Similarity in evoked responses does not imply similarity in macroscopic network states.

It is commonplace in neuroscience to assume that if two tasks activate the same brain areas in the same way, then they are recruiting the same underlying networks. Yet computational theory has shown that the same pattern of activity can emerge from many different underlying network representations. Here we evaluated whether similarity in activation necessarily implies similarity in network architecture by comparing region-wise activation patterns and functional correlation profiles from a large sample of healthy subjects (N = 242). Participants performed two executive control tasks known to recruit nearly identical brain areas, the color-word Stroop task and the Multi-Source Interference Task (MSIT). Using a measure of instantaneous functional correlations, based on edge time series, we estimated the task-related networks that differed between incongruent and congruent conditions. We found that the two tasks were much more different in their network profiles than in their evoked activity patterns at different analytical levels, as well as for a wide range of methodological pipelines. Our results reject the notion that having the same activation patterns means two tasks engage the same underlying representations, suggesting that task representations should be independently evaluated at both node and edge (connectivity) levels.

As a dynamical system, the brain can encode information at the module (e.g., brain regions) or the network level (e.g., connections between brain regions). This means that two tasks can produce the same pattern of activation, but differ in their network profile. Here we tested this using two tasks with largely similar cognitive requirements. Despite producing nearly identical macroscopic activation patterns, the two tasks produced different functional network profiles. These findings confirm prior theoretical work that similarity in task activation does not imply the same similarity in underlying network states.

A systems identification approach using Bayes factors to deconstruct the brain bases of emotion regulation.

Cognitive reappraisal is fundamental to cognitive therapies and everyday emotion regulation. Analyses using Bayes factors and an axiomatic systems identification approach identified four reappraisal-related components encompassing distributed neural activity patterns across two independent functional magnetic resonance imaging (fMRI) studies (n = 182 and n = 176): (1) an anterior prefrontal system selectively involved in cognitive reappraisal; (2) a fronto-parietal-insular system engaged by both reappraisal and emotion generation, demonstrating a general role in appraisal; (3) a largely subcortical system activated during negative emotion generation but unaffected by reappraisal, including amygdala, hypothalamus and periaqueductal gray; and (4) a posterior cortical system of negative emotion-related regions downregulated by reappraisal. These systems covaried with individual differences in reappraisal success and were differentially related to neurotransmitter binding maps, implicating cannabinoid and serotonin systems in reappraisal. These findings challenge 'limbic'-centric models of reappraisal and provide new systems-level targets for assessing and enhancing emotion regulation.

Stressor-evoked brain activity, cardiovascular reactivity, and subclinical atherosclerosis in midlife adults.

Background: Cardiovascular responses to psychological stressors have been separately associated with preclinical atherosclerosis and hemodynamic brain activity patterns across different studies and cohorts; however, what has not been established is whether cardiovascular stress responses reliably link indicators of stressor-evoked brain activity and preclinical atherosclerosis that have been measured in the same individuals. Accordingly, the present study used cross-validation and predictive modeling to test for the first time whether stressor-evoked systolic blood pressure (SBP) responses statistically mediated the association between concurrently measured brain activity and a vascular marker of preclinical atherosclerosis in the carotid arteries. Methods: 624 midlife adults (aged 28-56 years, 54.97% female) from two different cohorts underwent two information-conflict fMRI tasks, with concurrent SBP measures collected. Carotid artery intima-media thickness (CA-IMT) was measured by ultrasonography. A mediation framework that included harmonization, cross-validation, and penalized principal component regression was then employed, while significant areas in possible direct and indirect effects were identified through bootstrapping. Sensitivity analysis further tested the robustness of findings after accounting for prevailing levels of cardiovascular disease risk and brain imaging data quality control. Results: Task-averaged patterns of hemodynamic brain responses exhibited a generalizable association with CA-IMT, which was mediated by an area-under-the-curve measure of aggregate SBP reactivity. Importantly, this effect held in sensitivity analyses. Implicated brain areas in this mediation included the ventromedial prefrontal cortex, anterior cingulate cortex, insula and amygdala. Conclusions: These novel findings support a link between stressor-evoked brain activity and preclinical atherosclerosis accounted for by individual differences in corresponding levels of stressor-evoked cardiovascular reactivity.

