Momentary loneliness and intrusive thoughts among older adults: the interactive roles of mild cognitive impairment and marital status.

OBJECTIVES: Loneliness is associated with maladaptive cognitions, yet little is known about the association between loneliness and intrusive thinking during older adulthood. Links between loneliness and intrusive thoughts may be particularly strong among individuals with mild cognitive impairment (MCI), who may have greater difficulty regulating emotion and intrusive thoughts. In contrast, having close relationships (e.g. being married) may serve as a protective factor as marital status is associated with better overall well-being. METHOD: Participants were 316 older adults (recruited from the Bronx, NY, as part of a larger study) without dementia at study intake (40% Black; 13% Hispanic, Mage = 77.45 years, 67% women) who completed ecological momentary assessments five times daily for 14 consecutive days (13,957 EMAs total). Multilevel modeling was used to examine the association between momentary loneliness and intrusive thoughts and whether MCI and marital status interacted to moderate this association. RESULTS: There was a significant three-way interaction (ß = -0.17, p < 0.05), such that lagged momentary loneliness was positively associated with intrusive thoughts (3-4 h later) for those with MCI who were not married. CONCLUSION: Findings suggest that among older adults with MCI, being married may be a protective factor and being unmarried may be a risk factor for experiencing loneliness and subsequent intrusive thoughts.

Racial differences in links between perceived discrimination, depressive symptoms, and ambulatory working memory.

OBJECTIVES: Perceived discrimination is associated with racial cognitive health disparities. Links between discrimination and cognitive performance, like working memory, in everyday settings (i.e. ambulatory performance) require investigation. Depressive symptoms may be a mechanism through which discrimination relates to ambulatory working memory. METHOD: Discrimination, retrospective and momentary depressive symptoms/mood, and aggregated and momentary working memory performance among older Black and White adults were examined within the Einstein Aging Study. RESULTS: Racially stratified analyses revealed that discrimination did not relate to Black or White adults' ambulatory working memory. Among Black adults, however, more frequent discrimination was associated with greater retrospectively reported depressive symptoms, which related to more working memory errors across two weeks (indirect effect p < 0.05). This path was not significant among White adults. Links between discrimination and momentary working memory were not explained by momentary reports of depressed mood for Black or White adults. CONCLUSION: Depressive symptoms may play an important role in the link between discrimination and ambulatory working memory among Black adults across extended measurements, but not at the momentary level. Future research should address ambulatory cognition and momentary reports of discrimination and depression to better understand how to minimize cognitive health disparities associated with discrimination.

The heart of Detroit study: a window into urban middle-aged and older African Americans' daily lives to understand psychosocial determinants of cardiovascular disease risk.

BACKGROUND: Cardiovascular disease disproportionately affects African Americans. Psychosocial factors, including the experience of and emotional reactivity to racism and interpersonal stressors, contribute to the etiology and progression of cardiovascular disease through effects on health behaviors, stress-responsive neuroendocrine axes, and immune processes. The full pathway and complexities of these associations remain underexamined in African Americans. The Heart of Detroit Study aims to identify and model the biopsychosocial pathways that influence cardiovascular disease risk in a sample of urban middle-aged and older African American adults. METHODS: The proposed sample will be composed of 500 African American adults between the ages of 55 and 75 from the Detroit urban area. This longitudinal study will consist of two waves of data collection, two years apart. Biomarkers of stress, inflammation, and cardiovascular surrogate endpoints (i.e., heart rate variability and blood pressure) will be collected at each wave. Ecological momentary assessments will characterize momentary and daily experiences of stress, affect, and health behaviors during the first wave. A proposed subsample of 60 individuals will also complete an in-depth qualitative interview to contextualize quantitative results. The central hypothesis of this project is that interpersonal stressors predict poor cardiovascular outcomes, cumulative physiological stress, poor sleep, and inflammation by altering daily affect, daily health behaviors, and daily physiological stress. DISCUSSION: This study will provide insight into the biopsychosocial pathways through which experiences of stress and discrimination increase cardiovascular disease risk over micro and macro time scales among urban African American adults. Its discoveries will guide the design of future contextualized, time-sensitive, and culturally tailored behavioral interventions to reduce racial disparities in cardiovascular disease risk.

