Assessment of the human response to acute mental stress-An overview and a multimodal study.

Numerous vital signs are reported in association with stress response assessment, but their application varies widely. This work provides an overview over methods for stress induction and strain assessment, and presents a multimodal experimental study to identify the most important vital signs for effective assessment of the response to acute mental stress. We induced acute mental stress in 65 healthy participants with the Mannheim Multicomponent Stress Test and acquired self-assessment measures (Likert scale, Self-Assessment Manikin), salivary α-amylase and cortisol concentrations as well as 60 vital signs from biosignals, such as heart rate variability parameters, QT variability parameters, skin conductance level, and breath rate. By means of statistical testing and a self-optimizing logistic regression, we identified the most important biosignal vital signs. Fifteen biosignal vital signs related to ventricular repolarization variability, blood pressure, skin conductance, and respiration showed significant results. The logistic regression converged with QT variability index, left ventricular work index, earlobe pulse arrival time, skin conductance level, rise time and number of skin conductance responses, breath rate, and breath rate variability (F1 = 0.82). Self-assessment measures indicated successful stress induction. α-amylase and cortisol showed effect sizes of -0.78 and 0.55, respectively. In summary, the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system were successfully activated. Our findings facilitate a coherent and integrative understanding of the assessment of the stress response and help to align applications and future research concerning acute mental stress.

Validation of a non-invasive assessment technique for quantifying faecal glucocorticoid metabolite concentrations in the short-beaked echidna (Tachyglossus aculeatus).

The monotreme adrenocortical response to stress may not rely as heavily on the hypothalamic-pituitaryadrenal (HPA) axis compared to other mammals. This study aimed to validate a technique in which glucocorticoid metabolites could be quantified non-invasively in short-beaked echidna faeces by examining the secretion of glucocorticoids (GC) using an adrenocorticotrophic hormone (ACTH) challenge on sexually mature captive echidnas. Echidnas were housed individually for 15 days, with the ACTH challenge occurring on day five. Blood samples were collected on day five during the challenge and faecal samples were collected each morning for the 15 days. Both sample types were analysed for glucocorticoids (GC) or its metabolites. Plasma corticosterone concentrations increased significantly after 30 min and 60 min relative to time 0, whilst plasma cortisol concentrations increased significantly after 60 min. The ACTH challenge also resulted in an increase in glucocorticoid metabolite concentration in faecal samples from four of the six echidnas detected one to two days post ACTH injection, thereby validating a non-invasive method to assess adrenal response in the echidna. These results confirm that echidnas respond to a synthetic ACTH challenge in a similar manner to that of eutherian species indicating that echidnas appear to use the HPA axis in their stress response.

The Assessment of the Hypothalamic-Pituitary-Adrenal Axis After Oncological Treatment in Pediatric Patients with Acute Lymphoblastic Leukemia

Objective: Oncologic treatment can affect the adrenal glands, which in stressful situations may lead to life threatening adrenal crisis. The aim of the study was to assess adrenal function in pediatric acute lymphoblastic leukemia (ALL) survivors and to identify the best markers for this assessment. Methods: Forty-three ALL survivors, mean age 8.5±3.6 years and 45 age and sex-matched healthy controls were recruited to the study. ALL patients were assessed once within five years following oncological treatment completion. Fasting blood samples were collected from all participants to measure: fasting blood glucose (FBG); cortisol; aldosterone; plasma renin activity (PRA); dehydroepiandrostendione-sulfate (DHEA-S); and adrenocorticotropic hormone (ACTH). Moreover, diurnal profile of cortisol levels and 24-hour urinary free cortisol (UFC) were assessed. ALL survivors underwent a test with 1 ug of synthetic ACTH. Results: The study revealed lower level of PRA (1.94±0.98 ng/mL/h vs 3.61±4.85 ng/mL/h, p=0.029) and higher FBG (4.6±0.38 mmol/L vs 4.41±0.39 mmol/L, p=0.018) in the ALL group compared to controls. UFC correlated with evening cortisol (p=0.015, r=0.26), midnight cortisol (p=0.002, r=0.33), and DHEA-S (p=0.004, r=0.32). UFC also correlated with systolic and diastolic blood pressure (p=0.033, r=0.23 and p=0.005, r=0.31, respectively). The ACTH test confirmed impaired adrenal function in 4/43 ALL survivors (9%). Two of the patients who needed permanent hydrocortisone replacement had low UFC, midnight cortisol and DHEA-S levels. Conclusion: These results highlight the importance of reviewing adrenal gland functionality after chemo/radiotherapy in ALL survivors. DHEA-S proved to be a good marker to assess the adrenal glands after oncological therapy. Post-treatment disturbances of the adrenal axis could be associated with metabolic complications.

