Search

Describes the lymphocyte subset redistribution during acute laboratory stress in young adults. Distribution of the circulating lymphocyte subsets; Cause of the reduction of the plasma volume; Attribution of T-suppressor/cytotoxic and natural killer cells to hemoconcentration.

Introduction: Magnetic resonance imaging (MRI) at 7 Telsa (7T) has superior signal-to-noise ratio to 3 Telsa (3T) but also presents higher signal inhomogeneities and geometric distortions. A key knowledge gap is to robustly investigate the sensitivity and accuracy of 3T and 7T MRI in assessing brain morphometrics. This study aims to (a) aggregate a large number of paired 3T and 7T scans to evaluate their differences in quantitative brain morphological assessment using a widely available brain segmentation tool, FreeSurfer, as well as to (b) examine the impact of normalization methods for subject variability and smaller sample sizes on data analysis., Methods: A total of 452 healthy participants aged 29 to 68 were imaged at both 3T and 7T. Structural T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images were processed and segmented using FreeSurfer. To account for head size variability, the brain volumes underwent intracranial volume (ICV) correction using the Residual (regression model) and Proportional (simple division to ICV) methods. The resulting volumes and thicknesses were correlated with age using Pearson correlation and false discovery rate correction. The correlations were also calculated in increasing sample size from 3 to the whole sample to estimate the sample size required to detect aging-related brain variation., Results: 352 subjects (210 females) passed the image quality control with 100 subjects excluded due to excessive motion artifacts on 3T, 7T, or both. 7T MRI showed an overall stronger correlation between morphometrics and age and a larger number of significantly correlated brain volumes and cortical thicknesses. While the ICV is consistent between both field strengths, the Residual normalization method shows markedly higher correlation with age for 3T when compared with the Proportional normalization method. The 7T results are consistent regardless of the normalization method used., Conclusion: In a large cohort of healthy participants with paired 3T and 7T scans, we compared the statistical performance in assessing age-related brain morphological changes. Our study reaffirmed the inverse correlation between brain volumes and cortical thicknesses and age and highlighted varying correlations in different brain regions and normalization methods at 3T and 7T. 7T imaging significantly improves statistical power and thus reduces required sample size., Key Points: Compared to 3T, 7T has stronger inverse correlations of total grey matter, subcortical grey matter, and white matter volumes, and mean cortical thickness with age.Compared to 3T, 7T shows a greater number of brain volumes and cortical thicknesses that have statistically significant correlations with age.For comparable statistical power at 3T, the required sample size for 7T is reduced for cortical and subcortical volumes, and substantially reduced for cortical thicknesses.

Historical structural racism in the built environment contributes to health inequities, yet to date, research has almost exclusively focused on racist policy of redlining. We expand upon this conceptualization of historical structural racism by examining the potential associations of probable blockbusting, urban renewal, and proximity to displacement from freeway construction, along with redlining, to multiple contemporary health measures. Analyses linked historical structural racism, measured continuously at the census-tract level using archival data sources, to present-day residents' physical health measures drawn from publicly accessible records for Allegheny County, Pennsylvania. Outcome measures included average life expectancy and the percentage of residents reporting hypertension, stroke, coronary heart disease, smoking, insufficient sleep, sedentary behavior, and no health insurance coverage. Multiple regression analyses were conducted to examine separate and additive associations between structural racism and physical health measures. Redlining, probable blockbusting, and urban renewal were associated with shorter life expectancy and a higher prevalence of cardiovascular conditions, risky health behaviors, and residents lacking health insurance coverage. Probable blockbusting and urban renewal had the most consistent correlations with all 8 health measures, while freeway displacement was not reliably associated with health. Additive models explained a greater proportion of variance in health than any individual structural racism measure alone. Moreover, probable blockbusting and urban renewal accounted for relatively more variance in health compared to redlining, suggesting that research should consider these other measures in addition to redlining. These preliminary correlational findings underscore the importance of considering multiple aspects of historical structural racism in relation to current health inequities and serve as a starting point for additional research., (© 2024. The New York Academy of Medicine.)

Objective: Childhood trauma may contribute to lifelong health through chronic systemic inflammation. However, associations between childhood trauma and inflammation are mixed, indicating that distinct types of childhood trauma may relate to inflammation differently. Moreover, most studies use a single assessment of inflammatory markers that may not reliably estimate stable interindividual differences. The current study is the first to examine relationships between childhood trauma and an ecologically valid measure of inflammation derived from repeated assessments of interleukin (IL)-6 in daily life. We also examine the possibility that glucocorticoid sensitivity and patterns of daily cortisol may contribute to observed associations. Finally, we explore whether biological sex moderates relationships between childhood trauma and IL-6., Method: Participants were 283 healthy adults aged 40-64 (57% female, 23% Black, Indigenous, and People of Color) who completed the Childhood Trauma Questionnaire and self-collected dried blood spots at home on 4 days to measure IL-6. Measures of salivary cortisol and blood-based glucocorticoid sensitivity were also assessed., Results: Childhood trauma was not associated with IL-6 in the sample as a whole. However, exploratory analyses showed that childhood trauma related to IL-6 differently for males and females, such that total trauma and emotional neglect predicted higher IL-6 for males but not females. Results persisted after adjustment for covariates. There was no evidence for indirect effects via cortisol or glucocorticoid sensitivity., Conclusions: Childhood trauma and, specifically, emotional neglect were associated with IL-6 in daily life among middle-aged males. Additional research is needed to elucidate biological and behavioral pathways underlying these associations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: Childhood trauma may contribute to poor lifelong health in part through programming of the HPA-axis response to future life stressors. To date, empirical evidence shows an association of childhood trauma with dysregulation of the HPA-axis and blunted cortisol reactivity to acute stressors. Here, we conduct an initial examination of childhood trauma as a moderator of changes over time in perceived stress levels and HPA-axis response to a major chronic stressor in adulthood., Methods: Participants were 83 maternal caregivers of children newly diagnosed with cancer who completed the Childhood Trauma Questionnaire (CTQ), and who, over the year following their child's cancer diagnosis, had hair samples collected up to 7 times for the assessment of cortisol and completed monthly measures of perceived stress., Results: CTQ scores were in the expected range for a community sample and associated with changes in perceived stress and cortisol concentration over time (γ =.003, p =.002; γ = -.0004, p =.008, respectively) independently of age, education, treatment intensity and randomization to stress management intervention. Maternal caregivers who endorsed lower childhood trauma showed a steeper decline in perceived stress and a larger increase in cortisol levels across the year than caregivers who recalled more childhood trauma., Conclusions: Findings extend animal models and studies that examine cortisol reactivity to acute stressors and suggest that childhood trauma may program a phenotype that is more psychologically reactive but shows a blunted HPA-axis response to chronic stress. While adaptive in the short-term, this early life programming may incur long-term costs for health. Further work is warranted to examine this possibility., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The accumulation of day-to-day stressors can impact mental and physical health. How people respond to stressful events is a key mechanism responsible for the effects of stress, and individual differences in stress responses can either perpetuate or prevent negative consequences. Most research on daily stress processes has focused on affective responses to stressors, but stress responses can involve more than just affect (e.g., behavior, cognitions). Additionally, most research has studied the role of neuroticism in shaping those responses, but many other individual differences are associated with stress. In this study, we more broadly characterized daily stress processes by expanding the nomological networks of stress responses to include Big Five personality states. We also linked those stress responses to all Big Five traits, as well as individual differences in stress variety, severity, and controllability. We studied a sample of participants ( N = 1,090) who reported on stressful events, their appraisal of events in terms of severity and controllability, and their Big Five personality states daily for 8-10 days ( N = 8,870 observations). Multi-level structural equation models were used to separate how characteristics of the perceived stressful situation and characteristics of the person play into daily stress processes. Results showed that (1) all Big Five personality states shift in response to perceived stress, (2) all Big Five personality traits relate to average levels of perceived stress variety, severity, and controllability, (3) individual differences in personality and average perceived stress variety and perceived severity relate to the strength of personality state responses to daily stress, albeit in a more limited fashion. Our results point to new pathways by which stressors affect people in everyday life and begin to clarify processes that may explain individual differences in risk or resilience to the harmful effects of stress.

