Selective enrichment of plasma cell-free messenger RNA in cancer-associated extracellular vesicles.

Extracellular vesicles (EVs) have been shown as key mediators of extracellular small RNA transport. However, carriers of cell-free messenger RNA (cf-mRNA) in human biofluids and their association with cancer remain poorly understood. Here, we performed a transcriptomic analysis of size-fractionated plasma from lung cancer, liver cancer, multiple myeloma, and healthy donors. Morphology and size distribution analysis showed the successful separation of large and medium particles from other soluble plasma protein fractions. We developed a strategy to purify and sequence ultra-low amounts of cf-mRNA from particle and protein enriched subpopulations with the implementation of RNA spike-ins to control for technical variability and to normalize for intrinsic drastic differences in cf-mRNA amount carried in each plasma fraction. We found that the majority of cf-mRNA was enriched and protected in EVs with remarkable stability in RNase-rich environments. We observed specific enrichment patterns of cancer-associated cf-mRNA in each particle and protein enriched subpopulation. The EV-enriched differentiating genes were associated with specific biological pathways, such as immune systems, liver function, and toxic substance regulation in lung cancer, liver cancer, and multiple myeloma, respectively. Our results suggest that dissecting the complexity of EV subpopulations illuminates their biological significance and offers a promising liquid biopsy approach.

Hair glucocorticoids during pregnancy in the context of trauma exposure and their predictive value for the development of childbirth-related posttraumatic stress disorder symptoms.

BACKGROUND: Childbirth-related posttraumatic stress disorder (CB-PTSD) is gaining attention as a mental disorder with negative sequela for mothers and their offspring. Maternal trauma history is a well-known vulnerability factor for CB-PTSD symptoms (CB-PTSS). Furthermore, alterations of the hypothalamus-pituitary-adrenal axis have been linked to both trauma exposure and PTSD development. Hence, we investigated whether trauma history was associated with long-term glucocorticoid (GC) levels during pregnancy and their predictive role for CB-PTSS. Further, we examined whether GCs act as a mediator in the relationship between trauma history and CB-PTSS and whether this was moderated by the subjective birth experience. METHODS: 212 women participating in the prospective cohort study DREAMHAIR provided hair samples for quantification of long-term integrated cortisol and cortisone levels prior to their anticipated birth date accompanied by measures of trauma history. CB-PTSS and subjective birth experience were assessed two months postpartum. FINDINGS: Trauma history predicted elevated hair cortisol and hair cortisone during the third trimester of pregnancy, however associations did not remain significant when Bonferroni correction due to multiple testing was applied. Trauma history also predicted higher CB-PTSS. Hair GC levels during pregnancy neither predicted CB-PTSS two months after birth nor mediated the relationship between trauma history and CB-PTSS. The subjective birth experience moderated the relationship of hair cortisol and cortisone with CB-PTSS. CONCLUSION: Our data suggest that a history of trauma contributes to a higher risk to develop CB-PTSS and elevated long-term GC levels during the third pregnancy trimester. Further, the predictive role of hair cortisol and cortisone levels for CB-PTSS may depend on subjective birth experience. This highlights the need to consider the latter in future investigations when examining the role of stress-related biomarkers in more severely affected samples.

SMARCA4 biology in alveolar rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and phenocopies a muscle precursor that fails to undergo terminal differentiation. The alveolar subtype (ARMS) has the poorest prognosis and represents the greatest unmet medical need for RMS. Emerging evidence supports the role of epigenetic dysregulation in RMS. Here we show that SMARCA4/BRG1, an ATP-dependent chromatin remodeling enzyme of the SWI/SNF complex, is prominently expressed in primary tumors from ARMS patients and cell cultures. Our validation studies for a CRISPR screen of 400 epigenetic targets identified SMARCA4 as a unique factor for long-term (but not short-term) tumor cell survival in ARMS. A SMARCA4/SMARCA2 protein degrader (ACBI-1) demonstrated similar long-term tumor cell dependence in vitro and in vivo. These results credential SMARCA4 as a tumor cell dependency factor and a therapeutic target in ARMS.