Associations between multiple indicators of discrimination and allostatic load among middle-aged adults.

The objective of this paper is to examine associations between multiple measures of discrimination (i.e., everyday, lifetime, and appraised burden) and components of allostatic load (AL). We drew on pooled cross-sectional data from the Biomarker Project of the Midlife in the United States study (n = 2118). Ages ranged from 25 to 84 years and included mostly Black (n = 389) and white (n = 1598) adults. Quasi-Poisson models were fit to estimate prevalence ratios for each discrimination measure and high-risk quartiles across seven physiological systems (i.e., sympathetic and parasympathetic nervous system; HPA axis; inflammation; cardiovascular; metabolic glucose; and metabolic lipids) and overall AL scores. In fully adjusted models, everyday discrimination was associated with elevated lipids (aPR: 1.07; 95% CI 1.01, 1.13). Lifetime experiences of discrimination were associated with lower sympathetic nervous system (aPR: 0.82; 95% CI: 0.69, 0.98) and greater cardiovascular risk scores (aPR: 1.17; 95% CI: 1.02, 1.34) among those reporting three or more experiences, as well as increased inflammation (aPR: 1.13; 95% CI: 1.02, 1.25; aPR: 1.28; 95% CI: 1.14, 1.43), metabolic glucose (aPR: 1.35; 95% CI: 1.19, 1.54; aPR: 1.45; 95% CI: 1.24, 1.68), and metabolic lipids (aPR: 1.13; 95% CI: 1.03, 1.24; aPR: 1.28; 95% CI: 1.15, 1.43) scores for those reporting one to two and three or more experiences. Appraised burden yielded nuanced associations with metabolic glucose and parasympathetic nervous system scores. Everyday and lifetime measures were also associated with higher overall AL, though burden of discrimination was only associated with AL among those reporting "a little" burden. While AL summary scores provide insight into the cumulative impacts of discrimination on health, there appear to be distinct physiologic pathways through which varying forms of discrimination contribute to AL and, ultimately, to poorer health. These unique pathways may be useful in identifying potential points of intervention to mitigate the impacts of discrimination on health inequities.

Links Between Socioeconomic Status, Daily Depressive Affect, Diurnal Cortisol Patterns, and All-Cause Mortality.

OBJECTIVE: Socioeconomic status (SES) remains a robust risk factor for mortality. Various theoretical models postulate that lower SES is associated with higher negative affect, which then initiates a cascade of physiological disturbances that contribute to illness and early mortality. However, few studies have explicitly investigated the interplay between psychological and biological factors in determining SES disparities in mortality. This study examined the role of daily negative affect and cortisol secretion in explaining the SES-mortality link in a large sample of US adults. METHODS: Using data from the Midlife in the United States study (n = 1735, mean [standard deviation] age = 56.40 [12.10] years, 56.4% female), we tested longitudinal associations between SES, daily negative affect, daily cortisol levels, and all-cause mortality 13 years later. Daily negative affect was classified into three clusters reflecting depressive affect, anxiety, and anger. RESULTS: Higher SES was linked to a lower risk of all-cause mortality (hazard ratio = 0.94, 95% confidence interval = 0.90 to 0.97). Furthermore, there was a sequential link between higher SES and lower mortality through lower daily depressive affect and a steeper ("healthier") diurnal cortisol slope (indirect effect = -0.0007, 95% confidence interval = -0.0014 to -0.0002). Daily anxiety and anger were not associated with cortisol levels or mortality (p values > .05). CONCLUSIONS: These findings suggest that daily negative emotional experiences and the hypothalamic-pituitary-adrenal axis functioning may constitute important psychological and physiological pathways underlying the link between SES and all-cause mortality.