Abstract: The "geroscience hypothesis" posits that slowing the physiological processes of aging would lead to delayed disease onset and longer healthspan and lifespan. This shift from a focus on solely treating existing disease to slowing the aging process is a shift toward prevention, including a focus on risk factors found in the social environment. Although geroscience traditionally has focused on the molecular and cellular drivers of biological aging, more fundamental causes of aging may be found in the social exposome-the complex array of human social environmental exposures that shape health and disease. The social exposome may interact with physiological processes to accelerate aging biology. In this commentary, we review the potential of these insights to shape the emerging field of translational geroscience. The articles in this special issue highlight how social stress and social determinants of health are associated with biomarkers of aging such as inflammation, epigenetic clocks, and telomeres, and spotlight promising interventions to mitigate stress-related inflammation. For geroscience to incorporate the social exposome into its translational agenda, studies are needed that elucidate and quantify the effects of social exposures on aging and that consider social exposures as intervention targets. The life course perspective allows us to measure both exposures and aging biology over time including sensitive periods of development and major social transitions. In addition, given rapid changes in the measurement of aging biology, which include machine learning techniques, multisystem phenotypes of aging are being developed to better reflect whole body aging, replacing reliance on single system biomarkers. In this expanded and more integrated field of translational geroscience, strategies targeting factors in the social exposome hold promise for achieving aging health equity and extending healthy longevity., (Copyright © 2024 by the American Psychosomatic Society.)

Objective: Aging is associated with increased proinflammatory gene expression and systemic inflammation, and psychosocial stress may accelerate these changes. Mindfulness interventions show promise for reducing psychosocial stress and extending healthspan. Inflammatory pathways may play a role. In a sample of lonely older adults, we tested whether mindfulness training reduces proinflammatory gene expression and protein markers of systemic inflammation., Methods: Lonely older adults (65-85 years; N = 190) were randomly assigned to an 8-week Mindfulness-Based Stress Reduction (MBSR) or matched Health Enhancement Program (HEP). Blood was drawn before and after the intervention and at 3-month follow-up. In peripheral blood mononuclear cells, RNA profiling was used to assess transcriptional regulation by proinflammatory nuclear factor κB (NF-κB) as well as β-adrenergic cAMP response element-binding protein (CREB), antiviral interferon regulatory factor (IRF), and glucocorticoid receptor (GR) transcription factors. Plasma was assayed for proinflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP). Analyses tested time (pre, post, follow-up) by condition (MBSR versus HEP) effects., Results: MBSR reduced NF-κB ( d = 0.17, p = .028) but did not alter CREB ( d = 0.10, p = .20), IRF ( d = 0.13, p = .086), or GR activity ( d = 0.14, p = .063) relative to HEP over time. Contrary to predictions, there were no time by condition effects of MBSR compared with HEP on reducing circulating IL-6 or CRP., Conclusions: In lonely older adults, MBSR reduced cellular proinflammatory gene regulation in ways that would predict reduced disease risk. However, no similar effect was observed for circulating protein markers of inflammation. These results provide specificity about how mindfulness interventions may impact distinct inflammatory markers among aging adults in ways that may have important implications for healthspan., Trial Registration: Clinical Trials identifier NCT02888600., (Copyright © 2023 by the American Psychosomatic Society.)

Objective: Psychosocial stress is transduced into disease risk through energy-dependent release of hormones from the hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary axes. The levels of glucocorticoid and adrenergic hormones, together with the sensitivity of tissues to their signaling, define stress responses. To understand existing pathways responsible for the psychobiological transduction of stressful experiences, we provide a quantitative whole-body map of glucocorticoid and adrenergic receptor (AR) expression., Methods: We systematically examined gene expression levels for the glucocorticoid receptor (GR), α- and β-ARs (AR-α1B, AR-α2B AR-β2, and AR-β3), across 55 different organs using the Human Protein Atlas and Human Proteome Map datasets. Given that mitochondria produce the energy required to respond to stress, we leveraged the Human Protein Atlas and MitoCarta3.0 data to examine the link between stress hormone receptor density and mitochondrial gene expression. Finally, we tested the functional interplay between GR activation and AR expression in human fibroblast cells., Results: The GR was expressed ubiquitously across all investigated organ systems, whereas AR subtypes showed lower and more localized expression patterns. Receptor co-regulation, meaning the correlated gene expression of multiple stress hormone receptors, was found between GR and AR-α1B, as well as between AR-α1B and AR-α2B. In cultured human fibroblasts, activating the GR selectively increased AR-β2 and AR-α1B expression. Consistent with the known energetic cost of stress responses, GR and AR expressions were positively associated with the expression of specific mitochondrial pathways., Conclusions: Our results provide a cartography of GR and AR expression across the human body. Because stress-induced GR and AR signaling triggers energetically expensive cellular pathways involving energy-transforming mitochondria, the tissue-specific expression and co-expression patterns of hormone receptor subtypes may in part determine the resilience or vulnerability of different organ systems., (Copyright © 2024 by the American Psychosomatic Society.)

Objective: The Exercise Program in Cancer and Cognition (EPICC) Study was a randomized controlled trial (RCT) designed to determine whether six months of moderate-intensity aerobic exercise improves neurocognitive function in women with breast cancer (BC) receiving endocrine therapy (ET)., Methods: Postmenopausal women with hormone receptor+, early-stage BC, within two years post-primary therapy were randomized to the exercise intervention (six months, ≥150 minutes of moderate-intensity aerobic exercise/week) or usual care control condition. Outcomes were assessed at pre-randomization and after intervention completion. Groups were compared using linear mixed-effects modeling., Results: Participants (N=153) were X ¯ = 62.09 ± 8.27 years old, with stage I BC (64.1%) and a median of 4.7 months post-diagnosis. We found a group-by-time interaction (p=0.041) and a trend for the main effect of time (p=0.11) for processing speed with improved performance in the exercise group and no change in the controls. Similar main effects of time were observed for learning and memory (p=0.024) and working memory (p=0.01). Better intervention adherence was associated with improved processing speed (p=0.017)., Conclusions: Six months of moderate-intensity aerobic exercise improves processing speed in postmenopausal women with BC receiving ET who initiate exercise within two years of completing primary therapy (surgery +/- chemotherapy). This is the first large-scale study to examine the effects of aerobic exercise on neurocognitive function in women with BC. Additional research is needed to address the long-term effects of aerobic exercise on cognitive function.