Diminished Cellular Immunity and Executive Cognitive Functioning Among Middle-Aged and Elderly Adults.

OBJECTIVE: Within the field of psychoneuroimmunology, much attention has been given to immune dysregulation and its impact on cognitive functioning. Some of this work has focused on the association between high levels of basal proinflammatory cytokines and poorer performance on measures of executive functioning; however, effect sizes have been quite small in human studies. METHODS: We investigated whether Epstein-Barr virus (EBV) antibody titers, a marker of immune dysregulation related to cellular immunity, may be associated with executive functioning while also attempting to replicate prior studies using two markers of proinflammatory cytokine production (i.e., circulating and lipopolysaccharide [LPS]-stimulated cytokines [interleukin 6, interleukin 1ß, interferon-γ]). A total of 71 community-dwelling adults (mean [standard deviation] age = 60.87 [6.26] years) who were seropositive for EBV infection participated in the study. RESULTS: Findings indicated that greater EBV antibody titers were associated with poorer performance on measures of the executive functions of inhibition ( B = -2.36, standard error = 1.06, p = .028) and cognitive flexibility ( B = -2.89, standard error = 1.13, p = .013) when including circulating and LPS-stimulated cytokines and other relevant covariates (i.e., age, sex, and body mass index) in linear regression analyses. Neither circulating nor LPS-stimulated cytokines were associated with performance on the cognitive tasks in the regression analyses. CONCLUSIONS: These results suggest that EBV antibody titers may be an indicator of immune dysregulation that is more relevant to executive functioning performance than either circulating or stimulated proinflammatory cytokines among community-dwelling adults.

Inflammation and the dimensions of depression: A review.

Patients with depressive disorders show a wide range of clinical manifestations including cognitive and neurovegetative symptoms. Importantly, these symptoms can differ in terms of biological etiology, and deconstructing depression into specific symptoms may provide valuable insight into the underlying neurobiology. Little research has examined inflammation in the context of depressive dimensions. Here we conduct a narrative review of the existing literature (21 studies) to elucidate whether the depression-inflammation link is symptom specific. Overall, there is evidence that an association exists between neurovegetative symptoms of depression and inflammation, independent of cognitive symptoms. The same cannot be said of cognitive symptoms and inflammation. There is also some evidence of gender differences in the directionality of the relationship between depression and inflammation. Potential explanations for these findings, limitations of the existing literature and recommendations for future research design are discussed.

Perceived stress is linked to heightened biomarkers of inflammation via diurnal cortisol in a national sample of adults.

Exposure to and perceptions of stress have been associated with altered systemic inflammation, but the intermediate processes by which stress links to inflammation are not fully understood. Diurnal cortisol slopes were examined as a pathway by which self-reported psychosocial stress is associated with inflammation [i.e., C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, E-Selectin, and Intercellular Adhesion Molecule-1 (ICAM-1)] in a large sample of adults (the Midlife in the US study; N = 914; 55.9% female; aged 34-84 years). Structural equation modeling indicated that perceived psychological stress was associated with flattened diurnal cortisol slopes and flatter diurnal cortisol slopes were, in turn, associated with heightened inflammation in these cross-sectional analyses (index of indirect pathway, ω = 0.003, 95% CI [0.001, 0.004], ωSTD = 0.027; with covariates, ω = 0.001, [0.0002, 0.002], ωSTD = 0.011). A similar indirect effect was evident for self-reported traumatic life events (ω = 0.007, [0.004, 0.012], ωSTD = 0.030); however, inclusion of covariates (i.e., age, gender, race, ethnicity, body mass index, and other factors associated with physical health) accounted for this finding (ω = 0.001, [-0.001, 0.004], ωSTD = 0.005). These results support an allostatic load model of psychosomatic health, in which cortisol (along with other stress-responsive signaling molecules) is a necessary component for understanding links between stress exposure, perceived stress, and immune functioning.