Stress response asymmetries in African American emerging adults exposed to chronic social adversity.

Chronic stress is linked to social adversity and underlies many health disparities among ethnic minorities. Cortisol and salivary alpha-amylase (sAA) reflect sensitivity to adversity and are related to health outcomes. Our aim was to understand how social adversity influences biological responses to experimental and daily stressors in a sample of low-income African American emerging adults. In the three-week study, participants completed questionnaires, the Trier Social Stress Task (TSST), and provided four salivary samples. In week 2, participants collected saliva at home immediately after waking and just before bed for three days. Results demonstrated an asymmetrical pattern between cortisol and sAA reactivity that was related to experiences with racism and interpersonal trauma. Further, daily stress was related to lower morning and higher nighttime cortisol, indicating atypical diurnal rhythm. These findings are consistent with other forms of social adversity that lead to long-term changes in the HPA axis response pattern.LAY SUMMARYAfrican American emerging adults showed divergent cortisol and sAA responses.Social adversity predicted an asymmetrical response pattern for sAA and cortisol.Atypical diurnal rhythms were found for participants reporting high daily stress.

The social ecology of childhood and early life adversity.

An increasing prevalence of early childhood adversity has reached epidemic proportions, creating a public health crisis. Rather than focusing only on adverse childhood experiences (ACEs) as the main lens for understanding early childhood experiences, detailed assessments of a child's social ecology are required to assess "early life adversity." These should also include the role of positive experiences, social relationships, and resilience-promoting factors. Comprehensive assessments of a child's physical and social ecology not only require parent/caregiver surveys and clinical observations, but also include measurements of the child's physiology using biomarkers. We identify cortisol as a stress biomarker and posit that hair cortisol concentrations represent a summative and chronological record of children's exposure to adverse experiences and other contextual stressors. Future research should use a social-ecological approach to investigate the robust interactions among adverse conditions, protective factors, genetic and epigenetic influences, environmental exposures, and social policy, within the context of a child's developmental stages. These contribute to their physical health, psychiatric conditions, cognitive/executive, social, and psychological functions, lifestyle choices, and socioeconomic outcomes. Such studies must inform preventive measures, therapeutic interventions, advocacy efforts, social policy changes, and public awareness campaigns to address early life adversities and their enduring effects on human potential. IMPACT: Current research does not support the practice of using ACEs as the main lens for understanding early childhood experiences. The social ecology of early childhood provides a contextual framework for evaluating the long-term health consequences of early life adversity. Comprehensive assessments reinforced with physiological measures and/or selected biomarkers, such as hair cortisol concentrations to assess early life stress, may provide critical insights into the relationships between early adversity, stress axis regulation, and subsequent health outcomes.

Psychological stress and cortisol during pregnancy: An ecological momentary assessment (EMA)-Based within- and between-person analysis.

