied as a potential stress indicator in pigs and cattle. In addition, further research is necessary to elucidate the mechanisms by which cortisol is incorporated into the hair shaft., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

An exacerbated physiological response to stress is associated with the development of stress-related disorders (e.g., depression and anxiety disorders). Recently, it has been proposed that individuals with high expectancies of being able to deal with stressful situations will activate regulatory mechanisms during the anticipation of the stressful event that would improve stress regulation. To test this hypothesis, 52 women in young adulthood (M = 21.06; SD = 2.58) anticipated and performed a laboratory-based stress task after receiving positive or negative bogus feedback on their abilities to deal with stressful events. Heart rate variability and salivary cortisol were assessed throughout the experimental protocol. Participants receiving positive bogus feedback (i.e., High Expectancy group) showed a more positive anticipatory cognitive stress appraisal (i.e., they anticipated the stress task as less threatening/challenging, and they perceived that they were more able to deal with it), and they showed a lower cortisol response to stress. Moreover, a more positive anticipatory cognitive stress appraisal was associated with better anticipatory stress regulation (indexed as less decrease in heart rate variability), leading to a lower cortisol response. Our results indicate that people with positive expectancy initiate mechanisms of anticipatory stress regulation that enhance the regulation of the physiological stress response. Expectancy and anticipatory stress regulation may be key mechanisms in the development and treatment of stress-related disorders., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Chicken avidin and bacterial streptavidin are workhorses in biotechnology. We have used avidin as a scaffold protein to develop avidin variants with novel ligand-binding affinity, so-called antidins. This article covers the strategy applied in the development of antidins. Using a phage display developed for avidin, immobilized ligands were used to select binders from a phage pool displaying avidin variants with randomized sequence in the protein loops. Antidins binding various ligands with nanomolar affinity were obtained. Antidins have already been demonstrated to be suitable for a diagnostic assay measuring serum progesterone levels and they offer a promising alternative to antibodies for the recognition of small molecules., (© 2020 Elsevier Inc. All rights reserved.)

There is evidence that testosterone and cortisol levels are related to the attraction of a romantic partner; testosterone levels relate to a wide range of sexual behaviors and cortisol is a crucial component in the response to stress. To investigate this, we conducted a speed-dating study among heterosexual singles. We measured salivary testosterone and cortisol changes in men and women (n = 79) when they participated in a romantic condition (meeting opposite-sex others, i.e., potential romantic partners), as well as a control condition (meeting same-sex others, i.e., potential friends). Over the course of the romantic speed-dating event, results showed that women's but not men's testosterone levels increased and cortisol levels decreased for both men and women. These findings indicate that men's testosterone and cortisol levels were elevated in anticipation of the event, whereas for women, this appears to only be the case for cortisol. Concerning the relationship between attraction and hormonal change, four important findings can be distinguished. First, men were more popular when they arrived at the romantic speed-dating event with elevated cortisol levels. Second, in both men and women, a larger change in cortisol levels during romantic speed-dating was related to more selectivity. Third, testosterone alone was unrelated to any romantic speed-dating outcome (selectivity or popularity). However, fourth, women who arrived at the romantic speed-dating event with higher testosterone levels were more selective when their anticipatory cortisol response was low. Overall, our findings suggest that changes in the hormone cortisol may be stronger associated with the attraction of a romantic partner than testosterone., (Copyright © 2019. Published by Elsevier Inc.)