Purpose: The war metaphor is one strategy used frequently in breast cancer to inspire individuals in a "fight" against cancer and assist patients in navigating their illness experience. Despite prominent use, the emotional impact of this language has not been examined in the context of meaning making among women with metastatic breast cancer (MBC)., Methods: This study involved a semi-structured interview considering the war metaphor's impact on women's illness experience with MBC. Participants (n = 22) had been diagnosed with MBC for at least 6 months or following 1 disease progression and were undergoing treatment at an NCI-designated cancer center in Western Pennsylvania at the time of interview. Each participant underwent an individual interview exploring the war metaphor's impact on illness experience. Qualitative thematic analysis was performed to assess feelings about the war metaphor and emotional response to the lived experience of cancer., Results: Two themes were identified surrounding metaphor use and participants' experiences with meaning making in cancer. First, women with MBC perceive the diagnosis as an "unfair fight" due to its incurable nature. Second, patients use alternative language of "living life" and communicate resistance to being defined by their cancer diagnosis., Conclusion: War metaphors are one collection of terminology people use to understand their diagnosis. However, their use may apply pressure to prioritize positivity in the face of diagnosis and treatment, in a unique clinical context where this may not be adaptive. These findings affirm a need to consider patients' lived experiences to best facilitate psychological adjustment to illness., (© 2024. The Author(s).)

Introduction: Physical activity (PA) has beneficial effects on brain health and cardiovascular disease (CVD) risk. Yet, we know little about whether PA-induced changes to physiological mediators of CVD risk influence brain health and whether benefits to brain health may also explain PA-induced improvements to CVD risk. This study combines neurobiological and peripheral physiological methods in the context of a randomised clinical trial to better understand the links between exercise, brain health and CVD risk., Methods and Analysis: In this 12-month trial, 130 healthy individuals between the ages of 26 and 58 will be randomly assigned to either: (1) moderate-intensity aerobic PA for 150 min/week or (2) a health information control group. Cardiovascular, neuroimaging and PA measurements will occur for both groups before and after the intervention. Primary outcomes include changes in (1) brain structural areas (ie, hippocampal volume); (2) systolic blood pressure (SBP) responses to functional MRI cognitive stressor tasks and (3) heart rate variability. The main secondary outcomes include changes in (1) brain activity, resting state connectivity, cortical thickness and cortical volume; (2) daily life SBP stress reactivity; (3) negative and positive affect; (4) baroreflex sensitivity; (5) pulse wave velocity; (6) endothelial function and (7) daily life positive and negative affect. Our results are expected to have both mechanistic and public health implications regarding brain-body interactions in the context of cardiovascular health., Ethics and Dissemination: Ethical approval has been obtained from the University of Pittsburgh Institutional Review Board (IRB ID: 19020218). This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule., Trial Registration Number: NCT03841669., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Subjective social status (SSS) refers to a person's perception of their social rank relative to others and is cross-sectionally linked to systemic inflammation independently of objective socioeconomic status., Purpose: We test the extent to which SSS relates to multiyear changes in inflammation, or if associations differ by race or sex., Methods: Healthy adults (N = 331; 30-51 years) completed a baseline visit and 278 participants returned for a second visit 2.85 years later. At both visits, participants underwent a fasting blood draw and completed community (SSSC) and US (SSSUS) versions of the MacArthur Scale. Multiple linear regression analyses examined change in interleukin-6 (IL-6) and C-reactive protein (CRP) predicted by each type of SSS, adjusting for time between visits, sex, race, age, body mass index, smoking, baseline inflammation, and objective socioeconomic status. Additional analyses further adjusted for hopelessness and depressive symptoms. Interactions examined moderations by sex and race., Results: Lower SSSC was longitudinally associated with greater IL-6 independently of all covariates, including education and income (β = -0.06), hopelessness (β = -0.06), and depressive symptoms (β = -0.06). Lower SSSUS was longitudinally associated with greater IL-6 independently of demographic covariates including education and income (β = -0.06), but was slightly attenuated after adjusting for hopelessness (β = -0.06) and depressive symptoms (β = -0.06). There were no associations for CRP or moderation by race or sex., Conclusions: Lower SSS may be associated with greater circulating markers of inflammation over time as suggested by increases in IL-6., (© Society of Behavioral Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Physical activity (PA) in the form of aerobic exercise (AE) preserves and improves neurocognitive function across the lifespan. However, a mechanistic understanding of the pathways by which aerobic exercise impacts brain health is still lacking, particularly with respect to stress-related pathways. One mechanistic hypothesis is that AE improves neurocognitive health in part by modifying circulating levels of stress-related hormones and signaling factors associated with the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS), as commonly measured by the biomarkers cortisol (CORT) and salivary α-amylase (sAA). Thus, this hypothesis predicts that changes in stress biomarkers, such as CORT and sAA, are possible explanatory pathways mediating the positive effects of AE on neurocognitive health. In the present review article, we provide a summary of available studies examining the possibility that exercise-induced changes to stress biomarkers could partly account for exercise-related improvements in neurocognitive health. Our review indicates that despite the intuitive appeal of this hypothesis, there is insufficient evidence available to conclude that chronic and habitual AE affects neurocognitive health by altering stress biomarker pathways. The cross-sectional nature of the majority of reviewed studies highlights the need for well-controlled studies to adequately test this hypothesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Molina-Hidalgo, Stillman, Collins, Velazquez-Diaz, Ripperger, Drake, Gianaros, Marsland and Erickson.)

Importance: The months following inpatient psychiatric hospitalization are a period of high risk for suicidal behavior. Sexual and gender minority (SGM) individuals have elevated risk for suicidal behavior, but no prior research has examined whether SGM inpatients have disproportionate risk for suicidal behavior following discharge from psychiatric hospitalization., Objectives: To evaluate whether SGM patients have elevated risk for suicidal behavior following discharge from psychiatric hospitalization compared with heterosexual and cisgender patients and to examine whether differences in risk across groups were accounted for by demographic characteristics and clinical factors known to be associated with suicidal behavior., Design, Setting, and Participants: This prospective cohort study was conducted from August 2017 to July 2021 among inpatients aged 18 to 30 years who were voluntarily enrolled during psychiatric hospitalization. The study was conducted at an inpatient psychiatric hospital, with prospective data collected via follow-up visits and electronic health records., Main Outcomes and Measures: Onset and/or recurrence of suicidal behavior following discharge from psychiatric hospitalization, assessed at follow-up visits and through electronic health records., Results: A total of 160 patients were included, with 56 sexual minority (SM) and 15 gender minority (GM) patients. The median (IQR) age of the patients was 23.5 (20.4-27.6) years, 77 (48%) reported male sex assigned at birth, and 114 (71%) identified their race as White. During the follow-up period, 33 suicidal behavior events occurred (among 21% of patients). SM (hazard ratio [HR], 2.02; 95% CI, CI, 1.02-4.00; log-rank P = .04) and GM (HR, 4.27; 95% CI, 1.75-10.40; log-rank P < .001) patients had significantly higher risk for suicidal behavior compared with their heterosexual and cisgender counterparts, respectively, in bivariable analyses. Risk between SM and heterosexual patients was not different after controlling for demographic characteristics and clinical factors associated with suicidal behavior. GM patients exhibited elevated risk during the 100 days following discharge even after controlling for demographic and clinical characteristics (HR, 3.80; 95% CI, 1.18-11.19; P = .03)., Conclusions and Relevance: Within this cohort study of psychiatric patients, SGM patients had higher risk for suicidal behavior than non-SGM patients following discharge. While SM patients' risk was accounted for by clinical characteristics, GM patients' risk for suicidal behavior was not accounted for by their acute psychiatric state on admission. Future studies with larger subsamples of GM individuals are needed, and inpatient clinicians must attend to the unique needs of SGM individuals to ensure they receive affirming services.

