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Allostatic load is a model that is used to quantify the physiological damage from exposure to stressors. Stressful life events are chronic stressors that can lead to an elevated allostatic load through the physiological and behavioral stress responses. However, there is limited empirical studies that has tested the proposed behavioural pathway. Our study addresses this gap by examining the mediating role of combined modifiable lifestyle behaviors in the 12-years longitudinal association between stressful life events and allostatic load among participants from the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study cohort. A latent profile analysis was performed to identify latent subgroups with distinct behavioral clusters based on five modifiable lifestyle behaviors (smoking, sedentary behavior, physical activity, alcohol consumption, and diet quality). We then used a sequential mediation model design with path analysis to test the mediating effect of these latent subgroups in the associations between stressful life events and three measures of allostatic load. Indirect effects were estimated using the product of coefficient approach and the statistical significance was determined by the 95% bias-corrected bootstrap confidence intervals with 1000 replications. We identified three latent subgroups: "least healthy lifestyle" (12%; n = 396), "moderately healthy lifestyle" (78.7%; n = 2599), and "most healthy lifestyle" (9.2%; n = 306). Exposure to stressful life events was not associated with the allocation of participants in latent subgroups. Compared to the "moderately healthy lifestyle" subgroups, we found that the "least healthy lifestyle" behavioral cluster was not associated with allostatic load. However, there was a significant inverse association between the "most healthy lifestyle" behavioral cluster and allostatic load. Overall, we did not find significant indirect effects between stressful life events and three measures of allostatic load via the "least healthy lifestyle" and the "most healthy lifestyle" groups. In summary, the combinations of modifiable lifestyle behaviors did not explain the association between stressful life events and allostatic load. More longitudinal studies are needed to replicate our study to confirm this finding.

Background: In children and adolescents, chronic low-grade inflammation has been implicated in the pathogenesis of co- and multi-morbid conditions to mental health disorders. Diet quality is a potential mechanism of action that can exacerbate or ameliorate low-grade inflammation; however, the exact way dietary intake can regulate the immune response in children and adolescents is still to be fully understood. Methods: Studies that measured dietary intake (patterns of diet, indices, food groups, nutrients) and any inflammatory biomarkers in children and adolescents aged 2 to19 years and published until November 2020 were included in this systematic review, and were selected in line with PRISMA guidelines through the following databases: Academic Search Complete, CINAHL, Global Health, Medline COMPLETE andWeb of Science-Core Collection. A total of 53 articles were identified. Results: Results show that adequate adherence to healthful dietary patterns such as the Mediterranean diet, or food groups such as vegetables and fruit, or macro/micro nutrients such as fibre or vitamin C and E, are associated with decreased levels of pro-inflammatory biomarkers, mainly c-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), whereas adherence to aWestern dietary pattern, as well as intake of food groups such as added sugars, macro-nutrients such as saturated fatty acids or ultra-processed foods, is associated with higher levels of the same pro-inflammatory biomarkers. Conclusions: This is the first systematic review examining dietary intake and biological markers of inflammation in both children and adolescents. A good quality diet, high in vegetable and fruit intake, wholegrains, fibre and healthy fats ameliorates low-grade inflammation, and therefore represents a promising therapeutic approach, as well as an important element for disease prevention in both children and adolescents., A.B. and C.M.P. are funded by the UK Medical Research Council (grants MR/L014815/1, MR/J002739/1and MR/N029488/1), the European Commission Horizon 2020 (grant SC1-BHC-01- 2019) and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London; they have also received research funding from Johnson and Johnson for research on depression and inflammation, but this paper is independent from this funding. In addition, C.M.P. is funded by the Wellcome Trust strategy award to the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium (104025), which is also funded by Janssen, GlaxoSmithKline, Lundbeck and Pfizer, but, again, this paper is independent from this funding.

Exposure to stressors can evoke psychological, physiological, and behavioral stress responses, which may lead to the adoption of health-damaging behaviors that dysregulate multiple biological systems contributing to a high allostatic load. This review explored the role of combined modifiable lifestyle behaviors in the relationship between stressors and allostatic load among healthy adults.A systematic search was conducted in Medline Complete, PsycINFO, CINAHL, and Embase databases up to September 2021. The PRISMA guidelines guided reporting and study quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Checklist.Database searches identified 319 papers. Eight cross-sectional and two longitudinal studies met our inclusion criteria. Among the ten studies, combined modifiable lifestyle behaviors partly explained the association between exposure to stressors and elevated allostatic load in four cross-sectional and two longitudinal studies.Some evidence suggests that combined modifiable lifestyle behaviors may help explain the relationship between stressors and an elevated allostatic load. Further longitudinal studies with mediation analyses would strengthen these findings and help to confirm the mechanistic role of combined modifiable lifestyle behaviors underlying the relationship between stress exposure and allostatic load.

High Na intake and chronically elevated cortisol levels are independently associated with the development of chronic diseases. In adults, high Na intake is associated with high levels of urinary cortisol. We aimed to determine the association between urinary Na and K and urinary cortisol in a cross-sectional sample of Australian schoolchildren and their mothers. Participants were a sample of Australian children (n 120) and their mothers (n 100) recruited through primary schools. We assessed Na, K, free cortisol and cortisol metabolites in one 24 h urine collection. Associations between 24 h urinary electrolytes and 24 h urinary cortisol were assessed using multilevel mixed-effects linear regression models. In children, urinary Na was positively associated with urinary free cortisol (β=0·31, 95 % CI 0·19, 0·44) and urinary cortisol metabolites (β=0·006, 95 % CI 0·002, 0·010). Positive associations were also observed between urinary K and urinary free cortisol (β=0·65, 95 % CI 0·23, 1·07) and urinary cortisol metabolites (β=0·02, 95 % CI 0·03, 0·031). In mothers, urinary Na was positively associated with urinary free cortisol (β=0·23, 95 % CI 0·01, 0·50) and urinary cortisol metabolites (β=0·008, 95 % CI 0·0007, 0·016). Our findings show that daily Na and K intake were positively associated with cortisol production in children and their mothers. Investigation of the mechanisms involved and the potential impact of Na reduction on cortisol levels in these populations is warranted.

