Person:

Kubzansky, Laura

Background: Disproportionate life stress and consequent physiologic alteration (i.e., immune dysregulation) has been proposed as a major pathway linking socioeconomic position, environmental exposures, and health disparities. Asthma, for example, disproportionately affects lower-income urban communities, where air pollution and social stressors may be elevated. Objectives: We aimed to examine the role of exposure to violence (ETV), as a chronic stressor, in altering susceptibility to traffic-related air pollution in asthma etiology. Methods: We developed geographic information systems (GIS)–based models to retrospectively estimate residential exposures to traffic-related pollution for 413 children in a community-based pregnancy cohort, recruited in East Boston, Massachusetts, between 1987 and 1993, using monthly nitrogen dioxide measurements for 13 sites over 18 years. We merged pollution estimates with questionnaire data on lifetime ETV and examined the effects of both on childhood asthma etiology. Results: Correcting for potential confounders, we found an elevated risk of asthma with a 1-SD (4.3 ppb) increase in NO2 exposure solely among children with above-median ETV [odds ratio (OR) = 1.63; 95% confidence interval (CI), 1.14–2.33)]. Among children always living in the same community, with lesser exposure measurement error, this association was magnified (OR = 2.40; 95% CI, 1.48–3.88). Of multiple exposure periods, year-of-diagnosis NO(_2) was most predictive of asthma outcomes. Conclusions: We found an association between traffic-related air pollution and asthma solely among urban children exposed to violence. Future studies should consider socially patterned susceptibility, common spatial distributions of social and physical environmental factors, and potential synergies among these. Prospective assessment of physical and social exposures may help determine causal pathways and critical exposure periods.

Background: Lead exposure has been associated with cardiovascular disease (CVD) in animal and human studies. However, the mechanisms of action have not been fully elucidated. We therefore examined the relationship between lead and multiple biomarkers of CVD. Methods: Participants were older men from the Normative Aging Study without preexisting coronary heart disease, diabetes, or active infection at baseline (n = 426). Serum biomarkers included lipid profile [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides] and inflammatory markers [C-reactive protein, intercellular adhesion molecule-1, interleukin-6, and tumor necrosis factor receptor-2 (TNF-R2)]. We measured lead in blood and in bone by K-shell X-ray fluorescence. In this sample, 194 men (44.3%) had two or more repeated measures, resulting in 636 observations for analysis. We conducted analyses using mixed effects models with random subject intercepts. Results: Lead levels were associated with several CVD biomarkers, including levels of TNF-R2 and lipid markers. Specifically, in multivariable models, a 50% increase in blood lead level was associated with 26% increased odds of high TNF-R2 levels (> 5.52 ng/mL; odds ratio = 1.26; 95% confidence interval: 1.09, 1.45). There were positive associations of blood lead level with total cholesterol and HDL levels, and these associations were more evident when modeled as continuous outcomes than when categorized using clinically relevant cut points. In addition, longitudinal analyses indicated a significant increase in TNF-R2 levels over time to be associated with high blood lead level at the preceding visit. Conclusions: Blood lead level may be related with CVD in healthy older men through its association with TNF-R2 levels. In addition, the magnitude of the association of blood lead level with TNF-R2 level increased with age in the study population.

