Cortisol Accumulation Research Articles

Beef cattle performance and hair cortisol accumulation in silvopastoral and pastoral systems: a 2-year assessment.

The Mediterranean area is highly vulnerable to climate change. Silvopastoral practices, such as integrating trees into pastureland or grazing in woodland areas, are potential mitigation strategies to improve microclimate conditions and reduce heat stress risks. We conducted a 2-year on-farm experiment to compare growth performance, measuring average daily gain (ADG), hair cortisol accumulation, and blood glucose concentration in Maremmana breed steers and heifers reared in either a silvopastoral (SP) or pastoral (PA) system during spring and summer. Additionally, we monitored microclimate conditions in both systems via the black globe humidity index (BGHI) as a heat stress proxy for outdoor-reared animals. In both years, the highest ADG values were recorded in spring: 1.49kg/day in PA and 1.25kg/day in SP in 2021 and 1.24kg/day in PA and 1.17kg/day in SP in 2022. During spring, PA-reared animals performed best, likely because of favourable microclimate conditions and abundant pasture, making tree shade unnecessary. Conversely, in summer, as heat stress risk increased-indicated by higher BGHI levels-tree presence in the SP system mitigated heat stress impacts on ADG, resulting in superior SP performance over PA. The hair cortisol levels increased in both groups during the summer, with a significantly greater increase in the PA animals. In 2021, cortisol levels reached 35.04pg/mg in PAs and 26.62pg/mg in SPs. In 2022, cortisol levels rose further to 46.56pg/mg in PAs and 42.94pg/mg in SPs. A decrease of glucose levels in PA group was determined but further research is needed to clarify the effects of heat stress on physiological mechanisms that lead to a change in glucose levels. Effective pasture and system management have been shown to increase productivity, with higher spring stocking rates in open pastures improving animal performance in both years.

Pseudo-Hyperaldosteronism Arising from Licorice Cough Syrup Self-Ingestion: A Case Report

Background: Licorice (glycyrrhiza glabra) cough syrup intoxication is manifested with refractory hypokalemia, hypertension, and metabolic alkalosis. The transformation of glycyrrhiza glabra metabolic into glycyrrhetic acid after ingestion further inhibits the 11-β-hydroxysteroid dehydrogenase-2 enzyme, impeding the conversion of cortisol into cortisone. The accumulation of cortisol can also stimulate mineralocorticoid receptors, which leads to a pseudo-hyperaldosteronism-like effect. Case Presentation: We report a 60-year-old male patient with licorice intoxication due to the chronic consumption of licorice cough syrup. He exhibited a transient seizure lasting approximately one minute. Initially, hypokalemia (potassium level was 2.0 mmol/L), metabolic alkalosis, and QT interval prolongation with premature ventricular complexes were demonstrated on his electrocardiogram. Despite the administration of both intravenous and oral potassium supplements over two days, there was no significant improvement in hypokalemia. Spironolactone, an aldosterone receptor antagonist, was administered in addition to ongoing potassium supplementation from the 3rd day. This intervention led to a rapid normalization of hypokalemia in one day. The patient was ultimately discharged on the 6th day without any subsequent complications. Conclusions: The licorice-induced chronic intoxication, which led to pseudo-hyperaldosteronism and refractory hypokalemia, was successfully managed with aggressive potassium supplementation and spironolactone treatment.