Childhood trauma may confer risk for poorer adult health through changes in systemic inflammation. Emotion regulation may plausibly moderate associations between childhood trauma and adult psychological well-being, but it remains unclear whether moderation effects extend to differences in systemic inflammation. To examine whether childhood trauma and emotion regulation separately and interactively predict prospective changes in C-reactive protein (CRP) and interleukin-6 (IL-6) and whether biopsychosocial factors account for observed associations. Healthy midlife adults (N = 331) retrospectively reported on childhood trauma, current trait-level cognitive reappraisal and expressive suppression, and had their blood drawn. At baseline and then a median of 2.85 years later, 279 of the 331 participants had their blood drawn, body mass index calculated, and reported on health behaviours (smoking, sleep), psychological distress (perceived stress, depressive symptoms), and years of education. Childhood trauma predicted prospective increases in CRP (B = 0.004, p = 0.049), which were partially accounted for by differences in adiposity, psychological distress, and health behaviours. In contrast, cognitive reappraisal predicted prospective decreases in IL-6 (B = -0.007, p = 0.006), which were independent of biopsychosocial influences. Cognitive reappraisal further moderated the association between childhood trauma and prospective changes in IL-6 (B = -0.001, p = 0.012) such that childhood trauma predicted greater IL-6 increases but only among adults lower in cognitive reappraisal (B = 0.006, p = 0.007). There were no main or moderation effects of expressive suppression (ps > 0.05). Cognitive reappraisal may attenuate IL-6 changes over time and may moderate the prospective association between childhood trauma and systemic inflammation in midlife., (© 2022 John Wiley & Sons Ltd.)

Objective: Residing in communities characterized by socioeconomic disadvantage confers risk of cardiometabolic diseases. Residing in disadvantaged communities may also confer the risk of neurodegenerative brain changes via cardiometabolic pathways. This study tested whether features of communities-apart from conventional socioeconomic characteristics-relate not only to cardiometabolic risk but also to relative tissue reductions in the cerebral cortex and hippocampus., Methods: Participants were 699 adults aged 30 to 54 years (340 women; 22.5% non-White) whose addresses were geocoded to compute community indicators of socioeconomic disadvantage, as well as air and toxic chemical pollutant exposures, homicide rates, concentration of employment opportunities, land use (green space), and availability of supermarkets and local resources. Participants also underwent assessments of cortical and hippocampal volumes and cardiometabolic risk factors (adiposity, blood pressure, fasting glucose, and lipids)., Results: Multilevel structural equation modeling demonstrated that cardiometabolic risk was associated with community disadvantage ( β = 0.10, 95% confidence interval [CI] = 0.01 to 0.18), as well as chemical pollution ( β = 0.11, 95% CI = 0.02 to 0.19), homicide rates ( β = 0.10, 95% CI = 0.01 to 0.18), employment opportunities ( β = -0.16, 95% CI = -0.27 to -0.04), and green space ( β = -0.12, 95% CI = -0.20 to -0.04). Moreover, cardiometabolic risk indirectly mediated the associations of several of these community features and brain tissue volumes. Some associations were nonlinear, and none were explained by participants' individual-level socioeconomic characteristics., Conclusions: Features of communities other than conventional indicators of socioeconomic disadvantage may represent nonredundant correlates of cardiometabolic risk and brain tissue morphology in midlife., (Copyright © 2023 by the American Psychosomatic Society.)

Background: Several personality traits increase the risk for atherosclerotic cardiovascular disease. Because many of these traits are correlated, their associations with disease risk could reflect shared variance, rather than unique contributions of each trait. We examined a higher-order personality trait of Stability as related to preclinical atherosclerosis and tested whether any such relationship might be explained by correlated variation in cardiometabolic risk factors., Method: Among 798 community volunteers, lower-order traits of Neuroticism, Agreeableness, and Conscientiousness were modeled as latent variables (from self- and informant ratings) and used to estimate the second-order factor, Stability. Cardiometabolic risk was similarly modeled from indicators of glycemic control, blood pressure, adiposity, and lipids. Carotid artery atherosclerosis was measured as intima-media thickness (IMT) by duplex ultrasonography., Result: A structural equation model incorporating direct and indirect effects showed lower Stability associated with greater IMT, and this relationship was accounted for by the indirect pathway via cardiometabolic risk. Secondary analyses showed that: (1) Neuroticism, Agreeableness, and Conscientiousness were unrelated to IMT independent of Stability; and (2) Stability predicted variation in IMT when estimated from informant-, but not self-rated, traits., Conclusion: Personality traits may associate with atherosclerotic burden through their shared, rather than unique, variance, as reflected in Stability., (© 2022 Wiley Periodicals LLC.)