Background: Socioeconomic disadvantage and other social stressors in childhood have been linked with cardiometabolic diseases in adulthood; however the mechanisms underlying these observed associations and the timing of their emergence are unclear. The aim of this review was to evaluate research that examined relationships between socioeconomic disadvantage and other social stressors in relation to less-studied cardiometabolic risk factors among youth, including carbohydrate metabolism-related factors, lipids, and central adiposity. Methods: We searched PubMed and ISI Web of Science to identify relevant publications between 2001 and 2013.Studies were selected based on 4 criteria: (1) the study examined an association between at least one social or economic stressor and one relevant outcome prior to age 21; (2) the sample originated from a high-income country; (3) the sample was not selected based on a health condition; and (4) a central aim was to evaluate the effect of the social or economic stressor on at least one relevant outcome. Abstracts were screened and relevant publications were obtained and evaluated for inclusion criteria. We abstracted data from selected articles, summarized them by exposures and outcomes, and assigned an evidence grade. Results: Our search identified 37 publications from 31 studies. Socioeconomic disadvantage was consistently associated with greater central adiposity. Research to date does not provide clear evidence of an association between childhood stressors and lipids or carbohydrate metabolism-related factors. Conclusions: This review demonstrates a paucity of research on the relationship of socioeconomic disadvantage and other social stressors to lipid and carbohydrate metabolism-related factors in youth. Accordingly, it is not possible to form strong conclusions, particularly with regard to stressors other than socioeconomic disadvantage. Findings are used to inform priorities for future research. An improved understanding of these pathways is critical for identifying novel prevention targets and intervention opportunities to protect the long-term health of children and adolescents.

Background: Lead exposure and psychological stress have been independently associated with hypertension in various populations, and animal studies suggest that when they co-occur, their effects may be exacerbated. Objectives: We examined whether psychological stress modifies the impact of cumulative lead exposure (measured as bone lead levels) on hypertension and blood pressure in Boston-area community–exposed men participating in the Normative Aging Study. Methods: We evaluated the modifying effect of stress on lead exposure on baseline hypertension status (513 participants) and on blood pressure in those without hypertension (237 participants), cross-sectionally. In baseline nonhypertensives, we examined the same risk factors in relation to prospective risk of developing hypertension. Results: Cross-sectional analysis revealed a positive interaction between stress and tibia lead on systolic blood pressure, after adjusting for age, body mass index, family history of high blood pressure, education, smoking, alcohol consumption, physical activity, and nutritional factors. In prospective multivariate analyses, high stress also modified the effect of tibia lead and patella lead on the risk of developing hypertension. Those reporting high stress had 2.66 [95% confidence interval (CI), 1.43–4.95] times the risk of developing hypertension per standard deviation increase in tibia lead and had 2.64 (95% CI, 1.42–4.92) times the risk per standard deviation increase in patella lead. Conclusion: To our knowledge, these are the first analyses to look at interactive effects of stress and lead on hypertension in humans. These results suggest that the effect of lead on hypertension is most pronounced among highly stressed individuals, independent of demographic and behavioral risk factors.

Background: Different lines of evidence suggest that low-level lead exposure could be a modifiable risk factor for adverse psychological symptoms, but little work has explored this relation. Objective: We assessed whether bone lead—a biomarker of cumulative lead exposure—is associated with depression and anxiety symptoms among middle-age and elderly women. Methods: Participants were 617 Nurses’ Health Study participants with K-shell X-ray fluorescence bone lead measures and who had completed at last one Mental Health Index 5-item scale (MHI-5) and the phobic anxiety scale of the Crown-Crisp Index (CCI) assessment at mean ± SD age of 59 ± 9 years (range, 41–83 years). With exposure expressed as tertiles of bone lead, we analyzed MHI-5 scores as a continuous variable using linear regression and estimated the odds ratio (OR) of a CCI score ≥ 4 using generalized estimating equations. Results: There were no significant associations between lead and either outcome in the full sample, but associations were found among premenopausal women and women who consistently took hormone replacement therapy (HRT) between menopause and bone lead measurement (n = 142). Compared with women in the lowest tertile of tibia lead, those in the highest scored 7.78 points worse [95% confidence interval (CI): –11.73, –3.83] on the MHI-5 (p-trend = 0.0001). The corresponding OR for CCI ≥ 4 was 2.79 (95% CI: 1.02, 7.59; p-trend = 0.05). No consistent associations were found with patella lead. Conclusions: These results provide support for an association of low-level cumulative lead exposure with increased depressive and phobic anxiety symptoms among older women who are premenopausal or who consistently take postmenopausal HRT.