BACKGROUND: Although the linkage between psychological stress and cortisol is believed to mediate the association of stress with health outcomes, several studies have been unable to demonstrate this association. We suggest this inability may be a consequence of limitations in the measurement approach and/or reliance on analytic strategies that focus on associations across, rather than within individuals. The link between psychological stress and cortisol is of particular interest in the context of pregnancy and fetal development. Using an ecological momentary assessment (EMA) design, we examined the association between psychological stress and cortisol at the between- and the within-person level. METHODS: 152 participants completed a 4-day long EMA protocol serially in early, mid and late pregnancy to provide momentary stress appraisals (average of 150 measures/subject) and saliva samples (average of 55 samples/subject) for quantification of cortisol. The association between stress and cortisol was estimated using linear mixed models. RESULTS: After accounting for the effects of key determinants of variation in cortisol, momentary stress was significantly and positively associated with cortisol at the within-person level (B = .030, p = .031), but not at the between-person level. No association was evident for traditional retrospective measures of stress with cortisol at either the between- or the within-person level. CONCLUSIONS: Our study highlights the value of EMA methods and linear mixed-modeling approaches in linking maternal psychological and physiological states across pregnancy. These findings may have important implications for the development of personalized risk identification and "just-in-time" intervention strategies to optimize maternal and child health.

The effects of suppressing the biological stress systems on social threat-assessment following acute stress.

RATIONALE: Stress is associated with increased sensitivity to threat. Previous investigations examining how stress affects threat processing have largely focused on biomarker responses associated with either the sympathetic-nervous-system (SNS) or the hypothalamus-pituitary-adrenal (HPA) axis. OBJECTIVES: We pharmacologically suppressed activations of SNS, HPA, or both, prior to stress and investigated how each stress system modulates social threat assessment. METHODS: One hundred sixty-one healthy men and women were randomized in a between-subject design, to one of four pharmacological or placebo conditions: dexamethasone-placebo, placebo-propranolol, dexamethasone-propranolol, or placebo-placebo. Participants provided threat assessments for angry and neutral human faces on a baseline day, and immediately after stress induction on a testing day. RESULTS: With both systems responding normally to stress (placebo-placebo), threat assessment was higher for neutral faces compared with angry. Compared with placebo, SNS suppression resulted in increased threat assessment for angry faces. HPA suppression resulted in decreased threat assessment for neutral and angry faces. When both systems were suppressed, there was an increase in threat assessment for angry faces, and no difference from placebo for neutral. CONCLUSION: Our findings demonstrated that when intact, the biological stress systems adaptively support organisms during stress by focusing attention towards specific stimuli that are relevant to the threat. Dysregulations of the stress systems result in important system specific consequences on threat evaluation, such that suppression of either stress system alone resulted in reduced threat assessment for contextually relevant threatening stimuli, whereas when both systems were suppressed, individuals appear indiscriminately attentive to all potential threats in the environment, resulting in increased threat processing of both contextually relevant and irrelevant stimuli. Given that stress-related psychopathologies have been associated with dysregulations of the stress systems and biased responses to social threat, a systematic understanding of the mechanisms that underlie how stress systems modulate social threat assessment is needed, and can provide important insights into the cognitive processes that are involved in the development and maintenance of stress-related psychopathologies.

Systematic Review of Chronic Discrimination and Changes in Biology During Pregnancy Among African American Women.

Profound racial health disparities in maternal and infant health exist in the USA. Discrimination based on race may contribute to these disparities, but the biological pathways through which racial discrimination acts on health are not fully known. Even less is known about these pathways during development. Examining how racial discrimination becomes biology is paramount because it may shed light on how and when such social forces result in lasting biological consequences for health and wellbeing. To begin exploring this issue, we performed a systematic review of the relationships between experiences of chronic racial discrimination and relevant biomarkers measured during pregnancy among African American women. The literature search included studies published prior to August 2018 in the MEDLINE, Embase, and PsycINFO databases, and 11 studies met our inclusion criteria. We evaluated the articles based on the biological system that the authors investigated, which included the immune, neuroendocrine, and cardiovascular systems. We found that the current literature provides preliminary evidence that experiences of chronic racial discrimination are associated with changes in maternal biology during pregnancy. However, the literature was limited in both quantity and quality. We found only 11 studies that addressed this subject, four of which only provided indirect evidence, and many studies had small sample sizes. Future work in this area should develop more informative methods that consider the interaction between interpersonal and structural racial discrimination, individual variation, and sociocultural factors. We conclude researchers should continue to work in this area and focus on developing more effective study designs and larger sample sizes.

