Effects of work-related sleep restriction on acute physiological and psychological stress responses and their interactions: A review among emergency service personnel

Emergency work can expose personnel to sleep restriction. Inadequate amounts of sleep can negatively affect physiological and psychological stress responses. This review critiqued the emergency service literature (e.g., firefighting, police/law enforcement, defense forces, ambulance/paramedic personnel) that has investigated the effect of sleep restriction on hormonal, inflammatory and psychological responses. Furthermore, it investigated if a psycho-physiological approach can help contextualize the significance of such responses to assist emergency service agencies monitor the health of their personnel. The available literature suggests that sleep restriction across multiple work days can disrupt cytokine and cortisol levels, deteriorate mood and elicit simultaneous physiological and psychological responses. However, research concerning the interaction between such responses is limited and inconclusive. Therefore, it is unknown if a psycho-physiological relationship exists and as a result, it is currently not feasible for agencies to monitor sleep restriction related stress based on psycho- physiological interactions. Sleep restriction does however, appear to be a major stressor contributing to physiological and psychological responses and thus, warrants further investigation.

Hypothalamo-pituitary adrenal axis and sympatho-adrenal medullary system responses to psychological stress were not attenuated in women with elevated physical fitness levels

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.

The effects of bed-rest and countermeasure exercise on the endocrine system in male adults: evidence for immobilization-induced reduction in sex hormone-binding globulin levels

BACKGROUND AND AIM: There is limited data on the effects of inactivity (prolonged bed-rest) on parameters of endocrine and metabolic function; we therefore aimed to examine changes in these systems during and after prolonged (56- day) bed-rest in male adults. SUBJECTS AND METHODS: Twenty healthy male subjects underwent 8 weeks of strict bed-rest and 12 months of follow-up as part of the Berlin Bed Rest Study. Subjects were randomized to an inactive group or a group that performed resistive vibration exercise (RVE) during bed-rest. All outcome parameters were measured before, during and after bed-rest. These included body composition (by whole body dual X-ray absorptiometry), SHBG, testosterone (T), estradiol (E2), PRL, cortisol (C), TSH and free T3 (FT3). RESULTS: Serum SHBG levels decreased in inactive subjects but remained unchanged in the RVE group (p<0.001). Serum T concentrations increased during the first 3 weeks of bed-rest in both groups (p<0.0001), while E2 levels sharply rose with re-mobilization (p<0.0001). Serum PRL decreased in the control group but increased in the RVE group (p=0.021). C levels did not change over time (p≥0.10). TSH increased whilst FT3 decreased during bed-rest (p all ≤0.0013). CONCLUSIONS: Prolonged bed-rest has significant effects on parameters of endocrine and metabolic function, some of which are related to, or counteracted by physical activity.

Dual-axis hormonal covariation in adolescence and the moderating influence of prior trauma and aversive maternal parenting

Adversity early in life can disrupt the functioning of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes and increase risk for negative health outcomes. The interplay between these axes and the environment is complex, and understanding needs to be advanced by the investigation of the multiple hormonal relationships underlying these processes. The current study examined basal hormonal associations between morning levels of cortisol, testosterone, and dehydroepiandrosterone in a cohort of adolescents (mean age 15.56 years). The moderating influence of childhood adversity was also examined, as indexed by self-reported trauma (at mean age 14.91), and observed maternal aggressive parenting (at mean age 12.41). Between-person regressions revealed significant associations between hormones that were moderated by both measures of adversity. In females, all hormones positively covaried, but also interacted with adversity, such that positive covariation was typically only present when levels of trauma and/or aggressive parenting were low. In males, hormonal associations and interactions were less evident; however, interactions were detected for cortisol-testosterone - positively covarying at high levels of aggressive parenting but negatively covarying at low levels - and DHEA-cortisol - similarly positively covarying at high levels of parental aggression. These results demonstrate associations between adrenal and gonadal hormones and the moderating role of adversity, which is likely driven by feedback mechanisms, or cross-talk, between the axes. These findings suggest that hormonal changes may be the pathway through which early life adversity alters physiology and increases health risks, but does so differentially in the sexes; however further study is necessary to establish causation.

