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.

Systemic Inflammation Contributes to the Association Between Childhood Socioeconomic Disadvantage and Midlife Cardiometabolic Risk.

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 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 (ß = -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 (ß = -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 (ß = -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.

Support-Giving Is Associated With Lower Systemic Inflammation.

BACKGROUND: Support-giving has emerged as a health-relevant social behavior, such that giving more support is associated with better physical health. However, biological mechanisms by which support-giving and health are linked remain unclear. Whether support-giving uniquely relates to health relative to other psychosocial factors is also an open research question. PURPOSE: Two studies test the hypothesis that support-giving is uniquely (over-and-above other psychosocial factors) related to lower systemic inflammation, a biological correlate of health. METHODS: Cross-sectional associations of support-giving with markers of systemic inflammation (i.e., interleukin-6 [IL-6], C-reactive protein [CRP]) were examined in two independent samples of midlife adults (Study 1, n = 746; Study 2, n = 350). RESULTS: Consistent with hypotheses, giving to more social targets (to family and friends, and also volunteering for various causes), but not receiving support from similar targets, was associated with lower IL-6. In conceptual replication and extension with a different measure of support-giving, higher frequency of support-giving behavior was associated with lower IL-6, even after adjusting for social network size and individual differences in social desirability. There were no associations between support-giving and CRP in either sample. CONCLUSIONS: Future research needs to establish causality and directly test mechanistic pathways, but together, findings reaffirm the health-relevance of support-giving behavior and shed light on a promising biological mechanism by which such effects may occur.

Support-giving behavior and health are linked such that more support-giving is related to better health and longevity for the person giving. How such a link occurs, however, is an open question for research. Two cross-sectional studies test the hypothesis that support-giving behavior relates to lower systemic inflammation, a potential biological pathway linking supportive behavior with health. Results of Study 1 show that giving to more social targets (to family and friends, and also volunteering) is associated with lower inflammation. Receiving support was not associated with inflammation. In a replication and extension, Study 2 shows that a greater frequency of giving is also related to lower systemic inflammation, over and above the size of one's social network and individual differences in reporting socially desirable responses. Although more research is needed to establish whether support-giving causes systemic inflammation to change, the current findings highlight a promising pathway by which support-giving behavior benefits health.

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.

Conscientiousness and Cardiometabolic Risk: A Test of the Health Behavior Model of Personality Using Structural Equation Modeling.

BACKGROUND: High trait conscientiousness is associated with lower cardiometabolic risk, and health behaviors are a putative but relatively untested pathway that may explain this association. PURPOSE: To explore the role of key health behaviors (diet, physical activity, substance use, and sleep) as links between conscientiousness and cardiometabolic risk. METHODS: In a cross-sectional analysis of 494 healthy, middle-aged working adults (mean age = 42.7 years, 52.6% women, 81.0% White), participants provided self-reports of conscientiousness, physical activity, substance use, diet, and sleep, and wore monitors over a 7-day monitoring period to assess sleep (Actiwatch-16) and physical activity (SenseWear Pro3). Cardiometabolic risk was expressed as a second-order latent variable from a confirmatory factor analysis involving insulin resistance, dyslipidemia, obesity, and blood pressure. Direct, indirect, and specific indirect effect pathways linking conscientiousness to health behaviors and cardiometabolic risk were examined. Unstandardized indirect effects for each health behavior class were computed separately using bootstrapped samples. RESULTS: After controlling for demographics (sex, age, race, and education), conscientiousness showed the predicted, inverse association with cardiometabolic risk. Among the examined health behaviors, objectively-assessed sleep midpoint variability (b = -0.003, p = .04), subjective sleep quality (b = -0.003, p = .025), and objectively-assessed physical activity (b = -0.11, p = .04) linked conscientiousness to cardiometabolic risk. CONCLUSIONS: Physical activity and sleep partially accounted for the relationship between conscientiousness and cardiometabolic risk.

Day-to-day associations between sleep characteristics and affect in community dwelling adults.

