Measure Of Chronic Stress Research Articles

Allostatic Load as a Modifier of Associations Between Metals and Blood Pressure

BACKGROUND AND AIM: Disadvantaged populations are often co-exposed to high levels of metals and psychological stressors. While limited research suggests that stress may increase susceptibility to lead cardiotoxicity, the influence of stress on other metals remains unexplored. We examined whether allostatic load (AL), a measure of chronic stress, modifies associations between metals (cadmium, mercury, arsenic, antimony, cesium, cobalt, molybdenum, thallium, tungsten, uranium, or lead) and blood pressure (BP). METHODS: We analyzed cross-sectional data on 11 blood and urinary metal biomarkers and systolic and diastolic BP in 5,022 adults (20+ years) participating in NHANES 2003-2010 using linear regression models. We assessed whether associations were modified by AL using interaction terms and stratified analyses. Because there is no scientific consensus on how to measure AL, we compared four different approaches to dichotomize participants into high and low AL based on seven stress biomarkers. Final models for each metal were adjusted for age, sex, race/ethnicity, BMI, education level, serum cotinine, urinary creatinine (to account for urinary dilution), and other confounding metals (e.g., lead). RESULTS: For diastolic BP, we observed no significant interactions between any metals and AL, but stratified analyses indicated that blood lead and urinary cobalt were significantly associated with higher BP in the high AL group only. These results were robust to the method used to define AL. For systolic BP, we observed the opposite trend: blood lead and urinary cobalt were associated with higher BP in the low AL group but not the high AL group, though results varied by AL definition. CONCLUSIONS: AL may modify the association between certain metals and BP in adults. As results may differ by method used to define AL, future research should use multiple approaches to operationalize AL until consensus is reached on the most appropriate definition. KEYWORDS: Metals, Stress, Blood Pressure, Allostatic Load

The effect of cumulative early life adversities, and their differential mediation through hair cortisol levels, on childhood growth and cognition: Three-year follow-up of a birth cohort in rural India.

Background: Early adversities negatively impact children's growth and development, putatively mediated by chronic physiological stress resulting from these adverse experiences. We aimed to estimate the associations between prospectively measured cumulative early adversities with growth and cognition outcomes in rural Indian preschool children and to explore if hair cortisol concentration (HCC), a measure of chronic physiological stress, mediated the above association. Methods: Participants were recruited from the SPRING cRCT in rural Haryana, India. Adversities experienced through pregnancy and the first year of life were measured in 1304 children at 12-months. HCC was measured at 12-months in 845 of them. Outcome measures were height-for-age-z-score (HAZ), weight-for-age-z-score (WAZ) and cognition, measured in 1124 children followed up at 3-years. Cognition was measured using a validated tablet-based gamified tool named DEEP. Results: Cumulative adversities at 12-months were inversely associated with all outcomes measures at 3-years. Each unit increase in adversity score led to a decrease of 0·08 units [95% confidence interval (CI):-0·11,-0·06] in DEEP-z-score; 0·12 units [-0·14,-0·09] in HAZ and 0·11 units [-0·13,-0·09] in WAZ. 12-month HCC was inversely associated with DEEP-z-score (-0·09 [-0·16,-0·01]) and HAZ (-0·12 [-0·20,-0·04]), but the association with WAZ was not significant (p = 0·142). HCC marginally mediated the association between cumulative adversities and HAZ (proportion mediated = 0·06, p = 0·014). No evidence of mediation was found for the cognition outcome. Conclusions: Cumulative early adversities and HCC measured at 12-months have persistent negative effects on child growth and cognition at 3-years. The association between adversities and these two child outcomes were differentially mediated by HCC, with no evidence of mediation observed for the cognitive outcome. Future studies should focus on other stress biomarkers, and alternate pathways such as the immune, inflammation and cellular ageing pathways, to unpack key mechanisms underlying the established relationship between early adversities and poor child outcomes.