Cortical and subcortical brain networks predict prevailing heart rate.

Resting heart rate may confer risk for cardiovascular disease (CVD) and other adverse cardiovascular events. While the brainstem's autonomic control over heart rate is well established, less is known about the regulatory role of higher-level cortical and subcortical brain regions, especially in humans. The present study sought to characterize the brain networks that predict variation in prevailing heart rate in otherwise healthy adults. We used machine learning approaches designed for complex, high-dimensional datasets, to predict variation in instantaneous heart period (the inter-heartbeat-interval) from whole brain hemodynamic signals measured by fMRI. Task-based and resting-state fMRI, as well as peripheral physiological recordings, were taken from two datasets that included extensive repeated measurements within individuals. Our models reliably predicted instantaneous heart period from whole brain fMRI data both within and across individuals, with prediction accuracies being highest when measured within-participants. We found that a network of cortical and subcortical brain regions, many linked to psychological stress, were reliable predictors of variation in heart period. This adds to evidence on brain-heart interactions and constitutes an incremental step towards developing clinically-applicable biomarkers of brain contributions to CVD risk.

Psychological stress and the longitudinal progression of subclinical atherosclerosis.

OBJECTIVE: In a midlife sample of adults, the present study tested the extent to which changes in psychological stress relate to the progression of subclinical cardiovascular disease over multiple years and explored the potential moderating role of cardiometabolic risk. METHOD: Participants were screened to exclude those with clinical cardiovascular, respiratory, metabolic, and other chronic illnesses, as well as those taking psychotropic, cardiovascular, lipid, and glucose control medications. At baseline (N = 331) and then again at follow-up an average of 3 years later (N = 260), participants completed the 10-item Perceived Stress Scale, underwent assessments of their cardiometabolic risk, and underwent ultrasonography to measure carotid artery intima-media thickness (IMT), which is a surrogate indicator of subclinical atherosclerosis. RESULTS: Regression models showed that the change in psychological stress from baseline to follow-up was positively associated with the corresponding change in IMT, with covariate control for age at baseline, sex at birth, and variability in length of follow-up across participants. Cardiometabolic risk factors did not statistically moderate this longitudinal association. In exploratory analyses, cardiometabolic risk factors also did not statistically mediate this association. CONCLUSION: These longitudinal findings suggest that increases in psychological stress in midlife relate to corresponding increases in subclinical atherosclerosis. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effects of a laboratory-based aerobic exercise intervention on brain volume and cardiovascular health markers: protocol for a randomised clinical trial.

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.

Changes in stress pathways as a possible mechanism of aerobic exercise training on brain health: a scoping review of existing studies.

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.

Subjective Social Status and Longitudinal Changes in Systemic Inflammation.

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 (ß = -0.06), hopelessness (ß = -0.06), and depressive symptoms (ß = -0.06). Lower SSSUS was longitudinally associated with greater IL-6 independently of demographic covariates including education and income (ß = -0.06), but was slightly attenuated after adjusting for hopelessness (ß = -0.06) and depressive symptoms (ß = -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.

Subjective social status (SSS) refers to how people perceive their social rank compared with others and has been linked to meaningful differences in physical health. Increases in inflammation may contribute to associations between lower SSS and poorer physical health. In a sample of healthy adults, we examined whether SSS was associated with prospective, multiyear changes in markers of systemic inflammation and if this differed by sex or race. We found that adults who perceived their social status as lower than peers in their community exhibited an accelerated increase in interleukin-6, a marker of systemic inflammation, over a 3-year period. When participants were asked to compare themselves to people in the broader USA, the pattern was similar but less robust. Results were independent of individual differences in sociodemographic characteristics including family-adjusted income and education. Findings did not differ by sex or race and were not explained by differences in adiposity and symptoms of depression and hopelessness. Effects for C-reactive protein, a second marker of inflammation, were generally nonsignificant. Although preliminary, findings suggest an immune pathway by which perceived social status may relate to chronic diseases of aging.