Despite the high co-occurrence of sleep and mood disturbances, day-to-day associations between sleep characteristics (sleep duration, continuity, and timing) and dimensions of mood (positive affect and negative affect) remain unclear. The present study aimed to test whether there is a daily, bidirectional association between these sleep characteristics and affective states, while addressing methodological limitations in the extant literature by using actiography and ecological momentary assessment methods. Participants were community dwelling, midlife adults (aged 30-54 years, N = 462, 47% male) drawn from the Adult Health and Behavior Project-Phase 2 study. Participants' sleep patterns were assessed with actiography over a 7-day monitoring period, and on 4 of those days, participants completed an ecological momentary assessment protocol that included hourly assessments of positive affect and negative affect during their wake intervals. Using hierarchical linear modelling, we tested whether participants' sleep characteristics on a given night predicted next-day affect and vice versa. We also explored whether nocturnal sleep characteristics would differentially associate with affect at different times of day (morning, afternoon, and evening) while controlling for multiple health behaviours. We found that when participants reported higher positive affect on a given day, they slept later that night (B = 0.22, p = .010). Although we found no other statistically significant associations in our primary analyses (all p > .05), we found several sleep-affect associations specific to time of day (B ranges: 0.01-0.18, all p ≤ .02), which warrants further study. Overall, our findings suggest that healthy adults may be resilient to daily fluctuations in their sleep and mood.

Social Integration and Diurnal Cortisol Decline: The Role of Psychosocial and Behavioral Pathways.

OBJECTIVE: A growing number of studies have associated various measures of social integration, the diversity of social roles in which one participates, with alterations in hypothalamic-pituitary-adrenocortical (HPA) functioning. The pathways through which social integration may be linked to HPA functioning, however, are as yet unknown. The present study examined whether daily social interactions, affective responses, health behaviors, and personality help explain the association between social integration and diurnal cortisol slope. METHODS: A sample of 456 healthy, employed adults (53.9% female, 82.0% white, 72.2% bachelor's degree or greater, mean age of 42.86 years) completed a 4-day ecological momentary assessment protocol that measured cortisol, social interactions, affect, sleep, and physical activity at frequent intervals throughout the day. Social integration was measured at baseline. RESULTS: Regression results controlling for age, sex, race, and education indicated that more socially integrated individuals showed steeper cortisol slopes (B = -0.00253, p = .006). Exploratory analyses suggested that the consistency (i.e., reduced variability) in nightly sleep midpoint partially explained this association (B = -0.00042, 95% confidence interval = -0.00095 to -0.00001). Personality, mood, social interaction patterns, and nonsleep health behavior differences did not account for the association between social integration and HPA activity. CONCLUSION: This study replicates previous findings linking social integration and HPA functioning, and it examines patterns of nightly sleep as possible pathways through which the association may operate. Results have implications for understanding mechanisms for health risk and for development of future interventions.

The effects of omega-3 fatty acids on neuropsychological functioning and brain morphology in mid-life adults: a randomized clinical trial.

BACKGROUND: The diet of most adults is low in fish and, therefore, provides limited quantities of the long-chain, omega-3 fatty acids (LCn-3FAs), eicosapentaenoic and docosahexaenoic acids (EPA, DHA). Since these compounds serve important roles in the brain, we sought to determine if healthy adults with low-LCn-3FA consumption would exhibit improvements in neuropsychological performance and parallel changes in brain morphology following repletion through fish oil supplementation. METHODS: In a randomized, controlled trial, 271 mid-life adults (30-54 years of age, 118 men, 153 women) consuming ⩽300 mg/day of LCn-3FAs received 18 weeks of supplementation with fish oil capsules (1400 mg/day of EPA and DHA) or matching placebo. All participants completed a neuropsychological test battery examining four cognitive domains: psychomotor speed, executive function, learning/episodic memory, and fluid intelligence. A subset of 122 underwent neuroimaging before and after supplementation to measure whole-brain and subcortical tissue volumes. RESULTS: Capsule adherence was over 95%, participant blinding was verified, and red blood cell EPA and DHA levels increased as expected. Supplementation did not affect performance in any of the four cognitive domains. Exploratory analyses revealed that, compared to placebo, fish oil supplementation improved executive function in participants with low-baseline DHA levels. No changes were observed in any indicator of brain morphology. CONCLUSIONS: In healthy mid-life adults reporting low-dietary intake, supplementation with LCn-3FAs in moderate dose for moderate duration did not affect neuropsychological performance or brain morphology. Whether salutary effects occur in individuals with particularly low-DHA exposure requires further study.

Hostility Dimensions and Metabolic Syndrome in a Healthy, Midlife Sample.