Maternal prenatal mental health and placental 11β-HSD2 gene expression: initial findings from the mercy pregnancy and emotional wellbeing study

High intrauterine cortisol exposure can inhibit fetal growth and have programming effects for the child's subsequent stress reactivity. Placental 11beta-hydroxysteroid dehydrogenase (11β-HSD2) limits the amount of maternal cortisol transferred to the fetus. However, the relationship between maternal psychopathology and 11β-HSD2 remains poorly defined. This study examined the effect of maternal depressive disorder, antidepressant use and symptoms of depression and anxiety in pregnancy on placental 11β-HSD2 gene (HSD11B2) expression. Drawing on data from the Mercy Pregnancy and Emotional Wellbeing Study, placental HSD11B2 expression was compared among 33 pregnant women, who were selected based on membership of three groups; depressed (untreated), taking antidepressants and controls. Furthermore, associations between placental HSD11B2 and scores on the State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) during 12-18 and 28-34 weeks gestation were examined. Findings revealed negative correlations between HSD11B2 and both the EPDS and STAI (r = -0.11 to -0.28), with associations being particularly prominent during late gestation. Depressed and antidepressant exposed groups also displayed markedly lower placental HSD11B2 expression levels than controls. These findings suggest that maternal depression and anxiety may impact on fetal programming by down-regulating HSD11B2, and antidepressant treatment alone is unlikely to protect against this effect.

Repeated acute activation of the hypothalamo-pituitary adrenal axis prior to and during estrus did not affect reproductive performance in gilts

We investigated the effects of repeated acute activation of the hypothalamo-pituitary adrenal axis, prior to and during estrus, on reproduction in gilts. Individual gilts (n = 24 per treatment) either served as controls or were subjected to daily acute stress ("negative handling," brief electric shock with a battery-operated prodder during confinement with the experimenter) commencing, on average, 8 days prior to estrus. Gilts subjected to negative handling had a significant elevation in plasma concentrations of cortisol that lasted at least 3-4 h, and these gilts were slower than control gilts to approach and interact with the experimenter in a standard test. Nevertheless, reproductive performance--as measured by sexual receptivity and proceptivity, ovulation, the percentage of gilts that became pregnant, the number of embryos 20-21 days after insemination, and the weight of embryos--was not affected by repeated acute activation of the hypothalamo-pituitary adrenal axis. Our results suggest that repeated acute activation of the hypothalamo-pituitary adrenal axis prior to and during estrus does not affect the factors that control estrus and ovulation in gilts.

Effects of stress on reproduction in non-rodent mammals : the role of glucocorticoids and sex differences

The means by which stress influences reproduction is not clearly understood, but may involve a number of endocrine, paracrine and neural systems. Stress impacts on the reproductive axis at the hypothalamus (to affect GnRH secretion) and the pituitary gland (to affect gonadotrophin secretion), with direct effects on the gonads being of less importance. Different stressors have different effects and there are differences in response to short- and long-term stress. Many short-term stresses fail to affect reproduction and there are reports of stimulatory effects of some 'stressors'. There are species differences in the way that specific stressors affect reproduction. Sex differences in the effects of a particular stressor have been delineated and these may relate to effects of stress at different levels of the hypothalamo-pituitary axis. The significance of stress-induced secretion of cortisol varies with species. In some instances, there appears to be little impact of short-term increases in cortisol concentrations and protracted increases in plasma concentration seem to be required before any deleterious effect on reproduction is apparent. Issues of sex, sex steroid status, type of stressor and duration of stress need to be considered to improve understanding of this issue.

Susceptibility of reproduction in female pigs to impairment by stress and the role of the hypothalamo-pituitary-adrenal axis

Although it is generally considered that stress can impair reproduction, we suggest that the impact of acute or repeated acute stress or acute or repeated acute elevations of cortisol are of little consequence in female pigs, even if these occur during the series of endocrine events that induce oestrus and ovulation. It is important to understand the impact of acute stress on reproduction because, in the intensive production of livestock, animals are often subjected to short-term challenges. There seems little doubt that reproduction in a proportion of female pigs is susceptible to impairment by severe and prolonged stress or the sustained elevation of cortisol but only when this continues for a substantial period. In female pigs, where reproduction is susceptible to impairment by severe prolonged stress, it is possible that the mediators of this suppression are cortisol, corticotrophin-releasing factor and vasopressin but, in pigs, there is evidence to suggest that adrenocorticotrophic hormone is not involved. Other substances secreted during stress may be involved but these are not considered in this review. It is possible that the mediators of stress act at any level of the hypothalamo-pituitary-ovarian axis. Although a variety of experimental manipulations have provided potential mediators and mechanisms for the stress-induced suppression of reproduction, these experimental manipulations rarely represented physiological circumstances so it is not clear if such mechanisms would be important in a physiological context. The precise mediators and mechanisms by which hormones released during stress may inhibit reproductive processes during severe prolonged stress are yet to be determined.