Positive and Negative Affect and Salivary Markers of Inflammation Among Young Adults.

BACKGROUND: Emerging evidence suggests that higher circulating levels of inflammatory biomarkers in blood are associated with higher negative affect (NA) and lower positive affect (PA). To our knowledge, the unique associations between NA and PA in daily life and salivary biomarkers of inflammation have not been examined. This study examined these associations in young adults. METHODS: Measures of NA and PA were created from aggregated daily measures of affect (morning and evening ratings averaged across 14 days). We investigated associations between these measures and salivary C-reactive protein (CRP) and interleukin (IL)-6 in a sample of 108 young adults (60% female, mean age = 20.45 ± 1.47), a subset of whom had self-reported chronic back pain (n = 49). CRP and IL-6 were determined from saliva obtained at the end of the daily diary period. RESULTS: After covarying for age, gender, body mass index, chronic pain status, salivary flow rate, and NA, higher PA was associated with lower salivary CRP (ß = - 0.02, 95% CI (- 0.03, - 0.00) sr2 = .06, p = .01) but not IL-6; removing NA from this model did not change results. In a model with the same covariates (and PA), NA was not significantly related to CRP or IL-6. Chronic back pain status and gender did not moderate results. CONCLUSIONS: Findings suggest that higher PA may be associated with lower salivary CRP in young adults, even after accounting for NA and demographic characteristics. Findings highlight the utility of assessing emotional states in relation to salivary markers of inflammation in future biobehavioral research.

Prenatal cigarette smoking as a mediator between racism and depressive symptoms: The Biosocial Impact on Black Births Study.

OBJECTIVE: This study examined whether cigarette smoking mediated the association of racial discrimination with depressive symptoms among pregnant Black women. DESIGN: Cross-sectional. SAMPLE: Two hundred Black women at 8-29 weeks gestation. MEASUREMENTS: Women completed questionnaires including the Experiences of Discrimination and the Center for Epidemiologic Studies-Depression (CES-D) scales, as well as questions about sociodemographic characteristics and cigarette smoking. RESULTS: The mean age of the sample was 26.9 ± 5.7 years and the mean gestational age at data collection was 15.6 ± 5.7 weeks. Approximately 17% of women reported prenatal cigarette smoking; 27% had prenatal CES-D scores ≥23, which have been correlated with depression diagnoses; and 59% reported ever (lifetime) experiencing discrimination in at least one situation (e.g., at work). Path analysis results indicated that the standardized indirect effect of experiences of racial discrimination on CES-D scores through prenatal smoking was statistically significant (standardized indirect effect = 0.03; 95% CI: 0.001, 0.094; p = .042). CONCLUSION: Cigarette smoking during pregnancy partially mediated the association between lifetime experiences of racial discrimination and prenatal depressive symptoms among pregnant Black women. Smoking cessation programs should focus on identifying and treating depressive symptoms among pregnant Black women.

Negative and positive affect as predictors of inflammation: Timing matters.

Very little research has assessed how measures of negative and positive affect (NA and PA) derived from assessments at multiple time points per day (e.g., via ecological momentary assessment [EMA]), as opposed to questionnaires that rely on recall over a longer period, are related to levels of peripheral inflammation. We examined how different indicators of NA and PA predicted concentrations of C-reactive protein (CRP) and seven peripheral inflammatory cytokines (IL-1ß, IL-6, TNF-α, IL-8, IL-4, IL-10, and IFN-γ) that were examined in the form of an inflammatory composite. A community-based sample of 220 adults (62% Black/African-American and 25% Hispanic/Latino; aged 25-65; 65% female) completed questionnaires at baseline (including recalled affect "over the past month") and then provided EMA reports 5x/day for 14 days. Blood was drawn from each participant after completion of EMA and used to determine plasma levels of CRP and cytokines. Analyses examined if indicators of affect predicted inflammation, controlling for age, gender, body mass index, education, health conditions, and statin use. Neither recalled NA or PA nor momentary NA or PA (aggregated across the 14 days of EMA) were significantly associated with the cytokine composite or CRP. Negative mood more proximal to the blood draw (i.e., aggregated momentary NA in week 2 of EMA) was associated with the cytokine composite but not CRP. Exploratory moderation analyses revealed that the cytokine composite was also associated with PA in week 2 for men only, and with recalled NA for those with lower education. Exploratory analyses around temporal dynamics suggested that the timing of NA measurement relative to the blood draw mattered: Specifically, there were stronger trends of association between momentary NA and inflammatory cytokines when NA was assessed closer in time to blood collection. Future investigation of the relevance of temporal proximity and other measurement details may improve understanding of how affect relates to inflammation.

