Negative associations between maternal prenatal hair cortisol and child socioemotional problems.

Maternal prenatal distress can participate in the programming of offspring development, in which exposure to altered maternal long-term cortisol levels as measured by hair cortisol concentrations (HCC) may contribute. Yet, studies investigating whether and how maternal prenatal HCC associates with problems in child socioemotional development are scarce. Furthermore, questions remain regarding the timing and potential sex-specificity of fetal exposure to altered cortisol levels and whether there are interactions with maternal prenatal distress, such as depressive symptoms. The subjects were drawn from those FinnBrain Birth Cohort families that had maternal reports of child socioemotional problems (the Brief Infant-Toddler Social and Emotional Assessment [BITSEA] at 2 years and/or the Strengths and Difficulties Questionnaire [SDQ] at 5 years) as follows: HCC1 population: maternal mid-pregnancy HCC measured at gestational week 24 with 5 cm segments to depict cortisol levels from the previous five months (n = 321); and HCC2 population: end-of-pregnancy HCC measured 1-3 days after childbirth (5 cm segment; n = 121). Stepwise regression models were utilized in the main analyses and a sensitivity analysis was performed to detect potential biases. Negative associations were observed between maternal HCC2 and child BITSEA Total Problems at 2 years but not with SDQ Total difficulties at 5 years, and neither problem score was associated with HCC1. In descriptive analyses, HCC2 was negatively associated with Internalizing problems at 2 years and SDQ Emotional problems at 5 years. A negative association was observed among 5-year-old girls between maternal HCC1 and SDQ Total Difficulties and the subscales of Conduct and Hyperactivity/inattentive problems. When interactions were also considered, inverse associations between HCC2 and BITSEA Internalizing and Dysregulation Problems were observed in subjects with elevated prenatal depressive symptoms. It was somewhat surprising that only negative associations were observed between maternal HCC and child socioemotional problems. However, there are previous observations of elevated end-of-pregnancy cortisol levels associating with better developmental outcomes. The magnitudes of the observed associations were, as expected, mainly modest. Future studies with a focus on the individual changes of maternal cortisol levels throughout pregnancy as well as studies assessing both maternal and child HPA axis functioning together with child socioemotional development are indicated.

Cortisol and changes in depressive symptoms: The moderating role of DHEA.

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

Evaluating Mixtures of Urinary Phthalate Metabolites and Serum Per-/Polyfluoroalkyl Substances in Relation to Adolescent Hair Cortisol: The HOME Study.

Results of toxicological studies indicate that phthalates and per-/polyfluoroalkyl substances (PFAS), 2 classes of endocrine-disrupting chemicals, may alter the functioning of the hypothalamic-pituitary-adrenocortical (HPA) axis. We evaluated the associations of urinary phthalate metabolites and serum PFAS during gestation and childhood with adolescent hair cortisol concentrations (pg/mg hair) at age 12 years, an integrative marker of HPA axis activity (n = 205 mother-child pairs; Cincinnati, Ohio; enrolled 2003-2006). We used quantile-based g-computation to estimate associations between mixtures of urinary phthalate metabolites or serum PFAS and hair cortisol. We also examined whether associations of individual phthalate metabolites or PFAS with cortisol varied by the timing of exposure. We found that a 1-quartile increase in all childhood phthalate metabolites was associated with 35% higher adolescent hair cortisol (phthalate mixture ψ = 0.13; 95% confidence interval: 0.03, 0.22); these associations were driven by monoethyl phthalate, monoisobutyl phthalate, and monobenzyl phthalate. We did not find evidence that phthalate metabolites during gestation or serum PFAS mixtures were related to adolescent hair cortisol concentrations. We found suggestive evidence that higher childhood concentrations of individual PFAS were related to higher and lower adolescent hair cortisol concentrations. Our results suggest that phthalate exposure during childhood may contribute to higher levels of chronic HPA axis activity.

Relationships Among Number of Stressors, Perceived Stress, and Salivary Cortisol Levels During the Third Trimester of Pregnancy.