Purpose: The purpose of the current study, The National Institute of Child Health and Human Development (NICHD) Study of Health in Early and Adult Life (SHINE), was to build on the landmark Study of Early Child Care and Youth Development (SECCYD), a longitudinal birth cohort initiated in 1991, by conducting a health-focused follow-up of the now adult participants. This effort has produced an invaluable resource for the pursuit of life course research examining links between early life risk and resilience factors and adulthood health and disease risk., Participants: Of the 927 NICHD SECCYD participants available for recruitment in the current study, 705 (76.1%) participated in the study. Participants were between 26 and 31 years and living in diverse geographic locations throughout the USA., Findings to Date: In descriptive analyses, the sample exhibited risk on health status indicators, especially related to obesity, hypertension and diabetes. Of particular concern, the prevalence of hypertension (29.4%) and diabetes (25.8%) exceeded national estimates in similar-age individuals. Health behaviour indicators generally tracked with the parameters of poor health status, showing a pattern of poor diet, low activity and disrupted sleep. The juxtaposition of the sample's relatively young age (mean=28.6 years) and high educational status (55.6% college educated or greater) with its poor health status is noteworthy, suggesting a dissociation between health and factors that are typically health protective. This is consistent with observed population health trends, which show a worsening of cardiometabolic health status in younger generations of Americans., Future Plans: The current study, SHINE, lays the groundwork for future analyses in which the uniquely robust measures collected as a part of the original NICHD SECCYD will be leveraged to pinpoint specific early life risk and resilience factors as well as the correlates and potential mechanisms accounting for variability in health and disease risk indicators in young adulthood., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Psychosocial factors are related to immune, viral, and vaccination outcomes. Yet, this knowledge has been poorly represented in public health initiatives during the COVID-19 pandemic. This review provides an overview of biopsychosocial links relevant to COVID-19 outcomes by describing seminal evidence about these associations known prepandemic as well as contemporary research conducted during the pandemic. This focuses on the negative impact of the pandemic on psychosocial health and how this in turn has likely consequences for critically relevant viral and vaccination outcomes. We end by looking forward, highlighting the potential of psychosocial interventions that could be leveraged to support all people in navigating a postpandemic world and how a biopsychosocial approach to health could be incorporated into public health responses to future pandemics., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Childhood socioeconomic disadvantage is associated with increased risk for chronic inflammation and cardiometabolic disease at midlife., Purpose: As it is presently unknown whether inflammation mediates the relationship between childhood socioeconomic status (SES) and adulthood cardiometabolic risk, we investigated associations between retrospectively reported childhood SES, circulating levels of inflammatory markers, and a latent construct of cardiometabolic risk in midlife adults., Methods: Participants were 1,359 healthy adults aged 30-54 (Adult Health and Behavior I&II; 52% women, 17% Black) who retrospectively reported childhood SES (parental education, occupational grade). Measures included plasma interleukin (IL)-6, C-reactive protein (CRP), and cardiometabolic risk factors. Structural equation modeling was conducted, with cardiometabolic risk modeled as a second-order latent variable with adiposity, blood lipids, glucose control, and blood pressure as first-order components., Results: Lower childhood SES was associated with greater risk for cardiometabolic disease at midlife (β = -0.08, CI[-0.04, -0.01], p = .01) in models adjusted for demographics, but this association was attenuated in models that adjusted for adulthood SES and health behaviors. In fully-adjusted models, the relationship between lower childhood SES and adult cardiometabolic risk was partially explained by higher circulating levels of CRP (β = -0.05, CI[-0.02, -0.01], p = .001), but not by IL-6. In an exploratory model, lower adulthood SES was also found to independently contribute to the association between childhood SES and adult cardiometabolic risk (β = -0.02, CI[-0.01, -0.001], p = .02)., Conclusions: The current study provides initial evidence that systemic inflammation may contribute to childhood socioeconomic disparities in cardiometabolic risk in midlife. Future work would benefit from prospective investigation of these relationships., (© Society of Behavioral Medicine 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Peripheral immune markers are widely used to predict risk for inflammatory disease. However, whether single assessments of inflammatory biomarkers represent stable individual differences remains unclear. We reviewed 50 studies (N = 48,674; 57 % male; mean age 54 (range 13-79) years) that assessed markers of inflammation on >1 occasion, with time between measures ranging from 24 h to 7+ years. Separate random effects meta-analyses were conducted for each inflammatory marker and time interval. Markers that had broad coverage across most time intervals included C-reactive protein (CRP; k = 37), interleukin (IL)-6 (k = 22), TNF-α (k = 10), and fibrinogen (Fg; k = 9). For CRP, IL-6, and TNF-α, stability estimates generally decreased with time, with strong to moderate stability over intervals <6 months (r's = 0.80-0.61), modest to moderate stability over 6 months - 3 years (r's = 0.60-0.51), and low stability for >3 years (r's = 0.39-0.30). Estimates were less reliable for Fg for time intervals ≤ 3 years although they generally followed the same pattern; more reliable findings suggested greater stability for Fg than other markers for intervals >3 years (r = 0.53). These findings suggest that single measures of inflammatory biomarkers may be an adequate index of stable individual differences in the short term (<6 months), with repeated measures of inflammatory biomarkers recommended over intervals ≥ 6 months to 3 years, and absolutely necessary over intervals >3 years to reliably identify stable individual differences in health risk. These findings are consistent with stability estimates and clinical recommendations for repeated measurement of other cardiovascular measures of risk (e.g., blood lipids, blood pressure)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To test whether expectations of respect and appreciation from others, assessed in daily life, are associated with preclinical vascular disease., Method: Participants were an urban community sample of 483 employed adults (47% male, 17% Black, mean age = 42.8 years). Carotid intima-media thickness (IMT) was measured using B-mode ultrasound. Expectations of being treated with respect and appreciation were measured using the average of hourly assessments over the course of 4 days, and home and work averages were also examined separately., Results: Expectations of greater respect and appreciation from others were associated with significantly less carotid IMT even after adjustment for demographic factors, general positivity and negativity of social interactions, neuroticism, optimism, perceived discrimination, and concurrent biological risk factors. This association was similar across social contexts of work and home and also when expectations of respect and appreciation were examined separately. Lower expectations of respect and appreciation and more negative social interactions were both independently associated with greater IMT in fully adjusted models and effect sizes were similar to traditional biological risk factors such as BMI., Conclusions: Midlife adults who anticipate greater respect and appreciation from others in everyday life evidence less preclinical vascular disease. Consistent with the literature showing that anticipation of social threats and unfair treatment may increase cardiovascular risk, expectations of being valued and treated with respect by others is associated with decreased risk. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

DNA methylation-based (DNAm) measures of biological aging associate with increased risk of morbidity and mortality, but their links with cognitive decline are less established. This study examined changes over a 16-year interval in epigenetic clocks (the traditional and principal components [PC]-based Horvath, Hannum, PhenoAge, GrimAge) and pace of aging measures (Dunedin PoAm, Dunedin PACE) in 48 midlife adults enrolled in the longitudinal arm of the Adult Health and Behavior project (56% Female, baseline Age M = 44.7 years), selected for discrepant cognitive trajectories. Cognitive Decliners ( N = 24) were selected based on declines in a composite score derived from neuropsychological tests and matched with participants who did not show any decline, Maintainers ( N = 24). Multilevel models with repeated DNAm measures within person tested the main effects of time, group, and group by time interactions. DNAm measures significantly increased over time generally consistent with elapsed time between study visits. There were also group differences: overall, Cognitive Decliners had an older PC-GrimAge and faster pace of aging (Dunedin PoAm, Dunedin PACE) than Cognitive Maintainers. There were no significant group by time interactions, suggesting accelerated epigenetic aging in Decliners remained constant over time. Older PC-GrimAge and faster pace of aging may be particularly sensitive to cognitive decline in midlife.