Effects of dermal wounding on distal primary tumor immunobiology in mice.

BACKGROUND: Before primary oral tumors are treated, various prophylactic procedures that require tissue repair are often necessary (e.g. biopsies, tooth extractions, radiation, and tracheotomies). Wound healing and tumor growth harness similar immune/inflammatory mechanisms. Our previous work indicates that tumors impair wound healing, although the extent to which tissue repair conversely influences tumor growth is poorly understood. Here, we test the hypothesis that dermal wound healing exacerbates primary tumor growth and influences tumor immunobiology. MATERIALS AND METHODS: Female, immunocompetent mice were inoculated subcutaneously with murine oral cancer cells (AT-84) to induce flank tumors. Half of the mice received dermal excisional wounds (4 × 3.5 mm diameter) on their dorsum 16 days later, whereas the skin of controls remained intact. Tumor and blood tissues were harvested 1 and 5 days post wounding, and tumor myeloid cell populations and inflammatory gene expression were measured. Circulating myeloid cells, cytokines, and corticosterone were also quantified. RESULTS: Wounding increased tumor mass, early tumor infiltration of macrophages, and tumor inflammatory gene expression. While wounding attenuated tumor growth-induced increases in circulating myeloid cells, no effects of wounding on circulating cytokine/endocrine measures were observed. CONCLUSIONS: These results indicate that modest skin immune/inflammatory processes can enhance distal tumor growth and alter innate tumor immunity. The implication for this work is that, in the presence of a tumor, the benefits of tissue-damaging procedures that occur clinically must be weighed against the potential consequences for tumor biology.

The Impact of Neighborhood Conditions and Psychological Distress on Preterm Birth in African-American Women.

OBJECTIVE: Prior research suggests that adverse neighborhood conditions are related to preterm birth. One potential pathway by which neighborhood conditions increase the risk for preterm birth is by increasing women's psychological distress. Our objective was to examine whether psychological distress mediated the relationship between neighborhood conditions and preterm birth. DESIGN AND SAMPLE: One hundred and one pregnant African-American women receiving prenatal care at a medical center in Chicago participated in this cross-sectional design study. MEASURES: Women completed the self-report instruments about their perceived neighborhood conditions and psychological distress between 15-26 weeks gestation. Objective measures of the neighborhood were derived using geographic information systems (GIS). Birth data were collected from medical records. RESULTS: Perceived adverse neighborhood conditions were related to psychological distress: perceived physical disorder (r = .26, p = .01), perceived social disorder (r = .21, p = .03), and perceived crime (r = .30, p = .01). Objective neighborhood conditions were not related to psychological distress. Psychological distress mediated the effects of perceived neighborhood conditions on preterm birth. CONCLUSIONS: Psychological distress in the second trimester mediated the effects of perceived, but not objective, neighborhood conditions on preterm birth. If these results are replicable in studies with larger sample sizes, intervention strategies could be implemented at the individual level to reduce psychological distress and improve women's ability to cope with adverse neighborhood conditions.

Cytokine Patterns in Healthy Adolescent Girls: Heterogeneity Captured by Variable and Person-Centered Statistical Strategies.