OBJECTIVE: To examine relationships among the number of stressors, perceived stress, and salivary cortisol levels during the third trimester of pregnancy. DESIGN: Secondary analysis of cross-sectional data. SETTING: Participants' homes. PARTICIPANTS: Women during the third trimester of pregnancy (N = 73). METHODS: Participants provided saliva samples at four time points over 2 days for cortisol assay and completed questionnaires to assess stressors and perceived stress. We computed multiple linear regression models to examine the relationships among the number of stressors and perceived stress to cortisol awakening response, diurnal slope, and overall cortisol secretion. We also computed a multiple linear regression model to examine the relationship between perceived stress and the number of stressors. RESULTS: Greater perceived stress was associated with reduced overall cortisol secretion across the day (ß = -0.41, p = .01). The number of stressors was associated with perceived stress (ß = 0.48, p = .002) but not salivary cortisol measures. CONCLUSION: Elevated perceived stress and the related cortisol alterations that we identified could represent salient targets for enhancing hypothalamic-pituitary-adrenal axis function during the third trimester. Perceived stress may shape the relationship between exposure to stressors and cortisol response during pregnancy. Future research is warranted to confirm study results and to understand the implications for parturition and fetal development.

Psychological resilience and cortisol levels in adults: A systematic review.

Resilience or the capacity to "bend but not break" refers to the ability to maintain or regain psychobiological equilibrium during or after exposure to stressful life events. Specifically, resilience has been proposed as a potential resource for staving off pathological states that often emerge after exposure to repeated stress and that are related to alterations in circulating cortisol. The aim of this systematic review of the literature was to gather evidence related to the relationship between psychological resilience and cortisol levels in adult humans. An extensive systematic search was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method in the PubMed and Web of Science databases. In total, 1256 articles were identified and, of these, 35 peer-reviewed articles were included in the systematic review. We categorized findings according to (1) the short and long-term secretion period covered by the cortisol matrices selected by studies and also according to (2) the differentiated diurnal, phasic (acute), and tonic (basal) components of the HPA output to which they refer and their relationships with resilience. Reported relationships between psychological resilience and distinct cortisol output parameters varied widely across studies, finding positive, negative, and null associations between the two variables. Notably, several of the studies that found no relationship between resilience and cortisol used a single morning saliva or plasma sample as their assessment of HPA axis activity. Despite limitations such as the great variability of the instruments and methods used by the studies to measure both resilience and cortisol, together with their high heterogeneity and small sample sizes, the evidence found in this systematic review points to the potential of resilience as a modifiable key factor to modulate the physiological response to stress. Therefore, further exploration of the interaction between the two variables is necessary for the eventual development of future interventions aimed at promoting resilience as an essential component of health prevention.

Hair cortisol, cortisone and DHEA concentrations and the composition of microbiota in toddlers.

Animal research suggests that the gut microbiota and the HPA axis communicate in a bidirectional manner. However, human data, especially on early childhood, remain limited. In this exploratory design, we investigated the connections between long-term HPA axis functioning, measured as cortisol, cortisone or dehydroepiandrosterone concentrations and their ratios from hair segments of three centimeters, and gut microbiota profiles, (measured as diversity and bacterial composition by 16 S rRNA sequencing) in healthy 2.5-year-old toddlers (n = 135) recruited from the FinnBrain Birth Cohort Study. The alpha diversity of the microbiota was studied by linear regression. Beta diversity analyses with weighted UniFrac or Bray-Curtis distances were performed using PERMANOVA. The bacterial core genus level analyses were conducted using DESeq2 and ALDEx2. These analyses suggested that hair sample concentrations of separate hormones, cortisol/cortisone and cortisol/dehydroepiandrosterone ratios were associated with various gut bacterial genera such as the Veillonella, the [Ruminococcus] torques group and [Eubacterium] hallii group, although multiple testing correction attenuated the p-values. Alpha or beta diversity was not linked with either steroid concentrations or ratios. These findings in toddlers suggest that long-term HPA axis activity may be related to genera abundancies but not to ecosystem-level measures in gut microbiota. The influence of these observed interrelations on later child health and development warrants further research.

Lifetime discrimination, habitual and daily everyday discrimination, and diurnal cortisol among older African Americans adults.