The effect of cumulative early life adversities, and their differential mediation through hair cortisol levels, on childhood growth and cognition: Three-year follow-up of a birth cohort in rural India

Background: Early adversities negatively impact children’s growth and development, putatively mediated by chronic physiological stress resulting from these adverse experiences. We aimed to estimate the associations between prospectively measured cumulative early adversities with growth and cognition outcomes in rural Indian preschool children and to explore if hair cortisol concentration (HCC), a measure of chronic physiological stress, mediated the above association. Methods: Participants were recruited from the SPRING cRCT in rural Haryana, India. Adversities experienced through pregnancy and the first year of life were measured in 1304 children at 12-months. HCC was measured at 12-months in 845 of them. Outcome measures were height-for-age-z-score (HAZ), weight-for-age-z-score (WAZ) and cognition, measured in 1124 children followed up at 3-years. Cognition was measured using a validated tablet-based gamified tool named DEEP. Results: Cumulative adversities at 12-months were inversely associated with all outcomes measures at 3-years. Each unit increase in adversity score led to a decrease of 0·08 units [95% confidence interval (CI):-0·11,-0·06] in DEEP-z-score; 0·12 units [-0·14,-0·09] in HAZ and 0·11 units [-0·13,-0·09] in WAZ. 12-month HCC was inversely associated with DEEP-z-score (-0·09 [-0·16,-0·01]) and HAZ (-0·12 [-0·20,-0·04]), but the association with WAZ was not significant (p = 0·142). HCC marginally mediated the association between cumulative adversities and HAZ (proportion mediated = 0·06, p = 0·014). No evidence of mediation was found for the cognition outcome. Conclusions: Cumulative early adversities and HCC measured at 12-months have persistent negative effects on child growth and cognition at 3-years. The association between adversities and these two child outcomes were differentially mediated by HCC, with no evidence of mediation observed for the cognitive outcome. Future studies should focus on other stress biomarkers, and alternate pathways such as the immune, inflammation and cellular ageing pathways, to unpack key mechanisms underlying the established relationship between early adversities and poor child outcomes.

Hair cortisol as a viable tool for the assessment of an association between environmental noise exposure and chronic stress.

Entrenched in the well-established link between stress and health, noise exposure as a potential contributor to stress-related health effects receives tremendous attention. Indeed, exposure to noise can act as a stressor as evidenced through increased heart rate, blood pressure, adrenaline, epinephrine, and cortisol. Cortisol is secreted from the adrenal glands in response to stressor-induced activation of the hypothalamic-pituitary-adrenal axis. For assessment of environmental noise and stress, repeated sampling in blood, saliva, or urine is necessary to evaluate the association between environmental noise exposure and protracted changes in cortisol. Controlling for the many variables that influence the secretion of cortisol at discrete sampling intervals is challenging. Studies suggest that systemically produced cortisol integrates and remains in hair as it grows, providing a measure that integrates a cortisol response over a longer period, circumventing several limitations associated with multiple sampling. Robust evidence supports the integration of cortisol into hair, yet recent studies call into question the notion that cortisol is retained with growth. The current paper discusses the strengths and limitations of hair cortisol analysis with an emphasis on its utility as a measure of chronic stress in environmental noise studies.

Higher hair cortisol concentrations associated with shorter leukocyte telomere length in high-risk young adults

Chronic stress is associated with accelerated biological aging as indexed by short age-adjusted leukocyte telomere length (LTL). Exploring links of biological stress responses with LTL has proved challenging due to the lack of biological measures of chronic psychological stress. Hair cortisol concentration (HCC) has emerged as a measure of chronic hypothalamic pituitary adrenal (HPA) axis activation, allowing the examination of relationships between aggregate cortisol concentrations over time and LTL. Our sample includes 92 participants (38% women, Mage = 26 ± 3.7 years) from a high-risk sample of young adults with previous residential care placements. Two cm hair was collected for HCC, reflecting approximately eight weeks of cortisol secretion. LTL was measured with quantitative polymerase chain reaction (qPCR) in whole blood samples. All samples for LTL were run in triplicate and assayed twice. Linear and polynomial regression models were used to describe the association between HCC and LTL, adjusting for age and sex. HCC and LTL showed negative associations (std. ß = − 0.67, 95% CI [− 0.83, − 0.52], p < .001) in age- and sex-adjusted analyses, indicating that higher HCCs are associated with shorter LTL. Using polynomial regression, we found a curvilinear relationship indicating a stronger negative association at lower cortisol concentrations. Higher HCCs were associated with shorter LTL, supporting the hypothesized involvement of prolonged cortisol secretion in telomere attrition. Thus, HCC may prove useful as a biological indicator of chronic stress associated with aging-related processes in samples exposed to high levels of stress.