Postnatal impoverished housing impairs adolescent risk-assessment and increases risk-taking: A sex-specific effect associated with histone epigenetic regulation of Crfr1 in the medial prefrontal cortex.

While increasing evidence posits poor decision-making as a central feature of mental disorders, very few studies investigated the effects of early-life stress (ELS) on specific components of reward-related choice behaviors. Risk-taking (RT) involves the exposure to some danger, or negative consequences, in order to achieve a goal-directed behavior. Such behaviors are likely to be preceded by risk-assessment (RA), which is a dynamic cognitive process involving the acquisition of information in potentially dangerous situations. Here, we investigated the effects of being raised in impoverished housing conditions during early life (P2-P9) on RT, RA and dopaminergic and corticotrophinergic gene expression of adolescent male and female mice. Phenotypes were assessed by two protocols: the elevated plus-maze (EPM) and the predator-odor risk-taking (PORT). We found decreased RA in mice exposed to impoverished housing in the absence of a reward (EPM), with a more pronounced effect among females. Moreover, when exposed to a predatory olfactory cue, increased RT was observed in these females in a reward-related task (PORT), as well as decreased HPA axis responsivity. This sex-specific behavioral effect was associated with increased Crfr1 mRNA expression in the medial prefrontal cortex (mPFC) and higher levels of the histone mark H3R2me2s, a histone modification known to be involved in transcriptional activation, within the promoter of the Crfr1 gene. These findings revealed that ELS exposure can impair the acquisition of environmental information in dangerous situations and increase RT in reward-related scenarios among females, with an important role regarding epigenetic regulation of the Crfr1 gene.

Benefit finding and diurnal cortisol after prostate cancer: The mediating role of positive affect.

OBJECTIVE: Benefit finding (BF) has exhibited a salutary effect on psychological adjustment to cancer. However, few studies have examined its relationship with physiology or have examined BF in men with cancer. This study investigated whether BF is associated with hypothalamic-pituitary-adrenal axis activity (ie, diurnal salivary cortisol) in men treated for prostate cancer. Positive affect (PA) is proposed as a potential pathway linking BF to diurnal salivary cortisol. METHODS: A sample of 66 men treated for localized prostate cancer within the prior 2 years completed questionnaires and collected salivary cortisol 3 times per day over 3 consecutive days. Hierarchical linear modeling was used for estimating the effects of BF and PA on cortisol responses as measured by diurnal slope and area under the curve (AUCg). Confidence intervals for indirect effects were estimated using the Monte Carlo method for mediation testing. RESULTS: BF was significantly associated with diurnal cortisol slope, controlling for body mass index and age (B = -.12, P = .03), such that greater BF was associated with steeper cortisol slope. Analyses revealed that PA mediated the effect of BF on cortisol slope (Monte Carlo estimation 95% CI = -0.087, -0.001); negative affect did not mediate this relationship. BF was not significantly associated with AUCg. CONCLUSIONS: Deriving more benefit from one's experience with prostate cancer is associated with a healthier diurnal cortisol rhythm. Through its potential to enhance PA, the relationship of BF and physiological processes underscores the health relevant value of BF in prostate cancer survivors.

Assessment of Brain Derived Neurotrophic Factor in hair to study stress responses: A pilot investigation.

