Association between Maternal Perinatal Stress and Depression on Infant DNA Methylation in the First Year of Life.

Maternal stress and depression during pregnancy and the first year of the infant's life affect a large percentage of mothers. Maternal stress and depression have been associated with adverse fetal and childhood outcomes as well as differential child DNA methylation (DNAm). However, the biological mechanisms connecting maternal stress and depression to poor health outcomes in children are still largely unknown. Here we aim to determine whether prenatal stress and depression are associated with changes in cord blood mononuclear cell DNAm (CBMC-DNAm) in newborns (n = 119) and whether postnatal stress and depression are associated with changes in peripheral blood mononuclear cell DNAm (PBMC-DNAm) in children of 12 months of age (n = 113) from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort. Stress was measured using the 10-item Perceived Stress Scale (PSS) and depression was measured using the Center for Epidemiologic Studies Depression Questionnaire (CESD). Both stress and depression were measured at 18 weeks and 36 weeks of pregnancy and six months and 12 months postpartum. We conducted epigenome-wide association studies (EWAS) using robust linear regression followed by a sensitivity analysis in which we bias-adjusted for inflation and unmeasured confounding using the bacon and cate methods. To investigate the cumulative effect of maternal stress and depression, we created composite prenatal and postnatal adversity scores. We identified a significant association between prenatal stress and differential CBMC-DNAm at 8 CpG sites and between prenatal depression and differential CBMC-DNAm at 2 CpG sites. Additionally, we identified a significant association between postnatal stress and differential PBMC-DNAm at 8 CpG sites and between postnatal depression and differential PBMC-DNAm at 11 CpG sites. Using our composite scores, we further identified 2 CpG sites significantly associated with prenatal adversity and 7 CpG sites significantly associated with postnatal adversity. Several of the associated genes, including PLAGL1, HYMAI, BRD2, and ERC2 have been implicated in adverse fetal outcomes and neuropsychiatric disorders. This suggested that differential DNAm may play a role in the relationship between maternal mental health and child health.

Ambient PM2.5 and specific sources increase inflammatory cytokine responses to stimulators and reduce sensitivity to inhibitors.

Ambient exposure to fine particulate matter (PM2.5) is associated with increased morbidity and mortality from multiple diseases. Recent observations suggest the hypothesis that trained immunity contributes to these risks, by demonstrating that ambient PM2.5 sensitizes innate immune cells to mount larger inflammatory response to subsequent bacterial stimuli. However, little is known about how general and durable this sensitization phenomenon is, and whether specific sources of PM2.5 are responsible. Here we consider these issues in a longitudinal study of children. The sample consisted of 277 children (mean age 13.92 years; 63.8% female; 38.4% Black; 32.2% Latinx) who completed baseline visits and were re-assessed two years later. Fasting whole blood was ex vivo incubated with 4 stimulating agents reflecting microbial and sterile triggers of inflammation, and with 2 inhibitory agents, followed by assays for IL-1ß, IL-6, IL-8, and TNF-α. Blood also was assayed for 6 circulating biomarkers of low-grade inflammation: C-reactive protein, interleukin-6, -8, and -10, tumor necrosis factor-α, and soluble urokinase-type plasminogen activator receptor. Using machine learning, levels of 15 p.m.2.5 constituents were estimated for a 50 m grid around children's homes. Models were adjusted for age, sex, race, pubertal status, and household income. In cross-sectional analyses, higher neighborhood PM2.5 was associated with larger cytokine responses to the four stimulating agents. These associations were strongest for constituents released by motor vehicles and soil/crustal dust. In longitudinal analyses, residential PM2.5 was associated with declining sensitivity to inhibitory agents; this pattern was strongest for constituents from fuel/biomass combustion and motor vehicles. By contrast, PM2.5 constituents were not associated with the circulating biomarkers of low-grade inflammation. Overall, these findings suggest the possibility of a trained immunity scenario, where PM2.5 heightens inflammatory cytokine responses to multiple stimulators, and dampens sensitivity to inhibitors which counter-regulate these responses.

Racial Discrimination and Metabolic Syndrome in Young Black Adults.