Beyond Neighborhood Disadvantage: Local Resources, Green Space, Pollution, and Crime as Residential Community Correlates of Cardiovascular Risk and Brain Morphology in Midlife Adults.

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 ( ß = 0.10, 95% confidence interval [CI] = 0.01 to 0.18), as well as chemical pollution ( ß = 0.11, 95% CI = 0.02 to 0.19), homicide rates ( ß = 0.10, 95% CI = 0.01 to 0.18), employment opportunities ( ß = -0.16, 95% CI = -0.27 to -0.04), and green space ( ß = -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.

Does an Online Positive Psychological Intervention Improve Positive Affect in Young Adults During the COVID-19 Pandemic?

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.

Do trait-level emotion regulation strategies moderate associations between retrospective reports of childhood trauma and prospective changes in systemic inflammation?

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.

The personality meta-trait of stability and carotid artery atherosclerosis.

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.

Multivariate Brain Activity while Viewing and Reappraising Affective Scenes Does Not Predict the Multiyear Progression of Preclinical Atherosclerosis in Otherwise Healthy Midlife Adults.

Cognitive reappraisal is an emotion regulation strategy that is postulated to reduce risk for atherosclerotic cardiovascular disease (CVD), particularly the risk due to negative affect. At present, however, the brain systems and vascular pathways that may link reappraisal to CVD risk remain unclear. This study thus tested whether brain activity evoked by using reappraisal to reduce negative affect would predict the multiyear progression of a vascular marker of preclinical atherosclerosis and CVD risk: carotid artery intima-media thickness (CA-IMT). Participants were 176 otherwise healthy adults (50.6% women; aged 30-51 years) who completed a functional magnetic resonance imaging task involving the reappraisal of unpleasant scenes from the International Affective Picture System. Ultrasonography was used to compute CA-IMT at baseline and a median of 2.78 (interquartile range, 2.67 to 2.98) years later among 146 participants. As expected, reappraisal engaged brain systems implicated in emotion regulation. Reappraisal also reduced self-reported negative affect. On average, CA-IMT progressed over the follow-up period. However, multivariate and cross-validated machine-learning models demonstrated that brain activity during reappraisal failed to predict CA-IMT progression. Contrary to hypotheses, brain activity during cognitive reappraisal to reduce negative affect does not appear to forecast the progression of a vascular marker of CVD risk. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-021-00098-y.

Integrating multiple brain imaging modalities does not boost prediction of subclinical atherosclerosis in midlife adults.

BACKGROUND: Human neuroimaging evidence suggests that cardiovascular disease (CVD) risk may relate to functional and structural features of the brain. The present study tested whether combining functional and structural (multimodal) brain measures, derived from magnetic resonance imaging (MRI), would yield a multivariate brain biomarker that reliably predicts a subclinical marker of CVD risk, carotid-artery intima-media thickness (CA-IMT). METHODS: Neuroimaging, cardiovascular, and demographic data were assessed in 324 midlife and otherwise healthy adults who were free of (a) clinical CVD and (b) use of medications for chronic illnesses (aged 30-51 years, 49% female). We implemented a prediction stacking algorithm that combined multimodal brain imaging measures and Framingham Risk Scores (FRS) to predict CA-IMT. We included imaging measures that could be easily obtained in clinical settings: resting state functional connectivity and structural morphology measures from T1-weighted images. RESULTS: Our models reliably predicted CA-IMT using FRS, as well as for several individual MRI measures; however, none of the individual MRI measures outperformed FRS. Moreover, stacking functional and structural brain measures with FRS did not boost prediction accuracy above that of FRS alone. CONCLUSIONS: Combining multimodal functional and structural brain measures through a stacking algorithm does not appear to yield a reliable brain biomarker of subclinical CVD, as reflected by CA-IMT.

Resting (Tonic) Blood Pressure Is Associated With Sensitivity to Imagined and Acute Experiences of Social Pain: Evidence From Three Studies.