OBJECTIVE: Evidence links trait hostility with components of the metabolic syndrome (MetS), a clustering of cardiometabolic risk factors, but which hostility dimensions (e.g., expressive or cognitive hostility) relate to MetS are not well known. Further, there may be age and sex differences in the extent to which hostility dimensions relate to MetS. The present study evaluated associations between dimensions of hostility and the metabolic syndrome and its individual components as well as the moderating effects of sex and age. METHODS: In a cross-sectional sample of 478 employed adults, a principal component analysis from common trait hostility questionnaires yielded a two-factor solution: expressive hostility (anger and aggression) and cognitive hostility (cynicism). Each of these two components of hostility was examined as predictors of each of two aggregated MetS outcomes: a dichotomous measure of MetS, based upon the NCEP-ATP III definition, and a continuous measure based upon the average of standardized scores for each component; and they were examined as predictors of individual MetS components as well. RESULTS: Expressive hostility was associated with MetS severity (b = 0.110, p = 0.04) and waist circumference (b = 2.75, p = 0.01). Moderation analyses revealed that elevated expressive hostility was associated with elevated waist circumference in women but not men. Cognitive hostility was not related to any metabolic syndrome component or aggregated outcome, and no moderation was observed. CONCLUSIONS: Among multiple individual components and two aggregated scores, only trait dispositions to expressed hostile affect and behavior were associated with MetS severity and waist circumference. The effects were small but statistically significant. The association between cognitive hostility and metabolic syndrome measures may not be robust in a large sample of healthy, midlife adults.

Neurobiological Functioning and the Personality-Trait Hierarchy: Central Serotonergic Responsivity and the Stability Metatrait.

Trait domains of the five-factor model are not orthogonal, and two metatraits have often been estimated from their covariation. Here, we focus on the stability metatrait, which reflects shared variance in conscientiousness, agreeableness, and (inversely) neuroticism. It has been hypothesized that stability manifests, in part, because of individual differences in central serotonergic functioning. We explored this possibility in a community sample (N = 441) using a multiverse analysis of (a) multi-informant five-factor-model traits and (b) stability as a predictor of individual differences in central serotonergic functioning. Differences in serotonergic functioning were assessed by indexing change in serum prolactin concentration following intravenous infusion of citalopram, a selective serotonin reuptake inhibitor. Results were mixed, showing that trait neuroticism, agreeableness, and conscientiousness, as well as the stability metatrait, were significantly associated with prolactin response but that these findings were contingent on a number of modeling decisions. Specifically, these effects were nonlinear, emerging most strongly for participants with the highest levels (or lowest, for neuroticism) of the component traits.

Multidimensional assessment of impulsivity-related measures in relation to externalizing behaviors.

BACKGROUND: Trait impulsivity is thought to play a key role in predicting behaviors on the externalizing spectrum, such as drug and alcohol use and aggression. Research suggests that impulsivity may not be a unitary construct, but rather multidimensional in nature with dimensions varying across self-report assessments and laboratory behavioral tasks. Few studies with large samples have included a range of impulsivity-related measures and assessed several externalizing behaviors to clarify the predictive validity of these assessments on important life outcomes. METHODS: Community adults (N = 1295) between the ages of 30 and 54 completed a multidimensional assessment of impulsivity-related traits (including 54 self-report scales of personality traits implicated in impulsive behaviors, and four behavioral tasks purporting to assess a construct similar to impulsivity) and reported on five externalizing behavioral outcomes (i.e. drug, alcohol, and cigarette use, and physical and verbal aggression). We ran an exploratory factor analysis on the trait scales, and then a structural equation model predicting the externalizing behaviors from the three higher-order personality factors (i.e. Disinhibition v. Constraint/Conscientiousness, Neuroticism/Negative Emotionality, and Extraversion/Positive Emotionality) and the four behavioral tasks. RESULTS: Relations between the self-report factors and behavioral tasks were small or nonexistent. Associations between the self-report factors and the externalizing outcomes were generally medium to large, but relationships between the behavioral tasks and externalizing outcomes were either nonexistent or small. CONCLUSIONS: These results partially replicate and extend recent meta-analytic findings reported by Sharma et al. (2014) to further clarify the predictive validity of impulsivity-related trait scales and laboratory behavioral tasks on externalizing behaviors.

Circulating Interleukin-6 concentration covaries inversely with self-reported sleep duration as a function of polymorphic variation in the glucocorticoid receptor.