Meta-analyses indicate that positive psychological interventions are effective at increasing positive affect, as well as reducing anxiety and depression; however, it is unclear how well these effects generalize during periods of high stress. Therefore, the current study tested whether a 2-week online positive psychological intervention delivered during the COVID-19 pandemic, a naturalistic stressor, (1) increased positive affect; (2) improved psychological well-being, optimism, life satisfaction, perceived social support, and loneliness; (3) and reduced negative affect in college students, a group known to have high pandemic distress. Participants ( N = 250; 76.9% female) ages 18-45 were recruited from the University of Pittsburgh undergraduate subject pool between September and November of 2020. Participants were randomized to the online positive psychological intervention or active control condition and stratified by trait positive affect, sex, and year in college. Participants in both conditions completed one writing activity every other day for two consecutive weeks. Control participants documented their activities for that day (e.g., meals, going to gym). Intervention participants chose from six positive psychology activities. All outcome variables were assessed pre- and post-intervention by validated questionnaires. Across both conditions, positive and negative affect decreased from pre- to post-intervention. No other psychological factor differed by condition, time, or their interaction. The current null findings are in line with a more recent meta-analysis indicating that positive psychological interventions may have smaller effects on psychological well-being and depressive symptoms than was reported pre-pandemic. Study findings may suggest reduced efficacy of virtual positive psychological interventions under highly stressful circumstances., Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-022-00148-z., Competing Interests: Conflicts of InterestNot applicable., (© The Society for Affective Science 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In response to the COVID-19 pandemic, prior studies have modified the Trier Social Stress Test to be conducted remotely. The current study aimed to extend these studies to test whether a remote Trier Social Stress Test (rTSST) can elicit (a) affective, (b) blood pressure, and (c) heart rate responses relative to a control condition and whether these responses were reliable when assessed 1 week later. Participants (N = 99, 19.7 ± 3.5 years, 55% female) were randomized to a control or stress condition. Participants received blood pressure monitors in person. Controls completed easier versions of the tasks with a single, friendly researcher. Stress participants performed more difficult versions of the task in front of two judges who participants believed were rating their performance. Blood pressure and heart rate were measured every 2 min throughout, while affect was assessed at baseline, after the final task, and following recovery. The rTSST was feasible to administer with minimal technical issues reported. Participants reported lower positive affect and higher negative affect during the tasks in the stress condition relative to controls. Similarly, stress participants had higher cardiovascular responses during the tasks relative to controls, except that blood pressure was not elevated during mental arithmetic in stress participants relative to controls. Cardiovascular responses demonstrated good test-retest reliability when assessed 1 week later, especially when computed using area under the curve methods. Overall, a rTSST can be used to elicit affective and cardiovascular reactivity and provides an opportunity to increase the accessibility of research participation among diverse populations., (© 2022 Society for Psychophysiological Research.)

Despite enthusiasm for using intensive longitudinal designs to measure day-to-day manifestations of personality underlying differences between people, the validity of personality state scales has yet to be established. In this study, we evaluated the psychometrics of 20-item and 10-item daily, Big Five personality state scales in three independent samples ( N = 1,041). We used multilevel models to separately examine the validity of the scales for assessing personality variation at the between- and within-person levels. Results showed that a five-factor structure at both levels fits the data well, the scales had good convergent and discriminative associations with external variables, and personality states captured similar nomological nets as established global, self-report personality inventories. Limitations of the scales were identified (e.g., low reliability, low correlations with external criterion) that point to a need for more, systematic psychometric work. Our findings provide initial support for the use of personality state scales in intensive longitudinal designs to study between-person traits, within-person processes, and their interrelationship.

Loneliness is a potent psychosocial stressor that predicts poor health and mortality among older adults, possibly in part by accelerating age-related declines in immunocompetence. Mindfulness interventions have shown promise for reducing loneliness and improving markers of physical health. In a sample of lonely older adults, this two-arm parallel trial tested whether mindfulness training enhances stimulated interleukin-6 (IL-6) production, a measure of innate immune responsivity. Lonely older adults (65-85 years; N = 190) were randomized to an 8-week Mindfulness-Based Stress Reduction (MBSR) or control Health Enhancement Program (HEP) intervention. Lipopolysaccharide (LPS)-stimulated production of IL-6 was measured in vitro by blinded outcome assessors at pre-intervention, post-intervention, and 3-month follow-up. Mixed-effects linear models tested time (pre, post, follow-up) by condition (MBSR vs. HEP) effects. As predicted, a significant time × condition effect on stimulated IL-6 production was observed across pre, post, and follow-up timepoints. Significant MBSR vs. HEP differences emerged from pre- to post-intervention (p =.009, d = 0.38) and from pre-intervention to 3-month follow-up (p =.017, d = 0.35), with larger increases in IL-6 production following MBSR compared to HEP. No study-related adverse events were reported. Results show that mindfulness training may be effective for boosting innate immunocompetence among lonely older adults. Given that immunocompetence tends to decline with age, mindfulness training may help to counteract the effects of aging and psychosocial stress on infection risk and recovery from injury., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Patients with oxidative phosphorylation (OxPhos) defects causing mitochondrial diseases appear particularly vulnerable to infections. Although OxPhos defects modulate cytokine production in vitro and in animal models, little is known about how circulating leukocytes of patients with inherited mitochondrial DNA (mtDNA) defects respond to acute immune challenges. In a small cohort of healthy controls (n = 21) and patients (n = 12) with either the m.3243A > G mutation or single, large-scale mtDNA deletions, we examined (i) cytokine responses (IL-6, TNF-α, IL-1β) in response to acute lipopolysaccharide (LPS) exposure and (ii) sensitivity to the immunosuppressive effects of glucocorticoid signaling (dexamethasone) on cytokine production. In dose-response experiments to determine the half-maximal effective LPS concentration (EC 50 ), relative to controls, leukocytes from patients with mtDNA deletions showed 74-79% lower responses for IL-6 and IL-1β (p IL-6  = 0.031, p IL-1β  = 0.009). Moreover, whole blood from patients with mtDNA deletions (p IL-6  = 0.006), but not patients with the m.3243A > G mutation, showed greater sensitivity to the immunosuppressive effects of dexamethasone. Together, these ex vivo data provide preliminary evidence that some systemic OxPhos defects may compromise immune cytokine responses and increase the sensitivity to immune cytokine suppression by glucocorticoids. Further work in larger cohorts is needed to define the nature of immune dysregulation in patients with mitochondrial disease, and their potential implications for disease phenotypes. KEY MESSAGES: Little is known about leukocyte cytokine responses in patients with mitochondrial diseases. Leukocytes of patients with mtDNA deletions show blunted LPS sensitivity and cytokine responses. Leukocytes of patients with mtDNA deletions are more sensitive to glucocorticoid-mediated IL-6 suppression. Work in larger cohorts is needed to delineate potential immune alterations in mitochondrial diseases., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Patients with primary malignant brain tumors have high symptom burden and commonly rely on family caregivers for practical and emotional support. This can lead to negative mental and physical consequences for caregivers. We investigated effectiveness of an 8-week nurse-led online needs-based support program (SmartCare © ) with and without online self-guided cognitive behavioral therapy (CBT) for depression compared to enhanced care as usual (ECAU) on depressive symptoms, caregiving-specific distress, anxiety, mastery, and burden., Methods: Family caregivers scoring ≥ 6 on a depressive symptoms inventory were randomized to three groups: ECAU plus self-guided CBT and SmartCare © ; ECAU plus SmartCare © ; ECAU only. Primary outcomes (depressive symptoms; caregiving-specific distress) and secondary outcomes (anxiety, caregiver mastery, and caregiver burden) were assessed online. Intention to treat (ITT) and per protocol (PP) analyses of covariance corrected for baseline scores were performed for outcomes at 4 months., Results: In total, 120 family caregivers participated. Accrual and CBT engagement were lower than expected, therefore intervention groups were combined (n = 80) and compared to ECAU (n = 40). For depressive symptoms, no statistically significant group differences were found. Caregiving-specific distress decreased in the intervention group compared with ECAU (ITT: p = 0.01, partial ɳ 2  = 0.08; PP: p = 0.02, partial ɳ 2  = 0.08). A trend towards improvement in mastery for the intervention group compared with ECAU was identified (ITT: p = 0.08, partial ɳ 2  = 0.04; PP: p = 0.07, partial ɳ 2  = 0.05)., Conclusions: SmartCare © , with or without self-guided CBT, reduced caregiving-specific distress with a trend towards improving mastery. SmartCare © has the potential to improve the lives of families coping with a brain tumor diagnosis., Trial Registration Number: NCT02058745; 10 February 2014., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Aerobic exercise remains one of the most promising approaches for enhancing cognitive function in late adulthood, yet its potential positive effects on episodic memory remain poorly understood and a matter of intense debate. Prior meta-analyses have reported minimal improvements in episodic memory following aerobic exercise but have been limited by restrictive inclusion criteria and infrequent examination of exercise parameters., Methods: We conducted a meta-analysis of randomized controlled trials to determine if aerobic exercise influences episodic memory in late adulthood ( M  = 70.82 years) and examine possible moderators. Thirty-six studies met inclusion criteria, representing data from 2750 participants., Results: Here we show that aerobic exercise interventions are effective at improving episodic memory (Hedges' g  = 0.28; p  = 0.002). Subgroup analyses revealed a moderating effect of age ( p  = 0.027), with a significant effect for studies with a mean age between 55-68 but not 69-85. Mixed-effects analyses demonstrated a positive effect on episodic memory among studies with a high percentage of females (65-100%), participants with normal cognition, studies reporting intensity, studies with a no-contact or nonaerobic physical activity control group, and studies prescribing >3900 total minutes of activity (range 540-8190 min)., Conclusions: Aerobic exercise positively influences episodic memory among adults ≥55 years without dementia, with larger effects observed among various sample and intervention characteristics-the clearest moderator being age. These results could have far-reaching clinical and public health relevance, highlighting aerobic exercise as an accessible, non-pharmaceutical intervention to improve episodic memory in late adulthood., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