To study pathogenic stress-effects in health and disease, it is paramount to define easy access parameters for non-invasive analysis of biological change in response to stress. Hair samples successfully provide this access for the study of hypothalamus-pituitary-adrenal axis (HPA) changes. In this study, we assess the hair expression and corresponding epigenetic changes of a neurotrophin essential for autonomic nervous system function and mental health: brain derived neurotrophic factor (BDNF). In three independent studies in healthy academic volunteers (study I: German students, N=36; study II, German academic population sample, N=28; study III: Mexican students, N=115), BDNF protein expression or BDNF gene (BDNF) histone acetylation was determined. Simultaneously, mental distress and distress-associated somatic complaints were assessed by self-report. In study I, we found a negative correlation between hair-BDNF protein level and hair-cortisol as well as between hair-BDNF and somatic complaints, while hair-cortisol correlated positively with mental distress. In study II, we found a negative correlation between H4 histone acetylation at the BDNF gene P4-promoter and somatic complaints. Regression analysis confirmed confounder stability of associations in both studies. In study III, we confirmed study I and found lower hair-BDNF protein level in volunteers with high somatic complaints, who also reported higher mental distress during the end of term exams. The results indicate that BDNF protein levels can be detected in clipped hair and are associated with somatic complaints and stress in life. In addition, we concluded that plucked hair can provide material for the study of epigenetic changes in stress-affected tissues. These tools can prove valuable for future studies on distress, both under experimental and field conditions.

Income inequality, gene expression, and brain maturation during adolescence.

Income inequality is associated with poor health and social outcomes. Negative social comparisons and competition may involve the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes in underlying some of these complex inter-relationships. Here we investigate brain maturation, indexed by age-related decreases in cortical thickness, in adolescents living in neighborhoods with differing levels of income inequality and household income. We examine whether inter-regional variations relate to those in glucocorticoid receptor (HPA) and androgen receptor (HPG) gene expression. For each sex, we used a median split of income inequality and household income (income-to-needs ratio) to create four subgroups. In female adolescents, the high-inequality low-income group displayed the greatest age-related decreases in cortical thickness. In this group, expression of glucocorticoid and androgen receptor genes explained the most variance in these age-related decreases in thickness across the cortex. We speculate that female adolescents living in high-inequality neighborhoods and low-income households may experience greater HPA and HPG activity, leading to steeper decreases in cortical thickness with age.

Social context matters: Ethnicity, discrimination and stress reactivity.

Exposure to chronic discrimination is associated with increased morbidity and mortality. The study of biobehavioral pathways linking discrimination with health outcomes has mostly focused on the cardiovascular system, with fewer studies addressing the hypothalamus-pituitary-adrenal (HPA) axis. In this study we tested associations between Latino ethnicity, experiences of discrimination, and cortisol responses to an acute laboratory stressor. One hundred fifty eight individuals (92 female, 66 male) between the ages of 18 and 29 years participated in the study. Salivary cortisol was measured once before and eight times after administration of a laboratory stressor (the Trier Social Stress Test). Past experiences of discrimination were measured with the Experiences of Discrimination Scale. Findings from conditional process modeling suggest that Latino ethnicity predicted a) heightened cortisol reactivity and b) more pronounced cortisol recovery through discrimination experiences (mediator), and that this effect was further moderated by sex with a significant indirect effect only among males. The direct path from Latino ethnicity to cortisol reactivity or cortisol recovery was, however, not significant. In sum, findings suggest that Latino ethnicity and discrimination interact to predict cortisol dysregulation, which implies that an appropriate model for understanding minority health discrepancies must incorporate interactive processes and cannot simply rely on the effects of ethnicity or discrimination alone.

Determinants of cortisol during pregnancy - The ABCD cohort.

