Project description:The objective of this review is to provide an overview and discussion of recent epidemiologic and mechanistic studies of stress in relation to asthma incidence and morbidity.Recent findings suggest that stress, whether at the individual (i.e. epigenetics, perceived stress), family (i.e. prenatal maternal stress, early-life exposure, or intimate partner violence) or community (i.e. neighborhood violence; neighborhood disadvantage) level, influences asthma and asthma morbidity. Key recent findings regarding how psychosocial stress may influence asthma through Posttraumatic Stress Disorder, prenatal and postnatal maternal/caregiver stress, and community violence and deprivation are highlighted.New research illustrates the need to further examine, characterize, and address the influence of social and environmental factors (i.e. psychological stress) on asthma. Further, research and innovative methodologies are needed to characterize the relationship and pathways associated with stress at multiple levels to more fully understand and address asthma morbidity, and to design potential interventions, especially to address persistent disparities in asthma in ethnic minorities and economically disadvantaged communities.
Project description:BackgroundExposure to violence (ETV) or chronic stress may influence asthma through unclear mechanisms.MethodsEpigenome-wide association study (EWAS) of ETV or chronic stress measures and DNA methylation in nasal epithelium from 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed four measures of ETV and chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by p value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA).ResultsThree CpGs (in SNN, PTPRN2, and LINC01164) were associated with maternal perceived stress or gun violence (p = 1.28-3.36 × 10-7 ), but not with atopic asthma, in EVA-PR. In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence measures in EVA-PR, 12 CpGs (in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4, and ANAPC13) were associated with atopic asthma at FDR-p < .05.ConclusionsPending confirmation in longitudinal studies, our findings suggest that nasal epithelial methylation markers associated with measures of ETV and chronic stress may be linked to atopic asthma in children and adolescents.
Project description:Exposure to psychosocial stressors and ensuing stress physiology have been associated with spontaneous invasive mammary tumors in the Sprague-Dawley rat model of human breast cancer. Mammary gland (MG) development is a time when physiologic and environmental exposures influence breast cancer risk. However, the effect of psychosocial stress exposure on MG development remains unknown. Here, in the first comprehensive longitudinal study of MG development in nulliparous female rats (from puberty through young adulthood; 8-25 wks of age), we quantify the spatial gradient of differentiation within the MG of socially stressed (isolated) and control (grouped) rats. We then demonstrate that social isolation increased stress reactivity to everyday stressors, resulting in downregulation of glucocorticoid receptor (GR) expression in the MG epithelium. Surprisingly, given that chemical carcinogens increase MG cancer risk by preventing normal terminal end bud (TEB) differentiation, chronic isolation stress did not alter TEBs. Instead, isolation blunted MG growth and alveolobular differentiation and reduced epithelial cell proliferation in these structures. Social isolation also enhanced corpora luteal progesterone at all ages but reduced estrogenization only in early adulthood, a pattern that precludes modulated ovarian function as a sufficient mechanism for the effects of isolation on MG development. This longitudinal study of natural variation provides an integrated view of MG development and the importance of increased GR activation in nulliparous ductal growth and alveolobular differentiation. Thus, social isolation and its physiological sequelae disrupt MG growth and differentiation and suggest a contribution of stress exposure during puberty and young adulthood to the previously observed increase in invasive MG cancer observed in chronically socially-isolated adult Sprague-Dawley rats.
Project description:Background and objectivesAlthough community violence may influence asthma morbidity by increasing stress, no study has assessed exposure to gun violence and childhood asthma. We examined whether exposure to gun violence is associated with asthma in children, particularly in those reporting fear of leaving their home.MethodsCase-control study of 466 children aged 9-14 years with (n = 234) and without (n = 232) asthma in San Juan, Puerto Rico. Lifetime exposure to gun violence was defined as hearing a gunshot more than once. We also assessed whether the child was afraid to leave his/her home because of violence. Asthma was defined as physician-diagnosed asthma and wheeze in the prior year. We used logistic regression for the statistical analysis. All multivariate models were adjusted for age, gender, household income, parental asthma, environmental tobacco smoke, prematurity and residential distance from a major road.ResultsCases were more likely to have heard a gunshot more than once than control subjects (n = 156 or 67.2% vs. n = 122 or 52.1%, P < 0.01). In a multivariate analysis, hearing a gunshot more than once was associated with asthma (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.1-1.7, P = 0.01). Compared with children who had heard a gunshot not more than once and were not afraid to leave their home because of violence, those who had heard a gunshot more than once and were afraid to leave their home due to violence had 3.2 times greater odds of asthma (95% CI for OR = 2.2-4.4, P < 0.01).ConclusionsExposure to gun violence is associated with asthma in Puerto Rican children, particularly in those afraid to leave their home. Stress from such violence may contribute to the high burden of asthma in Puerto Ricans.