Depressive symptoms are not associated with long-term integrated testosterone concentrations in hair.

OBJECTIVES: The association between depressive symptomatology and endogenous testosterone levels is inconclusive. Large inter- and intra-individual testosterone differences suggest point measurements from saliva or serum to be inadequate to map basal testosterone concentrations highlighting the potential for long-term integrated testosterone levels from hair. METHODS: Using data from a prospective cohort study, a total of 578 participants (74% female) provided complete data on depressive symptomatology, clinical features, and hair samples for quantification of testosterone concentrations at baseline. Available data of three annual follow-up examinations were used for longitudinal analyses. RESULTS: Correlation analysis showed in both, men and women, hair testosterone across all the four time points not to be significantly related to depressive symptoms. Examined clinical features were not associated with testosterone levels, except for having a current diagnosis of a psychological disorder, which was associated with reduced testosterone levels in men, but not in women. Acceptable model fit for an autoregressive cross-lagged panel analysis emerged only for the female subsample suggesting inverse cross-relations for the prediction of testosterone by depressive symptomatology and vice versa. CONCLUSIONS: Findings from this study add to the literature by showing no association between long-term integrated testosterone in hair and depressive symptomatology in men and women.

Examination of peripheral basal and reactive cortisol levels in major depressive disorder and the burnout syndrome: A systematic review.

It is debated as to whether major depressive disorder (MDD) and the burnout syndrome represent different aspects of the same syndrome or whether they reflect separate entities. A dysregulation of the hypothalamus-pituitary-adrenal-axis has been related to both conditions separately. Dissecting the pathophysiology of the conditions and describing differences and similarities with regard to stress physiological systems might further clarify whether underlying etiological models of these syndromes differ. A systematic literature search including MDD and the burnout syndrome and peripheral cortisol measures was performed and resulted in 190 studies for inclusion in the qualitative synthesis. For MDD, findings suggest a general state of hypercortisolism and glucocorticoid resistance reflected by increased basal cortisol levels, reduced reactivity to psychosocial stress and a reduced cortisol suppression in pharmacological challenge tests. For the burnout syndrome, two central factors limit further conclusions: i) there is not a sufficient amount of studies examining the burnout syndrome and different cortisol secretion patterns to provide an evidence base, ii) the burnout syndrome is assessed heterogeneously reflecting imprecision of the measured constructs. Large prospective cohort studies examining both conditions in parallel rigorously controlling for confounders are required to further elucidate the differences and similarities of the HPA axis in MDD and the burnout syndrome.

Chronic HPA activity in mothers with preterm delivery: A pilot nested case-control study.

BACKGROUND: Chronic hypothalamic-pituitary-adrenal (HPA) axis activity role in the pathogenesis of preterm birth (PTB) remains unclear due to inconsistent measures with limited ability to monitor long-term cortisol concentrations. We explored this relationship using the novel method of assessing cortisol in hair, which is a valid and reliable measure of chronic HPA axis activity. METHODS: 137 participants (40 PTB cases and 97 controls from a birth cohort of pregnant women in Peru) were interviewed and invited to provide a 9-cm hair sample from the posterior vertex position of the scalp (mean = 13 weeks gestation). Hair cortisol concentration (HCC) was determined using luminescence immunoassay and values were natural-log transformed. PTB cases were defined as women who delivered before 37 gestational weeks. Case-control differences were assessed using multivariable linear and logistic regressions. RESULTS: Overall, combined pre-conception and first-trimester HCC was 13% lower among cases as compared with controls (p-value = 0.01). Compared with controls, maternal HCC among PTB cases were 14% (p = 0.11), 10% (p = 0.22) and 14% (p = 0.08) lower for 3-6 months pre-conception, 0-3 months pre-conception, and first trimester, respectively. After adjusting for putative confounders, a 1-unit increase in HCC was associated with 55% reduced odds of PTB (aOR = 0.45; 95% CI: 0.17-1.17). For a 1-unit increase in HCC in the scalp-intermediate and scalp-distal segments (representing HCC concentrations in 0-3 months pre-conception and first trimester), the corresponding odds for PTB were 0.53 (95% CI: 0.19-1.48) and 0.39 (95% CI: 0.13-1.13), respectively. CONCLUSIONS: Women who deliver preterm, as compared with those who deliver at term, have lower preconception and first trimester HCC. Our findings suggest that HPA axis activation, integral to the adaptive stress-response system, may be chronically dysregulated in women at increased risk of PTB.