Two key hypotheses emerge in the literature regarding the impact of stress on reproduction in females of any species. First, prolonged stress impairs reproduction in females. Secondly, acute stress impairs reproduction, if it occurs at a critical time during the precisely timed series of endocrine events that induce oestrus and ovulation. We reviewed studies conducted in female pigs to find support or opposition for these hypotheses in female pigs. We also considered the role of cortisol. We found confirmation that prolonged stress or the prolonged elevation of cortisol can impair reproductive processes in female pigs, but also found that there appear to be some female pigs in which reproduction is resistant to such treatments. Reproduction in female pigs appears to be resistant to acute or repeated acute stress or elevation of cortisol, even if these occur during the series of precisely timed endocrine events that induce oestrus and ovulation. Thus, we propose modified versions of the above hypotheses that are specific to female pigs. Furthermore, while cortisol may mediate the effects of prolonged stress on reproduction in female pigs, there is evidence that, in female pigs, ACTH may require the presence of the adrenal glands to impair reproduction rather than having direct effects.

Background Emerging evidence shows sedentary behaviour may be associated with mental health outcomes. Yet, the strength of the evidence linking sedentary behaviour and stress is still unclear. This study aimed to synthesise evidence regarding associations between time spent in sedentary behaviour and stress in adults. Methods A systematic search was conducted (January 1990 – September 2019). Following PRISMA guidelines, an evaluation of methodological quality, and best-evidence synthesis of associations between time in sedentary behaviour (including sitting time, TV viewing, computer use) and stress were presented. Twenty-six studies reporting on data from n = 72,795 people (age 18-98y, 62.7% women) were included. Results Across the studies (n = 2 strong-, n = 10 moderate- and n = 14 weak-quality), there was insufficient evidence that overall time spent in sedentary behaviour and sitting time were associated with stress, particularly when using self-report measures of sedentary behaviour or stress. There was strong evidence of no association between TV viewing, or computer use and stress. Amongst studies using objective measures of sedentary behaviour and/or stress there was also strong evidence of no association. Conclusion Although previous research suggested sedentary behaviour may be linked to mental health outcomes such as depression and anxiety, the evidence for an association between various types of sedentary behaviour and stress is limited in quality, and associations are either inconsistent or null. High-quality longitudinal/interventional research is required to confirm findings and determine the direction of associations between different contexts (i.e. purpose) and domains (i.e. leisure, occupational, transport) of sedentary behaviour and stress.

Working on-call with a night call resulted in a depressed (lower) cortisol awakening response (CAR) peak and post-awakening cortisol area under the curve with respect to ground (AUCG) the f...

Background Acute psychological stress activates the sympatho-adrenal medullary (SAM) system and hypothalamo-pituitary adrenal (HPA) axis. The relevance of this stress reactivity to long-term health and disease outcomes is of great importance. We examined prospective studies in apparently healthy adults to test the hypothesis that the magnitude of the response to acute psychological stress in healthy adults is related to future health and disease outcomes. Methods We searched Medline Complete, PsycINFO, CINAHL Complete and Embase up to 15 Aug 2019. Included studies were peer-reviewed, English-language, prospective studies in apparently healthy adults. The exposure was acute psychological stress reactivity (SAM system or HPA axis) at baseline. The outcome was any health or disease outcome at follow-up after ≥1 year. Results We identified 1719 papers through database searching and 1 additional paper through other sources. Forty-seven papers met our criteria including 32,866 participants (range 30–4100) with 1−23 years of follow-up. Overall, one third (32 %; 83/263) of all reported findings were significant and two thirds (68 %; 180/263) were null. With regard to the significant findings, both exaggerated (i.e. high) and blunted (i.e. low) stress reactivity of both the SAM system and the HPA axis at baseline were related to health and disease outcomes at follow-up. Exaggerated stress reactivity at baseline predicted an increase in risk factors for cardiovascular disease and decreased telomere length at follow-up. In contrast, blunted stress reactivity predicted future increased adiposity and obesity, more depression, anxiety and PTSD symptoms, greater illness frequency, musculoskeletal pain and regulatory T-Cell percentage, poorer cognitive ability, poorer self-reported health and physical disability and lower bone mass. Conclusion Exaggerated and blunted SAM system and HPA axis stress reactivity predicted distinct physical and mental health and disease outcomes over time. Results from prospective studies consistently indicate stress reactivity as a predictor for future health and disease outcomes. Dysregulation of stress reactivity may represent a mechanism by which psychological stress contributes to the development of future health and disease outcomes.

The present study examined the association between high-quality diet (using the Mediterranean diet (MD) as an example) and well-being cross-sectionally and prospectively in Spanish children and adolescents. Participants included 533 children and 987 adolescents at baseline and 527 children and 798 adolescents at 2-year follow-up, included in the UP&DOWN study (follow-up in schoolchildren and adolescents with and without Down’s syndrome). The present study excluded participants with Down’s syndrome. Adherence to an MD was assessed using the KIDMED index. Well-being was measured using the Positive and Negative Affect Schedule and the KIDSCREEN-10 questionnaire. Associations between MD adherence and well-being were assessed using multi-level, mixed-effects linear regression. At baseline, MD adherence was positively related to health-related quality of life in secondary school girls and boys (β=0·41, se 0·10, P, The UP&DOWN study was supported by the DEP 2010-21662-C04-00 grant from the National Plan for Research, Development and Innovation (R + D + i) MICINN. I. E.-C. is supported by a grant from the Alicia Koplowitz Foundation