Validation of the Long-term Difficulties Questionnaire-Youth version as a measure of chronic stress in adolescents in Sri Lanka.

As a validated stress questionnaire to assess ongoing adversities of adolescents in developing countries is not available, we developed a brief general checklist, the "Long-term Difficulties Questionnaire-Youth" version (LTD-Y) to measure daily stressors of adolescents and examine the psychometric properties of the instrument. In 2008, 755 schoolchildren in Sri Lanka (54% girls), age 12-16 years, completed a self-reported questionnaire with four sections. (1) demographic information (2) daily stressors and social support (3) trauma exposures measures; different trauma exposures and tsunami impact, (4) current psychological problem measures; posttraumatic stress symptoms, emotional and behavioral problems, functional impact, happiness at home, and happiness at school. In July 2009, a subsample of 90 adolescents repeated these measures. Internal consistency factor structure, concurrent validity, construct validity, and temporal stability were assessed in the scale. LTD-Y adequately identified the ongoing adversities of adolescents. The scale showed an excellent internal consistency with Cronbach's alpha = 0.79. The principal component analysis showed two-factor solutions which concern "external" and "internal" stressors. The concurrent validity was indicated by its positive association with all measures of current psychological problems. The discriminant ability of the adversity measure was evident in cumulative trauma exposure and all variables with current psychological problems. The stability of reporting was satisfactory. This school-based screening showed that the LTD-Y has sufficient validity, competency, and stability in measuring ongoing adversities of adolescents.

Hair Cortisol as a Measure of Chronic Stress in Ewes Grazing Either Hardwood Silvopastures or Open Pastures

Hair cortisol is a relatively non-invasive and reliable measure of chronic stress, but it has received limited use, especially in pasture systems. A two-year study was carried out to compare behavioral and physiological (intravaginal temperature, hair, and blood cortisol) responses of ewes (Ovis aries) that grazed black walnut (Juglans nigra) silvopasture (BSP), honeylocust (Gleditsia triacanthos) silvopasture (HSP), or open pastures (OP) treatments. Ewe weights and intravaginal temperatures were recorded once for every 3-week interval. Plasma and hair cortisol concentrations were determined by ELISA. Trail cameras detected animal behavior. Ewe average daily gain was greater in HSP compared with OP (p = 0.0456) but did not differ with BSP (p = 0.4686) across both years. Ewes on OP had higher (p &lt; 0.0001) hair cortisol concentrations than ewes on silvopasture treatments both summers. Ewes on OP had ≥ 0.4 °C higher (p ≤ 0.03) intravaginal temperatures during portions of the afternoon than ewes managed in silvopasture treatments. Ewes on OP spent 500–700% more (p &lt; 0.0001) time standing and 125–150% less (p &lt; 0.0001) time lying down compared with ewes on silvopasture treatments. Hair cortisol measures could be an effective and relatively non-invasive technique for determining long-term chronic stress in grazing animals.

Abstract 3663: Allostatic load, tumor genomics, and outcomes in NSCLC

Abstract Introduction: Allostatic load (AL) is a multi-system measure of chronic stress shown to be an emerging framework for understanding disparities in cancer outcomes, but there have been no AL studies in lung cancer. Methods: We conducted a retrospective review of patients diagnosed with stage IV lung adenocarcinoma from 2016 - 2020 at the University of Illinois Hospital and Health System. An AL index included 9 biomarkers (systolic blood pressure, diastolic blood pressure, resting heart rate, BMI, albumin, eGFR, creatinine, glucose, and use of medications for hypertension, diabetes, or hypocholesteremia) with 1 point assigned for each biomarker meeting a pre-determined cutoff. AL was dichotomized between AL-high (5-9) and AL-low (0-4) with median progression-free survival of first-line therapy (mPFS1) and median overall survival (mOS) estimated for both groups with Kaplan-Meier curves. Rates of clinically actionable driver mutations (driver-POS), including EGFR, ALK, ROS1, BRAF V600e, RET, MET, NTRK, and KRAS G12C, were compared for both groups using chi-squared test. Mean AL was compared between those who were driver-POS and those who did not have a clinically actionable driver mutation (driver-NEG) using independent samples t-test. Results: A total of 61 patients were identified with 56% female and 74% former or current tobacco users. The cohort was 49% Black, 21% White, and 13% Hispanic or Latino. Mean AL at diagnosis was 3.3 (+/- 1.4). AL-high patients comprised 20% (12) of the cohort compared with 80% (49) AL-low. Between AL-high and AL-low cohorts, there was no statistically significant difference in mPFS1 (15 vs. 13 months, P = 0.98) and mOS (34 vs. 18 months, P = 0.33). Rates of driver-POS were lower in AL-high compared with AL-low (25% vs 69%, P &amp;lt;0.01). Mean AL was higher in the driver-NEG population compared with driver-POS population (3.79 vs 3.03, P = 0.04). Conclusions: Patients whose tumors did not have a clinically actionable driver mutation were associated with a higher AL, suggestive of higher chronic stress playing a role in more aggressive tumor biology. No statistically significant survival difference was observed in AL-high versus AL-low populations for mPFS1 and mOS. Larger, prospective trials are planned to correlate AL at diagnosis with clinical and biomarker data. AL, which serves as a measure of physiological dysfunction due to chronic stress associated with social disadvantage, may have implications for tumor biology and clinical outcomes in lung cancer. Citation Format: Ryan H. Nguyen, Michael Weinfeld, Mary Pasquinelli, Frank Weinberg, Natalie Reizine, Lawrence Feldman, Vijayakrishna K. Gadi. Allostatic load, tumor genomics, and outcomes in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3663.