Objective: Acute inflammation-induced sickness behavior involves changes in social behavior that are believed to promote recovery. Whether chronic inflammation can influence social behaviors in ways that promote recovery is unknown. In a sample of mothers of a child with cancer, this report explores the relationship between inflammation that accompanies the stress of diagnosis and changes in social network, cancer-related stress, and inflammation across 1 year. Three hypotheses tested whether a) initial levels of stress associate with initial levels of inflammation, b) initial levels of inflammation predict social network changes over time, and c) social network changes over time buffer changes in stress and inflammation over time., Methods: Cancer-related stress (Impact of Events Scale), social network (social roles and contacts from the Social Network Inventory), and systemic inflammation (circulating interleukin [IL]-6) were assessed in 120 mothers three times after their child's cancer diagnosis: after diagnosis (T1), 6-month follow-up (T2), and 12-month follow-up (T3)., Results: Consistent with predictions, greater cancer-related stress after diagnosis (T1) was associated with higher IL-6 after diagnosis (T1; b = 0.014, standard error [SE] = 0.01, p = .008). In turn, higher IL-6 after diagnosis (T1) was associated with a decrease in social roles over time (T1 ➔ T3; B = -0.030, SE = 0.01, p = .041). Finally, dropping social roles over time (T1 ➔ T3) was associated with decreases in cancer-related stress (B = 25.44, SE = 12.31, p = .039) and slower increases in IL-6 (B = 1.06, SE = 0.52, p = .040) over time., Conclusions: This study provides a first indication that chronic stress-related systemic inflammation may predict changes in social behavior that associate with stress recovery and slower increases in inflammation in the year after a major life stressor., (Copyright © 2021 by the American Psychosomatic Society.)

Study Objectives: Sleep quantity and continuity vary across the lifespan. Actigraphy is a reliable and widely used behavioral measure of sleep in research and personal health monitoring. This meta-analysis provides a novel examination of whether age (in years) is associated with actigraphy-assessed sleep across the lifespan., Methods: A systematic search of PubMed, Embase.com, Cochrane CENTRAL, and PsycINFO using "actigraphy" and "sleep" terms provided 7079 titles/abstracts; studies of individuals with known psychiatric or medical comorbidities were excluded. Ninety-one articles (N = 23 365) provided data for six meta-analyses examining sleep duration (k = 89), sleep efficiency (k = 58), bedtime (k = 19) and waketime (k = 9) for individuals ages 6-21, and bedtime (k = 7) and waketime (k = 7) for individuals ages 22 and older., Results: At older ages, sleep duration was shorter (r = -0.12) and sleep efficiency was lower (r = -0.05). Older age was associated with later bedtime (r = 0.37) and wake-up time (r = 0.24) from ages 6-21, whereas older age was associated with earlier bedtime (r = -0.66) and wake-up time (r = -0.59) for ages 22 and above. The strength of these associations was modified by study continent, but not by any other moderator., Conclusions: Age was negatively associated with actigraphy-assessed sleep duration and efficiency, but the effects were small in magnitude. On the other hand, large associations were observed between age and sleep timing, despite a smaller literature and the absence of analyzable data for ages 30-60. Changes in sleep timing, rather than changes in sleep duration or continuity, may better characterize the effects of age on human sleep., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Activation of the HPA-axis and SNS are widely accepted to link chronic stress with elevated levels of peripheral pro-inflammatory markers in blood. Yet, empirical evidence showing that peripheral levels of glucocorticoids and/or catecholamines mediate this effect is equivocal. Recent attention has turned to the possibility that cellular sensitivity to these ligands may contribute to inflammatory mediators that accompany chronic stress. We review current evidence for the association of chronic stress with glucocorticoid receptor (GR) and β-adrenergic receptor (β-AR) signaling sensitivity. Across 15 mouse, 7 primate, and 19 human studies, we found that chronic stress reliably associates with downregulation in cellular GR sensitivity, alterations in intracellular β-AR signaling, and upregulation in pro-inflammatory biomarkers in peripheral blood. We also present evidence that alterations in GR and β-AR signaling may be specific to myeloid progenitor cells such that stress-related signaling promotes release of cells that are inherently less sensitive to glucocorticoids and differentially sensitive to catecholamines. Our findings have broad implications for understanding mechanisms by which chronic stress may contribute to pro-inflammatory phenotypes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Mindfulness interventions have been effective for improving a range of health outcomes; however, pathways underlying these effects remain unclear. Inflammatory processes may play a role, possibly through increased resistance of immune cells to the anti-inflammatory effects of glucocorticoids (i.e., glucocorticoid resistance, or GCR). Here, we conducted an initial examination of whether mindfulness training mitigates GCR among lonely older adults., Methods: Lonely older adults (65-85 years; n = 190) were randomly assigned to an 8-week Mindfulness-Based Stress Reduction (MBSR) or a matched Health Enhancement Program (HEP). Whole blood drawn before and after the intervention and at 3-month follow-up was incubated with endotoxin and varying concentrations of dexamethasone, and interleukin-6 production was assessed using enzyme-linked immunosorbent assay. GCR was assessed as the concentration of dexamethasone required to decrease the stimulated interleukin-6 response by 50% (half maximal inhibitory concentration), with higher concentrations indicating greater GCR. Mixed-effects linear models tested time (pre, post, follow-up) by condition (MBSR versus HEP) effects., Results: There was no overall time by condition effect on GCR across all time points. However, a significant time by condition effect was observed from preintervention to postintervention (d = 0.29), such that MBSR buffered increases in GCR observed in the HEP group. Although MBSR showed small, nonsignificant reductions in GCR from preintervention to 3-month follow-up, group differences were not maintained at the 3-month follow-up (d = 0.10)., Conclusions: Results suggest that MBSR may protect against declines in the sensitivity of immune cells to the anti-inflammatory effects of glucocorticoids among at-risk lonely older adults and show value in studying this biological mechanism in future trials.Trial Registration: Clinical Trials identifier NCT02888600., (Copyright © 2021 by the American Psychosomatic Society.)