This research tested the hypothesis that women who had higher levels of physical fitness will have lower hypothalamo–pituitary–adrenal axis (cortisol) and sympatho-adrenal medullary system (blood pressure and heart rate) responses to food intake compared with women who had low levels of physical fitness. Lower fitness (n = 22; maximal oxygen consumption = 27.4 ± 1.0 mL∙kg−1·min−1) and higher fitness (n = 22; maximal oxygen consumption = 41.9 ± 1.6 mL∙kg−1·min−1) women (aged 30–50 years; in the follicular phase of the menstrual cycle) who participated in levels of physical activity that met (lower fitness = 2.7 ± 0.5 h/week) or considerably exceeded (higher fitness = 7.1 ± 1.4 h/week) physical activity guidelines made their own lunch using standardised ingredients at 1200 h. Concentrations of cortisol were measured in blood samples collected every 15 min from 1145–1400 h. Blood pressures and heart rate were also measured every 15 min between 1145 h and 1400 h. The meal consumed by the participants consisted of 20% protein, 61% carbohydrates, and 19% fat. There was a significant overall response to lunch in all of the parameters measured (time effect for all, p < 0.01). The cortisol response to lunch was not significantly different between the groups (time × treatment, p = 0.882). Overall, both groups showed the same pattern of cortisol secretion (treatment p = 0.839). Systolic blood pressure, diastolic blood pressure, mean arterial pressure, or heart rate responses (time × treatment, p = 0.726, 0.898, 0.713, and 0.620, respectively) were also similar between higher and lower fitness women. Results suggest that the physiological response to food intake in women is quite resistant to modification by elevated physical fitness levels.

Women living in socioeconomically disadvantaged neighbourhoods are at heightened risk of experiencing psychological stress. Therefore, identifying potential risk factors for stress is important to support positive mental health. A growing body of research has linked sedentary behaviour with mental ill-health (e.g., depression and anxiety); however, little research has specifically investigated potential linkages between sedentary behaviour and stress. Therefore, the aim of this study was to investigate the association between common types of sedentary behaviour and objectively-measured stress (as measured by hair cortisol levels) amongst women living in socioeconomically disadvantaged neighbourhoods. During 2012–2013, 72 women (aged 18–46 years) living in socioeconomically disadvantaged neighbourhoods self-reported sedentary behaviour (TV viewing, computer use, overall sitting time) and provided hair samples. Hair cortisol levels were measured using enzyme-linked immunosorbent assay. Linear regression models examined cross-sectional associations between sedentary behaviour and hair cortisol levels. There was no association between any type of sedentary behaviour (TV viewing, computer use, or overall sitting time) and hair cortisol levels in either crude or adjusted models. Sedentary behaviour may not be linked to hair cortisol level (stress) in women living in socioeconomically disadvantaged neighbourhoods. Further studies utilising objective measures of both sedentary behaviour and stress are required to confirm these findings.

Background: Acute psychological stress activates the sympatho-adrenal medullary system (SAMS) and hypothalamo-pituitary adrenal axis (HPAA). The relevance of this stress reactivity to long-term health and disease outcomes remains a hotly debated topic. We tested the hypothesis that the magnitude of the response to acute psychological stress in healthy participants is related to future health and disease outcomes. Methods: We searched Medline Complete, PsycINFO, CINAHL Complete and Embase up to Nov 2017. Included studies were peer-reviewed, English-language, prospective studies in apparently healthy adults. The exposure was acute psychological stress reactivity (SAMS or HPAA) at baseline. The outcome was any health or disease outcome at follow-up after ≥ 1 year. Results: We identified 1,499 papers through database searching and 1 additional paper through other sources. Forty-eight papers met our criteria with follow-up duration ranging from 1-18 years. Exaggerated (i.e. high) stress reactivity at baseline predicted higher blood pressure and more incident hypertension, greater carotid artery inter-media thickness and carotid artery calcification, more rapid telomere attrition and, in males, lower bone mass at follow-up. Blunted (i.e. low) stress reactivity at baseline predicted greater BMI, waist circumference, skin-fold thickness and increased likelihood of obesity, higher depression scores, more PTSD symptomology after exposure to trauma, reduced cognition scores, poorer self-reported health and a greater decline in physical disability at follow-up. Conclusion: Exaggerated and blunted stress reactivity predicted different negative health and disease outcomes over time. Future research should examine biological pathways by which both exaggerated and blunted stress reactivity may impact health.

We tested the hypothesis that overweight/obese men aged 50–70 years will have a greater salivary cortisol, salivary alpha amylase and heart rate (HR) responses to psychological stress compared with age matched lean men. Lean (BMI=20–25 kg/m2; n=19) and overweight/obese (BMI=27–35 kg/m2; n=17) men (50–70 years) were subjected to a well-characterised psychological stress (Trier Social Stress Test, TSST) at 1500 h. Concentrations of cortisol and alpha amylase were measured in saliva samples collected every 7–15 min from 1400 to 1700 h. HR was recorded using electrocardiogram. Body weight, BMI, percentage body fat, resting systolic and diastolic blood pressure and mean arterial pressure were significantly higher (PP=0.187, P=0.288, P=0.550, respectively). There were no significant differences between the groups for pretreatment values, peak height, difference between pretreatment values and peak height (reactivity) or area under the curve for salivary cortisol, salivary alpha amylase or HR (P>0.05 for all). The results showed that, for men with a moderate level of overweight/obesity who were otherwise healthy, the response of salivary cortisol, salivary alpha amylase and HR to acute psychological stress was not impaired.