BACKGROUND: Little is known about variation in individual cytokines/cytokine profiles for a large healthy, pediatric population. When cytokines in a healthy group are not abnormally high as in a disease state, it is challenging to determine appropriate statistical strategies. The aims of the study were (1) to describe variation among cytokine concentrations and profiles in healthy adolescent girls, (2) to illustrate utility of data reduction approaches novel to cytokine research, (variable-centered [principal factor analysis, PFA], person-centered [latent profile analysis, LPA]), and (3) to demonstrate utility of such methods in linking cytokine profiles to health outcomes (e.g., depressive, anxiety symptoms). METHOD: Serum was analyzed for 13 cytokines representing adaptive and innate immune responses in 262 girls (age = 11, 13, 15, and 17 years). RESULTS: There was great variation in cytokine concentrations. PFA revealed a four-factor solution explaining 73.13% of the shared variance among 13 cytokines (e.g., factor 1 included interleukin [IL]-4, IL-13, IL-5, interferon gamma; 26.65% of the shared variance). The LPA supported classifying girls into subgroups characterized by "high overall" (7.3% of sample), "high adaptive" (26.7%), "high innate" (21%), or "low overall" (45%) cytokine levels. Factors and profiles were useful in describing individual differences in depressive/anxiety symptoms (e.g., factor 1 positively associated with depressive symptoms but negatively with trait anxiety; increased depressive symptoms or trait anxiety was associated with greater likelihood of being in the "high adaptive" group). CONCLUSIONS: Healthy girls showed differences in cytokine levels and patterns of variation and important associations with psychological variables. PFA and LPA offer novel approaches useful for examining cytokine panels in healthy populations.

A randomized controlled pilot study feasibility of a tablet-based guided audio-visual relaxation intervention for reducing stress and pain in adults with sickle cell disease.

AIM: To test feasibility of a guided audio-visual relaxation intervention protocol for reducing stress and pain in adults with sickle cell disease. BACKGROUND: Sickle cell pain is inadequately controlled using opioids, necessitating further intervention such as guided relaxation to reduce stress and pain. DESIGN: Attention-control, randomized clinical feasibility pilot study with repeated measures. METHODS: Randomized to guided relaxation or control groups, all patients recruited between 2013-2014 during clinical visits, completed stress and pain measures via a Galaxy Internet-enabled Android tablet at the Baseline visit (pre/post intervention), 2-week posttest visit and also daily at home between the two visits. Experimental group patients were asked to use a guided relaxation intervention at the Baseline visit and at least once daily for 2 weeks. Control group patients engaged in a recorded sickle cell discussion at the Baseline visit. Data were analysed using linear regression with bootstrapping. RESULTS: At baseline, 27/28 of consented patients completed the study protocol. Group comparison showed that guided relaxation significantly reduced current stress and pain. At the 2-week posttest, 24/27 of patients completed the study, all of whom reported liking the study. Patients completed tablet-based measures on 71% of study days (69% in control group, 72% in experiment group). At the 2-week posttest, the experimental group had significantly lower composite pain index scores, but the two groups did not differ significantly on stress intensity. CONCLUSION: This study protocol appears feasible. The tablet-based guided relaxation intervention shows promise for reducing sickle cell pain and warrants a larger efficacy trial. TRIAL REGISTRATION: The ClinicalTrials.gov Identifier is: NCT02501447.

Racial discrimination predicts greater systemic inflammation in pregnant African American women.

PURPOSE: Chronic exposure to racial discrimination by pregnant African American women may lead to allostatic overload; thereby, predisposing women to systemic inflammation. Thus, the goal of this study was to examine if experiences of racial discrimination are related to systemic inflammation in pregnant African Americans. METHODS: A sample of 96 African American women from Chicago completed questionnaires and had blood drawn during the second trimester of pregnancy (19.7±2.5 weeks). RESULTS: Experiences of racial discrimination were associated with higher cytokine levels of interleukin (IL)-4 (B=2.161, 95% CI = 1.02-3.30, p<.001) and IL-6 (B=1.859, 95% CI=.61-3.11, p=.004) when controlling for covariates. CONCLUSION: These findings suggest that experiences of racial discrimination may cause physiological wear and tear on the body leading to alteration of immune functions. Nurses should inquire about women's experiences of racial discrimination and make referrals for community or church support groups for women who report racial discrimination.