Noradrenaline, but not neuropeptide Y, is elevated in cerebrospinal fluid from the third cerebral ventricle following audiovisual stress in gonadectomised rams and ewes

There are sex differences in the activation of the hypothalamo-pituitary-adrenal axis in response to stress, but the source of these differences is unknown. The hypothalamo-pituitary-adrenal axis is regulated by corticotropin-releasing hormone and arginine-vasopressin neurones located in the paraventricular nucleus and these, in turn, are regulated by neural systems that include afferent noradrenergic and neuropeptide Y (NPY)-producing neural pathways. We tested the hypothesis that concentrations of noradrenaline and NPY will be elevated in cerebrospinal fluid (CSF) sampled from the third cerebral ventricle in response to stress, and these responses will differ in males and females. We collected concurrent samples of CSF (1 ml) from the third ventricle and blood (5 ml) from the jugular vein from gonadectomised rams (n = 7) and ewes (n = 5) at 10-min intervals for 3 h. This procedure was conducted on a day when no stress was imposed and on a day when audiovisual stress was imposed for 5 min after 1 h of sampling. Following the audiovisual stress, plasma concentrations of cortisol and CSF concentrations of noradrenaline were elevated (p < 0.05), but CSF concentrations of NPY did not change. Adrenaline was not detected in samples of CSF. The rise in plasma cortisol following the stress was greater (p < 0.05) in ewes than in rams, but there were no sex differences in the rise in noradrenaline. Basal concentrations of NPY in the CSF were higher (p < 0.05) in rams than in ewes. We conclude that the sex differences in the stress-induced activity of the hypothalamo-pituitary-adrenal axis in sheep are not likely to be due to differences in the level of noradrenergic and/or NPY input to the hypothalamus.

Effects of commercial diets and temperature on the growth performance and stress response of hapuku (Polyprion oxygeneios)

There is a growing interest in the development of hapuku (Polyprion oxygeneios) for aquaculture in New Zealand and Australia. This is driven by the high value of this species prized for its excellent flesh quality, texture and its rapid growth capability. As a relatively new aquaculture candidate, little is currently known about their thermal tolerance and stress response. Juveniles inhabit surface waters, have a high rate of growth and move into a demersal habitat at an age between 3 and 4 years, where water temperature is cooler (7-15. °C) and more stable. The sea surface temperature in New Zealand can reach 22. °C during the summer months in more northerly locations, and captive rearing has indicated that during periods of high temperature, growth is reduced and it is possible that the physiological response is compromised. We examined the effects of two rearing temperatures (18. °C and 22. °C) and three commercial diets on the growth of P. oxygeneios during a 14 week trial. At the end of this trial, fish were exposed to a crowding stressor, and their stress response (plasma cortisol, glucose and cholesterol levels) determined. In addition, we examined the temporal stress response of P. oxygeneios acclimated to 18. °C and 22. °C subjected to a single acute handling stress. Specific growth rate and condition factor significantly increased over time in fish reared at 18. °C, but not at 22. °C. Plasma cortisol levels in hapuku prior to and after application of the stressors were within the range observed in other teleost species and the magnitude of the cortisol response was higher in hapuku subjected to crowding than handling stress. In summary, the results indicated that rearing P. oxygeneios at temperatures of 22. °C compromised their growth and that all three diets tested promoted growth in hapuku reared at 18. °C but not at 22. °C.Statement of relevanceHapuku over 1 kg had better growth rates at 18. °C than 22. °C.

The influence of maternal mental health, attachment and hormonal factors on a mother’s attachment to her fetus during pregnancy

 The thesis investigated the role of maternal mental health, maternal attachment and hormones in the development of maternal-fetal attachment during pregnancy. The study found that oxytocin and cortisol were associated with maternal-fetal attachment throughout pregnancy. The study also found that maternal mental health, particularly anxiety, stress and depression during the prenatal period impacted on the development of maternal-fetal attachment across pregnancy. The findings have clinical and research implications with regard to early intervention for attachment and maternal well-being.

The acute physiological stress response to an emergency alarm and mobilization during the day and at night

The purpose of this study was to investigate the acute physiological stress response to an emergency alarm and mobilization during the day and at night. Sixteen healthy males aged 25 ± 4 years (mean ± SD) spent four consecutive days and nights in a sleep laboratory. This research used a within-participants design with repeated measures for time, alarm condition (alarm or control), and trial (day or night). When an alarm sounded, participants were required to mobilize immediately. Saliva samples for cortisol analysis were collected 0 min, 15 min, 30 min, 45 min, 60 min, 90 min, and 120 min after mobilization, and at corresponding times in control conditions. Heart rate was measured continuously throughout the study. Heart rate was higher in the day (F20,442 = 9.140, P < 0.001) and night (F23,459 = 8.356, P < 0.001) alarm conditions compared to the respective control conditions. There was no difference in saliva cortisol between day alarm and day control conditions. Cortisol was higher (F6,183 = 2.450, P < 0.001) following the night alarm and mobilization compared to the night control condition. The magnitude of difference in cortisol between night control and night alarm conditions was greater (F6,174 = 4.071, P < 0.001) than the magnitude of difference between the day control and day alarm conditions. The augmented heart rate response to the day and night alarms supports previous observations in field settings. Variations in the cortisol responses between conditions across the day and night may relate to differences in participants' ability to interpret the alarm when sleeping versus when awake.