Positive adaptation of HPA axis function in women during 44 weeks of infantry-based military training.

BACKGROUND: Basic military training (BMT) is a useful model of prolonged exposure to multiple stressors. 8-12 week BMT is associated with perturbations in the hypothalamic-pituitary-adrenal (HPA) axis which could predispose recruits to injury and psychological strain. However, characterisations of HPA axis adaptations during BMT have not been comprehensive and most studies included few if any women. METHODS: We studied women undertaking an arduous, 44-week BMT programme in the UK. Anxiety, depression and resilience questionnaires, average hair cortisol concentration (HCC), morning and evening saliva cortisol and morning plasma cortisol were assessed at regular intervals throughout. A 1-h dynamic cortisol response to 1 µg adrenocorticotrophic hormone-1-24 was performed during weeks 1 and 29. RESULTS: Fifty-three women (aged 24 ± 2.5 years) completed the study. Questionnaires demonstrated increased depression and reduced resilience during training (F 6.93 and F 7.24, respectively, both p < 0.001). HCC increased from 3 months before training to the final 3 months of training (median (IQR) 9.63 (5.38, 16.26) versus 11.56 (6.2, 22.45) pg/mg, p = 0.003). Morning saliva cortisol increased during the first 7 weeks of training (0.44 ± 0.23 versus 0.59 ± 0.24 µg/dl p < 0.001) and decreased thereafter, with no difference between the first and final weeks (0.44 ± 0.23 versus 0.38 ± 0.21 µg/dl, p = 0.2). Evening saliva cortisol did not change. Fasting cortisol decreased during training (beginning, mid and end-training concentrations: 701 ± 134, 671 ± 158 and 561 ± 177 nmol/l, respectively, p < 0.001). Afternoon basal cortisol increased during training while there was a trend towards increased peak stimulated cortisol (177 ± 92 versus 259 ± 13 nmol/l, p = 0.003, and 589 ± 164 versus 656 ± 135, p = 0.058, respectively). DISCUSSION: These results suggest a normal stress response in early training was followed quickly by habituation, despite psychological and physical stress evidenced by questionnaire scores and HCC, respectively. There was no evidence of HPA axis maladaptation. These observations are reassuring for women undertaking arduous employment.

Do dehydroepiandrosterone, progesterone, and testosterone influence women's depression and anxiety levels? Evidence from hair-based hormonal measures of 2105 rural Indian women.

Depressive and anxiety disorders substantially contribute to the global burden of disease, particularly in poor countries. Higher prevalence rates for both disorders among women indicate sex hormones may be integrated in the pathophysiology of these disorders. The Kshetriya Gramin Financial Services study surveyed a random sample of 4160 households across 876 villages in rural Tamil Nadu, India. An interviewer-administered questionnaire was conducted to quantify depressive (K6-D) and anxiety (K6-A) symptoms. Alongside, hair samples for sex hormone profiling were collected from a subsample of 2105 women aged 18-85 years. Importantly, 5.9%, 14.8%, and 46.3% of samples contained non-detectable hormone levels for dehydroepiandrosterone, progesterone, and testosterone, respectively. Our primary analysis imputes values for the non-detectable sample and we check robustness of results when non-detectable values are dropped. In this cohort of women from rural India, higher depressive symptomatology is associated with lower levels of dehydroepiandrosterone and higher depressive and anxiety symptoms are associated with higher levels of testosterone. Progesterone shows no clear association with either depressive or anxiety symptoms. These results support a potential protective effect of higher endogenous dehydroepiandrosterone levels. An important caveat on the potential negative effect of hair testosterone levels on women's mental health is that the testosterone analysis is sensitive to how non-detectable values are treated.

The association of potential stressors with hair steroids in parents with small children: The Ulm SPATZ health study.