Project description:BackgroundLittle is known about paternal psychosocial factors and childhood asthma.ObjectiveWe sought to examine the link between maternal and paternal psychosocial stress and asthma outcomes in young children.MethodsParents of 339 pairs of Puerto Rican twins were interviewed individually about their own psychosocial stress and about asthma in their children at age 1 year and again about their child's asthma at age 3 years. Fathers were asked about symptoms of posttraumatic stress disorder (PTSD), depression, and antisocial behavior. Mothers were asked about depressive symptoms. Outcomes assessed in children included recent asthma symptoms, oral steroid use and hospitalizations for asthma in the prior year, and asthma diagnosis. Generalized estimated equation models were used for the multivariate analysis of parental psychosocial stress and asthma morbidity in childhood.ResultsAfter multivariable adjustment, paternal PTSD symptoms, depression, and antisocial behavior were each associated with increased asthma symptoms at age 1 year (eg, odds ratio, 1.08 for each 1-point increase in PTSD score; 95% CI, 1.03-1.14). Maternal depressive symptoms were associated with an increased risk of asthma hospitalizations at age 1 year. At age 3 years, maternal depressive symptoms were associated with asthma diagnosis and hospitalizations for asthma (odds ratio for each 1-point increase in symptoms, 1.16; 95% CI, 1.00-1.36). In an analysis combining 1- and 3-year outcomes, paternal depression was associated with oral steroid use, maternal depressive symptoms were associated with asthma hospitalizations and asthma diagnosis, and parental depression was associated with hospitalizations for asthma.ConclusionsBoth paternal and maternal psychosocial factors can influence asthma morbidity in young Puerto Rican children.
Project description:BackgroundLittle is known about the determinants of asthma among youth with high T helper 2 (Th2) immunity. We hypothesized that exposure to violence (ETV) and violence-related distress are associated with asthma in children and adolescents with high Th2 immunity.MethodsWe analyzed data from Puerto Ricans with high Th2 immunity aged 9-20 years in the Puerto Rico Genetics of Asthma and Lifestyle (PR-GOAL) and the Epigenetic Variation of Childhood Asthma in Puerto Ricans (EVA-PR) studies, and in a prospective study (PROPRA). High Th2-immunity was defined as ≥1 positive allergen-specific IgE and/or a total IgE ≥ 100 IU/mL and/or an eosinophil count ≥ 150 cells/μL. Asthma was defined as physician-diagnosed asthma and current wheeze. ETV and violence-related distress were assessed with the validated ETV Scale and Checklist of Children's Distress Symptoms (CCDS) questionnaires, respectively.ResultsIn multivariable analyses, each 1-point increment in ETV score was significantly associated with 1.13-1.17 times increased odds of asthma in PR-GOAL and in EVA-PR (both at p ≤ 0.01), and each 1-point increment in CCDS score was significantly associated with 1.53-1.54 increased odds of asthma in PR-GOAL and in EVA-PR (both at p ≤ 0.03). Further, a persistently high ETV score was significantly associated with asthma in PROPRA (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.10-7.29). Similar results were obtained in a sensitivity analysis using an eosinophil count ≥ 300 cells/μL instead of ≥150 cells/μL to define high Th2 immunity.ConclusionsETV during childhood is associated with increased risk of persistent or new-onset asthma in youth with high Th2 immunity.