Instrumental learning, i.e., learning that specific behaviors lead to desired outcomes, occurs through goal-directed and habit memory systems. Exposure to acute stress has been shown to result in less goal-directed control, thus rendering behavior more habitual. The aim of the current studies was to replicate and extend findings on stress-induced prompting of habitual responding and specifically focused on the role of stress-induced cortisol reactivity. Study 1 used an established outcome devaluation paradigm to assess goal-directed and habitual control. Study 2 utilized a modified version of this paradigm that was intended to establish stronger habitual responding through more extensive reward training and applying a relevant behavioral devaluation procedure (i.e., eating to satiety). Both studies failed to replicate that stress overall, i.e., independent of cortisol reactivity, shifted behavior from goal-directed to habitual control. However, both studies found that relative to stress-exposed cortisol non-responders and no-stress controls, participants displaying stress-induced cortisol reactivity displayed prominent habitual responding. These findings highlight the importance of stress-induced cortisol reactivity in facilitating habits., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Stress before encoding is often linked to impaired memory. Further influences of stress on memory are arousal of the to be learned material and memory retrieval type (free recall vs. recognition). In the current study we tested the influence of stress on memory encoding for neutral and negative arousing pictures in healthy young adults. A total of 80 participants (40 men) were subjected either to the socially evaluated cold pressure test or a control condition before encoding of arousing and neutral pictures. One day later participants underwent a recognition test. Results show different relationships between the obtained stress markers and recognition memory. Higher perceived stress ratings predicted poorer overall accuracy for arousing material. Lower perceived stress ratings and larger blood pressure increase predicted higher recollection values for arousing material. In contrast, a larger cortisol increase predicted lower familiarity values for arousing material. Concluding, activity of the sympathetic nervous system (SNS) and a lower feeling of perceived stress predict better recollection. HPA axis activity predicts lower familiarity. Pre-encoding induced changes in the perceived feeling of stress, activity of the SNS, and activity of the HPA axis show specific and distinct relationships to recognition memory., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Acute stress influences reward-seeking tendencies and risky decision-making. However, it is unclear how acute stress influences decision-making in situations in which individuals must learn to either maximize long-term or immediate rewards from experience. Consequently, this study sought to investigate whether acute stress enhances salience of small, immediate or large, delayed rewards on decision-making under uncertainty. The Socially Evaluated Cold Pressor Task (SECPT) was used to induce acute stress. Participants in Experiment 1 (N = 50) were exposed to either the SECPT or a warm-water control condition and then completed a decision-making task in which participants needed to learn to forego immediate rewards in favor of larger delayed rewards. The results demonstrated that acute stress enhanced decisions that maximized long-term, large rewards over immediate, small rewards. Experiment 2 (N = 50) included an assessment of salivary cortisol. Results replicated the behavioral findings in Experiment 1 and demonstrated that the acute stress manipulation increased salivary cortisol, thus providing a potential physiological mechanism for these results. This work suggests that moderate acute stress can improve decision-making under uncertainty that depends on learning to maximize long-term rewards from experience., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Certain susceptibility factors, such as genetic variants or specific physiological responses to stress, can dictate the effects of stress on learning and memory. Here, we examined the influence of the BclI polymorphism of the glucocorticoid receptor gene on the time-dependent effects of pre-learning stress on long-term memory. Healthy individuals were exposed to the socially evaluated cold pressor test or a control condition immediately or 30 min before word list learning. Participants' memory for the words was tested immediately and 24 h after learning, and saliva samples were collected to genotype participants for the BclI polymorphism and to assess cortisol responses to the stressor. Results revealed that stress immediately before learning enhanced memory, while stress 30 min before learning impaired memory; these effects were largely selective to males and non-arousing words. Additionally, stress, independent of when it was administered, enhanced memory in non-carriers of the BclI polymorphism, while impairing memory in carriers; these effects were largely selective to males and participants exhibiting a robust cortisol response to stress. These results provide further evidence for time-dependent effects of stress on long-term memory and suggest that carriers of the BclI polymorphism might be more sensitive to the negative effects of corticosteroids on learning., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Smith, Floerke, and Thomas (2016) demonstrated that learning by repeated testing, or retrieval practice, reduced stress-related memory impairment when compared to learning by repeatedly studying material. In the present experiment, we tested whether, relative to study practice, retrieval practice would improve post-stress memory by increasing access to both item and source information. Participants learned two wordlists, which were temporally segregated to facilitate distinction between the two lists. Participants returned one week later for stress induction and two memory tests. Each test featured a recognition test that was given to assess item memory accessibility, and a list-discrimination task that was given to assess source memory. Relative to study practice, successful retrieval practice during learning reduced false alarms but did not improve source memory on the post-stress test. Results are discussed as they relate to current theories surrounding stress effects and retrieval practice effects., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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