Previous studies have reported weak associations between questionnaire-based stress measurements and hair steroids. A stronger relationship may exist in highly stressed subpopulations or with stress brought up by novel or unpredictable situations. In the Ulm SPATZ Health Study, conducted in Ulm, Germany, baseline recruitment 04/2012 to 05/2013, we analyzed data of families enrolled shortly after childbirth. Mothers completed standardized questionnaires assessing sociodemographic, health- and family-life-related factors, and the Screening Scale of the Trier Inventory of Chronic Stress (TICS) at 6 months (T2) and 12 months postpartum (T3). Their current partners completed SSCS-TICS and an Effort-Reward Imbalance (ERI) Questionnaire obtained at 6 weeks postpartum (T1). Partners (n = 375 at T1) and mothers (n = 654 at T2 or T3) provided a 2 to 3-cm hair segment for hair analysis. Adjusted linear and cubic spline regressions were used to analyze (non-)linear relationships between potential stressors and hair cortisol (hairF) and hair cortisone (hairE) concentrations as well as the respective change scores between 12 months and 6 months. Lacking social recognition and high paternal work overload were significantly associated with paternal hairF in cubic spline models (test for overall association, chi2 = 8.24, p = 0.041, chi2 = 8.41, p = 0.038) but not in linear models. However, the association between ERI and hairF (chi2 = 7.54, p = 0.059) was marginally significant. Maternal education was related to maternal hairF and hairE at T2. No association was observed between maternal postpartum employment and hair steroids at T2 or T3. Conversely, we could show a relationship between some change scores of stress and hairE in mothers. Considering non-linearity and family-related stressors, there are few associations between questionnaire-based stress measurements and hairF or hairE. Novelty of stressors was not shown to be a relevant factor.

Stress reactivity in preschool-aged children: Evaluation of a social stress paradigm and investigation of the impact of prenatal maternal stress.

Prenatal maternal stress is an established risk factor for somatic and psychological health of the offspring. A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in offspring has been suggested as an important mechanism. However, the impact of prenatal stress on stress reactivity in preschool-aged children is not yet well understood. This is partly due to the fact that for this age group there is no stress test as well established as for older children and adults. In the present work a previously published stress test (Kryski et al., 2011) was evaluated in a large sample of 45-month-old children (n = 339). Furthermore, the relation between measures of prenatal maternal stress and cortisol reactivity was investigated. Prenatal stress was defined as psychopathology (self-report available for n = 339; expert-rating available for a subsample of n = 246) and perceived stress (n = 244) during pregnancy. The stress paradigm elicited significant increases in salivary cortisol 30 and 40 min after the test, and 60.8% of the children were classified as responders. Lower cortisol levels after the stress test were observed in the group of children with prenatal stress defined as maternal psychopathology (both self-reported and expert-rated). Maternal perceived stress as a continuous measure was not significantly associated with cortisol levels. However, when comparing children in the highest quartile of maternal perceived stress to all other children, significantly lower cortisol values were observed in the prenatally stressed group. The present study confirms the paradigm by Kryski et al. as an effective stress test for preschool-aged children. Moreover, it provides further evidence that prenatal stress impacts HPA axis reactivity. Future studies should target the timing, nature, and intensity of prenatal stressors and their effect on the stress response in offspring at different developmental stages.

Inherited anxiety-related parent-infant dyads alter LHPA activity.

The pathogenesis of post-traumatic stress disorder (PTSD) is incompletely understood. We hypothesize that disruptions in mother-child relations may be a key contributor to development of PTSD. A normal and healthy separation-individuation process requires adaptations of self- and interactive contingency in both the mother and her child, especially in early childhood development. Anxious mothers are prone to overprotection, which may hinder the individuation process in their children. We examined long-term stress hormones and other stress markers in subjects three generations removed from the Holocaust, to assess the long-term consequences of inherited behavioral and physiological responses to prior stress and trauma. Jewish subjects who recalled overprotective parental behavior had higher hairsteroid-concentrations and dampened limbic-hypothalamic-pituitary-adrenal (LHPA) axis reactivity compared to German and Russian-German subjects with overprotective parents. We suggest that altered LHPA axis activity in maternally overprotected Jewish subjects may indicate a transmitted pathomechanism of "frustrated individuation" resulting from cross-generational anti-Semitic experiences. Thus measurements of hairsteroid-concentrations and parenting practices may have clinical value for diagnosis of PTSD. We propose that this apparent inherited adaptivity of LHPA axis activity could promote higher individual stress resistance, albeit with risk of an allostatic overload.