Project description:The objective of this study was analysis of the whole saliva transcriptome to search for biomarkers of psychosocial stressor exposure and substance use in young adults drawn from a population-based longitudinal cohort, the Oregon Youth Substance Use Project. We conducted genome-wide gene expression analysis on whole saliva RNA from 48 individuals stratified by psychosocial stressor exposure using an Affymetrix Gene ST 1.0 array. We applied Weighted Gene Co-expression Network Analysis (WCGNA) to characterize the high-level structure in the data and to relate expression patterns among samples to participant clinical characteristics. This approach finds clusters of correlated genes (modules) which can reflect clinical, histological, or intracellular organization and function. Using WCGNA, we constructed a gene expression network from saliva genome-wide gene expression data, which we found to be similar to a network we constructed from publicly available cell-free saliva genome-wide gene expression data. Functional characterization of the WGCNA modules suggested that the samples varied in composition between an expression profile similar to circulating antigen presenting cell types and a glycoprotein-containing expression profile. We identified a significant relation between one module of whole saliva genome-wide gene expression and smoking behavior, and one with psychosocial stressor exposure. The smoking-related module was related to mitochondrial gene expression, and ever-smokers were found to have reduced overall mitochondrial gene expression. To determine whether reduced expression could be explained by reduction in mitochondrial DNA, we measured mtDNA copy number variation within genomic DNA from 400 OYSUP participants. Surprisingly, we found that more frequent smoking is associated with increased mtDNA copy number. The network structure of whole saliva and its association with clinically assessed exposures and behaviors are reported here for the first time.
Project description:BACKGROUND:Asthma may worsen during adolescence, due to both health risk behaviors and psychosocial stressors commonly encountered during this life stage. METHODS:Cross-sectional study of 24?612 high school students who participated in the 2009 and 2011 National Youth Risk Behavior Survey. Multivariable logistic regression was used to examine the relation between self-reported health risk behaviors or psychosocial stressors and current asthma. Mediation analysis was performed to assess whether depressive symptoms or suicidal behavior contribute to the link between psychosocial stressors and asthma. RESULTS:Current asthma was reported by 13.1% of the study participants. In a multivariable analysis, female sex, obesity, shorter sleep duration, frequent soda/pop consumption, and marijuana use were each significantly associated with 14-36% increased odds of asthma. Any violent behavior (adjusted odds ratio [OR]?=?1.12, 95% confidence interval [CI]?=?1.02-1.24), any victimization (OR?=?1.43, 95%CI?=?1.29-1.58), any suicidal behavior (OR?=?1.41, 95%CI?=?1.22-1.64) and having felt sad or hopeless in the past year (OR?=?1.57, 95%CI?=?1.40-1.75) were each associated with current asthma. In a mediation analyses, having felt sad/hopeless and suicidal behaviors accounted for 21% and 14%, respectively, of the victimization-asthma association. CONCLUSION:Potentially modifiable risk factors, including obesity, short sleep duration, frequent soda/pop consumption, and psychosocial stressors are associated with asthma in US adolescents. Promoting healthier lifestyles, as well as screening for violence exposure and treating depressive symptoms, could help reduce asthma burden in this population.
Project description:Prenatal maternal psychosocial stress might influence the development of childhood asthma. Evaluating paternal psychosocial stress and conducting a sibling comparison could provide further insight into the role of unmeasured confounding. We examined the associations of parental psychosocial stress during and after pregnancy with asthma at age 7 years in the Norwegian Mother and Child Cohort Study (n = 63,626; children born in 2000-2007). Measures of psychosocial stress included lifetime major depressive symptoms, current anxiety/depression symptoms, use of antidepressants, anxiolytics, and/or hypnotics, life satisfaction, relationship satisfaction, work stress, and social support. Childhood asthma was associated with maternal lifetime major depressive symptoms (adjusted relative risk (aRR) = 1.19, 95% confidence interval (CI): 1.09, 1.30), in addition to symptoms of anxiety/depression during pregnancy (aRR = 1.17, 95% CI: 1.06, 1.29) and 6 months after delivery (aRR = 1.17, 95% CI: 1.07, 1.28). Maternal negative life events during pregnancy (aRR = 1.10, 95% CI: 1.06, 1.13) and 6 months after delivery (aRR = 1.14, 95% CI: 1.11, 1.18) were also associated with asthma. These associations were not replicated when evaluated within sibling groups. There were no associations with paternal psychosocial stress. In conclusion, maternal anxiety/depression and negative life events were associated with offspring asthma, but this might be explained by unmeasured maternal background characteristics that remain stable across deliveries.