Experiences of discrimination can be major life events or daily chronic hassles that occur in various social contexts (e.g., housing, education, employment) and have been found to predict adverse health outcomes, including dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. Previous work on daily cortisol dynamics has generally revealed an association between discrimination and flatter cortisol slopes, particularly among racial minorities. However, most of the existing studies have focused on youth and young adults, with little work among older adults. The current study aimed to investigate the relationship between three measures of discrimination (lifetime discrimination, habitual everyday discrimination, and daily everyday discrimination) and diurnal cortisol secretion in a sample of 203 older African Americans. Study results indicated that individuals reporting higher levels of lifetime discrimination experienced morning hypocortisolism and flatter diurnal cortisol slopes. Exploratory analyses also showed that prior daily everyday discrimination was significantly associated with blunted cortisol awakening response (CAR) the next day. Our findings underline the role of discrimination in modulating daily cortisol dynamics among older African American adults and advance knowledge on how social stressors influence healthy aging.

Association between trauma exposure and glucocorticosteroid concentration in hair during pregnancy.

BACKGROUND: Traumatic events, including child abuse and intimate partner violence, are highly prevalent among women of child-bearing age. These traumatic experiences may impact maternal and offspring physical and mental health. A proposed mechanism for these effects is maternal hypothalamic-pituitary-adrenal (HPA) axis dysregulation which can be measured using hair corticosteroid levels. AIMS: This study aims to examine the association of child abuse and intimate partner violence exposure with HPA axis functioning, as measured by hair corticosteroid levels in a cohort of pregnant women. METHODS: We included data from 1822 pregnant women (mean gestational age 17 weeks) attending a prenatal clinic in Lima, Peru. We extracted cortisol and cortisone concentrations from hair samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Each participant provided 6-cm hair samples: 3 cm hair segment closest to the scalp reflecting HCC in early pregnancy (first three months), and 3-6 cm from the scalp reflecting HCC in pre-pregnancy (three months prior to conception). Multivariable linear regression procedures were used to assess the association between maternal trauma exposure and hair corticosteroid levels. RESULTS: Overall, women who experienced child abuse on average had higher levels of cortisol (p < 0.01) and cortisone (p < 0.0001) after adjustment for age, race, adult access to basic foods and hair treatments. For the hair segment reflecting early pregnancy, presence of child abuse was associated with a 0.120 log unit increase in cortisol and a 0.260 log unit increase in cortisone (p < 0.001). For the hair segment reflecting pre-pregnancy, a history of child abuse was associated with a 0.100 log unit increase in cortisol and a 0.180 log unit increase in cortisone (p < 0.01). Results also suggested an impact of intimate partner violence on HPA regulation; however, associations were not statistically significant after controlling for child abuse. CONCLUSIONS: These results underscore the long-lasting impacts of exposure to adversity and trauma during early life. Our study findings will have implications for research investigating HPA axis function and long-term effects of violence on corticosteroid regulation.

Maternal hair cortisol concentrations and its association with increased insulin resistance in midpregnancy.

PURPOSE: Stress and elevated maternal glycemia have negative effects on pregnancy. We evaluated the association of hair cortisol concentrations (HCC), a marker of chronic stress, with insulin resistance and gestational diabetes (GDM). METHODS: In total, 527 women from Lima, Peru, provided a hair sample in the second trimester of their pregnancy to measure HCC using liquid chromatography-tandem mass spectrometry. Each 6 cm of hair captured HCC in early (T1=1-12 weeks) and midpregnancy (T2 = 13-24 weeks). GDM diagnosis was conducted in midpregnancy. Multivariable regression models adjusted for putative risk factorsincluding maternal sociodemographic factors, diabetes history, and hair characteristics, were used to estimate the association of HCC with GDM and various glycemic traits. RESULTS: GDM was diagnosed in 122 (23%) women. Mean HCC across pregnancy was T1 = 3.7 (±3.4) pg/mg and T2 = 4.8 (±3.4) pg/mg. HCC was associated with increased log-transformed units of fasting insulin (T1 = 0.15 [0.03, 0.27], T2 = 0.17 [0.04, 0.30]), homeostasis model assessment for insulin resistance (T1 = 0.14 [0.01, 0.26], T2 = 0.17 [0.03, 0.30]), and homeostasis model assessment for ß-cell function (T1 = 0.20 [0.05, 0.34], T2 = 0.20 [0.04, 0.36]), but not with GDM (T1 = 0.95 [0.63, 1.40], T2 = 1.11 [0.74, 1.67]). CONCLUSIONS: Elevated maternal HCC was associated with abnormal insulin homeostasis in pregnancy. Dysregulation of the hypothalamic-pituitary-adrenal axis, as reflected by high HCC, may also contribute to insulin resistance syndrome in pregnancy.