According to the 'cross stressor adaptation hypothesis', regular exercise acts as a buffer against the detrimental effects of stress. Nevertheless, evidence that higher levels of cardiorespiratory fitness moderate hemodynamic responses to acute psychological stress is inconclusive, especially in women. Women aged 30-50 years (in the mid-follicular phase of the menstrual cycle) with higher (n = 17) and lower (n = 17) levels of fitness were subjected to a Trier Social Stress Test (TSST). Continuous, non-invasive measurements were made of beat-to-beat, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), left ventricular ejection time (LVET), maximum slope, pulse interval (PI) and total peripheral resistance (TPR). Maximal oxygen consumption was significantly (p

The effect of weight loss on psychological stress is unknown. The study aimed to investigate the effect of diet-induced weight loss in overweight and obese adults on psychological measures of stress through a meta-analysis of randomized controlled trials (RCTs). Databases including Medline Complete, Embase and PsycINFO were searched up to February 2018 for diet-induced weight loss RCTs, which included self-reported assessment of psychological stress. The mean difference between the intervention and control group of changes in stress (intervention—baseline) was used. Ten RCTs were included with 615 participants (502 women, age range 20–80 years). Overall, there was no change in stress (mean difference −0.06, 95% CI: −0.17, 0.06, p = 0.33) and no change in the five studies with a significant reduction in weight in the intervention group compared to a control group that lost no weight (mean difference in weight −3.9 Kg, 95% CI: −5.51, −2.29, p < 0.0001; mean difference in stress 0.04, 95% CI: −0.17, 0.25, p = 0.71). For all analyses, there was low heterogeneity. The benefits of weight loss for those who are overweight and obese do not appear to either increase or reduce psychological stress at the end of the weight loss period.

Two experiments were conducted to test the hypothesis that cortisol interferes with the positive feedback action of estradiol that induces the luteinizing hormone (LH) surge. Ovariectomized sheep were treated sequentially with progesterone and estradiol to create artificial estrous cycles. Cortisol or vehicle (saline) was infused from 2 h before the estradiol stimulus through the time of the anticipated LH surge in the artificial follicular phase of two successive cycles. The plasma cortisol increment produced by infusion was ∼1.5 times greater than maximal concentrations seen during infusion of endotoxin, which is a model of immune/inflammatory stress. In experiment 1, half of the ewes received vehicle in the first cycle and cortisol in the second; the others were treated in reverse order. All ewes responded with an LH surge. Cortisol delayed the LH surge and reduced its amplitude, but both effects were observed only in the second cycle. Experiment 2 was modified to provide better control for a cycle effect. Four treatment sequences were tested (cycle 1-cycle 2): vehicle-vehicle, cortisol-cortisol, vehicle-cortisol, cortisol-vehicle. Again, cortisol delayed but did not block the LH surge, and this delay occurred in both cycles. Thus, an elevation in plasma cortisol can interfere with the positive feedback action of estradiol by delaying and attenuating the LH surge.

We have shown that cortisol infusion reduced the luteinizing hormone (LH) response to fixed hourly GnRH injections in ovariectomized ewes treated with estradiol during the non-breeding season (pituitary-clamp model). In contrast, cortisol did not affect the response to 2 hourly invariant GnRH injections in hypothalamo-pituitary disconnected ovariectomized ewes during the breeding season. To understand the differing results in these animal models and to determine if cortisol can act directly at the pituitary to suppress responsiveness to GnRH, we investigated the importance of the frequency of GnRH stimulus, the presence of estradiol and stage of the circannual breeding season. In experiment 1, during the non-breeding season, ovariectomized ewes were treated with estradiol, and pulsatile LH secretion was restored with i.v. GnRH injections either hourly or 2 hourly in the presence or absence of exogenous cortisol. Experiments 2 and 3 were conducted in hypothalamo-pituitary disconnected ovariectomized ewes in which GnRH was injected i.v. every 2 h. Experiment 2 was conducted during the non-breeding season and saline or cortisol was infused for 30 h in a cross-over design. Experiment 3 was conducted during the non-breeding and breeding seasons and saline or cortisol was infused for 30 h in the absence and presence of estradiol using a cross-over design. Samples were taken from all animals to measure plasma LH. LH pulse amplitude was reduced by cortisol in the pituitary clamp model with no difference between the hourly and 2-hourly GnRH pulse mode. In the absence of estradiol, there was no effect of cortisol on LH pulse amplitude in GnRH-replaced ovariectomized hypothalamo-pituitary disconnected ewes in either season. The LH pulse amplitude was reduced in both seasons in experiment 3 when cortisol was infused during estradiol treatment. We conclude that the ability of cortisol to reduce LH secretion does not depend upon the frequency of GnRH stimulus and that estradiol enables cortisol to act directly on the pituitary of ovariectomized hypothalamo-pituitary disconnected ewes to suppress the responsiveness to GnRH; this effect occurs in the breeding and non-breeding seasons.

Disadvantaged communities provide adverse psychosocial exposures that have been linked to high levels of stress, and this may provide one explanatory pathway linking socioeconomic disadvantage to obesity. This study used hair cortisol analysis to quantify associations between stress and body mass index (BMI), and between hair cortisol and perceived psychological stress levels, in women and children living in socioeconomically disadvantaged neighborhoods. Participants were a volunteer sample of 70 women from the Resilience for Eating and Activity Despite Inequality study, including 30 maternal-child pairs. Women self-reported body weight, height and perceived psychological stress using the Perceived Stress Scale (PSS), and provided hair samples for themselves and their child. Children's body weight and height were measured. Following extraction, hair cortisol levels were measured using enzyme-linked immunosorbent assay. Multiple linear regression models examined associations between stress and BMI, and between hair cortisol and perceived stress levels in women and children. Women's hair cortisol levels were not associated with their BMI or PSS scores. Women's PSS scores were positively associated with their BMI (p = 0.015). Within maternal-child pairs, mothers and children's hair cortisol levels were strongly positively associated (p = 0.006). Maternal hair cortisol levels and PSS scores were unrelated to their child's zBMI. Children's hair cortisol levels were not associated with their zBMI or with their mother's PSS score. Findings suggest that cortisol-based and perceived psychological measures of stress may be distinct among women and children living in disadvantaged neighborhoods. Perceived psychological measures may be more important predictors of weight-related risk.