Social pain is a common experience that has potent implications for health. However, individuals differ in their sensitivity to social pain. Recent evidence suggests that sensitivity to social pain varies according to a biological factor that modulates sensitivity to physical pain: resting (tonic) blood pressure. The current studies extended this evidence by testing whether blood pressure relates to sensitivity to imagined (Study 1: N = 762, 51% female adults) and acute (Study 2, preregistered: N = 204, 57% female adults) experiences of social pain and whether associations extend to general emotional responding (Studies 1-3; Study 3: N = 162, 59% female adults). In line with prior evidence, results showed that higher resting blood pressure was associated with lower sensitivity to social pain. Moreover, associations regarding blood pressure and sensitivity to social pain did not appear to be explained by individual differences in general emotional responding. Findings appear to be compatible with the interpretation that social and physical pain share similar cardiovascular correlates and may be modulated by convergent interoceptive pathways.

An online Trier social stress paradigm to evoke affective and cardiovascular responses.

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.

Cortisol activity partially accounts for a relationship between community socioeconomic position and atherosclerosis.

Compared to others, individuals living in communities of socioeconomic disadvantage experience more atherosclerotic cardiovascular disease (CVD) and a greater extent of preclinical atherosclerosis. Although the mechanisms underlying these associations remain unclear, it is widely hypothesized that alterations in normative cortisol release from the Hypothalamic Pituitary Adrenal (HPA) axis may play a role in linking lower community socioeconomic position (C-SEP) to CVD risk. The current study examined this hypothesis in relation to a marker of preclinical atherosclerosis among 488 healthy midlife adults (30-54 years, Mean age= 43, 52% Female, 81% White). All participants were employed and without clinical CVD. C-SEP was estimated from census tract data, and atherosclerosis was measured as intima-medial thickness of the carotid arteries (cIMT) by duplex ultrasonography. Four indicators of HPA activity [cortisol at awakening and the cortisol awakening response (CAR), rate of diurnal decline in cortisol (diurnal slope), and total output expressed as area under the curve (AUC)] were derived from salivary cortisol measurements obtained from 5 samples on each of 3 working days. Path analyses were used to examine associations of C-SEP with cIMT and HPA activity and to test whether individual differences in HPA activity could account for any association of C-SEP with cIMT using bootstrapping (5000 iterations). All models were adjusted for age, sex, race, and composite measures of both individual-level socioeconomic position (income, education, occupation), and cardiometabolic risk (systolic and diastolic blood pressure, waist circumference, fasting lipids and glucose). Lower C-SEP was related to both greater cIMT (b = -0.004, p = .021) and a flatter diurnal slope of cortisol (b = -0.001, p = .039). An indirect effect showed attenuated diurnal slope to partially mediate the relationship between C-SEP and cIMT (95% CI = -0.0018 to -0.0001), and a residual direct effect of C-SEP on cIMT remained significant (95% CI = -0.0097 to -0.004). These results suggest that low C-SEP associations with preclinical atherosclerosis may be due in part to correlated variation in adrenocortical activity.

Long-Term Ambient Air Pollution Exposures and Circulating and Stimulated Inflammatory Mediators in a Cohort of Midlife Adults.

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-1ß, 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 (PM2.5)] 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 PM2.5 and BC with stimulated production of IL-6, IL-1ß, and TNF-α. Pb, Mn, Fe, and Zn exposures were positively associated with stimulated production of IL-1ß and TNF-α. No pollutants were associated with circulating IL-6 or CRP levels. DISCUSSION: Exposure to PM2.5, 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.

The self in context: brain systems linking mental and physical health.

Increasing evidence suggests that mental health and physical health are linked by neural systems that jointly regulate somatic physiology and high-level cognition. Key systems include the ventromedial prefrontal cortex and the related default-mode network. These systems help to construct models of the 'self-in-context', compressing information across time and sensory modalities into conceptions of the underlying causes of experience. Self-in-context models endow events with personal meaning and allow predictive control over behaviour and peripheral physiology, including autonomic, neuroendocrine and immune function. They guide learning from experience and the formation of narratives about the self and one's world. Disorders of mental and physical health, especially those with high co-occurrence and convergent alterations in the functionality of the ventromedial prefrontal cortex and the default-mode network, could benefit from interventions focused on understanding and shaping mindsets and beliefs about the self, illness and treatment.