Growing evidence links extremes of self-reported sleep duration with higher circulating markers of inflammatory disease risk, although not all findings are consistent. Extremes of sleep duration also associate with activation of the hypothalamic-pituitary-adrenocortical (HPA) system and the peripheral release of cortisol, a glucocorticoid (GC) important in downregulating transcription of pro-inflammatory molecules. Polymorphic variation in the gene encoding the GC receptor (GR; NR3C1) modulates cellular sensitivity to GC-mediated anti-inflammatory signaling, thereby affecting levels of pro-inflammatory molecules. Thus, we hypothesized that extremes of self-reported sleep duration may covary with circulating levels of inflammatory markers as a function of allelic variation in NR3C1. Specifically, we examine the possibility that a single nucleotide polymorphism of the GR gene-(rs6198), the minor (G) allele of which confers reduced GR sensitivity-moderates an association of sleep duration with interleukin (IL)-6 and C-reactive protein (CRP) among a large sample (IL-6: N = 857; CRP: N = 929) of midlife community volunteers of European ancestry. Findings showed that sleep duration varied inversely with IL-6 (ß = -0.087, p = .012), and this association was stronger among individuals homozygous for the rs6198 G-allele compared to alternate genotypes (ß = -0.071, p = .039). We also found that sleep duration showed a U-shaped association with CRP (polynomial term: ß = 0.093, p = .006), which was not moderated by rs6198 genotype. In conclusion, we show that a common genetic variant in the GR moderates an inverse association of self-reported sleep duration with circulating IL-6, possibly contributing to the increased disease risk observed among some short sleepers.

The interaction between monoamine oxidase A (MAOA) and childhood maltreatment as a predictor of personality pathology in females: Emotional reactivity as a potential mediating mechanism.

Research consistently demonstrates that common polymorphic variation in monoamine oxidase A (MAOA) moderates the influence of childhood maltreatment on later antisocial behavior, with growing evidence that the "risk" allele (high vs. low activity) differs for females. However, little is known about how this Gene × Environment interaction functions to increase risk, or if this risk pathway is specific to antisocial behavior. Using a prospectively assessed, longitudinal sample of females (n = 2,004), we examined whether changes in emotional reactivity (ER) during adolescence mediated associations between this Gene × Environment and antisocial personality disorder in early adulthood. In addition, we assessed whether this putative risk pathway also conferred risk for borderline personality disorder, a related disorder characterized by high ER. While direct associations between early maltreatment and later personality pathology did not vary by genotype, there was a significant difference in the indirect path via ER during adolescence. Consistent with hypotheses, females with high-activity MAOA genotype who experienced early maltreatment had greater increases in ER during adolescence, and higher levels of ER predicted both antisocial personality disorder and borderline personality disorder symptom severity. Taken together, findings suggest that the interaction between MAOA and early maltreatment places women at risk for a broader range of personality pathology via effects on ER.

Ambulatory Blood Pressure Reactivity as a Moderator in the Association Between Daily Life Psychosocial Stress and Carotid Artery Atherosclerosis.

OBJECTIVE: We examined whether associations between daily psychosocial stressor exposures and carotid artery intima-medial thickness (IMT) may be stronger among those showing larger stress-related cardiovascular reactivity (CVR) during the course of daily living. METHODS: A total of 474 healthy working adults (ages 30-54 years) collected ambulatory blood pressure and recorded their daily experiences, using electronic diaries, during two 2-day periods for a week. Measures of mean momentary task strain and social conflict were used as indices of stressor exposure, and partial regression coefficients linking momentary strain and conflict with ambulatory blood pressure fluctuations were used as measures of CVR. IMT was assessed in the carotid arteries using B-mode ultrasound. RESULTS: After covariate adjustment, associations between mean task strain exposure and IMT were significant among those high in CVR to strain (for systolic blood pressure, p = .006, for diastolic blood pressure, p = .011) but not among those low in strain CVR. Similarly, associations involving mean conflict exposure were significant among those high in CVR to social conflict (p < .001 for systolic blood pressure, p = .001 for diastolic blood pressure) but not among low social conflict reactors. Significant moderation effects were more consistently shown for task strain than for social conflict, but the overall pattern of results was robust across two different types of statistical modeling procedures. CONCLUSIONS: Individual differences in CVR may moderate the effects of daily psychosocial stress on subclinical CVD among healthy employed adults. Using ecological momentary assessment to measure stress exposure as well as stress reactivity may facilitate our ability to detect these effects.

Socioeconomic Position and Age-Related Disparities in Regional Cerebral Blood Flow Within the Prefrontal Cortex.