On-call work is becoming an increasingly common work pattern, yet the human impacts of this type of work are not well established. Given the likelihood of calls to occur outside regular work hours, it is important to consider the potential impact of working on-call on stress physiology and sleep. The aims of this review were to collate and evaluate evidence on the effects of working on-call from home on stress physiology and sleep. A systematic search of Ebsco Host, Embase, Web of Science, Scopus and ScienceDirect was conducted. Search terms included: on-call, on call, standby, sleep, cortisol, heart rate, adrenaline, noradrenaline, nor-adrenaline, epinephrine, norepinephrine, nor-epinephrine, salivary alpha amylase and alpha amylase. Eight studies met the inclusion criteria, with only one study investigating the effect of working on-call from home on stress physiology. All eight studies investigated the effect of working on-call from home on sleep. Working on-call from home appears to adversely affect sleep quantity, and in most cases, sleep quality. However, studies did not differentiate between night's on-call from home with and without calls. Data examining the effect of working on-call from home on stress physiology were not sufficient to draw meaningful conclusions.

This study investigated sex differences in the stress-induced activation of neurons containing corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP) and enkephalin in the paraventricular nucleus (PVN) of gonadectomized male and female sheep. Groups (n=3) of both sexes were either subjected to 90 min isolation and restraint stress (stress group) or were not stressed. Blood samples were taken every 10 min for 90 min prior to and after stress to monitor cortisol levels in plasma. Brains were harvested after 90 min of stress. Stress caused elevation of plasma cortisol levels to a similar extent in both sexes. Double-labeling immunohistochemistry for Fos and either CRH, AVP or enkephalin was undertaken to quantify the numbers of neurons staining for CRH, AVP and enkephalin that also immunostained for Fos. Stress increased Fos immunostaining in all cell types. There was a greater proportion of CRH than AVP neurons activated in stressed animals. There were no sex differences in the activation of CRH and AVP neurons although females had a greater proportion of enkephalin cells staining for Fos than males in both control and stressed animals. There were no differences between control and stressed animals in the proportion of cells co-staining for CRH and AVP. We conclude that isolation and restraint stress activates neurons producing CRH, AVP and enkephalin in sheep and that CRH may play a greater role than AVP in regulating adrenocorticotrophic hormone secretion in response to this stressor in sheep. Finally, isolation and restraint stress does not influence co-localization of CRH and AVP in sheep.

It is not clear if higher levels of cardiorespiratory fitness are associated with lower hypothalamo-pituitary adrenal (HPA) axis and sympatho-adrenal medullary (SAM) system reactivity to psychological stress in women. The association between cardio-metabolic risk markers and acute physiological responses to psychological stress in women who differ in their cardiorespiratory fitness status has also not been investigated. Women with high (n = 22) and low (n = 22) levels of fitness aged 30-50 years (in the mid-follicular phase of the menstrual cycle) were subjected to a Trier Social Stress Test (TSST) at 1500 h. Plasma concentrations of cortisol, adrenaline (Adr), noradrenaline (NA), and dopamine (DA) were measured in samples collected every 7-15 min from 1400 to 1700 h. Heart rate and blood pressure were measured at the same time points. Low-fit women had elevated serum triglyceride, cholesterol/HDL ratio, fasting glucose, and HOMA-IR levels compared with high-fit women. While cortisol, Adr, NA, HR, and blood pressure all demonstrated a significant response to the TSST, the responses of these variables did not differ significantly between high- and low-fit women in response to the TSST. Dopamine reactivity was significantly higher in the low-fit women compared with high-fit women. There was also a significant negative correlation between VO2 max and DA reactivity. These findings suggest that, for low-fit women aged 30-50 years, the response of HPA axis and SAM system to a potent acute psychological stressor is not compromised compared to that in high-fit women.

We investigated the effect of the presence and absence of lambs and suckling by lambs to attenuate activation of the hypothalamo-pituitary-adrenal (HPA) axis to isolation and restraint stress in lactating sheep. In experiment 1, blood samples were collected every 10 min from nonlactating (n = 5) and lactating (n = 5) ewes for 4 h before and during stress. In experiment 2, ewes (n = 6) were allocated to 1) nonlactating, 2) lactating with lambs absent, 3) lactating with lambs present but unable to suckle, and 4) lactating with lambs present and able to suckle. Blood samples were collected over 8 h with no stress (control day) and for 4 h before and 4 h during stress (stress day). In experiment 1, the mean (±sem) cortisol concentrations increased significantly (P < 0.05) in nonlactating ewes during stress but did not change in lactating ewes. In experiment 2, cortisol did not vary on the control day or pretreatment of the stress day but increased (P < 0.05) during stress in all groups except lactating ewes with lambs present and able to suckle. The greatest cortisol response occurred in nonlactating ewes followed by lactating ewes with lambs absent and lactating ewes with lambs present but unable to suckle. During stress, the ACTH concentrations increased (P < 0.05) in nonlactating ewes and lactating ewes with lambs absent but not in lactating ewes with lambs present. We conclude that the activity of the HPA axis during isolation and restraint is reduced in lactating ewes and that the presence of lambs increases this level of attenuation.