BACKGROUND: Psychosocial stress during pregnancy has been proposed as a major contributor of glucocorticoid-mediated programming of the fetal hypothalamic-pituitary adrenal (HPA) axis, with later adverse health consequences. However, evidence linking maternal stress to maternal cortisol values during pregnancy is inconclusive. A possible explanation for this is that other maternal factors overshadow any potential effects of stress on cortisol levels. We studied a large cohort of pregnant women with extensive data on pregnancy characteristics to determine the respective contributions of biological, environmental and psychosocial stress factors to cortisol levels in pregnancy. METHODS: We used data from 3039 women from the Amsterdam Born Children and their Development-study cohort. Serum cortisol was measured in blood, collected at the first prenatal visit, at different gestational ages (median=91days, range=40-256days), and at various time points during the day (median=11:45h, range=08:00-18:30h). We assessed associations between maternal serum cortisol in pregnancy and biological factors, lifestyle factors and stress factors, including depression, anxiety, pregnancy-related anxiety, work stress, parenting stress and fatigue. RESULTS: In multivariable analysis, variables that were associated with higher cortisol levels in pregnancy were lower maternal age [1.5nmol/l, 95%CI (0.6-2.4)], being nulliparous [21.5 nmol/l (15.9-27.1)], lower pre-pregnancy body mass index (BMI) [1.3nmol/l (0.3-2.4)], higher C-reactive protein (CRP) [1.0nmol/l (0.4-1.5)], carrying a female fetus [9.2nmol/l (1.8-16.5)], non-smoking [14.2nmol/l (0.6-27.7)], sufficient sleep [8.5nmol/l (0.9-16.1)], and being unemployed [12.7nmol/l (2.2-23.2)]. None of the psychosocial stressors was significantly associated with serum cortisol levels in pregnancy. A total of 32% of all variance in cortisol was explained by gestational age, maternal age, time of day, parity, pre-pregnancy BMI, CRP, fetal sex, smoking behavior, self-reported sleep sufficiency, and employment. CONCLUSIONS: Our data suggest that maternal cortisol during pregnancy is mainly affected by biological and lifestyle factors, but not by psychosocial factors. We suggest that psychosocial stress in pregnancy might program the fetus through other mechanisms than through altering maternal cortisol levels.

Assessment of the role of intracranial hypertension and stress on hippocampal cell apoptosis and hypothalamic-pituitary dysfunction after TBI.

In recent years, hypopituitarism caused by traumatic brain injury (TBI) has been explored in many clinical studies; however, few studies have focused on intracranial hypertension and stress caused by TBI. In this study, an intracranial hypertension model, with epidural hematoma as the cause, was used to explore the physiopathological and neuroendocrine changes in the hypothalamic-pituitary axis and hippocampus. The results demonstrated that intracranial hypertension increased the apoptosis rate, caspase-3 levels and proliferating cell nuclear antigen (PCNA) in the hippocampus, hypothalamus, pituitary gland and showed a consistent rate of apoptosis within each group. The apoptosis rates of hippocampus, hypothalamus and pituitary gland were further increased when intracranial pressure (ICP) at 24 hour (h) were still increased. The change rates of apoptosis in hypothalamus and pituitary gland were significantly higher than hippocampus. Moreover, the stress caused by surgery may be a crucial factor in apoptosis. To confirm stress leads to apoptosis in the hypothalamus and pituitary gland, we used rabbits to establish a standard stress model. The results confirmed that stress leads to apoptosis of neuroendocrine cells in the hypothalamus and pituitary gland, moreover, the higher the stress intensity, the higher the apoptosis rate in the hypothalamus and pituitary gland.

Brief report: Neighborhood disadvantage and hair cortisol among older urban African Americans.

Previous studies have shown that living in poor neighborhoods is associated with increased morbidity and mortality. However, researchers are now investigating the biological pathways responsible for the deleterious effects of neighborhood disadvantage on health. This study investigated whether neighborhood disadvantage (i.e., a measure of relative neighborhood quality derived by combining social and built environmental conditions) was associated with hair cortisol-a retrospective indicator of long-term hypothalamic pituitary adrenal (HPA) axis activation-and whether this link would be mediated by self-reported neighborhood satisfaction. Forty-nine older African Americans were recruited from thirty-nine Detroit census tracts across five strata of census tract adversity. Participants were interviewed face-to-face to collect psychosocial measures. Each provided a hair sample for analysis of cortisol. Multiple regression analyses revealed that higher neighborhood disadvantage was associated with higher levels of hair cortisol levels and that neighborhood satisfaction partially explained this association. These results are the first to our knowledge to demonstrate a direct link between neighborhood disadvantage and hair cortisol in a sample of older adults and to show that self-reported neighborhood satisfaction may be a psychological intermediary of this association.