Does Training Motivation Influence Resilience Training Outcome on Chronic Stress? Results from an Interventional Study.

Resilience is understood as an acquired skill which aids in coping with acute and chronic stress. Accordingly, the present study aimed to determine the effect of resilience training on mental health problems during chronic stress. To this end, we conducted a quasi-experimental study with 127 male cadets (mean age: 21 years) of the Swiss Armed Forces officers’ school. Whereas the intervention group (IG) received resilience training in addition to the standard officer’s education program, the control group (CG) completed the officers’ school as usual. Data assessment included pre- and post- measurement of chronic stress, symptoms of depression, and vital exhaustion in both groups. Motivation for training was collected before the first training session. Those who received the resilience training reported no change in chronic stress, whereas participants in the CG showed a significant increase in chronic stress over time (ηp2 = 0.025). Furthermore, significant differences between IG and CG were only found for symptoms of depression: Participants in the IG reported significantly decreased symptoms of depression, while this was not the case for participants in the CG. Within the IG, participants’ training motivation strongly influenced the effectiveness of the resilience training. More specifically, motivated individuals were more likely to benefit from the resilience training than unmotivated ones. Outcome data suggest that resilience training appeared to favorably affect chronic stress and related mental health symptoms; however, the motivation for the training seemed to be an essential prerequisite.

Chronic stress, omics, and asthma

The U.S. has the highest rate of firearm‐related deaths of all economically developed nations. Current evidence suggests that exposure to violence (ETV) and violence‐related distress may cause or worsen asthma. Indeed, violence‐related distress may affect asthma pathogenesis through direct effects including abnormal responses to catecholamines and glucocorticoid therapy, and altered immune responses resulting in airway inflammation. Violence‐related distress may also affect asthma through indirect effects such as decreased physical activity and weight gain.We previously showed that ETV is associated with asthma in a high‐risk population (Puerto Ricans), in whom ETV is also associated with methylation of a CpG site in the promoter of the gene for the pituitary adenylate cyclase activating polypeptide 1 type 1 receptor (ADCYAP1R1) in white blood cells. Moreover, we reported that such methylation is associated with childhood asthma in Puerto Ricans.Based on previous results, we hypothesized that ETV and violence‐related distress would be linked to asthma through airway epithelial methylation of genes regulating autonomic, neuroendocrine, and immune responses. To examine this hypothesis, we carried out a epigenome‐wide association study (EWAS) of ETV or chronic stress measures and nasal (airway) epithelial methylation in 487 Puerto Rican participants (aged 9 to 20 years) in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA‐PR]). We evaluated four measures of ETV and chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Linear regression was used for each of the EWASs, with CpGs as dependent variables and the violence or stress scale as a predictor, adjusting for age, sex, principal components, and latent factors. We then selected the top 100 CpGs (by P‐value) associated with each scale in EVA‐PR. Since no replication cohort had data on stress or violence, we conducted a meta‐analysis of the selected CpGs and atopic asthma using data from EVA‐PR and two other cohorts (Project Viva and PIAMA).Three CpGs (in SNN, PTPRN2,and LINC01164) were associated with maternal stress or gun violence (P=1.28 to 3.36 ×10‐7), but not with atopic asthma, in EVA‐PR. In a meta‐analysis of three cohorts, which included the top CpGs associated with stress/violence measures in EVA‐PR, 12 CpGs (in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4 and ANAPC13) were associated with atopic asthma at FDR‐P&lt; 0.05. PLCB1 has been associated with bronchodilator response and is differentially expressed in children with treatment‐resistant asthma compared with children with controlled persistent asthma or healthy controls.Pending confirmation in longitudinal studies, our results suggest that nasal epithelial methylation markers associated with ETV and chronic stress may be linked to atopic asthma in youth.