Glycyrrhizic acid induced acquired apparent mineralocorticoid excess syndrome with a hyperadrenergic state: a case report

BackgroundSyndrome of apparent mineralocorticoid excess (AME) is characterized by excessive MR stimulation despite low levels of aldosterone. 11Beta-hydroxysteroid dehydrogenase-2 (11βDSH-2) inactivates cortisol to cortisone, preventing cortisol-induced MR activation. Genetic defects in 11βDSH-2 cause AME through accumulation of cortisol in the distal nephron, leading to MR activation induced hypertension, hypokalemia and metabolic alkalosis. Acquired AME can occur due to the ingestion of glycyrrhizic acid, found in licorice root, which inhibits 11βDSH-2 and has additional effects on cortisol homeostasis through inhibition of 11βDSH-1.Case reportWe present a case of acquired AME with a hyperadrenergic symptoms induced by ingestion of Advanced Liver Support, a nutritional supplement produced by Advanced BioNutritionals(R), in a 65-year-old Caucasian female who presented with accelerated hypertension, hypokalemia, metabolic alkalosis and adrenergic symptoms. Cessation of the licorice-containing supplement resulted in complete resolution of the patient's hypertension, symptoms and abnormal lab values. To our knowledge this is the first reported case of AME from this supplement, and the first to describe accompanying hyperadrenergic symptoms.ConclusionsGlycyrrhizic acid is increasingly being found in unregulated nutritional supplements and has the potential to induce a reversable syndrome of AME. Acquired AME should be suspected in individuals who present with hypertension along with hypokalemia, metabolic alkalosis and low plasma renin and serum aldosterone levels.

The relationship between hair cortisol concentration and autism diagnosis

Autistic children are prone to experience heightened levels of distress and physiological reactivity to a range of sensory, social, and emotional stimuli. In line with this, multiple studies have demonstrated that autistic children have higher acute cortisol stress responses to adverse or threatening stimuli and altered cortisol awakening responses. However, few studies have examined whether this sensitivity may relate to heightened levels of chronic stress and persistently elevated hypothalamic-pituitary-adrenal (HPA) axis activity. The measurement of cortisol accumulation in hair is considered a non-invasive biomarker of chronic stress and has been associated with several childhood diseases. Here, we investigated whether hair cortisol concentration in a large sample of autistic children differed from non-autistic children, and after accounting for a range of child, parental and family-level characteristics. Hair cortisol concentration was measured in 307 autistic children and 282 non-autistic controls aged between 2 and 17 years recruited from four Australian states who participated in providing hair samples and demographic data to the Australian Autism Biobank. Independent samples t-test or one-way analysis of variance (ANOVA) were conducted to determine significant differences in the mean hair cortisol concentration (pg/mg) between potential covariates. Primary analysis included multivariable regression modelling of the collapsed sample to identify variables that were significantly associated with hair cortisol concentration after controlling for covariates. We also accounted for the potential interaction of multiple biological (e.g., age, sex, BMI) and psychosocial characteristics at the level of the child, the mother and the father, and the family unit. Our findings suggest that the diagnosis of autism was not a significant predictor of chronic stress, as measured by hair cortisol concentration. However, findings of the multivariable regression analysis showed that key factors such as area of residence (Queensland vs Victorian state of residence) and decrease in child's age were significantly associated with higher hair cortisol concentration whereas lower family income was significantly associated with higher hair cortisol concentration. To our knowledge, this is the first study to show that socioeconomic factors such as family annual income affect hair cortisol status in autistic children, indicating that the psychosocial environment may be a potential mediator for chronic stress in autistic children just as it has been demonstrated in non-autistic children.

Maternal early life and prenatal stress in relation to birth outcomes in Argentinian mothers.

Environmental influences before and during pregnancy significantly impact offspring development. This study investigates open research questions regarding the associations between maternal early life stress (ELS), prenatal psychosocial stress, prenatal hair cortisol (HC), and birth outcomes in Argentinian women. Data on ELS, prenatal life events, HC (two samples representing first and second half of pregnancy), and birth outcomes were collected from middle-class Argentinian women (N=69) upon delivery. Linear mixed models indicated that HC increased from the first half to the second half of pregnancy with considerable variability in the starting values and slopes between individuals. Mothers who experienced more ELS, were taller, or more educated, tended to show lower increases in HC. Older age was positively related to HC increases. Our data did not suggest an interaction between ELS and prenatal life events in relation to HC. We found that the change in HC was most likely negatively associated with birth weight. Our data are most compatible with either a weak or the absence of an association between ELS or prenatal life events and absolute values of HC. Mothers with stronger increases in hair cortisol tended to have newborns with slightly lower birth weight. Hence, ELS and birthweight may either have been related to changes in cortisol exposure during pregnancy or to factors that influence accumulation or retention of cortisol in hair.