Context Anxiety disorders are common, with a lifetime prevalence of 20% in the U.S., and are responsible for substantial burdens of disability, missed work days and health care utilization. To date, no causal genetic variants have been identified for anxiety, anxiety disorders, or related traits. Objective: To investigate whether a phobic anxiety symptom score was associated with 3 alternative polygenic risk scores, derived from external genome-wide association studies of anxiety, an internally estimated agnostic polygenic score, or previously identified candidate genes. Design: Longitudinal follow-up study. Using linear and logistic regression we investigated whether phobic anxiety was associated with polygenic risk scores derived from internal, leave-one out genome-wide association studies, from 31 candidate genes, and from out-of-sample genome-wide association weights previously shown to predict depression and anxiety in another cohort. Setting and Participants: Study participants (n = 11,127) were individuals from the Nurses' Health Study and Health Professionals Follow-up Study. Main Outcome Measure: Anxiety symptoms were assessed via the 8-item phobic anxiety scale of the Crown Crisp Index at two time points, from which a continuous phenotype score was derived. Results: We found no genome-wide significant associations with phobic anxiety. Phobic anxiety was also not associated with a polygenic risk score derived from the genome-wide association study beta weights using liberal p-value thresholds; with a previously published genome-wide polygenic score; or with a candidate gene risk score based on 31 genes previously hypothesized to predict anxiety. Conclusion: There is a substantial gap between twin-study heritability estimates of anxiety disorders ranging between 20–40% and heritability explained by genome-wide association results. New approaches such as improved genome imputations, application of gene expression and biological pathways information, and incorporating social or environmental modifiers of genetic risks may be necessary to identify significant genetic predictors of anxiety.

While research has suggested that being married may confer a health advantage, few studies to date have investigated the role of marital status in the development of type 2 diabetes. We examined whether men who are not married have increased risk of incident type 2 diabetes in the Health Professionals Follow-up Study. Men (n = 41,378) who were free of T2D in 1986, were followed for ≤22 years with biennial reports of T2D, marital status and covariates. Cox proportional hazard models were used to compare risk of incident T2D by marital status (married vs unmarried and married vs never married, divorced/separated, or widowed). There were 2,952 cases of incident T2D. Compared to married men, unmarried men had a 16% higher risk of developing T2D (95%CI:1.04,1.30), adjusting for age, family history of diabetes, ethnicity, lifestyle and body mass index (BMI). Relative risks (RR) for developing T2D differed for divorced/separated (1.09 [95%CI: 0.94,1.27]), widowed (1.29 [95%CI:1.06,1.57]), and never married (1.17 [95%CI:0.91,1.52]) after adjusting for age, family history of diabetes and ethnicity. Adjusting for lifestyle and BMI, the RR for T2D associated with widowhood was no longer significant (RR:1.16 [95%CI:0.95,1.41]). When allowing for a 2-year lag period between marital status and disease, RRs of T2D for widowers were augmented and borderline significant (RR:1.24 [95%CI:1.00,1.54]) after full adjustment. In conclusion, not being married, and more specifically, widowhood was more consistently associated with an increased risk of type 2 diabetes in men and this may be mediated, in part, through unfavorable changes in lifestyle, diet and adiposity.

Background: Recent toxicological and epidemiological evidence suggests that chronic psychosocial stress may modify pollution effects on health. Thus, there is increasing interest in refined methods for assessing and incorporating non-chemical exposures, including social stressors, into environmental health research, towards identifying whether and how psychosocial stress interacts with chemical exposures to influence health and health disparities. We present a flexible, GIS-based approach for examining spatial patterns within and among a range of social stressors, and their spatial relationships with air pollution, across New York City, towards understanding their combined effects on health. Methods: We identified a wide suite of administrative indicators of community-level social stressors (2008–2010), and applied simultaneous autoregressive models and factor analysis to characterize spatial correlations among social stressors, and between social stressors and air pollutants, using New York City Community Air Survey (NYCCAS) data (2008-2009). Finally, we provide an exploratory ecologic analysis evaluating possible modification of the relationship between nitrogen dioxide (NO2) and childhood asthma Emergency Department (ED) visit rates by social stressors, to demonstrate how the methods used to assess stressor exposure (and/or consequent psychosocial stress) may alter model results. Results: Administrative indicators of a range of social stressors (e.g., high crime rate, residential crowding rate) were not consistently correlated (rho = - 0.44 to 0.89), nor were they consistently correlated with indicators of socioeconomic position (rho = - 0.54 to 0.89). Factor analysis using 26 stressor indicators suggested geographically distinct patterns of social stressors, characterized by three factors: violent crime and physical disorder, crowding and poor access to resources, and noise disruption and property crimes. In an exploratory ecologic analysis, these factors were differentially associated with area-average NO2 and childhood asthma ED visits. For example, only the ‘violent crime and disorder’ factor was significantly associated with asthma ED visits, and only the ‘crowding and resource access’ factor modified the association between area-level NO2 and asthma ED visits. Conclusions: This spatial approach enabled quantification of complex spatial patterning and confounding between chemical and non-chemical exposures, and can inform study design for epidemiological studies of separate and combined effects of multiple urban exposures. Electronic supplementary material The online version of this article (doi:10.1186/1476-069X-13-91) contains supplementary material, which is available to authorized users.