The effect of cumulative early life adversities, and their differential mediation through hair cortisol levels, on childhood growth and cognition: Three-year follow-up of a birth cohort in rural India.

Background: Early adversities negatively impact children's growth and development, putatively mediated by chronic physiological stress resulting from these adverse experiences. We aimed to estimate the associations between prospectively measured cumulative early adversities with growth and cognition outcomes in rural Indian preschool children and to explore if hair cortisol concentration (HCC), a measure of chronic physiological stress, mediated the above association. Methods: Participants were recruited from the SPRING cRCT in rural Haryana, India. Adversities experienced through pregnancy and the first year of life were measured in 1304 children at 12-months. HCC was measured at 12-months in 845 of them. Outcome measures were height-for-age-z-score (HAZ), weight-for-age-z-score (WAZ) and cognition, measured in 1124 children followed up at 3-years. Cognition was measured using a validated tablet-based gamified tool named DEEP. Results: Cumulative adversities at 12-months were inversely associated with all outcomes measures at 3-years. Each unit increase in adversity score led to a decrease of 0·08 units [95% confidence interval (CI):-0·11,-0·06] in DEEP-z-score; 0·12 units [-0·14,-0·09] in HAZ and 0·11 units [-0·13,-0·09] in WAZ. 12-month HCC was inversely associated with DEEP-z-score (-0·09 [-0·16,-0·01]) and HAZ (-0·12 [-0·20,-0·04]), but the association with WAZ was not significant (p = 0·142). HCC marginally mediated the association between cumulative adversities and HAZ (proportion mediated = 0·06, p = 0·014). No evidence of mediation was found for the cognition outcome. Conclusions: Cumulative early adversities and HCC measured at 12-months have persistent negative effects on child growth and cognition at 3-years. The association between adversities and these two child outcomes were differentially mediated by HCC, with no evidence of mediation observed for the cognitive outcome. Future studies should focus on other stress biomarkers, and alternate pathways such as the immune, inflammation and cellular ageing pathways, to unpack key mechanisms underlying the established relationship between early adversities and poor child outcomes.

Abstract MP47: IFNγ-Mediated Associations Between Chronic Stress Related-Neural Activity And PCSK9: Data From The Washington, D.C. Cardiovascular Health And Needs Assessment

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player in dyslipidemia and is linked to cardiovascular disease risk. To our knowledge, the potential link between psychosocial stressors, PCSK9 levels, and related dyslipidemia has not been evaluated. Hypothesis: IFNγ mediates the association between amygdalar activity (AmygA) and PCSK9. Methods: Participants from the D.C. Cardiovascular Health and Needs Assessment (DC-CHNA), a community-engaged cohort study, were recruited to the NIH Clinical Center and underwent phenotyping, including 18 FDG PET/CT to assess AmygA as a marker of chronic stress-related neural activity. Cytokines, PCSK9, and lipoprotein (a) (Lp(a)) were measured using ELISA-based techniques. Regression modeling identified associations between AmygA and PCSK9 and between PCSK9 and Lp(a) while adjusting for atherosclerotic cardiovascular disease (ASCVD) 10-year risk score and body mass index (BMI). Mediation analysis was used to evaluate IFNγ, TNFα, and IL-6 as potential mediators. Results: The DC-CHNA consisted of 60 African American participants (mean age 61±11 years, 93% female) at risk for ASCVD. AmygA associated with PCSK9 and IFNγ after adjusting for ASCVD and BMI; additionally, IFNγ associated with PCSK9 ( Figure ). Mediation analysis indicated that IFNγ mediated 45.8% of the AmygA and PCSK9 relationship. TNFα and IL-6 did not mediate the relationship. Lastly, PCSK9 associated with Lp(a) independent of ASCVD risk factors (β=0.34, p=0.013). Conclusions: The role of psychosocial stressors in PCSK9 related-dyslipidemia is not well known. Thus, we show that AmygA, a measure of chronic stress, associated with PCSK9 in an IFNγ-mediated fashion. PCSK9 then associated with Lp(a) which is notable as Lp(a) is thought to be largely genetically determined and highly atherogenic. Future research should further this hypothesis-generating study by prospectively investigating the impact of psychosocial stressors on PCSK9 and dyslipidemia in larger, diverse populations.