Feasibility of Hair Collection for Cortisol Measurement in Population Research on Adolescent Health.

BACKGROUND: Black-White disparities in adolescent health are widespread and thought to be explained, in part, by exposure to chronic stress. Cortisol assayed from hair is increasingly recognized as a valid and reliable measure for chronic physiological stress, but the feasibility of collecting hair among large probability samples of diverse adolescents is unknown. PURPOSE: The aim of the study was to investigate participation in hair collection for cortisol analyses in a probability sample of racially and socioeconomically diverse adolescents, including the extent to which sociodemographic factors and adverse exposures were associated with participation. METHODS: The study included a probability sample of 516 adolescents conducted in conjunction with a prospective cohort study on adolescent health. Data were collected over 1 week via in-home interviews, ecological momentary assessment, global positioning system methods, and in-home hair collection at the end of the week. RESULTS: Of the 516 eligible youth, 471 (91.3%) participated in the hair collection. Of the 45 youth who did not provide hair samples, 18 had insufficient hair, 25 refused, and 2 did not participate for unknown reasons. Multivariable logistic regression results indicated that non-Hispanic Black youth were less likely than their non-Hispanic White peers to participate due to insufficient hair or refusal (OR = 0.24, 95% CI [0 .09, 0.60]). Despite lower rates of participation, the proportion of Black youth in the participating sample was representative of the study area. No significant differences in participation were found by other sociodemographic characteristics or adverse exposures. CONCLUSIONS: Hair collection for cortisol measurement is feasible among a probability sample of racially and socioeconomically diverse adolescents. Hair cortisol analyses may accelerate research progress to understand the biological and psychosocial bases of health disparities.

Socioeconomic status in children is associated with hair cortisol levels as a biological measure of chronic stress.

INTRODUCTION: Low socioeconomic status (SES) may be associated with a high risk of lifestyle-related diseases such as cardiovascular diseases. There is a strong association between parental SES, stress and indicators of child health and adult health outcome. The exact mechanisms underlying this association have not yet been fully clarified. Low SES may be associated with chronic stress, which may lead to activation of the hypothalamic-pituitary-adrenal (HPA)-axis, resulting in a higher circulating level of the stress hormone cortisol. Therefore, chronic stress may mediate the association between low SES and elevated cortisol levels and its adverse outcomes. AIM: We investigated whether SES was associated with a chronic measure of cortisol exposure in a child population. METHODS: Cortisol and cortisone were measured in scalp hair in 270 children and adolescents, aged 4-18 years, enrolled through school visits. Neighborhood level SES was based on a score developed by the Netherlands Institute for Social Research using postal codes, and this includes neighborhood measures of income education and unemployment. Maternal and paternal education level were used as indicators of family SES. RESULTS: Neighborhood level socioeconomic status score was significantly associated with hair cortisol (ß=-0.103, p=0.007, 95%CI [-0.179, -0.028]) and hair cortisone (ß=-0.091, p=0.023, 95%CI [-0.167, -0.015]), adjusted for age and sex. Additionally, hair cortisol was significantly correlated with maternal education level and hair cortisone was significantly correlated with paternal education level. CONCLUSION: The results of our study suggest that the widely shown association between low family SES and adverse child health outcomes may be mediated by chronic stress, given the chronically higher levels of cortisol in children and adolescents in families with low SES. It is especially notable that the association between SES and cortisol was already found in children of young age as this can have major consequences, such as increased risk of cardio metabolic diseases in later life.