Importance: Metabolic syndrome (MetS) is a common health condition that predisposes individuals to cardiovascular disease (CVD) and disproportionately affects Black and other racially and ethnically minoritized people. Concurrently, Black individuals also report more exposure to racial discrimination compared with White individuals; however, the role of discrimination in the development of MetS over time and associated mediators in these pathways remain underexplored. Objective: To evaluate the association between racial discrimination and MetS in rural Black individuals transitioning from late adolescence into early adulthood and to identify potential mediating pathways. Design, Setting, and Participants: This longitudinal cohort study included Black adolescents enrolled in the Strong African American Families Healthy Adults (SHAPE) Project between June 2009 and May 2021. Families resided in rural counties of Georgia, where poverty rates are among the highest in the nation. Analyses included 322 of the 500 participants who originally enrolled in SHAPE and who were eligible to participate. Guardians provided information about socioeconomic disadvantage. Analyses were conducted in April 2023. Exposures: Youths reported exposure to racial discrimination annually from ages 19 to 21 years. Main Outcomes and Measures: MetS was the main health outcome and was measured at ages 25 and 31 years. MetS was diagnosed according to the International Diabetes Federation guidelines, which requires central adiposity (ie, waist circumference ≥94 cm for males and ≥80 cm for females) and at least 2 of the 4 additional components: signs of early hypertension (ie, systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥85 mm Hg); elevated triglyceride levels (ie, >150 mg/dL); elevated fasting glucose level (ie, ≥100 mg/dL); or lowered high-density lipoprotein levels (ie, <40 mg/dL in men and <50 mg/dL in women). At age 25 years, markers of inflammatory activity (ie, soluble urokinase plasminogen activator receptor [suPAR]) and sleep problems were collected to consider as potential mediators. Results: In 322 participants (210 [65.2%] female) ages 19 to 21 years, more frequent exposure to racial discrimination was associated with higher suPAR levels (b = 0.006; 95% CI, 0.001-0.011; P = .01) and more sleep problems at age 25 years (b = 0.062; 95% CI, 0.028-0.097; P < .001) as well as a 9.5% higher risk of MetS diagnosis at age 31 years (odds ratio [OR], 1.10; 95% CI, 1.01-1.20; P = .03). Both suPAR (b = 0.015; 95% CI, 0.002-0.037) and sleep problems (b = 0.020; 95% CI, 0.002-0.047) at age 25 years were significant indirect pathways. No significant interactions between sex and discrimination emerged. Conclusions and Relevance: This study suggests that racial discrimination in late adolescence is associated with MetS among Black young adults through biobehavioral pathways. Thus, health interventions for MetS in Black adults will need to contend with sleep behaviors and inflammatory intermediaries as well as address and reduce exposure to racial discrimination to narrow disparities and promote health equity.

Family Disadvantage, Education, and Health Outcomes Among Black Youths Over a 20-Year Period.

Importance: Upward mobility (via educational attainment) is highly valued, but longitudinal associations with mental and physical health among Black youths are less understood. Objective: To examine associations of childhood family disadvantage and college graduation with adult mental and physical health in Black youths followed up into adulthood. Design, Setting, and Participants: This longitudinal, prospective cohort study of Black youths from the state of Georgia who were studied for 20 years (ages 11 to 31 years) was conducted between 2001 and 2022. Participants for this study were drawn from the Strong African American Healthy Adults Program. Data analysis was conducted from April 2023 to January 2024. Exposures: Family economic disadvantage (measured during the adolescent years) and college graduation (indicating upward mobility). Main Outcomes and Measures: Primary outcomes included mental health, substance use, and physical health. Mental health included a composite of internalizing and disruptive problems (anxiety, depression, anger, aggressive behaviors, and emotional reactivity). Substance use included a composite of smoking, drinking, and drug use. Physical health included metabolic syndrome (MetS) and proinflammatory phenotypes (immune cells mounting exaggerated cytokine responses to bacterial challenge and being insensitive to inhibitory signals from glucocorticoids). Mental and physical health measures were taken at age 31 and during the adolescent years. Linear and logistic regression analyses, as well as mediated moderation analyses, were conducted. Results: The study population consisted of 329 Black youths (212 women [64%]; 117 men [36%]; mean [SD] age at follow-up, 31 [1] years). Compared with those who did not graduate college, those who graduated from college had 0.14 SD fewer mental health problems (b = -1.377; 95% CI, -2.529 to -0.226; ß = -0.137; P = .02) and 0.13 SD lower levels of substance use (b = -0.114; 95% CI, -0.210 to -0.018; ß = -0.131; P = .02). Residualized change scores revealed that college graduates showed greater decreases from age 16 to 31 years in mental health problems (b = -1.267; 95% CI, -2.360 to -0.174; ß = -0.133; P = .02) and substance use problems (b = -0.116; 95% CI, -0.211 to -0.021; ß = -0.136; P = .02). For physical health, significant interactions between childhood family disadvantage and college completion emerged in association with MetS (OR, 1.495; 95% CI, 1.111-2.012; P = .008) and proinflammatory phenotype (b = 0.051; 95% CI, 0.003 to 0.099; ß = 0.131; P = .04). Among youths growing up in disadvantaged households, college completion was associated with a 32.6% greater likelihood of MetS (OR, 3.947; 95% CI, 1.003-15.502; P = .049) and 0.59 SD more proinflammatory phenotype (mean difference, 0.249, 95% CI, 0.001 to 0.497; P = .049). Conversely, among those from economically advantaged backgrounds, college completion was correlated with lower MetS and less proinflammatory phenotype. Findings held after controlling for body mass index at age 19 years. Conclusions and Relevance: In this longitudinal cohort study of Black youths, graduating from college was associated with an adult profile of better mental health but poorer physical health among those from economic disadvantage. These findings suggest that developing interventions that foster healthy outcomes across multiple life domains may be important for ensuring that striving for upward mobility is not accompanied by unintended cardiometabolic risk.