Investigation of cross-sectional and longitudinal associations between work-related burnout and hair cortisol: The Regensburg Burnout Project.

BACKGROUND: Burnout is characterized by feelings of exhaustion, depersonalization as well as reduced personal accomplishment and is linked to various negative health effects. Previous studies on biological correlates of burnout have focused on the hypothalamic-pituitary-adrenal (HPA) axis. However, especially studies on hair cortisol concentrations (HCC) were often based on cross-sectional data and yielded inconsistent results, probably due to the heterogeneity of the selected samples. Accordingly, the aim of the present study was to investigate cross-sectional as well as longitudinal associations between burnout and HCC within a sample consisting of a strictly specified group of individuals suffering from burnout (BO group) and a healthy comparison group (HC group). METHODS: After a multi-stage recruitment procedure based on burnout symptoms and pathogenesis, eligible subjects (out of an initial sample of 1022 volunteers) were assigned either to a BO (n = 55) or HC group (n = 59), as described in detail in Bärtl et al. (2022). Burnout symptoms as well as HCC (1 cm hair samples) were measured repeatedly at two sampling time points t1 (n = 114) and t2 (n = 100) with an interval of M = 7.20 months (SD = 1.16) between assessments. RESULTS: In the total study sample, no cross-sectional associations between burnout and HCC were found either at t1 or at t2. When the analysis was restricted to the BO group, HCC was positively related to burnout symptomatology at t1 but not t2. In the longitudinal analysis, burnout symptoms at t1 were significant negative predictors of HCC at t2. However, the change in HCC from t1 to t2 was not associated with the change in burnout symptoms. CONCLUSIONS: In the present study, we investigated the association between HCC and burnout in a strictly defined sample of subjects suffering from burnout and healthy controls. Our findings mainly do not support our hypotheses. At least, the positive association between HCC and burnout symptoms only within the BO group supports the idea that HPA axis alterations in burnout might only become apparent once a certain threshold of burnout symptomatology has been exceeded, while the longitudinal data provide some empirical evidence for the potential long-term development of hypocortisolism in burnout. However, respective results remain relatively inconclusive.

Associations between psychological distress and hair cortisol during pregnancy and the early postpartum: A meta-analysis.

Pregnancy and the early postpartum signify a period of high stress. Perinatal stress can include psychological distress (PD), such as anxiety, depression, and stress, as well as neuroendocrine stress, indexed by activation of the hypothalamic-pituitary-adrenal (HPA) axis and the production of the hormone cortisol. Elevated PD and cortisol levels during the perinatal period can have long-term implications for the mother and child. Methodological advances have enabled the sampling of cortisol from hair, to provide a retrospective marker of HPA axis activity over several months. Despite knowing that maternal PD and HPA activity during the perinatal period independently impact health and development, research to date is unclear as to the association between maternal PD and hair cortisol. The present meta-analysis included 29 studies to assess the strength of the relation between maternal PD and hair cortisol levels during pregnancy and the early postpartum period. Several sample and methodological factors were assessed as moderators of this effect. Analyses were conducted using multilevel meta-analysis. Results of the multilevel meta-analysis indicated that the overall effect size between PD and HCC was small but not significant z = 0.039, 95% CI [- 0.001, 0.079]. Moderator analyses indicated that the strength of the association between PD and hair cortisol was moderated by pregnancy status (i.e., effects were stronger in pregnant compared to postpartum samples), timing of HCC and PD measurements (i.e., effects were larger when PD was measured before HCC) and geographic location (i.e., effects were larger in North American studies). The findings advance our understanding of the link between PD and HPA activity during the perinatal period, a time of critical impact to child development.

Ambient PM2.5 exposure and salivary cortisol output during pregnancy in a multi-ethnic urban sample.