Higher prenatal anxiety predicts lower neonatal hair cortisol

Prenatal glucocorticoids are one of the most widely proposed prenatal programming mechanisms, yet few studies exist that measure fetal cortisol via neonatal hair. Neonatal hair provides a window into the fetal experience and represents cortisol accumulation in the third trimester of pregnancy. In the current study, we test the links between two types of anxiety over the course of gestation (pregnancy-related anxiety and general anxiety) with neonatal hair cortisol. Pregnant individuals (N = 107) and their neonates (59.8% female) participated in the current study. Prenatal pregnancy-related anxiety and general anxiety were measured using the Pregnancy Related Anxiety Scale (PRAS) and the State-Trait Anxiety Inventory (STAI), in each trimester of pregnancy. Hierarchical linear modeling was used to model the intercept and slope of each type of anxiety over gestation. Neonatal hair samples were collected shortly after birth (Median days = 1.17, IQR = 0.75-2.00). Both higher pregnancy-related anxiety and general anxiety at the beginning of pregnancy and a flatter decline of pregnancy-related anxiety over gestation were associated with lower neonatal hair cortisol. After inclusion of gestational age at birth and parity as covariates, pregnancy-related anxiety (intercept: β = -0.614, p =.012; slope: β = -0.681, p =.006), but not general anxiety (intercept: β = -0.389, p =.114; slope: β = -0.302, p =.217) remained a significant predictor. Further, when both general and pregnancy-related anxiety were entered into the same model, only pregnancy-related anxiety (intercept and slope) were significant predictors of neonatal hair cortisol, indicating an association with pregnancy-related anxiety above and beyond general anxiety. Cortisol plays a central role in maturation of fetal organ systems, and at the end of gestation, higher cortisol has beneficial effects such as promoting fetal lung maturation. Further, lower maternal cortisol is linked to less optimal cognitive development and altered brain development. As maternal higher anxiety in early pregnancy and a flatter decrease over time are both associated with lower neonatal hair cortisol, maternal pregnancy-related anxiety could be a target of future intervention efforts.

Are hair cortisol levels dependent on hair growth rate? A pilot study in rhesus macaques

Research incorporating the analysis of glucocorticoids, specifically cortisol, in hair samples has exploded over the past 10-15years, 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) 3months 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 3months 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.

Abstract 2856: Age-induced chronic accumulation of cortisol drives chemotherapy resistance in lung cancer

Abstract Lung cancer accounts for the largest number of cancer-associated deaths in the United States. While great strides have been made due to the introduction of immunotherapies and targeted therapies against oncogenic drivers, chemotherapies remain the standard of care for the majority of lung cancer patients. However, many patients do not respond to these treatments or relapse following an initial response. We postulate that part of the problem is the lack of consideration in preclinical research and clinical trials of the main driver of lung tumorigenesis, the aging process. Here, we show that the organismal reprogramming that occurs with aging makes lung tumors in an aged host more conducive to withstand chemotherapies. We traced this to an age-induced chronic accumulation of the stress hormone cortisol in circulation. Mechanistically our data show that chronic accumulation of cortisol drives the upregulation of metallothioneins—small, highly conserved, cysteine-rich metal-binding proteins—through activation of the glucocorticoid receptor in lung cancer cells, which in turn rewire these cells to be refractory to chemotherapies. Together, our work demonstrates a role for age-induced cortisol levels in promoting resistance to standard of care chemotherapies in lung cancer and offers a rationale for using therapeutic agents that block the glucocorticoid receptor to sensitize the average and most vulnerable lung cancer patients, the elderly, to chemotherapy. Citation Format: Devesh Raizada, Stanislav Drapela, Joanne Tejero, Nadir Sarigul, Didem Ilter, Ana Gomes. Age-induced chronic accumulation of cortisol drives chemotherapy resistance in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2856.