Comparability, stability, and reliability of internet-based mental chronometry in domestic and laboratory settings.

The internet-based assessment of response time (RT) and error rate (ERR) has recently become a well-validated alternative to traditional laboratory-based assessment, because methodological research has provided evidence for negligible setting- and setup-related differences in RT and ERR measures of central tendency. However, corresponding data on potential differences in the variability of such performance measures are still lacking, to date. Hence, the aim of this study was to conduct internet-based mental chronometry in both poorly standardized domestic and highly standardized laboratory environments and to compare the variabilities of the corresponding performance measures. Using the Millisecond Inquisit4Web software, 127 men and women completed three different RT-based cognitive paradigms (i.e., go/no-go, two-back, and number-letter). Each participant completed all paradigms in two environments (i.e., at home and in the laboratory), with a time lag of seven days and in a counterbalanced order. Mixed-effects modeling was employed to estimate the between-setting variability across a comprehensive set of performance measures, including conventional measures of central tendency (i.e., mean RT and ERR) and further measures characterizing the joint distribution of RT/ERR. The latter measures were estimated using the diffusion model. The results suggested negligible differences between the domestic and laboratory settings. Thus, this study provides novel evidence suggesting that the statistical power of internet-based mental chronometry is commonly not compromised by increased environmental variance. The within- and between-session reliabilities were in a satisfactory range-that is, comparable to performance measures collected offline in laboratory settings. In consequence, our results support the broad applicability, robustness, and cost efficiency of mental chronometry assessment using the internet.

Persistent LHPA Activation in German Individuals Raised in an Overprotective Parental Behavior.

Parental upbringing may affect their offspring's mental state across the entire lifespan. Overprotective parental child-rearing style may increase the disease burden in the offspring. Furthermore, this child-rearing style may also play a pathogenetic role by transmitting trauma- and stressor-related disorders (TSRD) across generations. Studies with animals have demonstrated that the mother's immediate and expansive protection of the newborn decreases the limbic-hypothalamic-pituitary-adrenal (LHPA) axis activity in the offspring. However, few studies have investigated how stress impact humans raised in an overprotective manner. In a cross-sectional study with 40 healthy students recalling their overprotective upbringing, we show an increase in the dehydroepiandrostendione (DHEA) concentration and a reduction in the cortisol/DHEA-ratio in hair. Additionally, this child rearing style was associated with heightened indications of mental burden, depressiveness, and sense of coherence. Our results provide insight into the roots and consequences of psychological trauma across several generations. Further investigations focusing particularly on multigenerational transmission in extremely burdened families will augment our results.

High hair cortisol concentrations predict worse cognitive outcome after stroke: Results from the TABASCO prospective cohort study.

BACKGROUND AND PURPOSE: The role of stress-related endocrine dysregulation in the development of cognitive changes following a stroke needs further elucidation. We explored this issue in a longitudinal study on stroke survivors using hair cortisol concentrations (HCC), a measure of integrated long-term cortisol levels. METHODS: Participants were consecutive cognitively intact first-ever mild-moderate ischemic stroke/transient ischemic attack (TIA) survivors from the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study. They underwent 3T magnetic resonance imaging (MRI) scanning and were cognitively assessed at admission, and at 6, 12 and 24 months post-stroke. Scalp hair samples were obtained during the initial hospitalization. RESULTS: Full data on baseline HCC, MRI scans and 2 years neuropsychological assessments were available for 65 patients. Higher HCC were significantly associated with a larger lesion volume and with worse cognitive results 6, 12 and 24 months post-stroke on most of the neurocognitive tests. 15.4% of the participants went on to develop clinically significant cognitive decline in the follow-up period, and higher HCC at baseline were found to be a significant risk factor for this decline, after adjustment for age, gender, body mass index and APOE e4 carrier status (HR=6.553, p=0.038). CONCLUSIONS: Our findings suggest that individuals with higher HCC, which probably reflect higher long-term cortisol release, are prone to develop cognitive decline following an acute stroke or TIA.