Salivary markers of inflammation in response to acute stress.

There is burgeoning interest in the ability to detect inflammatory markers in response to stress within naturally occurring social contexts and/or across multiple time points per day within individuals. Salivary collection is a less invasive process than current methods of blood collection and enables intensive naturalistic methodologies, such as those involving extensive repeated measures per day over time. Yet the reliability and validity of saliva-based to blood-based inflammatory biomarkers in response to stress remains unclear. We review and synthesize the published studies that have examined salivary markers of inflammation following exposure to an acute laboratory stressor. Results from each study are reviewed by analyte (IL-1ß, TNF-α, IL-6, IL-2, IL-4, IL-10, IL-12, CRP) and stress type (social-cognitive and exercise-physical), after which methodological issues and limitations are addressed. Although the literature is limited, several inflammatory markers (including IL-1ß, TNF-α, and IL-6) have been reliably determined from saliva and have increased significantly in response to stress across multiple studies, with effect sizes ranging from very small to very large. Although CRP from saliva has been associated with CRP in circulating blood more consistently than other biomarkers have been associated with their counterparts in blood, evidence demonstrating it reliably responds to acute stress is absent. Although the current literature is presently too limited to allow broad assertion that inflammatory biomarkers determined from saliva are valuable for examining acute stress responses, this review suggests that specific targets may be valid and highlights specific areas of need for future research.

The Effects of Stress on Cognitive Aging, Physiology and Emotion (ESCAPE) Project.

BACKGROUND: Despite evidence that psychological stress is an important risk factor for age-related cognitive loss, little research has directly evaluated psychological and physiological mediators of the relationship between stressful experiences and cognitive function. A key objective of the ESCAPE (Effects of Stress on Cognitive Aging, Physiology, and Emotion) project is to evaluate whether engaging in stress-related unconstructive repetitive thought (URT) is a pathway through which stressful experiences negatively affect cognitive health over the short- and long-term. Over the short-term, we hypothesize that engaging in URT will deplete attentional resources and result in worse cognitive performance in daily life. Over the long-term, we expect that the effects of chronic stress, from repeated exposure to stressors and regular engagement in URT, will be apparent in dysregulated hypothalamic-pituitary-adrenal (HPA) axis function and inflammation. Over time, stress-related physiological dysregulation will result in accelerated cognitive decline. METHODS/DESIGN: This study utilizes a prospective longitudinal measurement-burst design. A systematic probability sample of participants aged 25 to 65 is recruited from residents of the Bronx, NY. Consenting participants complete a baseline assessment and follow-up waves at 9, 18, and 27 months post-baseline. At each wave, participants complete a 14 day measurement burst of brief surveys and cognitive assessments delivered via study smartphones during daily life. Participants provide saliva samples four times each day for five days during the measurement burst and fasting blood samples at the end of each burst from which cortisol and dehydroepiandrosterone sulfate (DHEAS), circulating inflammatory markers, and stimulated inflammatory responses to lipopolysaccharide in whole blood are determined. DISCUSSION: This study takes a multi-pronged approach to assessing stress (i.e., early adversity, chronic strains, major events, daily hassles), psychological mediators (e.g., URT), biological mechanisms (i.e., HPA function, inflammation) and outcomes across different time-scales (i.e., momentary cognitive performance, cognitive decline across years). The systematic probability sample is locally representative and can be compared with national norms on key markers of health and well-being. The findings will improve our understanding of how environmental, psychological, and physiological stress-related influences accumulate to affect cognitive health and identify potential targets (e.g., URT, inflammation) for prevention and intervention promoting cognitive health.

Relationships among psychosocial factors, biomarkers, preeclampsia, and preterm birth in African American women: a pilot.