Background: Chronic exposure to air pollution may prime the immune system to be reactive, increasing inflammatory responses to immune stimulation and providing a pathway to increased risk for inflammatory diseases, including asthma and cardiovascular disease. Although long-term exposure to ambient air pollution has been associated with increased circulating markers of inflammation, it is unknown whether it also relates to the magnitude of inflammatory response., Objectives: The aim of this study was to examine associations between chronic ambient pollution exposures and circulating and stimulated levels of inflammatory mediators in a cohort of healthy adults., Methods: Circulating interleukin (IL)-6, C-reactive protein (CRP) ( n = 392 ), and lipopolysaccharide stimulated production of IL- 1 β , IL-6, and tumor necrosis factor ( TNF ) - α ( n = 379 ) were measured in the Adult Health and Behavior II cohort. Fine particulate matter [particulate matter with aerodynamic diameter less than or equal to 2.5 μm ( PM 2.5 )] and constituents [black carbon (BC), and lead (Pb), manganese (Mn), zinc (Zn), and iron (Fe)] were estimated for each residential address using hybrid dispersion land use regression models. Associations between pollutant exposures and inflammatory measures were examined using linear regression; models were adjusted for age, sex, race, education, smoking, body mass index, and month of blood draw., Results: There were no significant correlations between circulating and stimulated measures of inflammation. Significant positive associations were found between exposure to PM 2.5 and BC with stimulated production of IL-6, IL- 1 β , and TNF- α . Pb, Mn, Fe, and Zn exposures were positively associated with stimulated production of IL- 1 β and TNF- α . No pollutants were associated with circulating IL-6 or CRP levels., Discussion: Exposure to PM 2.5 , BC, Pb, Mn, Fe, and Zn was associated with increased production of inflammatory mediators by stimulated immune cells. In contrast, pollutant exposure was not related to circulating markers of inflammation. These results suggest that chronic exposure to some pollutants may prime immune cells to mount larger inflammatory responses, possibly contributing to increased risk for inflammatory disease. https://doi.org/10.1289/EHP7089.

Objective: The current meta-analysis tested whether trait indicators of well-being associate with stressor-evoked physiological reactivity and recovery in healthy adults., Method: Medline, PsycINFO, and PubMed were used to identify relevant articles. Articles were included if they (a) measured cardiovascular or neuroendocrine (but not immune) physiology during or after an acute laboratory stress paradigm (b) measured indicators of hedonic well-being, eudaimonic well-being, or optimism, and (c) included healthy adult participants. Laboratory stress tasks included frustrating cognitive tasks, emotional recall tasks, and tasks involving social evaluation. Physiological variables were aggregated across cardiac (heart rate and cardiac output), hemodynamic (mean arterial pressure, systolic blood pressure, and diastolic blood pressure), HPA (cortisol), and autonomic (high frequency heart rate variability, skin conductance, and catecholamines) markers. Twenty-seven studies were included (n = 3,390; 54.6% women). Effect sizes and confidence intervals were estimated using a random-effects model with pooled variance., Results: Contrary to expectations, optimism was associated with greater cardiac reactivity to cognitive stressors but did not associate with stress recovery. By contrast, hedonic well-being was associated with enhanced hemodynamic recovery following laboratory stressors but was not associated with stress reactivity., Conclusions: Hedonic well-being, but not optimism, could potentially buffer against the effects of psychological stressors on physiological responding by relating to more complete recovery. Identifying the mechanisms contributing to these patterns of association may provide insights into psychological interventions for well-being and stress-related disease risk. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objective: The present study evaluated distinct facets of impulsivity related to cardiometabolic risk (CMR) to identify specific behavioral mechanisms driving these relationships., Method: Community adults ( N = 1,295) between 30 and 54 years old (53% female, 84% White) completed a battery of impulsivity measures, reported their engagement in health behaviors over the past week (i.e., cigarette smoking, alcohol use, physical activity, and dietary intake), and were assessed for CMR factors (i.e., blood pressure, insulin resistance, adiposity, and blood lipids). Structural equation modeling was used to estimate previously established hierarchical models of distinct facets of impulsivity and CMR. Indirect effects through the observed health behaviors were examined for each association between the latent impulsivity factors identified and the latent CMR factor., Results: Neuroticism/negative emotionality was the only latent impulsivity factor directly related to heightened CMR (β = 0.09, 95% confidence interval [CI] [0.01, 0.16], p = .020). Extraversion/positive emotionality indirectly related to lower CMR through greater physical activity (β = -0.04, 95% CI [-0.06, -0.02], p < .001), and measures of inhibition (β = 0.02, 95% CI [0.001, 0.04], p = .045) and delay discounting (β = 0.08, 95% CI [0.001, 0.15], p = .049) indirectly related to CMR through saturated fat intake., Conclusions: These findings indicate that distinct facets of impulsivity differentially relate to CMR through varied behavioral pathways and identify physical activity and saturated fat intake as being particularly important health behaviors to target when tailoring treatment approaches to the unique behavioral characteristics of individuals high on certain facets of impulsivity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objective: Mothers of children with cancer confront life stress that can impact their psychological and physical health and, in turn, the health of the family. Recommendations advocate preemptive stress-management interventions; however, few studies have investigated their efficacy. Here, we report results of a parallel randomized pilot trial examining health benefits of a stress management intervention designed to teach coping skills., Methods: One hundred twenty mothers (age 36 ± 8 years) of children newly diagnosed with cancer were randomized to a 12-session stress management intervention (n = 60) or usual care (n = 60). Sessions took place in the inpatient or outpatient setting of a children's hospital. Primary outcome variables included psychological function and physical health assessed preintervention and postintervention and at 6-month follow-up (∼12 months postdiagnosis)., Results: Enrollment, retention, and satisfaction data supported feasibility and acceptability. Latent change score models showed the intervention reduced perceived stress (d = -0.37, p = 0.03), anxiety symptoms (ds = -0.38 and -0.56, ps < .03) and, a nonsignificant effect for depressive symptoms (d = -0.29, p = .11) across the 6 months following diagnosis. Intervention participants also endorsed fewer depressive symptoms than controls ∼12 months after diagnosis. The intervention improved stress management skills, which associated with the psychological benefits of participation. There were no intervention-related changes in perceived health or markers of inflammation., Conclusion: Intervention-related improvements in stress management skills may result in better psychological health in the face of caring for a child with cancer., Trial Registration: ClinicalTrials.gov identifier: NCT02022449., (Published by Oxford University Press on behalf of the Society of Pediatric Psychology 2020. This work is written by US Government employees and is in the public domain in the US.)