OBJECTIVE: Socioeconomic position (SEP) is associated with cerebrovascular health and brain function, particularly in prefrontal cortex and medial temporal lobe regions that exhibit plasticity across the life course. However, it is unknown whether SEP associates with resting cerebral blood flow (CBF), an indicator of baseline brain function, in these regions in midlife, and whether the association is (a) period specific, with independent associations for childhood and adulthood SEP, or driven by life course SEP, and (b) explained by a persistent disparity, widening disparity, or the leveling of disparities with age. METHODS: To address these questions, we analyzed cerebral perfusion derived by magnetic resonance imaging in a cross-sectional study of healthy adults (N = 443) who reported on childhood and adult SEP. Main effects were examined as an index of persistent disparity and age by SEP interactions as reflecting widening or leveling disparities. RESULTS: Stable high SEP across the lifespan was associated with higher global CBF and regional CBF (rCBF) in inferior frontal gyrus. However, childhood SEP was associated with rCBF in middle frontal gyrus, as moderated by age (ß = 0.04, p = .035): rCBF was inversely associated with age only for those whose parents had a high school education or below. No associations were observed for the hippocampus or amygdala. CONCLUSIONS: Life course SEP associations with rCBF in prefrontal cortex are suggestive of persistent disparities, whereas the age by childhood SEP interaction suggests that childhood disadvantage relates to a widening disparity, independent of global differences. These differential patterns in midlife may relate to disparities in later-life cerebrovascular and neurocognitive outcomes.

Associations of immunometabolic risk factors with symptoms of depression and anxiety: The role of cardiac vagal activity.

OBJECTIVES: This study examined 1) the cross-sectional relationships between symptoms of depression/anxiety and immunometabolic risk factors, and 2) whether these relationships might be explained in part by cardiac vagal activity. METHODS: Data were drawn from the Adult Health and Behavior registries (n = 1785), comprised of community dwelling adults (52.8% women, aged 30-54). Depressive symptoms were measured with the Center for Epidemiological Studies Depression Scale (CES-D) and the Beck Depression Inventory-II (BDI-II), and anxious symptoms with the Trait Anxiety scale of the State-Trait Anxiety Inventory (STAI-T). Immunometabolic risk factors included fasting levels of triglycerides, high-density lipoproteins, glucose, and insulin, as well as blood pressure, waist circumference, body mass index, C-reactive protein, and interleukin-6. Measures of cardiac autonomic activity were high- and low-frequency indicators of heart rate variability (HRV), standard deviation of normal-to-normal R-R intervals, and the mean of absolute and successive differences in R-R intervals. RESULTS: Higher BDI-II scores, in contrast to CES-D and STAI-T scores, were associated with increased immunometabolic risk and decreased HRV, especially HRV likely reflecting cardiac vagal activity. Decreased HRV was also associated with increased immunometabolic risk. Structural equation models indicated that BDI-II scores may relate to immunometabolic risk via cardiac vagal activity (indirect effect: ß = .012, p = .046) or to vagal activity via immunometabolic risk (indirect effect: ß = -.015, p = .021). CONCLUSIONS: Depressive symptoms, as measured by the BDI-II, but not anxious symptoms, were related to elevated levels of immunometabolic risk factors and low cardiac vagal activity. The latter may exhibit bidirectional influences on one another in a meditational framework. Future longitudinal, intervention, an nonhuman animal work is needed to elucidate the precise and mechanistic pathways linking depressive symptoms to immune, metabolic, and autonomic parameters of physiology that predispose to cardiovascular disease risk.

A Sensitive and Specific Neural Signature for Picture-Induced Negative Affect.

Neuroimaging has identified many correlates of emotion but has not yet yielded brain representations predictive of the intensity of emotional experiences in individuals. We used machine learning to identify a sensitive and specific signature of emotional responses to aversive images. This signature predicted the intensity of negative emotion in individual participants in cross validation (n =121) and test (n = 61) samples (high-low emotion = 93.5% accuracy). It was unresponsive to physical pain (emotion-pain = 92% discriminative accuracy), demonstrating that it is not a representation of generalized arousal or salience. The signature was comprised of mesoscale patterns spanning multiple cortical and subcortical systems, with no single system necessary or sufficient for predicting experience. Furthermore, it was not reducible to activity in traditional "emotion-related" regions (e.g., amygdala, insula) or resting-state networks (e.g., "salience," "default mode"). Overall, this work identifies differentiable neural components of negative emotion and pain, providing a basis for new, brain-based taxonomies of affective processes.

Community Socioeconomic Disadvantage in Midlife Relates to Cortical Morphology via Neuroendocrine and Cardiometabolic Pathways.