It is important to understand factors that may influence responses to stress, as these factors may also influence vulnerability to pathologies that can develop when stress responses are excessive or prolonged. It is clear that, in adults, the sex of an individual can influence the cortisol response to stress in a stressor specific manner. Nevertheless, the stage of development at which these sex differences emerge is unknown. We tested the hypothesis that there are sex differences in the cortisol response to tail docking and ACTH in lambs of 1 and 8 weeks of age. We also established cortisol responses in males when tail docking was imposed alone and in combination with castration at these ages. In experiment 1, 1 and 8 week old male and female lambs were subjected to sham handling, tail docking or, in males, a combination of tail docking and castration. In experiment 2, we administered ACTH (1.0 IU/kg) to male and female lambs at 1 and 8 weeks of age. There were significant cortisol responses to all treatments at both ages. Sex differences in the cortisol responses to tail docking and ACTH developed between 1 and 8 weeks of age, with females having greater responses than males. The data suggest that the mechanism for the sex difference in response to tail docking may involve the adrenal glands. At both ages, in males, the cortisol response to the combined treatment of tail docking and castration was significantly greater than that for tail docking alone.

The paraventricular nucleus (PVN) is integral to regulation of the hypothalamo-pituitary-adrenal (HPA) axis and contains cells producing corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP) and enkephalin. We used immunohistochemistry to map these peptides and to resolve the extent of co-localization within PVN cells in intact and gonadectomized male and female sheep. Immunoreactive (ir) CRH, AVP and enkephalin cells were mapped in two rams and two ewes at 180 mum intervals throughout the rostro-caudal extent of the PVN. Similar distributions of AVP-ir cells occurred in both sexes whereas CRH-ir and enkephalin-ir cells extended more rostrally in rams. In groups (n=4) of intact and gonadectomized sheep of both sexes, co-localization and distribution of neuropeptides was influenced by sex and gonadectomy. Males had more AVP and CRH cells than females. Intact animals had more AVP cells than gonadectomized animals. There were no differences between groups in the number or percentage of cells that stained for both CRH and AVP or in the number of cells that stained for both CRH and enkephalin. Differences were observed in the percentage of enkephalin cells that contained CRH with males having a greater percentage of co-localized cells than did females. Differences were also observed in the number and percentage of cells that stained for both enkephalin and AVP; the number of cells that stained for both neuropeptides was greater in males than in females and greater in intact animals than in gonadectomized animals. Differences were observed in the percentage of AVP cells that contained enkephalin, and in the percentage of enkephalin cells that contained AVP with males having a greater percentage of co-localized cells than did females. We conclude that sex and gonadal status affect peptide distribution in the PVN of the sheep which may provide an anatomical basis for sex differences in HPA axis responses to stress.

Background: The detrimental effects on health of high sodium intake and chronically elevated cortisol levels are well known. There is also evidence in adults that high sodium intake is associated with high levels of urinary cortisol excretion (1). We aimed to assess in children if urinary excretion of sodium was related to urinary excretion of cortisol and cortisol metabolites. Methods: A cross-sectional sample of school children and their mothers who performed 24 hour urine collection in which sodium, potassium, free cortisol (enzyme-linked immunosorbent assay) and cortisol metabolites (gas chromatography-mass spectrometry) were measured. Results: School children (n=120; mean(±SD) age = 9.2±2.0 years) and their mothers (n=102; 41.7±5.1 years) participated. Sodium and potassium excretion was 104.2±61.8 (mean±SD) and 46.8±18.5 mmol/24h, respectively, in children and 120.0±41.3 and 67.6±18.5 mmol/24h, respectively, in mothers. Multiple regression analysis adjusting for age, sex and BMI z score indicated that children's urinary sodium excretion was positively associated (P

Increased adiposity is often associated with over activation of the hypothalamo-pituitary adrenal axis (HPA axis) and the sympatho-adrenal medullary system (SAM system) and excessive activation of these pathways in response to physiological challenges may be linked with the development of diseases. We tested the hypothesis that overweight/obese men aged 50–70 years will have greater HPA axis and SAM system responses to food intake compared with age matched lean men. Lean (Body Mass Index; BMI = 20-25 kg/m2; n = 19) and overweight/obese (BMI = 27-35 kg/m2; n = 17) men (50–70 years) made their own lunch using standardised ingredients at 1200 h. Concentrations of cortisol and alpha amylase were measured in saliva samples collected every 15 min from 1145 h-1400 h with the exception of during lunch (1215 h) where no sample was collected. Blood pressures and heart rate were measured at 1145 h and every 15 minutes between 1245 h and 1400 h. Overweight/obese men had significantly higher body weight, BMI, percentage body fat and waist and hip circumferences compared to lean men (p

We tested the hypothesis that sustained and repeated acute elevation of cortisol would impair the LH surge, estrus, and ovulation in gilts. Cortisol was injected intramuscularly, to achieve a sustained elevation of plasma concentrations of cortisol, or intravenously, to achieve an acute elevation of plasma concentrations of cortisol. Control gilts received i.m. injections of oil and i.v. injections of saline. These treatments were administered to gilts (n = 6 per treatment) at 12-h intervals from Days 7 to 11 of the estrous cycle until after estrus ceased or until Day 27 or 28 of the estrous cycle, whichever came first. The repeated acute elevation of cortisol had no effect on the LH surge, estrus, or ovulation. In contrast, when the elevation of cortisol was sustained, the LH surge, estrus, and ovulation were inhibited. We conclude that cortisol is capable of direct actions to impair reproductive processes in female pigs but that plasma concentrations of cortisol need to be elevated for a substantial period for this to occur.