OBJECTIVES: Evidence from murine research supports that fine particulate matter (PM2.5) may stimulate the hypothalamic-pituitary-adrenal axis, leading to elevated circulating glucocorticoid levels. Epidemiologic research examining parallel associations document similar associations. We examined these associations among a diverse sample of pregnant individuals exposed to lower levels of ambient PM2.5. MATERIALS AND METHODS: Participants included pregnant individuals enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) pre-birth cohort. Daily residential PM2.5 exposure was estimated using a satellite-based spatial-temporal hybrid model. Maternal 3rd trimester salivary cortisol levels were used to calculate several features of the diurnal cortisol rhythm. We used multivariable linear regression to examine PM2.5 during the pre-conception period and during each trimester in relation to cortisol awakening rise (CAR), slope, and area under the curve relative to ground (AUCG). RESULTS AND DISCUSSION: The average PM2.5 exposure level across pregnancy was 8.13 µg/m3. PM2.5 in each exposure period was positively associated with AUCG, a measure of total cortisol output across the day. We also observed an inverse association between PM2.5 in the 3rd trimester and diurnal slope, indicating a steeper decline in cortisol throughout the day with increasing exposure. We did not detect strong associations between PM2.5 and slope for the other exposure periods or between PM2.5 and CAR for any exposure period. CONCLUSIONS: In this sample, PM2.5 exposure across the preconception and pregnancy periods was associated with increased cortisol output, even at levels below the U.S. National Ambient Air Quality Annual Standard for PM2.5 of 12.0 µg/m3.

Diurnal Cortisol in Left-Behind Adolescents: Relations to Negative Family Expressiveness and Internalizing Problems.

Despite the accumulating evidence for increased risks for behavioral problems in left-behind adolescents in China, little research has explored their HPA axis functioning, which is hypothesized to play a central role in the association between early adversity and health. In the present study, we designed a longitudinal study to examine HPA axis function in left-behind adolescents and its mediating role in the association between family emotional expressiveness and internalizing problems. Participants were 81 adolescents (44 female; 37 male) aged 11-16 years. Salivary cortisol samples were collected six times a day for two consecutive days on regular school days. Negative family expressiveness (NFE) and internalizing problems were measured using self-report questionnaires. The results showed that NFE was negatively associated with diurnal cortisol, and diurnal cortisol was negatively associated with internalizing problems. Further analysis showed that diurnal cortisol secretion measured by AUC (area under the curve) mediated the association between NFE and internalizing problems. Our findings extended the existing literature about left-behind children via a psychoneuroendocrinological perspective, documenting the negative consequences of the family environment for youth health and development.

Increased cortisol levels caused by acute resistance physical exercise impair memory and learning ability.

Acute physical exercise works as an activator of the responses of the human organism to stress. This is based on the activation of the hypothalamic-pituitary-adrenal (HPA) axis, affecting physical, physiological and psychological levels. This study aimed to analyse the effects of a single bout of high-intensity resistance exercise on cognitive-behavioural responses: visuo-spatial path learning and memory, as well as physiological responses (salivary cortisol levels). Nineteen healthy male military-trained powerlifting subjects were tested in a within-subject design on two experimental days with an interval of 48 h. The stress and cognitive variables were measured by cortisol levels and Ruff-Light trail-learning test (RULIT) test scores, respectively. The results showed the immediate influence of acute exercise on cortisol, with significantly higher cortisol levels found in subjects after completion of the acute resistance exercise. In addition, this study found a significant deterioration of memory and learning ability after a dose of intense resistance exercise. In conclusion, the study highlights the relative effects of resistance exercise on cortisol and cognitive performance depending on the intensity and type of the exercise, the moment of measurement and the cerebral areas implicated.

Hair cortisol levels in schizophrenia and metabolic syndrome.

AIM: Individuals with schizophrenia demonstrate higher rates of metabolic syndrome (MetS) than the general population. Hair cortisol concentrations (HCC) reflect longer-term cortisol secretion and can provide additional insights into the role of the hypothalamic pituitary adrenal (HPA) axis in schizophrenia and co-occurring MetS. METHODS: In a case-control study of 16 patients with schizophrenia (11 first episode psychosis [FEP] and 5 chronic) and 21 controls hair samples, representing a 3-month retrospective window of cortisol, were collected and analysed utilizing liquid chromatography tandem mass spectrometry. We investigated whether schizophrenia and MetS co-occurrence were associated with HCC utilizing multivariate regression models. We also explored the longitudinal trajectory of HCC in FEP patients by conducting a mixed models analysis. RESULTS: At baseline HCC were significantly lower (Cohen's d = 0.88) in patients with schizophrenia than in controls (p = .014). HCC increased from baseline to month-12 in FEP patients compared to controls, demonstrating a trend towards significance (p = .097). MetS was not associated with HCC at baseline, but HCC increased significantly from baseline to month-12 in relation to MetS (p = .037). CONCLUSIONS: In a subgroup of schizophrenia patients, psychosis may be associated with a blunted HPA axis with lower long-term cortisol output. MetS was associated with an increase in HCC and elevated cortisol levels observed in schizophrenia may be related to increased rates of MetS in schizophrenia patients.