Circumcision does not alter long-term glucocorticoids accumulation or psychological effects associated with trauma- and stressor-related disorders.

Male infants and boys through early adolescence can undergo circumcision either for the sake of upholding religious traditions or for medical reasons. According to both, Jewish as well as Islamic tenets, circumcision is a religious rite symbolizing the bond with God. The World Health Organization (WHO), the United Nations Council (UNC) as well as the American Academy of Pediatrics (AAP), and the Centers for Disease Control and Prevention (CDC) strongly recommend circumcision to promote hygiene and prevent disease. This procedure has frequently been criticized by various communities claiming that circumcision in infancy and early adolescence were psychologically traumatizing with medical implications up into old age. Due to the lack of evidence concerning an alleged increase in vulnerability, we measured objective and subjective stress and trauma markers, including glucocorticoids from hair samples, in circumcised and non-circumcised males. We found no differences in long-term limbic-hypothalamic-pituitary-adrenal axis activity, subjective stress perception, anxiety, depressiveness, physical complaints, sense of coherence and resilience. Rather, an increase in the glucocorticoid levels indicated a healthy lifestyle and appropriate functioning. Thus, our findings provide evidence that male circumcision does not promote psychological trauma. Moreover, a qualitative approach, the ambivalence construct, was used for the discussion, aiming at a discourse devoid of biases.

Adrenal medullary dysfunction as a feature of obesity.

BACKGROUND AND OBJECTIVE: Although there is strong evidence linking obesity with increased sympathoneural activity, involvement of the adrenal medulla is less clear. We therefore investigated adrenal medullary function under fasting and feeding conditions in normal weight (NW, n=33), overweight (OW, n=28) and obese (OB, n=36) adults (59% women). SUBJECTS AND METHODS: Ninety-seven healthy adults participated in a cross-sectional study with recruitment stratified according to BMI. Plasma for catecholamines and metanephrines was sampled in the fasting state, at 30-min intervals during a 120-min glucose tolerance test and during an euglycaemic-hyperinsulinaemic clamp (40 mU m-2 min-1 insulin dose). Body composition was determined by leg-to-leg bioelectrical impedance analysis. RESULTS: Obese subjects had the lowest fasting plasma concentrations of epinephrine (NW: 0.17, 95% confidence interval (CI): 0.14-0.20 nmol l-1; OW: 0.16, 95% CI: 0.12-0.19 nmol l-1; OB: 0.11, 95% CI: 0.08-0.13 nmol l-1; P=0.018) and metanephrine (NW: 0.17, 95% CI: 0.15-0.19 nmol l-1; OW: 0.15, 95% CI: 0.13-0.16 nmol l-1; OB: 0.13, 95% CI: 0.12-0.15 nmol l-1; P=0.022), the latter reflecting adrenal medullary store size. Fasting plasma epinephrine (r=-0.437; P<0.001) and metanephrine (r=-0.477; P<0.001) concentrations were additionally inversely correlated with whole-body fat percentage. Suppression of epinephrine secretion in response to carbohydrate ingestion was significantly blunted in overweight and obese subjects compared with the normal weight subjects (Pinteraction=0.045). Most of the variance in basal epinephrine was related to whole-body fat percentage (ß=-0.389, 95% CI: -0.09 to -0.69; P=0.012) that explained the lower concentrations of epinephrine and metanephrine in women than men. CONCLUSIONS: We provide evidence that adrenomedullary dysfunction is a characteristic feature of obesity that involves both reduced adrenal secretion of epinephrine and size of adrenal medullary epinephrine stores.

Genetic influences on hormonal markers of chronic hypothalamic-pituitary-adrenal function in human hair.