A significant body of literature suggests that aquatic pollutants can interfere with the physiological function of the fish hypothalamic-pituitary-interrenal (HPI) axis, and eventually impair the ability to cope with subsequent stressors. For this reason, development of accurate techniques to assess fish stress responses have become of growing interest. Fish scales have been recently recognized as a biomaterial that accumulates cortisol, hence it can be potentially used to assess chronic stress in laboratory conditions. We, therefore, aimed to evaluate the applicability of this novel method for cortisol assessment in fish within their natural environment. Catalan chub (Squalius laietanus) were sampled from two sites; a highly polluted and a less polluted (reference) site, in order to examine if habitat quality could potentially influence the cortisol deposition in scales. We also evaluated the seasonal variation in scale cortisol levels by sampling fish at three different time points during spring-summer 2014. In each sampling, blood was collected to complement the information provided by the scales. Our results demonstrated that blood and scale cortisol levels from individuals inhabiting the reference site were significantly correlated, therefore increasing the applicability of the method as a sensitive-individual measure of fish HPI axis activity, at least in non-polluted habitats. Since different environmental conditions could potentially alter the usefulness of the technique, results highlight that further validation is required to better interpret hormone fluctuations in fish scales. Scale cortisol concentrations were unaffected by habitat quality although fish from the polluted environment presented lower circulating cortisol levels. We detected a seasonal increase in scale cortisol values concurring with an energetically costly period for the species, supporting the idea that the analysis of cortisol in scales reveals changes in the HPI axis activity. Taken together, the present study suggests that cortisol levels in scales are more likely to be influenced by mid-term, intense energetically demanding periods rather than by long-term stressors. Measurement of cortisol in fish scales can open the possibility to study novel spatio-temporal contexts of interest, yet further research is required to better understand its biological relevance., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Non-invasive measures of glucocorticoid (GC) hormones and their metabolites, particularly in feces and hair, are gaining popularity as wildlife management tools, but species-specific validations of these tools remain rare. We report the results of a validation on black-tailed prairie dogs (Cynomys ludovicianus), a highly social engineer of the grasslands ecosystem that has experienced recent population declines. We captured adult female prairie dogs and brought them into temporary captivity to conduct an adrenocorticotropic hormone (ACTH) stimulation test, assessing the relationship between plasma GC and fecal glucocorticoid metabolite (FGM) levels following a single injection of a low (4 IU/kg) or high dose (12 IU/kg) of ACTH, compared to a single injection of saline. We also gave repeated injections of ACTH to adult females to assess whether this would result in an increase of hair cortisol concentrations, compared with control individuals repeatedly injected with saline. A single injection of ACTH at either low or high dose peaked plasma cortisol levels after 30 min, and thereafter the cortisol levels declined until 120 min, where they returned to pre-treatment levels comparable to those of the saline injected group. Despite the significant elevation of plasma cortisol in the treatment groups following ACTH injection, the elevation of FGM levels in the treatment groups were not significantly different from those in the control group over the following 12 h. Repeated injection of a high dose of ACTH failed to increase hair cortisol concentration in treatment animals. Instead, hair cortisol levels remained comparable to the pre-treatment mean, despite an increase in post-treatment hair cortisol levels seen in the saline-injected group. The magnitude of increase in the saline control group was comparable to natural seasonal variation seen in unmanipulated individuals. These results highlight that while measurement of GCs and their metabolites in feces and hair are potentially valuable conservation tools for black-tailed prairie dogs, further validation work is required before these matrices can be to real-world conservation applications., (Copyright © 2019. Published by Elsevier Inc.)

The vertebrate stress response enables individuals to react to and cope with environmental challenges. A crucial aspect of the stress response is the elevation of circulating glucocorticoids. However, continued activation of the stress response under repeated exposure to stressors can be damaging to fitness. Under certain circumstances it may therefore be adaptive to habituate to repeated exposures to a particular stressor by reducing the magnitude of any associated release of glucocorticoids. Here, we investigate whether Trinidadian guppies (Poecilia reticulata) habituate to repeated exposure to a mild stressor, using a waterborne hormone sampling approach that has previously been shown to elicit a stress response in small fish. We also test for individual variation in the extent of habituation to this stressor. Concentrating on freely circulating cortisol, we found that the first exposure to the assay induced high cortisol release rates but that guppies tended to habituate quickly to subsequent exposures. There were consistent differences among individuals in their average cortisol