Disruption of the Diurnal Cortisol Hormone Pattern by Pesticide Use in a Longitudinal Study of Farmers in Thailand.

Alteration of the hypothalamic-pituitary-adrenal (HPA) axis hormones has been associated with a range of chronic metabolic and cardiovascular health conditions. This study evaluated whether type of farming (organic versus conventional) or the number of self-reported days of spraying pesticides in the past 8 months was associated with diurnal cortisol levels. Salivary cortisol levels were measured four times a day (waking, 30 min after waking, 6 h after waking and bedtime) longitudinally, 8 months apart during three rounds of data collection. Pesticide using (conventional) and organic farmers were recruited to participate. Pesticide use in the previous 8 months was determined as the number of spray days for each type of pesticide used (herbicide, insecticide, fungicide) from self-reported questionnaires. Estimates of cortisol levels at four time points, the cortisol awakening response (CAR), and the diurnal cortisol slope (DCS) were estimated with a longitudinal mixed model that accounted for the non-linearity of cortisol levels across the day. Conventional farmers had significantly lower cortisol levels at waking than organic farmers (3.39 versus 3.86 ng ml-1), 30 min after waking (5.87 versus 6.96 ng ml-1), 6 h after waking (1.62 versus 1.88 ng ml-1), and lower diurnal cortisol slope (-2.26 versus -2.51 ng ml-1). Farmers who frequently applied herbicides (90th percentile of the number of spray days in the past 8 months) had significantly lower waking, 30 min after waking, 6 h after waking, bedtime and diurnal cortisol slopes compared with those with no spray days of herbicide in the past 8 months (organic and some of the conventional farmers). Those who frequently applied insecticides in the past 8 months had significantly lower bedtime levels and diurnal cortisol slopes, compared with those with no spray days of insecticide in the past 8 months. There were no significant differences in cortisol hormones between those who frequently applied fungicides and those who did not spray fungicides. Repeated pesticide use appears to be disrupting the HPA axis and depressing the normal diurnal cortisol rhythm among conventional Thai farmers.

Reconstruction of the Hypothalamo-Neurohypophysial System and Functional Dissection of Magnocellular Oxytocin Neurons in the Brain.

The hypothalamo-neurohypophysial system (HNS), comprising hypothalamic magnocellular neuroendocrine cells (MNCs) and the neurohypophysis, plays a pivotal role in regulating reproduction and fluid homeostasis by releasing oxytocin and vasopressin into the bloodstream. However, its structure and contribution to the central actions of oxytocin and vasopressin remain incompletely understood. Using viral tracing and whole-brain imaging, we reconstruct the three-dimensional architecture of the HNS and observe collaterals of MNCs within the brain. By dual viral tracing, we further uncover that subsets of MNCs collaterally project to multiple extrahypothalamic regions. Selective activation of magnocellular oxytocin neurons promote peripheral oxytocin release and facilitate central oxytocin-mediated social interactions, whereas inhibition of these neurons elicit opposing effects. Our work reveals the previously unrecognized complexity of the HNS and provides structural and functional evidence for MNCs in coordinating both peripheral and central oxytocin-mediated actions, which will shed light on the mechanistic understanding of oxytocin-related psychiatric diseases.

Violence exposure and social deprivation is associated with cortisol reactivity in urban adolescents.