Background: Oxytocin is known to be related to social behaviors, including trust. However, few studies have investigated the association between oxytocin levels and social capital. Thus, we tested the hypothesis that endogenous oxytocin levels are positively associated with social capital. We also considered whether the association differed across gender because previous studies have shown differential effects of OT on social behaviors depending on gender. Methods: We recruited a convenience sample of 50 women and 31 men in Japan via community sampling from whom we obtained urine sample with which to measure oxytocin levels. Individual-level cognitive social capital (social trust and mutual aid) and structural social capital (community participation) were assessed using a questionnaire. We used multivariate regression, adjusted for covariates (age, number of children, self-rated health, and education), and stratified by gender to consider associations between oxytocin and social capital. Results: Among women, oxytocin was inversely associated with social trust and mutual aid (p<0.05). However, women participating in only 1 organization in the community showed higher oxytocin than women who participated in either no organizations (p<0.05) or 2 or more organization (i.e. inverse-U shape association). Among men, no association was observed between oxytocin and either form of cognitive and structural social capital. Conclusion: Women who perceived low cognitive social capital showed higher oxytocin levels, while structural social capital showed inverse-U shape association with oxytocin. No association between oxytocin and social capital was found among men. Further study is needed to elucidate why oxytocin was inversely associated with cognitive social capital only among women.

Background: Despite moderate heritability estimates for depression-related phenotypes, few robust genetic predictors have been identified. Potential explanations for this discrepancy include the use of phenotypic measures taken from a single time point, rather than integrating information over longer time periods via multiple assessments, and the possibility that genetic risk is shaped by multiple loci with small effects. Methods: We developed a 14-year long-term average depression measure based on 14 years of follow-up in the Nurses' Health Study (NHS; N = 6989 women). We estimated polygenic scores (PS) with internal whole-genome scoring (NHS-GWAS-PS). We also constructed PS by applying two external PS weighting algorithms from independent samples, one previously shown to predict depression (GAIN-MDD-PS) and another from the largest genome-wide analysis currently available (PGC-MDD-PS). We assessed the association of all three PS with our long-term average depression phenotype using linear, logistic, and quantile regressions. Results: In this study, the three PS approaches explained at most 0.2% of variance in the long-term average phenotype. Quantile regressions indicated PS had larger impacts at higher quantiles of depressive symptoms. Quantile regression coefficients at the 75th percentile were at least 40% larger than at the 25th percentile in all three polygenic scoring algorithms. The interquartile range comparison suggested the effects of PS significantly differed at the 25th and 75th percentiles of the long-term depressive phenotype for the PGC-MDD-PS (P = 0.03), and this difference also reached borderline statistical significance for the GAIN-MDD-PS (P = 0.05). Conclusions: Integrating multiple phenotype assessments spanning 14 years and applying different polygenic scoring approaches did not substantially improve genetic prediction of depression. Quantile regressions suggested the effects of PS may be largest at high quantiles of depressive symptom scores, presumably among people with additional, unobserved sources of vulnerability to depression.