You're stressing me out! Effect of interspecific competition from red deer on roe deer physiological stress response

AbstractCortisol is the main glucocorticoid hormone commonly measured to assess adrenocortical activity in vertebrates in response to potential stressors. Competition and habitat quality may act as chronic stressors leading to an increase in cortisol accumulation. Moreover, chronic cortisol concentrations may seriously hamper the reproductive potential, health status and body condition of a species. Using hair collected from the rump of 88 adult roadkill roe deer Capreolus capreolus in the north‐eastern Italy, we aimed to assess the effect of both ungulate competitor population densities and habitat suitability on the long‐term physiological stress response of roe deer, using hair cortisol as a reference parameter. Our findings revealed that roe deer showed higher cortisol concentrations in response to higher red deer Cervus elaphus population density, most likely as a consequence of direct interspecific competition. No significant cortisol changes were however recorded in response to both wild boar Sus scrofa and roe deer population densities, probably as a result of reduced competition because of abundant feeding resources, different species population densities and spatial/temporal avoidance among species. Moreover, the absence of a significant effect as far as habitat suitability is concerned, suggest that roe deer are well adapted to live even in poor quality habitats most likely as long as they are close to better quality habitats which provide access to food resources and refuge sites. Our results highlight the importance of hair cortisol as a suitable parameter to assess physiological chronic stress response towards different environmental/ecological conditions.

A matter of habit? Stressful life events and cognitive flexibility in 15-month-olds

Exposure to chronic stress is associated with habitual learning in adults. We studied the origins of this association by examining the link between stressful life events and infant cognitive flexibility. The final sample consisted of N=72 fifteen-month-old infants and their mothers. Mothers completed a survey on pre- and postnatal negative life events. To assess chronic stress physiologically, infant and maternal hair cortisol concentrations were determined for cortisol accumulation during the past 3 months. Each infant participated in two cognitive tasks in the laboratory. An instrumental learning task tested infants' ability to disengage from a habituated action when this action became ineffective (Seehagen et al., 2015). An age-adequate version of the A-not-B task tested infants' ability to find a toy at location B after repeatedly finding it at location A. Correlations between cortisol concentrations and postnatal negative life events (number, perceived impact) did not yield significance. Infant and maternal hair cortisol concentrations were not correlated. Infants' ability to shift to a new action in either task, controlled for acute stress, correlated neither with pre- and postnatal negative life events nor with cortisol concentrations. Taken together, these results indicate that the potential link between long-term stress exposure and cognitive flexibility might not be present in samples with low levels of psychosocial stress.

A claws and hair cortisol levels correlation in cats.

The accumulation of cortisol in hair and claws, which grow slowly, makes it possible to retrospectively assess chronic stress levels. The study involved 47 cats from a shelter for homeless animals. Hair from the lumbosacral region and the dead part of claws from the front paw were collected. The average cortisol levels were 0.85 ng/ml in the cats’ hair and 4.56 ng/ml in the claws. There was no significant relationship between cortisol levels in hair and claws. To date, too little research has been done on the correlation between cortisol levels in the hair and claws of cats. It is insufficient to unequivocally prove the existence of such a relationship.