release rate (after accounting for effects of variables such as body size) over repeated exposures. Our analyses did not find evidence of individual differences in habituation rate, although limitations in statistical power could account for this finding. We repeated the analysis for free 11-ketotestosterone, which can also respond to stressors, but found no obvious habituation pattern and no among-individual variation. We also present data on conjugated forms of both hormones, which were repeatable but did not show the expected time-lagged habituation effect. We discuss consistent individual differences around the general pattern of habituation in the flexible stress response, and highlight the potential for individual variation in habituation to facilitate selection against the deleterious effects of chronic stress., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The Apolipoprotein E4 (ApoE-ε4) allele has been suggested as the main risk factor for late onset Alzheimer's disease (AD), whereas the ApoE-ε2 allele has been proposed as a protective factor. These proposals have increased the interest in the effect of the ApoE genotype in healthy people. Additionally, high cortisol levels have been related to negative effects on cognition. However, few studies have investigated the relationship between cognitive performance and cortisol, taking into account the different ApoE alleles. For this reason, the aim of this study was to evaluate different cognitive domains (declarative and working memory, attention, and executive function) and their relationship with cortisol, considering the ApoE-ε2, ApoE-ε3, and ApoE-ε4 alleles in healthy older people (55-77 years old). Two saliva samples were collected during the neuropsychological session to obtain cortisol levels and the ApoE genotype. Results showed an association between the ApoE genotype and declarative memory, specifically learning ability, where ApoE-ε2 group performed better than ApoE-ε4 and ApoE-ε3 groups. No differences in cortisol levels were obtained considering the ApoE genotype. In addition, higher mean cortisol levels were related to a worse performance on declarative memory, for the whole sample, and when considering the three allelic variation, for the ApoE-ε4 group. On the contrary, an increase of cortisol levels during the neuropsychological session was associated to a better performance on declarative memory for the whole sample, and for the ApoE-ε3 group when considering the three alleles. Besides, ApoE-ε3 group also showed an association between higher mean cortisol levels and a better attention performance. Therefore, our results suggest that carrying the ApoE-ε4 allele may be a vulnerability factor in the adverse effects of Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation on cognition during aging, while ApoE-ε3 allele could be associated to a more adaptive HPA axis response., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Examining the effects of acute stress across multiple modalities (behavioral, physiological, and endocrinological) can increase our understanding of the interplay among stress systems, and may improve the efficacy of stress detection. A multimodal approach also allows for verification of the biological stress response, which can vary between individuals due to myriad internal and external factors, thus allowing for reliable interpretation of behavioral markers of stress. Here, controlling for variables known to affect the magnitude of the stress response, we utilized the Trier Social Stress Test (TSST) to elicit an acute stress response in 80 healthy adult men and women. The TSST involves an interview-style oral presentation and critical social evaluation, and is highly effective in inducing psychosocial stress. Participants completed the study in individual 2 h sessions, during which we collected voice, polygraph and salivary hormone measures in baseline, stress, and relaxation phases. Our results show sizeable systematic increases in voice pitch (mean, minimum and variation in fundamental frequency, F0), hormone levels (cortisol) and decreases in skin temperature and hand movement during psychosocial stress, with striking similarities between men and women. However, cortisol and skin temperature only weakly predicted changes in voice pitch during stress, in either women or men, respectively. Thus, while our results provide compelling evidence that psychosocial stress manifests itself behaviorally by increasing voice pitch and its variability alongside simultaneous activation of physiological and endocrinological stress systems, our results also highlight a relatively weak degree of intra-individual 'response coherence' across these stress systems, with dissociations among different stress measures related most strongly to sex., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Sex hormones are significant regulators of stress reactivity, however, little is known about how genetic variation in hormone receptors contributes to this process. Here we report interactions between biological sex and repeat polymorphisms in genes encoding sex hormone receptors, and their effects on salivary cortisol reactivity in a sample of 100 participants (47 men & 53 women; 24.7 ± 3.23 years). Three genes were investigated: estrogen receptors alpha (ESR1) and beta (ESR2), and the androgen receptor (AR). Participants were classified as carrying 'Short' or 'Long' alleles based on median splits of the repeat distribution for each gene. Measures of physiological reactivity were collected before and after exposure to a canonical laboratory stressor and converted to traditional summary measures for analyses. Overall, men exhibited greater cortisol (p = 0.001) and mean arterial pressure reactivity (p = 0.002), while women displayed elevated heart rate throughout the session (p = 0.02). The effect of polymorphisms on salivary cortisol was sex sensitive. ESR1 was associated with differential reactivity in men (p = 0.04), but not women (p = 0.24). ESR2 genotype interacted with sex such that each additional 'Long' allele was associated with a 6.4% decrease in salivary cortisol in men, but a 9.5% increase in the levels