Perceived Stress in Older Dementia Caregivers: Mediation by Loneliness and Depression.

Coupled with aging, chronic stress experienced by dementia caregivers often leads to deteriorating health. Comparing caregivers and non-caregivers, we tested whether depression and loneliness mediate the relationship between caregiver status and a measure of chronic stress, the Perceived Stress Scale. Seventy-six cognitively normal older adults (mean age 72.7) were identified as caregivers or non-caregivers based on the functional independence of a paired family member. Caregivers reported more perceived stress, depression, and loneliness than non-caregivers. Using multiple mediation analyses, we found that loneliness and depression mediated the relationship of caregiver status with perceived stress. The loneliness effect on perceived stress was both direct and via its relationship with depressive symptoms. The findings suggest loneliness as a likely point of intervention to reduce caregiver stress. Initiatives to enable caregivers to maintain or develop social relationships apart from caregiver responsibilities may mitigate stress and its negative impact on mental and physical health.

Chronic stress, autonomic dysregulation and prospective drug use among African American emerging adults.

Chronic stress is associated with increased vulnerability to drug use and may contribute to drug-related health disparities in the African American community. The underlying physiological mechanisms by which chronic stress confers this increased risk remain unclear. The present study aimed to characterize the impact of chronic and race-related stress exposure on regulatory mechanisms of the autonomic nervous system (ANS) in response to acute stress, to examine John Henryism as potential moderator of this relationship, and to investigate the association between ANS reactivity and subsequent drug use among a sample of African American emerging adults (18-25 years old) in the Southern United States (U.S.). Participants (N = 276) completed self-report measures of chronic and race-related stress and John Henryism and underwent a laboratory-based stressor. ANS reactivity was assessed via heart rate variability (HRV) and skin conductance levels (SCL). At 90-day follow-up, retrospective reports of drug use were provided. Race-related stress was associated with greater SCL reactivity. John Henryism moderated the relationship between chronic stress exposure and HRV reactivity. SCL reactivity was associated with higher rates of alcohol and marijuana use at 90-day follow-up. HRV reactivity was associated with tobacco use at 90-day follow-up. Chronic stress exposure and active coping may interact to affect regulatory mechanisms of the ANS. ANS (dys)regulation may be an important endophenotype for increasing drug use vulnerability among African American emerging adults. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Single-Cell Transcriptional Changes in Hypothalamic Corticotropin-Releasing Factor–Expressing Neurons After Early-Life Adversity Inform Enduring Alterations in Vulnerabilities to Stress

BackgroundMental health and vulnerabilities to neuropsychiatric disorders involve the interplay of genes and environment, particularly during sensitive developmental periods. Early-life adversity (ELA) and stress promote vulnerabilities to stress-related affective disorders, yet it is unknown how transient ELA dictates lifelong neuroendocrine and behavioral reactions to stress. The population of hypothalamic corticotropin-releasing factor (CRF)–expressing neurons that regulate stress responses is a promising candidate to mediate the long-lasting influences of ELA on stress-related behavioral and hormonal responses via enduring transcriptional and epigenetic mechanisms. MethodsCapitalizing on a well-characterized model of ELA, we examined ELA-induced changes in gene expression profiles of CRF-expressing neurons in the hypothalamic paraventricular nucleus of developing male mice. We used single-cell RNA sequencing on isolated CRF-expressing neurons. We determined the enduring functional consequences of transcriptional changes on stress reactivity in adult ELA mice, including hormonal responses to acute stress, adrenal weights as a measure of chronic stress, and behaviors in the looming shadow threat task. ResultsSingle-cell transcriptomics identified distinct and novel CRF-expressing neuronal populations, characterized by both their gene expression repertoire and their neurotransmitter profiles. ELA-provoked expression changes were selective to specific subpopulations and affected genes involved in neuronal differentiation, synapse formation, energy metabolism, and cellular responses to stress and injury. Importantly, these expression changes were impactful, apparent from adrenal hypertrophy and augmented behavioral responses to stress in adulthood. ConclusionsWe uncover a novel repertoire of stress-regulating CRF cell types differentially affected by ELA and resulting in augmented stress vulnerability, with relevance to the origins of stress-related affective disorders.