The developmental consequences of early adverse care on infant macaques: A cross-fostering study

Early life adversity/stress (ELA/ELS), particularly adverse caregiving experiences such as child maltreatment (MALT), is a main risk factor for psychopathology, including psychiatric disorders such as anxiety, depression, ADHD, and substance abuse. Yet how these alterations unfold during development and the underlying mechanisms remain poorly understood, as it is difficult to prospectively and longitudinally study early developmental phases in humans, and nearly impossible to disentangle postnatal caregiving effects from heritable traits. This study examined the specific effects of "nurture" (maternal care) versus "nature" (heritable, biological maternal factors) on nonhuman primate infant socioemotional, stress neuroendocrine, and physical development. For this we used a translational and naturalistic macaque model of infant maltreatment by the mother with randomized assignment at birth to either mothers with a history of maltreating their infants (MALT group, n=22) or to competent mothers (Control group, n=20). Over the first 6 months of life (roughly equivalent to 2 years in humans), we examined the development of the mother-infant relationship, as well as infants' social behavior and emotional reactivity. In parallel, we assessed hypothalamic-pituitary-adrenal (HPA) axis function longitudinally, using measures of hair cortisol accumulation, and basal morning plasma cortisol. We identified broad impairments in maternal care exhibited by MALT foster mothers, beyond maltreatment (physical abuse, rejection) events, suggesting that MALT foster mothers provide an overall lower quality of care to their infants compared to Controls. MALT infants exhibited alterations in their initiations and breaks of proximity towards their mothers, as well as heightened emotional reactivity in comparison to Controls. Most striking are the HPA axis findings, with MALT infants showing higher levels of plasma cortisol across the first 6 postnatal months as well as higher hair cortisol accumulation from birth through month 6 (a signature of chronic stress) than Controls. No caregiving effects were detected on physical growth, which ruled out confounding effects of maternal nutrition, metabolism, etc. Taken together, these results suggest that the developmental trajectory of MALT and Control infants is different, marked by heightened levels of emotional reactivity, increased HPA activity and alterations in mother-infant interactions in MALT animals. These findings appear to be due to specific effects of postnatal maternal care, and not to biological/ behavioral traits inherited from the mother, or due to prenatal programming caused by prenatal stress, as the cross-fostering design controlled for these potential factors. However, we also detected a couple of interesting biological effects suggesting heritable transmission of some phenotypes. The prolonged HPA axis activation during the first 6 postnatal months of life is expected to have long-term consequences for brain, physiological, and behavioral development in MALT offspring.

Household Income, Cortisol, and Obesity During Early Childhood: A Prospective Longitudinal Study

To prospectively evaluate the relationship between household income, children's cortisol, and body mass index (BMI) trajectories over a 3-year period in early childhood. Household income, child hair cortisol levels, and BMI were measured at baseline, 12-, 24-, and 36-month follow-up visits in the Now Everybody Together for Amazing and Healthful Kids (NET-Works) Study (n=534, children ages 2-4years, and household income <$65 000/year at baseline). Relationships were examined between very low household income (<$25 000/year) at baseline, income status over time (remained <$25 000/year or had increasing income), cortisol accumulation from hair samples, and BMI percent of the 95th percentile (BMIp95) trajectories using adjusted linear growth curve modeling. Households with baseline income between $25 000 and $65 000/year were the reference group for all analyses. Children from very low-income households at baseline had annual changes in BMIp95 that were higher (P<.001) than children from reference group households (0.40 vs -0.62 percentage units/year). Annual increases in BMIp95 were also greater among children from households that remained very low income (P<.01, .34 percentage units/year) and among those with increasing income (P=.01, .51 percentage units/year) compared with the reference group (-0.61 percentage units/year). Children from households that remained very low income had higher hair cortisol accumulations (0.22 pg/mg, P=.02) than reference group children, whereas hair cortisol concentrations of children from households with increasing income (0.03 pg/mg) did not differ significantly from the reference group. Cortisol was not related to BMIp95. The economic circumstances of families may impact children's BMI trajectories and their developing stress systems, but these processes may be independent of one another.