of women (p = 0.02 for interaction). For the X-linked AR, the 'Long' allele was associated with decreased cortisol levels in men (p = 0.047), but in women had no effect (p = 0.75). Together, these results provide evidence for the saliency of genetic variation in sex hormone receptors on stress reactivity in humans and highlight their important role as mediators of hormonal activity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Human paternal behavior is multidimensional, and extant research has yet to delineate how hormone patterns may be related to different dimensions of fathering. Further, although studies vary in their measurement of hormones (i.e., basal or reactivity), it remains unclear whether basal and/or reactivity measures are predictive of different aspects of men's parenting. We examined whether men's testosterone and cortisol predicted fathers' involvement in childcare and play with infants and whether fathers' testosterone and cortisol changed during fathers' first interaction with their newborn. Participants were 298 fathers whose partners gave birth in a UNICEF-designated "baby-friendly" hospital, which encourages fathers to hold their newborns 1 h after birth, after mothers engage in skin-to-skin holding. Salivary testosterone and cortisol were measured before and after fathers' first holding of their newborns. Basal and short-term changes in cortisol and testosterone were analyzed. Fathers were contacted 2-4 months following discharge to complete questionnaires about childcare involvement. Fathers' cortisol decreased during the time they held their newborns on the birthing unit. Fathers' basal testosterone in the immediate postnatal period predicted their greater involvement in childcare. Both basal and reactivity cortisol predicted fathers' greater involvement in childcare and play. Results suggest that reduced basal testosterone is linked with enhanced paternal indirect and direct parenting effort months later, and that higher basal cortisol and increases in cortisol in response to newborn interaction are predictive of greater paternal involvement in childcare and play, also months later. Findings are discussed in the context of predominating theoretical models on parental neuroendocrinology., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study aims to establish a protocol for evaluating the object recognition memory and object location tasks in zebrafish. We evaluated novel the object recognition memory and analyzed the exploration time of the objects during training and testing. Zebrafish explored more the new object in comparison to the familiar object (61% of exploration time during test session). We also tested the object location task and measured the exploration time of each object in the familiar and novel object location. There was a preference to explore the object in the novel location (63% of exploration time during test session). The effect of the non-competitive NMDA receptor antagonist MK-801 was investigated on the object recognition and object location memory. Control (water only) and treated animals (5 μM MK-801) presented a significant preference in exploring the familiar object in comparison to the new object (66 and 68% of exploration time, respectively, during test session); however, 10 μM MK-801-treated animals did not show differences in the exploration time of the objects. In the object location task, the animals treated with the 5 or 10 μM MK-801 did not show a preference for the familiar or novel location whereas the control group had a higher preference in exploring the object in the familiar location (64% of exploration time during test session). Considering the different responses of the control group between original task and in the regimen treatment, we evaluated the impact of habituation on cortisol levels of animals in three different protocols: (1) habituated at the experiment apparatus for 3 days (C1 condition), (2) habituated at the experiment apparatus for 3 days plus treatment tank exposure at fourth day (C2 condition), (3) habituated at the treatment tank and experiment apparatus for 3 days and exposed to treatment tank again at fourth day (C3 condition). The results showed higher levels of cortisol in animals submitted to C2 and C3 conditions compared to animals submitted to C1. When introduced to an acute stressor during C1 condition, we observed an increase in the cortisol levels and an absence of preference for the objects in comparison to control group, which had a preference for novel object and novel location. Fluoxetine treatment induced a decrease in cortisol levels and an absence of preference for the objects in C2 and C3 conditions in comparison to control group, which had a preference for familiar object. However, fluoxetine treatment induced a preference to the novel location in C2 and C3 conditions in comparison to control group, which had a preference for familiar location. These results indicate that treatment tank exposure induced a different performance in object recognition and object location memory due to stress responses. Therefore, these tasks are prone to evaluate memory in physiological and pathological conditions, but its use is limited due to sensitivity to stress caused by manipulation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Hypocortisolism has been found in CFS patients in blood, urine, and saliva. It is unclear if hypocortisolism can also be demonstrated using long-term cortisol measurements, such as cortisol in hair. In addition, the interaction between the HPA axis and the immune system, both expected to play an important role in CFS, is unclear. The objective of the current study was to compare hair and salivary cortisol concentrations in a cohort of female CFS patients to those in healthy controls, and to test the effect of an interleukin-1 receptor antagonist (anakinra) on the HPA axis. Salivary cortisol concentrations of 107 CFS patients were compared to 59 healthy controls, with CFS patients showing a decreased cortisol awakening response (4.2 nmol/L ± 5.4 vs 6.1 nmol/L ± 6.3, p = 0.036). Total cortisol output during the day did not differ significantly in saliva, but