Effects of exercise on the desire to smoke and physiological responses to temporary smoking abstinence: a crossover trial

RATIONALE: Exercise has been shown to attenuate cigarette cravings during temporary smoking abstinence; however, the mechanisms of action are not clearly understood. OBJECTIVES: The objectives of the study were to compare the effects of three exercise intensities on desire to smoke and explore potential neurobiological mediators of desire to smoke. METHODS: Following overnight abstinence, 40 participants (25 males, 18-59 years) completed three 15 min sessions of light-, moderate-, or vigorous-intensity exercise on a cycle ergometer in a randomized crossover design. Ratings of desire to smoke were self-reported pre- and post-exercise and heart rate variability was measured throughout. Saliva and blood were analyzed for cortisol and noradrenaline in a sub-sample. RESULTS: Exercise influenced desire to smoke (F [2, 91] = 7.94, p < 0.01), with reductions greatest immediately after vigorous exercise. There were also significant time x exercise intensity interaction effects for heart rate variability and plasma noradrenaline (F [8, 72] = 2.23, p = 0.03), with a bias in noradrenaline occurring between light and vigorous conditions (adjusted mean difference [SE] = 2850 ng/ml [592], p < 0.01) at 5 min post-exercise. There was no interaction of time x exercise intensity for plasma and salivary cortisol levels. CONCLUSIONS: These findings support the use of vigorous exercise to reduce cigarette cravings, showing potential alterations in a noradrenergic marker.

Bias in emerging biomarkers for bipolar disorder

BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed/Medline, EMBASE and PsycInfo electronic databases were searched up to May 2015. Two independent authors conducted searches, examined references for eligibility, and extracted data. Meta-analyses in any language examining peripheral non-genetic biomarkers in participants with BD (across different mood states) compared to unaffected controls were included. RESULTS: Six references, which examined 13 biomarkers across 20 meta-analyses (5474 BD cases and 4823 healthy controls) met inclusion criteria. Evidence for excess of significance bias (i.e. bias favoring publication of 'positive' nominally significant results) was observed in 11 meta-analyses. Heterogeneity was high for (I 2 ⩾ 50%) 16 meta-analyses. Only two biomarkers met criteria for suggestive evidence namely the soluble IL-2 receptor and morning cortisol. The median power of included studies, using the effect size of the largest dataset as the plausible true effect size of each meta-analysis, was 15.3%. CONCLUSIONS: Our findings suggest that there is an excess of statistically significant results in the literature of peripheral biomarkers for BD. Selective publication of 'positive' results and selective reporting of outcomes are possible mechanisms.

One size does not fit all : monitoring faecal glucocorticoid metabolites in marsupials

Marsupial research, conservation, and management can benefit greatly from knowledge about glucocorticoid (GC) secretion patterns because GCs influence numerous aspects of physiology and play a crucial role in regulating an animal's response to stressors. Faecal glucocorticoid metabolites (FGM) offer a non-invasive tool for tracking changes in GCs over time. To date, there are relatively few validated assays for marsupials compared with other taxa, and those that have been published generally test only one assay. However, different assays can yield very different signals of adrenal activity. The goal of this study was to compare the performance of five different enzyme immunoassays (EIAs) for monitoring adrenocortical activity via FGM in 13 marsupial species. We monitored FGM response to two types of events: biological stressors (e.g., transport, novel environment) and pharmacological stimulation (ACTH injection). For each individual animal and assay, FGM peaks were identified using the iterative baseline approach. Performance of the EIAs for each species was evaluated by determining (1) the percent of individuals with a detectable peak 0.125-4.5days post-event, and (2) the biological sensitivity of the assay as measured by strength of the post-event response relative to baseline variability (Z-score). Assays were defined as successful if they detected a peak in at least 50% of the individuals and the mean species response had a Z⩾2. By this criterion, at least one assay was successful in 10 of the 13 species, but the best-performing assay varied among species, even those species that were closely related. Furthermore, the ability to confidently assess assay performance was influenced by the experimental protocols used. We discuss the implications of our findings for biological validation studies.