Maternal programming by high-energy diets primes ghrelin sensitivity in the offspring of rats exposed to chronic immobilization stress

Maternal overnutrition during pregnancy leads to metabolic and immune alterations, including obesity, hyperphagia, and central and peripheral inflammation in offspring. Exposure to high-energy diets during pregnancy primes ghrelin sensitivity to overfeeding in the offspring at early stages of life. Overfeeding has also been partially related to the early stages of chronic stress. We hypothesized that maternal programming sensitizes ghrelin-induced overfeeding following a chronic stress schedule in the offspring. We used a nutritional programming model exposing female Wistar rats to a cafeteria (CAF) or control diet from prepregnancy to weaning. Male offspring were injected with ghrelin and then subjected to a chronic immobilization stress (CIS) schedule, after which food intake was determined. Hypothalamic and plasma accumulation of cytokines and cortisol were evaluated using BioPlex analysis and enzyme-linked immunosorbent assay, respectively. We found that rats exposed to the CAF diet exhibited overfeeding after fasting and peripheral ghrelin administration, which was exacerbated in rats exposed to chronic stress. Offspring exposed to the CAF diet accumulated pro-inflammatory interleukin-6 (IL-6), interferon-γ, and monocyte chemoattractant protein-1 cytokines in plasma, and IL-6 cytokine in the hypothalamus. Ghrelin-sensitive overfeeding in rats exposed to CAF diet+CIS display increased cortisol levels and decreased IL-6 accumulation in plasma. Together, our results suggest that maternal nutritional programming primes susceptibility to ghrelin response for overfeeding after a CIS schedule that mirrors plasma cortisol accumulation in male offspring.

Explorative study on scale cortisol accumulation in wild caught common dab (Limanda limanda)

BackgroundFlatfish live in a diverse marine ecosystem that is changing due to natural variations and anthropogenic influences. These changes can evoke a stress response mainly resulting in production of the glucocorticoid cortisol, which mediates effects on various levels of biological organization. The finding that cortisol accumulates in fish scales, offering a retrospective view on cortisol production, provides opportunities to use this matrix for chronic stress assessment. The present study is the first to gather information on scale cortisol concentration in wild-caught common dab (Limanda limanda), based on a two-pronged approach using (1) field measurements and (2) a laboratory in vivo-study where wild-caught dab were fed by cortisol-spiked feed during 30 or 90 days to demonstrate the possible accumulation of cortisol in the scales and to evaluate its impact on fish health.ResultsBased on the field measurements, the average scale cortisol concentration in wild-caught fish was 0.0034 ± 0.0046 µg kg−1 scale (n = 67). This indicates that wild common dab is indeed able to incorporate cortisol in the scales.Based on the experimental data, the cortisol-fed fish showed an increased plasma cortisol concentration (80.16 ± 82.58 µg L−1) compared to the control group (4.54 ± 9.57 µg L−1) after 30 days of cortisol feeding. The increase in plasma cortisol concentration was positively correlated with an increased cortisol concentration in the scale after 30 days of cortisol-spiked feeding. This correlation was, however, no longer observed after 90 days of cortisol-spiked feeding. Interestingly, cortisol concentration of the scales on the pigmented side was significantly higher compared to the non-pigmented side. Some health parameters such as epidermal thickness, body condition and Ichthyobodo sp. parasitic infection showed a correlation with scale cortisol concentration after 30 days.ConclusionsWe have demonstrated that common dab is able to accumulate cortisol in its scales. This seems to occur proportionally to circulating concentrations of plasma cortisol in fish fed with cortisol supplemented feed after 30 days.