Perceived chronic stress influences the effect of acute stress on cognitive flexibility

Executive functions are cognitive processes that facilitate goal-directed behavior by enabling us to direct and control our thoughts. Cognitive flexibility is an executive function characterized by the ability to mentally shift between rules, strategies, or tasks. Several studies have reported that acute (brief) stress impairs cognitive flexibility. Even though an individual’s perception of their chronic stress levels is shown to influence effects of future stressors, the interactive effect of acute and perceived chronic stress on cognitive flexibility is not known. We conducted two experiments to address this gap. In both studies, perceived chronic stress was measured using the Perceived Stress Scale. Acute stress was induced using the Cold Pressor Test. Number of perseverative errors on the Wisconsin Card Sorting Test was used as an indicator of cognitive flexibility. In Study 2, we also measured salivary alpha amylase as a marker of the physiological stress response. Data from our two studies are consistent with the hypothesis that an individual’s perception of their chronic stress level may impact the effect of acute stress on perseveration. In Study 1, we observed a significant interaction between acute and perceived chronic stress on perseverative errors, such that only individuals who reported high levels of perceived chronic stress prior to acute stress exposure showed no change in perseveration following the acute stress manipulation. This effect did not differ based on participant sex. In Study 2, we found a similar interaction effect of acute and perceived chronic stress on perseverative errors in an all-woman sample. After identifying salivary alpha amylase responders and non-responders, we observed a strong, negative correlation between perceived chronic stress and perseverative errors amongst the responders only. Our data highlight the value in studying salivary alpha amylase in response to acute stress exposure. Additionally, perceived chronic stress emerged as a key variable in the relationship between acute stress and cognitive flexibility. Overall, our work suggests that future research interested in interrogating moderators in the relationship between acute stress and cognition would benefit from inclusion of measures of chronic stress.

Chronic stress and executive functioning: A specification-curve analysis

To investigate the association between chronic stress and executive functioning (EF), we assessed 514 young to middle-aged adults in three EF tasks (i.e., Number-Letter, 2-Back, Go/Nogo) that assessed shifting, updating, and inhibition. Chronic stress was assessed by various self-report measures and hair cortisol concentrations as indicators of subjective and objective chronic stress, respectively. In order to test the association between chronic stress and EF, we fit a structural equation model with a latent common EF factor predicted by subjective and objective chronic stress on Kaplan-Meier estimates of response times. Controlling for participants' sex, age household income and the delay between cognitive testing and hair sample collection, neither subjective nor objective chronic stress showed a meaningful association with common EF. Exploratory analyses suggested a moderation effect of income on the association between subjective chronic stress and common EF, with a smaller association for high-income participants. Additionally, we conducted a specification-curve analysis on the association between chronic stress and EF to assess the influence of different analysis choices on results in our dataset. This analysis confirmed the absence of a coherent association between chronic stress and EF by showing that the majority of analytical choices produced null effects and only a small number of analytical choices produced meaningful associations (negative or positive). Taken together, our findings suggest that common EF likely remains preserved under the influence of chronic stress. Our specification-curve analysis, however, also shows that chronic stress may also have either a positive or a negative effect on EF, depending on the choice of covariates and measures of chronic stress and EF. Consequently, more research on the role of these factors for the association between chronic stress and EF is needed to avoid the interpretation of non-replicable stress-EF associations caused by analytical choices or selection bias.