Residing in communities of socioeconomic disadvantage confers risk for chronic diseases and cognitive aging, as well as risk for biological factors that negatively affect brain morphology. The present study tested whether community disadvantage negatively associates with brain morphology via 2 biological factors encompassing cardiometabolic disease risk and neuroendocrine function. Participants were 448 midlife adults aged 30-54 years (236 women) who underwent structural neuroimaging to assess cortical and subcortical brain tissue morphology. Community disadvantage was indexed by US Census data geocoded to participants' residential addresses. Cardiometabolic risk was indexed by measurements of adiposity, blood pressure, glucose, insulin, and lipids. Neuroendocrine function was indexed from salivary cortisol measurements taken over 3 days, from which we computed the cortisol awakening response, area-under-the-curve, and diurnal cortisol decline. Community disadvantage was associated with reduced cortical tissue volume, cortical surface area, and cortical thickness, but not subcortical morphology. Moreover, increased cardiometabolic risk and a flatter (dysregulated) diurnal cortisol decline mediated the associations of community disadvantage and cortical gray matter volume. These effects were independent of age, sex, and individual-level socioeconomic position. The adverse risks of residing in a disadvantaged community may extend to the cerebral cortex via cardiometabolic and neuroendocrine pathways.

Omega-3 Supplementation and the Neural Correlates of Negative Affect and Impulsivity: A Double-Blind, Randomized, Placebo-Controlled Trial in Midlife Adults.

OBJECTIVE: In clinical trials, omega-3 fatty acid supplementation improves symptoms in psychiatric disorders involving dysregulated mood and impulse control, yet it is unclear whether in healthy adults, omega-3 fatty acid supplementation affects mood, impulse control, and the brain systems supporting these processes. Accordingly, this study tested the hypotheses that eciosapentaenoic (EPA) and docosahexaenoic (DHA) acid supplementation reduces negative affect and impulsive behaviors in healthy adults and that these changes correspond to alterations in corticolimbic and corticostriatal brain systems, which support affective and impulsive processes. METHODS: Healthy volunteers (N = 272) consuming 300 mg/d or less of EPA and DHA were enrolled in a double-blind, randomized, placebo controlled clinical trial. The participants received either capsules providing 1000 mg of EPA and 400 mg of DHA versus identical appearing soybean oil capsules per day for 18 weeks. Negative affect and impulsivity were measured by questionnaire and ecological momentary assessment, as well as functional alterations in corticolimbic and corticostriatal brain systems evoked by standardized functional magnetic resonance imaging tasks. RESULTS: There were no group by time interactions for any questionnaire or ecological momentary assessment measures of mood and impulsivity. Likewise, no group by time interactions were observed for functional magnetic resonance imaging responses evoked within corticolimbic and corticostriatal systems. CONCLUSIONS: In healthy adults with low intake of omega-3 fatty acids, moderate-dose supplementation for 18 weeks did not alter affect or impulsive behaviors nor alter corticolimbic and corticostriatal brain functionality. TRIAL REGISTRATION: Trial number NCT00663871.

Systemic inflammation and resting state connectivity of the default mode network.

The default mode network (DMN) encompasses brain systems that exhibit coherent neural activity at rest. DMN brain systems have been implicated in diverse social, cognitive, and affective processes, as well as risk for forms of dementia and psychiatric disorders that associate with systemic inflammation. Areas of the anterior cingulate cortex (ACC) and surrounding medial prefrontal cortex (mPFC) within the DMN have been implicated specifically in regulating autonomic and neuroendocrine processes that relate to systemic inflammation via bidirectional signaling mechanisms. However, it is still unclear whether indicators of inflammation relate directly to coherent resting state activity of the ACC, mPFC, or other areas within the DMN. Accordingly, we tested whether plasma interleukin (IL)-6, an indicator of systemic inflammation, covaried with resting-state functional connectivity of the DMN among 98 adults aged 30-54 (39% male; 81% Caucasian). Independent component analyses were applied to resting state fMRI data to generate DMN connectivity maps. Voxel-wise regression analyses were then used to test for associations between IL-6 and DMN connectivity across individuals, controlling for age, sex, body mass index, and fMRI signal motion. Within the DMN, IL-6 covaried positively with connectivity of the sub-genual ACC and negatively with a region of the dorsal medial PFC at corrected statistical thresholds. These novel findings offer evidence for a unique association between a marker of systemic inflammation (IL-6) and ACC and mPFC functional connectivity within the DMN, a network that may be important for linking aspects of immune function to psychological and behavioral states in health and disease.