A multi-suckling system combined with an enriched housing environment during the growing period promotes resilience to various challenges in pigs

Little is known about the impact of social and environmental enrichment on improving livestock resilience, i.e. the ability to quickly recover from perturbations. We evaluated the effect of an alternative housing system (AHS) on resilience of pigs, as compared to conventional housing (CONV). The AHS consisted of multi-litter housing during lactation, delayed weaning, extra space allowance and environmental enrichment at all times. We assessed recovery to a 2 h-transport challenge, an LPS injection, 2 h-heat stress and a biopsy wound in 96 pigs. Additionally, indicators of long-term “wear and tear” on the body were determined. AHS pigs had better physiological recoveries with quicker returns to baseline in the transport and LPS challenges, showed lower cortisol accumulation in hairs and lower variance in weight gain over the experimental period compared to conventionally-housed (CONV) pigs. They also had higher levels of natural antibodies binding KLH than CONV pigs. Their response to heat stress revealed a different strategy compared to CONV pigs. Taken together, AHS pigs appear to be more resilient and experience less chronic stress. Enhancing welfare by provision of social and environmental enrichment that better meets the behavioural needs of pigs seems to be a promising approach to improve their resilience.

Perinatal determinants of neonatal hair glucocorticoid concentrations

Adult hair glucocorticoid concentrations reflect months of hypothalamic-pituitary-adrenal axis activity. However, little is known about the determinants of neonatal hair glucocorticoids. We tested associations between perinatal exposures and neonatal hair glucocorticoids. Cortisol and cortisone were measured by LC-MS/MS in paired maternal and infant hair samples collected within 10 days of birth (n = 49 term, n = 47 preterm), with neonatal samples collected at 6-weeks in n = 54 preterm infants. We demonstrate cortisol accumulation in hair increases with fetal maturity, with hair cortisol being higher in term than preterm born infants after delivery (median 401 vs 106 pg/mg; p < 0.001). In term born infants, neonatal hair cortisol is positively associated with maternal hair cortisol concentration (β = 0.240, p = 0.045) and negatively associated with birthweight z-score (β = −0.340, p = 0.006). Additionally, being born without maternal labour is associated with lower hair cortisol concentrations (β = −0.489, p < 0.001) and a lower ratio of cortisol to cortisone (β = −0.484, p = 0.001). In preterm infants, histological chorioamnionitis is associated with a higher cortisol to cortisone ratio in hair (β = 0.459, p = 0.001). In samples collected 6 weeks after preterm birth, hair cortisol concentration is associated with cortisol hair concentrations measured after birth (β = 0.523, p < 0.001), chorioamnionitis (β = 0.250, p = 0.049) and postnatal exposures including intravenous hydrocortisone therapy (β = 0.343, p < 0.007) and neonatal sepsis (β = 0.290, p = 0.017). In summary, neonatal hair cortisol is associated with birth gestation, maternal hair cortisol concentration and fetal growth. Additionally, exposures at delivery are important determinants of hair cortisol, and should be considered in the design of future research investigating how neonatal hair cortisol relates to prenatal exposures or fetal development.

Retrospective Hair Cortisol Concentrations from Pretreatment to Early Recovery in Alcohol Use Disorder.

Cortisol profiles are known to vary across phases of alcohol use disorder (AUD; e.g. chronic use, withdrawal and early/sustained recovery). These patterns have largely been established through between-subjects contrasts. Using a segmental hair cortisol concentrations (HCC) approach, retrospective longitudinal analyses are feasible. Here, we examine monthly cortisol secretion in treatment-seekers with AUD from alcohol use to abstinence. At ~6weeks of recovery we collected hair samples from individuals with moderate-to-severe AUD. We examined HCC from three consecutive segments; proximal to the scalp representing the most recent month (sustained abstinence from alcohol), the midsegment representing the previous month in which abstinence was attained, and the distal segment representing 2months prior during active drinking. Analyses examined main and interactive effects of segment and sex, controlling for monthly alcohol consumption. Best fit by a quadratic shape, within-subject change was significant (F1,15=5.27, P=0.04, ηpartial2=0.26). The distal and midsegments did not differ from one another (P=0.51). The proximal segment was significantly lower than both the distal (M∆=0.200, P=0.004) and mid (M∆=0.175, P<0.001) segments. An effect of sex approached significance suggesting women had modestly higher HCC than men (MWOMEN=1.37 vs. MMEN=1.02, P=0.10). Consistent with previous cross-sectional reports, these data confirm nonlinear patterns of cortisol accumulation with elevations apparent during periods of alcohol consumption and a decrease in abstinence. Capturing these within-subject patterns via HCC trajectories may serve as a valuable resource in identifying profiles associated with increased risk and post-treatment outcomes.