It has been proposed that short-term activation of the hypothalamo-pituitary adrenal axis, with a consequent increase in the secretion of cortisol, amy disrupt the endocrine events prior to ovulation and thereby impair reproduction in females. We investigated this concept in gilts in which oestrus was detected by introduction to boars, where intense physical contact is possible, or by applying pressure to the back of gilts (back-pressure test) during fence-line exposure to boars, where intense physical contact is prohibited. We expected that there would be a greater release of cortisol and that reproduction would be inhibited in gilts introduced to boars compared to gilts in which the back-pressure test was used. As expected, introduction of gilts to boars resulted in a significant transient increase in plasma concentrations of cortisol while there was no significant effect of using the back-pressure test on plasma cortisol. Nevertheless, introduction of gilts to boars did not impair reproduction and there was no effect of method of detecting oestrus on duration of oestrus, sexual receptivity, fertility or fecundity. The length of the oestrous cycle was decreased and ovulation rate increased in gilts that were introduced to boars compared to gilts that underwent the back-pressure test, indicating that introduction of gilts to boars may have stimulated these aspects of reproduction. These stimulatory effects may have been due to an increased exposure of gilts to sexual behaviour and stimuli from boars when introduced to boars and/or to stimulatory effects of the hypothalamo-pituitary adrenal axis on some aspects of reproduction.

This study tested the hypothesis that the efficiency of detecting oestrus in gilts, using the back pressure test (BPT), will be reduced when gilts are housed adjacent to a boar of high sexual motivation compared to when gilts are housed adjacent to a boar of low sexual motivation. The experiment was a 2 × 2 Latin square design with three replicates. Boars of high and low sexual motivation were selected on the basis of the total number of copulations and the mean reaction time to first mount during three mating tests. Twelve boars were observed in mating tests and the three highest and lowest ranking boars were assigned to three pairs, each pair containing a boar of high and a boar of low sexual motivation. One pair was used in each replicate. In each replicate, two groups of six ovariectomised gilts were housed for 14 days, commencing 7 days prior to hormonally induced oestrus, adjacent to a boar of either high or low sexual motivation. All gilts were checked twice daily for oestrus using the BPT. In the first replicate, the level proceptive behaviour of the gilts was quantified immediately after checking for oestrus in a 3-min test in which the amount of time that the gilts spent within 0.5 m of a pen containing a sexually mature boar was recorded. There were no effects of housing gilts adjacent to boars of high or low sexual motivation on the percentage of gilts detected in oestrus, the percentage of gilts detected in oestrus for more than 1 day, the duration of oestrus or the level of proceptive behaviour of gilts. These data suggest that the level of sexual motivation of boars does not influence the efficiency of detecting hormonally induced oestrus, using the BPT, in ovariectomised gilts housed adjacent to boars.

Anxiety is the most prevalent type of mental disorder and a significant health concern. Cross-sectional studies have detected a positive association between obesity and anxiety. What is less clear is whether weight loss can reduce anxiety. We sought to answer three questions: 1. Can weight loss improve symptoms of anxiety in the overweight and obese population? 2. Does the macronutrient content of energy-restricted diets that induce weight loss affect anxiety? 3. Is the change in anxiety related to the amount of weight lost? We investigated the findings from seven interventional studies, which induced weight loss by dietary intervention, in overweight and obese individuals, using established anxiety assessment tools. Mean weight loss ranged from 0.7 to 18.6 kg (SD 4.5) and in three of the studies, anxiety fell by 9.2% to 11.4% and did not change in four studies. When macronutrient content was considered, only one of four interventional studies and one pilot study reported a beneficial effect of a moderate-fat diet on anxiety. There appears to be no strong evidence to indicate that diet-induced weight loss has a beneficial effect on anxiety, however, none of the diet-induced weight loss studies assessed had a detrimental effect on anxiety.

PURPOSE: Prevention of the female athlete triad is essential to protect female athletes' health. The aim of this study was to investigate the knowledge, attitudes and behaviours of regularly exercising adult females towards eating patterns, menstrual cycles and bone health. METHODS: A total of 191 female exercisers, aged 18-40 y, engaging in ≥2 hr/wk of strenuous activity, completed a survey. After excluding 11 surveys (due to incomplete answers), the 180 participants were categorised into lean-build sports (n=82; running/athletics, triathlon, swimming, cycling, dancing, rowing), non lean-build sports (n=94; basketball, netball, soccer, hockey, volleyball, tennis, trampoline, squash, Australian football) or gym/fitness activities (n=4). RESULTS: Mean (±SD) training volume was 9.0±5.5 hr/wk, with participants competing from local up to international level. Only 10% of respondents could name the 3 components of the female athlete triad. Regardless of the reported history of stress fracture, 45% of the respondents did not think that amenorrhoea (absence of menses for ≥ three months) could affect bone health, and 22% of those involved in lean-build sports would do nothing if experiencing amenorrhoea (vs. 3.2% in non lean-build sports, p=0.005). Lean-build sports, history of amenorrhoea and history of stress fracture were all significantly associated with not taking action in the presence of amenorrhoea (all p0.005). CONCLUSIONS: Few active Australian women are aware of the detrimental effects of menstrual dysfunction on bone health. Education programs are needed to prevent the female athlete triad and ensure appropriate actions are taken by athletes when experiencing amenorrhoea.

We have undertaken a critical analysis of the role of sex and sex steroids in influencing stress responsiveness. We have reviewed the current literature regarding the manner in which the stress-induced activation of the sympatho-adrenal medullary system and the hypothalamopituitary adrenal axis are influenced by the sex of individuals and the sex steroids that are present and how these vary with different types of stress and in different physiological conditions. The chapter focuses predominantly on sheep and human research, although research in rodents is introduced where pertinent. Where appropriate, we draw on our extensive research published over the last two decades using sheep as an experimental model and consider how these data inform and compliment the current findings in human studies. It is clear from the literature reviewed here that there is a major need for research to understand stress responsiveness. The gaps in knowledge requiring this research are highlighted.