BACKGROUND: Cortisol is the primary output of the hypothalamic-pituitary-adrenal (HPA) axis and is central to the biological stress response, with wide-ranging effects on psychiatric health. Despite well-studied biological pathways of glucocorticoid function, little attention has been paid to the role of genetic variation. Conventional salivary, urinary and serum measures are strongly influenced by diurnal variation and transient reactivity. Recently developed technology can be used to measure cortisol accumulation over several months in hair, thus indexing chronic HPA function. METHOD: In a socio-economically diverse sample of 1070 twins/multiples (ages 7.80-19.47 years) from the Texas Twin Project, we estimated effects of sex, age and socio-economic status (SES) on hair concentrations of cortisol and its inactive metabolite, cortisone, along with their interactions with genetic and environmental factors. This is the first genetic study of hair neuroendocrine concentrations and the largest twin study of neuroendocrine concentrations in any tissue type. RESULTS: Glucocorticoid concentrations increased with age for females, but not males. Genetic factors accounted for approximately half of the variation in cortisol and cortisone. Shared environmental effects dissipated over adolescence. Higher SES was related to shallower increases in cortisol with age. SES was unrelated to cortisone, and did not significantly moderate genetic effects on either cortisol or cortisone. CONCLUSIONS: Genetic factors account for sizable proportions of glucocorticoid variation across the entire age range examined, whereas shared environmental influences are modest, and only apparent at earlier ages. Chronic glucocorticoid output appears to be more consistently related to biological sex, age and genotype than to experiential factors that cluster within nuclear families.

Hypocortisolism and preterm birth.

OBJECTIVE: We sought to determine whether hypocortisolism is associated with preterm birth, using hair cortisol as a marker of long term hypothalamic-pituitary-adrenal axis activity. STUDY DESIGN: In a prospective, matched, case-control study, 29 women who had a preterm birth at 24-36w5d gestation were compared to 29 women who delivered at term, matched for maternal age, gestational age, and ethnicity. Cases' samples were collected within 72 h of preterm birth and controls at the same gestational age as the corresponding case. Participants completed validated questionnaires regarding general stress and childhood trauma. The Wilcoxon signed-rank test was used to compare the distribution of mean hair cortisol scores between cases and controls. Conditional logistic regression was used to predict case vs. control by hair cortisol score, controlling for relevant covariates. RESULTS: Baseline characteristics of cases and controls did not differ. Hair cortisol levels were significantly lower among cases in the adjusted analysis. Hair cortisol level was a predictor of case versus control. Each 10-pg.mg-1 increase in hair cortisol level was associated with an estimated 33% decreased odds of being a case. The only significant difference in the validated questionnaires was an increased measure of emotional neglect in the preterm group. CONCLUSION: Our study suggests that women who deliver prematurely may have lower hair cortisol levels than women who deliver at term. Normal hypothalamic-pituitary-adrenal axis activation is a physiologic, adaptive response to stress. One hypothesis to explain our results are that women who are stressed, but unable to mount an adequate stress response could be at particular risk for preterm birth.

Pilot study of adrenal steroid hormones in hair as an indicator of chronic mental and physical stress.

Currently, the quantitative analysis of moderators affecting the function of the hypothalamus-pituitary-adrenal (HPA)-axis in health and sickness is still unreliable. This is, in particular, due to physiological factors such as pulsatile ultradian and circadian glucocorticoid secretion as well as to methodological limitations of the current techniques for steroid hormone determination. Based on this background, the determination of long-term hair steroid concentrations is an important methodological improvement allowing for the quantitative analysis of chronic HPA axis-activation. In order to determine the relationship between chronic mental and physical stress and a chronic activation of the HPA axis, we performed a cross-sectional pilot-study with 40 healthy students and examined the relationships between physical activity, mental burden(s), subjective stress perceptions, depressiveness, anxiety, physical complaints, sense of coherence, resilience, and the long-term integrated steroid hormone levels in hair. The results showed that the concentrations of cortisol, cortisone, and dehydroepiandrosterone in hair were significantly correlated to mental (p = 0.034) and physical stress (p = 0.001) as well as to subjective stress perception (p = 0.006). We conclude that steroid concentrations in hair are decisive predictors for an increase in the long-term-HPA axis activity. Moreover, this biomarker is suitable for capturing the stresslevel after burdening events and physical activity.