The present study tested how two different dimensions of childhood adversity, violence exposure and social deprivation, were associated with the cortisol response to the Socially Evaluated Cold-Pressor task in a sample of 222 adolescents (n = 117 girls, n = 167 African American). Participants were part of the Fragile Families and Child Wellbeing Study, a probability sample of births in large US cities (>200,000) between 1998 and 2000. Our subsample includes births in three cities: Detroit, Toledo, and Chicago. The study design called for an oversampling of births to unmarried parents (3:1) which led to a large number of minority and economically disadvantaged adolescents. When children were ages 3, 5, and 9, mothers reported on exposures to violence and social deprivation that occurred in the past year. Exposures from the three waves were averaged to reflect violence exposure and social deprivation during childhood. Greater levels of violence exposure from ages 3 to 9 were associated with a blunted cortisol response to stress at age 15, even after controlling for social deprivation and other factors known to influence cortisol reactivity. Social deprivation from ages 3 to 9 was not associated with the cortisol response to stress; though in an exploratory analysis, social deprivation moderated the association between violence exposure and cortisol peak activation. In line with the Dimensional Model of Adversity and Psychopathology, these findings suggest that experiences of violence, but not social deprivation, during childhood may contribute to cortisol blunting that has been previously reported in samples with high levels of social deprivation. Findings from the present longitudinal study on a relatively large sample of under-represented minority youth provide insight into the ways two different dimensions of childhood adversity impact the cortisol response to stress.

Hair cortisol and depressive symptoms in youth: An investigation of curvilinear relationships.

BACKGROUND: As the prevalence of depression is increasing among youth in the U.S., research on the utility of biomarkers in predicting depressive symptomatology is burgeoning. Hair cortisol may be a useful biomarker as it is a retrospective and longer-term measure of the mean cortisol level. However, studies have yet to examine the relationships between hair cortisol and depressive symptoms in samples of youth, and findings with adult samples are mixed. This study examined hair cortisol as a predictor of depressive symptoms, including the potential for nonlinear relationships. METHODS: A representative community sample of 432 adolescents aged 11 to 17 years was examined. Depressive symptoms were measured using a 9-item short-form of the Center for Epidemiologic Studies-Depression scale. Hair was cut from the posterior vertex region of the scalp using thinning shears. Hair was washed, minced, ground and assayed with Salimetrics® Cortisol Enzyme Immunoassay Kit. Hair cortisol levels were logged for statistical analysis. RESULTS: In multivariable regression analysis, no significant linear relationship was found in model 1 between hair cortisol and depressive symptoms (b= -0.036, se = 0.02, p = 0.13). In model 2, a marginally significant linear association (b= -0.044, se = 0.02, p-value = 0.06) and a significant curvilinear relationship (b = 0.039, se = 0.01, p-value = 0.005) were found between hair cortisol and depressive symptoms. The results were graphed depicting a u-shaped curve such that hair cortisol levels on the lower and higher end of the distribution predicted depressive symptoms. CONCLUSIONS: The findings highlight the need to consider investigation of nonlinear associations between cortisol and depressive symptoms. Longitudinal mechanistic research is needed to elucidate the causal relationships between hypothalamic-pituitary-adrenal axis dysregulation and depressive symptoms as well as a better understanding of the biological mechanisms through which cortisol may contribute to depressive symptoms and psychopathology.

The relationship between salivary cortisol and perinatal depression in women undergoing termination of pregnancy for fetal anomaly: A prospective cohort study.

BACKGROUND: The hypothalamic-pituitary-adrenal axis plays a crucial role in the neurobiological pathways for depression. The aim of this study was to determine the relationship between salivary cortisol and depression in women before and after termination of pregnancy due to fetal anomaly. STUDY DESIGN: A prospective cohort study was conducted. One-way ANOVA and linear correlation were conducted to analyse the relationship between salivary cortisol and depression before and after termination of pregnancy. RESULTS: No significant difference in morning and evening cortisol levels between women underwent TOP for fetal anomaly without depression and those with depression, but the women underwent TOP for fetal anomaly had significantly higher levels of morning and evening cortisol than women with healthy pregnancy. Cortisol awakening response was lower in women underwent termination of pregnancy, than in women with normal pregnancy; lower in women underwent termination of pregnancy with depression than in those women without depression. Cortisol awakening response also had a negative correlation with depression, and the correlation coefficients for cortisol awakening response and depression after TOP (R = 0.461) were higher than the correlation coefficients for cortisol awakening response and depression before TOP(R = 0.238). CONCLUSIONS: Our results were not only useful to support the hypothesis that hypothalamic-pituitary-adrenal axis functioning would turn hypoactive, with depression progressing to increase in severity, but also helpful with insights into the predictive effects of cortisol awakening response in depression after TOP. We suggest that further research should be conducted on the relationship between salivary cortisol and depression before and after TOP for fetal anomaly.