AIM: To explore the relationships among psychosocial factors (optimism, uncertainty, social support, coping, psychological distress), biomarkers (cortisol, cytokines), preeclampsia, and preterm birth in African American women. METHODS: Forty-nine pregnant African American women completed psychosocial questionnaires and had blood collected for biomarkers between 26 and 36 weeks of gestation. Birth outcomes were obtained from birth records. RESULTS: Women reporting higher levels of social support had lower levels of pro-inflammatory cytokines (IL-2, IL-5, and IL-6). Surprisingly, compared with low-risk pregnant women, women diagnosed with preeclampsia reported more optimism and less avoidance, and had lower levels of cortisol and IFN-γ. Similarly, compared to women with full-term birth, women with preterm birth reported higher levels of optimism and lower levels of avoidance, and had lower levels of IL-10. CONCLUSION: Psychosocial factors influence inflammation and pregnancy outcomes. Close assessment and monitoring of psychosocial factors may contribute to improved pregnancy outcomes.

Contrasting mechanisms by which social isolation and restraint impair healing in male mice.

Stress modulates vital aspects of immune functioning in both human and non-human animals, including tissue repair. For example, dermal wounds heal more slowly and are associated with prolonged inflammation and increased bacterial load in mice that experience chronic physical restraint. Social stressors also negatively affect healing; however, previous studies suggest that the affected healing mechanisms may be stress model-specific. Here, the effects of either social isolation or physical restraint on dermal wound healing (3.5 mm wounds on the dorsum) were compared in hairless male mice. Social isolation beginning 3 weeks prior to wounding delayed healing comparably to physical restraint (12 h/day for eight days), in spite of marked differences in metabolic and hormonal consequences (i.e. body mass) between the two stress models. Additionally, isolated mice exhibited reductions in wound bacterial load and inflammatory gene expression (interleukin-1beta [IL-1ß], monocyte chemoattractant protein [MCP]), whereas restraint significantly increased both of these parameters relative to controls. Experimentally augmenting bacterial concentrations in wounds of isolated mice did not ameliorate healing, whereas this treatment accelerated healing in controls. This work indicates that social isolation and restraint stressors comparably impair healing, but do so through disparate mechanisms and at different phases of healing.

Neighborhood racial composition and experiences of racial discrimination: Associations with cytokines during pregnancy among African American women.

Background: Preterm birth rates are consistently higher in African American (AA) pregnancies compared to White pregnancies in the United States. Neighborhood racial composition, experiences of racial discrimination, and systemic inflammation are factors that have been associated with preterm birth and other adverse pregnancy outcomes that may account for these disparities. Here, we investigated whether perceived neighborhood racial composition and experiences of discrimination were predictive of cytokine levels during pregnancy among AA individuals. Methods: 545 AA individuals completed surveys and had blood samples collected at prenatal clinics in the Midwest at three timepoints (8-18,19-29, and 30-36 weeks gestation) throughout pregnancy. Pro-inflammatory [interferon (IFN)-γ, interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, macrophage migration inhibitory factor (MIF)] and anti-inflammatory cytokines (IL-10) were quantified. Multivariate and multilevel models were used to examine associations of perceived neighborhood racial composition and experiences of racial discrimination with cytokine levels, controlling for relevant covariates. Results: Perceived neighborhood racial composition was significantly associated with MIF at 30-36 weeks gestation in multivariate regression (p < 0.001). Living in neighborhoods with more compared to fewer White people was predictive of higher levels of MIF (b = 0.599, SE = 0.12, p < 0.001). Experiences of discrimination were also associated with higher levels of MIF (ß = 0.141, SE = 0.07, p = 0.036). Neither predictor was associated with other cytokines. Follow-up analyses revealed that neighborhood racial composition was also predictive of higher MIF levels at 8-18 weeks gestation (p = 0.02) and at 19-29 weeks gestation (p = 0.04). Conclusions: Living in neighborhoods with more White individuals and having more lifetime experiences of racial discrimination were positively related to levels of the pro-inflammatory cytokine, MIF, among pregnant AA individuals. MIF's known positive relationships with chronic stress and preterm birth suggest that these elevations in MIF may have negative health consequences. Future studies should explore whether MIF serves as a pathway between neighborhood racial composition or experiences of racial discrimination and preterm birth risk among AA individuals.