there was a trend to lower hair cortisol in a subset of 46 patients compared to 46 controls (3.8 pg/mg ± 2.1 vs 4.3 pg/mg ± 1.8, p = 0.062). After four weeks of treatment with either daily anakinra (100 mg/day) or placebo, there was a slight decrease of hair cortisol concentrations in the anakinra group compared to an increase in the placebo group (p = 0.022). This study confirms the altered dynamics of the HPA axis in a group of CFS patients, and for the first time shows that this might also be present for long-term cortisol measures., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Psychosocial stress is known to crucially influence learning and memory processes. Several studies have already shown an impairing effect of elevated cortisol concentrations on memory retrieval. These studies mainly used learning material consisting of stimuli with a limited ecological validity. When using material with a social contextual component or with educational relevant material both impairing and enhancing stress effects on memory retrieval could be observed. In line with these latter studies, the present experiment also used material with a higher ecological validity (a coherent text consisting of daily relevant numeric, figural and verbal information). After encoding, retrieval took place 24 h later after exposure to psychosocial stress or a control procedure (20 healthy men per group). The stress group was further subdivided into cortisol responders and non-responders. Results showed a significantly impaired retrieval of everyday information in non-responders compared to responders and controls. Altogether, the present findings indicate the need of an appropriate cortisol response for the successful memory retrieval of everyday information. Thus, the present findings suggest that cortisol increases - contrary to a stressful experience per se - seem to play a protective role for retrieving everyday information. Additionally, it could be speculated that the previously reported impairing stress effects on memory retrieval might depend on the used learning material., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Systemic steroid hormone measurements are often used in the assessment of reproductive, developmental, and stress physiology in vertebrates. In protected wildlife, such as the common bottlenose dolphin (Tursiops truncatus), these measures can provide critical information about health and fitness to aid in effective conservation and management. Circulating steroid hormone concentrations are typically measured by immunoassays, which have imperfect specificity and are limited to the measurement of a single hormone per assay. Here we demonstrate that reverse phase solid phase extraction (SPE) coupled to liquid chromatography tandem mass spectrometry (LC-MS/MS) allows for the simultaneous, precise (<15% relative standard deviation), and accurate (between 70% and 120% recovery of spiked quantities) measurement of at least seven steroid hormones in dolphin plasma. These seven steroid hormones include three hormones that have been measured previously in bottlenose dolphin blood (progesterone, testosterone, and cortisol) and three hormones which have never been quantified in dolphin blood (17-hydroxyprogesterone, androstenedione, cortisone, and corticosterone). While 17β-estradiol was not detected endogenously, we were able to accurately and precisely measure spiked quantities estradiol. Measures from plasma were more precise (i.e., lower RSD) than serum, and thus we recommend plasma as the preferred matrix for this analytical method. In order to facilitate comparison of current and future plasma-based studies to previous serum-based studies, we characterized the relationships between hormone measurements in matched plasma and serum, and found that measurements across matrices are significantly and positively correlated. Lastly, to demonstrate potential applications of this method, we examined how steroid hormone profiles vary by pregnancy, sexual maturity, and stress status - pregnancy was associated with elevated progesterone, adult males had higher testosterone, and capture stress was associated with elevated corticosteroids. Overall, we conclude that this method will enable investigators to more thoroughly and efficiently evaluate steroid hormone homeostasis in bottlenose dolphins compared to immunoassay methods. These methods can potentially be applied to the assessment of sexual maturity/seasonality, pregnancy status, and stress in free-ranging bottlenose dolphins as well as those maintained under human care, and potentially other marine mammals., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Animal models and a few human investigations suggest progesterone may be associated with anxiety. Progesterone naturally fluctuates across the menstrual cycle, offering an opportunity to understand how within-person increases in progesterone and average progesterone levels across the cycle correspond to women's anxiety. Across two longitudinal studies, we simultaneously modeled the between- and within-person associations between progesterone and anxiety using multilevel modeling. In Study 1, 100 Polish women provided saliva samples and reported their anxiety at three phases of the menstrual cycle: follicular, peri-ovulatory, and luteal. A significant between-person effect emerged, revealing that women with higher average progesterone levels across their cycles reported higher levels of anxiety than women with lower progesterone cycles. This effect held controlling for estradiol. In Study 2, 61 American women provided saliva samples and reported their attachment anxiety during laboratory sessions during the same three cycle phases. A significant between-person and within-person association emerged: women with higher average progesterone levels reported higher levels of attachment anxiety, and as women's progesterone levels increased across their cycles, so too did their attachment anxiety. These effects held controlling for cortisol. In sum, both studies provide support for a link between menstrual cycle progesterone levels and subjective anxiety., (Copyright © 2018 Elsevier Inc. All rights reserved.)