PSX-B-18 Behavioral and physiological responses of ewes in hardwood silvopastures vs. open pastures

Abstract Managing livestock in silvopasture systems can help reduce heat stress and improve animal behavior and productivity. However, quantifying physiological benefits for animals in pastoral systems is challenging because the sampling procedures require animal handling; this is stressful and elevates plasma cortisol, a stress hormone. Hair cortisol (HC) is a relatively non-invasive and reliable measure of chronic stress, but it has received limited use especially in pasture systems. We compared behavioral and physiological (temperature, hair and blood cortisol) responses of ewes that grazed mid-stage hardwood silvopastures vs. open pastures. The study site consists of 0.27-ha black walnut (Juglans nigra; BW) and honeylocust (Gleditsia triacanthos; HL) silvopastures and open pasture (OP) treatments, each replicated three times. Thirty-six Katahdin ewes were assigned to one of the treatments for a 6-week summer grazing trial. Ewe weights and intravaginal temperatures were recorded routinely; trail cameras captured animal behavior. Blood was collected via jugular venipuncture; hair grown during the trial was collected from the loin region. Blood and hair cortisol concentration was determined by ELISA. Body weight gains and plasma cortisol levels did not differ among treatments. Ewes on OP had higher HC on Day-21 and Day-42 (P ≤ 0.007) and 0.5–1.0 °C hotter (P ≤ 0.04) intravaginal temperatures between 1200h-1700h than ewes on silvopasture treatments. Overall, ewes on OP spent more (P &amp;lt; 0.001) time loafing and less (P &amp;lt; 0.10) time lying down compared to ewes on silvopasture treatments. Trees within the silvopastures moderated ambient conditions, both reducing stress and improving the behavioral and physiological responses of ewes.

Allostatic load, unhealthy behaviors, and depressive symptoms in the Hispanic Community Health Study/Study of Latinos.

BackgroundThe Environmental Affordances Model (EAM) proposes that the effects of chronic stress on depression are moderated by unhealthy behaviors and race/ethnicity. The unique social structures and contexts of Hispanics/Latinos in the U.S. may influence such relationships. This study evaluated whether unhealthy behaviors weakened the relationship between allostatic load, a measure of chronic stress, and future elevated depressive symptoms among Hispanic Community Health Study/Study of Latinos participants.MethodsLongitudinal data (2008–2011 and 2014–2017) from 11,623 participants were analyzed. The exposure was allostatic load, an index of twelve established biomarkers categorized using clinically relevant cut points, at Visit 1. Elevated depressive symptoms were operationalized as a score of ≥10 (out of 30) on the CES-D 10 at Visit 2. An index of unhealthy behaviors, with one point each for cigarette smoking, excessive/binge drinking, sedentary behavior, and poor diet quality at Visit 1, was examined as an effect modifier. Multivariable logistic regression, in the overall sample and among Mexicans specifically and adjusted for demographic characteristics and elevated depressive symptoms at Visit 1, was used to model allostatic load, unhealthy behavior index (range: 0–4), and their interaction in relation to elevated depressive symptoms at Visit 2.ResultsOverall, greater allostatic load was associated with higher odds of elevated depressive symptoms after at least 6 years (aOR = 1.06, 95% CI = 1.01, 1.10). Overall, individuals with greater allostatic load and an unhealthy behavior index = 1, compared to those with an unhealthy behavior index = 0, had lower odds of elevated depressive symptoms at follow-up (aβ = −0.065, 95% CI = −0.12, −0.007).ConclusionsThe relationship between chronic stress and depression was partially moderated among Hispanics/Latinos who engaged in unhealthy behavior, which may have reduced their risk of elevated depressive symptoms given more chronic stress.

Structural Equation Modeling of a Global Stress Index in Healthy Soldiers.

Accumulation of stress is a prognostic trigger for cardiovascular disease. Classical scores for cardiovascular risk estimation typically do not consider psychosocial stress. The aim of this study was to develop a global stress index (GSI) from healthy participants by combining individual measures of acute and chronic stress from childhood to adult life. One-hundred and ninety-two female and male soldiers completed the Perceived Stress Scale (PSS4), Trier Inventory for Chronic Stress (TICS), Hospital Anxiety and Depression Scale (HADS), Childhood Trauma Questionnaire (CTQ), Posttraumatic Diagnostic Scale Checklist (PDS), and the Deployment Risk and Resilience Inventory (DRRI-2). The underlying structure for the GSI was examined through structural equation modeling. The final hierarchical multilevel model revealed fair fit by taking modification indices into account. The highest order had a g-factor called the GSI. On a second level the latent variables stress, HADS and CTQ were directly loading on the GSI. A third level with the six CTQ subscales was implemented. On the lowest hierarchical level all manifest variables and the DRRI-2/PDS sum scores were located. The presented GSI serves as a valuable and individual stress profile for soldiers and could potentially complement classical cardiovascular risk factors.