Effects of Obesity and Insulin on Tissue-Specific Recycling Between Cortisol and Cortisone in Men.

Context 11β-Hydroxysteroid dehydrogenase 1 (11βHSD1) reduces inert cortisone into active cortisol but also catalyzes reverse dehydrogenase activity. Drivers of cortisol/cortisone equilibrium are unclear. With obesity, 11βHSD1 transcripts are more abundant in adipose, but the consequences for oxidation vs reduction remain unknown.ObjectiveThis work aimed to determine whether 11βHSD1 equilibrium in metabolic tissues is regulated by insulin and obesity.MethodsA 2-phase, randomized, crossover, single-blinded study in a clinical research facility was conducted of 10 lean and obese healthy men. 11β-Reductase and 11β-dehydrogenase activities were measured during infusion of 9,11,12,12-[2H]4-cortisol and 1,2-[2H]2-cortisone, respectively, on 2 occasions: once during saline infusion and once during a hyperinsulinemic-euglycemic clamp. Arterialized and venous samples were obtained across forearm skeletal muscle and abdominal subcutaneous adipose. Steroids were quantified by liquid chromatography–tandem mass spectrometry and adipose tissue transcripts by quantitative polymerase chain reaction.ResultsNeither whole-body nor tissue-specific rates of production of cortisol or cortisone differed between lean and obese men, however insulin attenuated the diurnal decrease. Whole-body 11β-HSD1 reductase activity tended to be higher in obesity (~ 10%) and was further increased by insulin. Across adipose tissue, 11β-reductase activity was detected in obese individuals only and increased in the presence of insulin (18.99 ± 9.62 vs placebo 11.68 ± 3.63 pmol/100 g/minute; P < .05). Across skeletal muscle, 11β-dehydrogenase activity was reduced by insulin in lean men only (2.55 ± 0.90 vs 4.50 ± 1.42 pmol/100 g/minute, P < .05).ConclusionsRegeneration of cortisol is upregulated by insulin in adipose tissue but not skeletal muscle. In obesity, the equilibrium between 11β-reductase and 11β-dehydrogenase activities likely promotes cortisol accumulation in adipose, which may lead to adverse metabolic consequences.

Assessment of prenatal stress-related cortisol exposure: focus on cortisol accumulation in hair and nails.

Prenatal stress adversely affects offspring development. Although cortisol is hypothesized to be a key mediator of stress-induced developmental deficits, determining the amount of fetal cortisol exposure produced by maternal stress has proved challenging. Current approaches, such as measuring cortisol concentrations in maternal plasma, saliva, or urine, amniotic fluid, fetal plasma, or cord blood, all have significant limitations for assessing cumulative fetal cortisol exposure over time. A recently emerging approach is to measure cortisol concentrations in maternal hair and/or newborn hair or nail samples. Maternal hair cortisol potentially shows long-term production across each trimester of pregnancy, whereas neonatal hair or nail cortisol is thought to reflect mainly third trimester hormone accumulation. This review first describes fetal adrenocortical development, placental cortisol metabolism, and the various sources of fetal cortisol exposure across pregnancy. We then summarize the results obtained from "classical" methods of assessing prenatal cortisol exposure prior to the advent of hair and nail cortisol measurement. Lastly, we discuss the initial development and validation of the hair cortisol methodology, its subsequent application to studies of chronic stress, and recent findings regarding maternal and neonatal hair or nail cortisol concentrations in relation to prenatal stress and other variables of interest.