Maintaining low body weight for the sake of performance and aesthetic purposes is a common feature among young girls and women who exercise on a regular basis, including elite, college and high-school athletes, members of fitness centres, and recreational exercisers. High energy expenditure without adequate compensation in energy intake leads to an energy deficiency, which may ultimately affect reproductive function and bone health. The combination of low energy availability, menstrual disturbances and low bone mineral density is referred to as the 'female athlete triad'. Not all athletes seek medical assistance in response to the absence of menstruation for 3 or more months as some believe that long-term amenorrhoea is not harmful. Indeed, many women may not seek medical attention until they sustain a stress fracture. This review investigates current issues, controversies and strategies in the clinical management of bone health concerns related to the female athlete triad. Current recommendations focus on either increasing energy intake or decreasing energy expenditure, as this approach remains the most efficient strategy to prevent further bone health complications. However, convincing the athlete to increase energy availability can be extremely challenging. Oral contraceptive therapy seems to be a common strategy chosen by many physicians to address bone health issues in young women with amenorrhoea, although there is little evidence that this strategy improves bone mineral density in this population. Assessment of bone health itself is difficult due to the limitations of dual-energy X-ray absorptiometry (DXA) to estimate bone strength. Understanding how bone strength is affected by low energy availability, weight gain and resumption of menses requires further investigations using 3-dimensional bone imaging techniques in order to improve the clinical management of the female athlete triad.

Margarita D. Tsiros 1,∗, Alison M. Coates1, Peter R.C. Howe2, Jeff Walkley3, Andrew P. Hills 4, Rachel E. Wood5, Jonathann D. Buckley1 1 Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia 2 School of Biomedical Sciences & Pharmacy, University of Newcastle, Newcastle, NSW, Australia 3 School of Health Sciences, RMIT University, Bundoora, Vic, Australia 4 Mater Research Institute, Mater Mothers’ Hospital, South Brisbane, QLD, Australia 5 School of Exercise and Nutrition Sciences, Queensland University of Technology, Kelvin Grove, QLD, Australia

Two experiments were conducted to test the hypothesis that cortisol interferes with the positive feedback action of estradiol that induces the luteinizing hormone (LH) surge. Ovariectomized sheep were treated sequentially with progesterone and estradiol to create artificial estrous cycles. Cortisol or vehicle (saline) was infused from 2 h before the estradiol stimulus through the time of the anticipated LH surge in the artificial follicular phase of two successive cycles. The plasma cortisol increment produced by infusion was approximately 1.5 times greater than maximal concentrations seen during infusion of endotoxin, which is a model of immune/inflammatory stress. In experiment 1, half of the ewes received vehicle in the first cycle and cortisol in the second; the others were treated in reverse order. All ewes responded with an LH surge. Cortisol delayed the LH surge and reduced its amplitude, but both effects were observed only in the second cycle. Experiment 2 was modified to provide better control for a cycle effect. Four treatment sequences were tested (cycle 1-cycle 2): vehicle-vehicle, cortisol-cortisol, vehicle-cortisol, cortisol-vehicle. Again, cortisol delayed but did not block the LH surge, and this delay occurred in both cycles. Thus, an elevation in plasma cortisol can interfere with the positive feedback action of estradiol by delaying and attenuating the LH surge.

Stress disrupts the preovulatory luteinizing hormone (LH) surge in females, but the mechanisms are unknown. We tested the hypothesis that cortisol compromises the ability of estrogen to induce a preovulatory-like LH surge in ovariectomized ewes in both the breeding and nonbreeding season. Luteinizing hormone surges were induced in ovariectomized ewes by treatment with progesterone followed by a surge-inducing estradiol-17beta (E2) stimulus using a crossover design. The experiment was replicated in the breeding and nonbreeding seasons. Cortisol reduced the incidence of LH surges irrespective of season. Cortisol increased the latency from E2 stimulus to the onset of the surge in the breeding season only and suppressed the LH surge amplitude during both seasons (P

Various stressors suppress pulsatile secretion of luteinizing hormone (LH) in ewes and cortisol has been shown to be a mediator of this effect under various conditions. In contrast, little is known about the impact of stress and cortisol on sexual behavior in the ewe. Therefore, we tested the hypothesis that both psychosocial stress and stress-like levels of cortisol will reduce the level of attractivity, proceptivity and receptivity in addition to suppressing LH secretion in the ewe. In Experiment 1, a layered stress paradigm of psychosocial stress was used, consisting of isolation for 4 h with the addition of restraint, blindfold and noise of a barking dog (predator stress) at hourly intervals. This stress paradigm reduced LH pulse amplitude in ovariectomized ewes. In Experiment 2, ovariectomized ewes were artificially induced into estrus with progesterone and estradiol benzoate treatment and the layered stress paradigm was applied. LH was measured and sexual behavior was assessed using T-mazes and mating tests. Stress reduced pulsatile LH secretion, and also reduced attractivity and proceptivity of ewes but had no effect on receptivity. In Experiment 3, ewes artificially induced into estrus were infused with cortisol for 30 h. Cortisol elevated circulating plasma concentrations of cortisol, delayed the onset of estrus and resulted in increased circling behavior of ewes (i.e. moderate avoidance) during estrus and increased investigation and courtship from rams. There was no effect of cortisol on attractivity, proceptivity or receptivity during estrus. We conclude that psychosocial stress inhibits LH secretion, the ability of ewes to attract rams (attractivity) and the motivation of ewes to seek rams and initiate mating (proceptivity), but cortisol is unlikely to be the principal mediator of these effects.

We tested the hypothesis that there are sex differences in the inhibitory effect of cortisol on pulsatile LH secretion and pituitary responsiveness to GnRH in gonadectomized sheep. In experiment 1, pulsatile LH secretion was examined in gonadectomized ewes and rams infused with either saline, a low (250 microg/kg.h) or a high (500 microg/kg.h) dose of cortisol for 30 h. In experiment 2, direct pituitary actions of cortisol were assessed by monitoring LH pulse amplitude in response to exogenous GnRH in hypothalamo-pituitary disconnected ewes and rams infused with the low dose of cortisol. In experiment 1, the mean (+/-sem) plasma LH concentration was (P