Interpersonal violence exposure and inflammation during adolescence and young adulthood.

Exposure to violence increases young peoples' risk of developing mental and physical health problems. Chronic stress-related upregulation of innate immune system activity and the development of low-grade inflammation may partially underlie this health risk. However, much of the previous research has been limited to cross-sectional studies utilizing between-person analytic designs, susceptible to confounding by unmeasured factors. In this six-wave panel study of N=157 female adolescents and young adults, we tested within-person associations between interpersonal violence exposure and multiple measures of inflammatory activity. Ex vivo culture studies suggested that participants' immune cells were more reactive to microbial stimulation and less sensitive to inhibition by glucocorticoids after violence. Numbers of circulating monocyte cells increased after violence, but serum levels of interleukin-6 and c-reactive protein did not. Findings from this within-person analysis suggest that violence exposure up-regulates innate immune system activity during adolescence and young adulthood in ways that may increase mental and physical health risk.

Prenatal exposure to maternal disadvantage-related inflammatory biomarkers: associations with neonatal white matter microstructure.

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal serum levels of four cytokines (IL-6, IL-8, IL-10, TNF-α) over the course of pregnancy in relation to offspring white matter microstructure and socioeconomic disadvantage. Higher average maternal IL-6 was associated with very low socioeconomic status (SES; INR < 200% poverty line) and lower neonatal corticospinal fractional anisotropy (FA) and lower uncinate axial diffusivity (AD). No other cytokine was associated with SES. Higher average maternal IL-10 was associated with lower FA and higher radial diffusivity (RD) in corpus callosum and corticospinal tracts, higher optic radiation RD, lower uncinate AD, and lower FA in inferior fronto-occipital fasciculus and anterior limb of internal capsule tracts. SES moderated the relationship between average maternal TNF-α levels during gestation and neonatal white matter diffusivity. When these interactions were decomposed, the patterns indicated that this association was significant and positive among very low SES neonates, whereby TNF-α was inversely and significantly associated with inferior cingulum AD. By contrast, among the more advantaged neonates (lower-to-higher SES [INR ≥ 200% poverty line]), TNF-α was positively and significantly associated with superior cingulum AD. Taken together, these findings suggest that the relationship between prenatal cytokine exposure and white matter microstructure differs as a function of SES. These patterns are consistent with a scenario where gestational inflammation's effects on white matter development diverge depending on the availability of foundational resources in utero.

Reflections on resilience.

Resilience research has long sought to understand how factors at the child, family, school, community, and societal levels shape adaptation in the face of adversities such as poverty and war. In this article we reflect on three themes that may prove to be useful for future resilience research. First is the idea that mental and physical health can sometimes diverge, even in response to the same social process. A better understanding of explanations for this divergence will have both theoretical and public health implications when it comes to efforts to promote resilience. Second is that more recent models of stress suggest that stress can accelerate aging. Thus, we suggest that research on resilience may need to also consider how resilience strategies may need to be developed in an accelerated fashion to be effective. Third, we suggest that if psychological resilience interventions can be conducted in conjunction with efforts to enact system-level changes targeted at adversities, this may synergize the impact that any single intervention can have, creating a more coordinated and effective set of approaches for promoting resilience in young people who confront adversity in life.

Exposure to parental depression in adolescence and proinflammatory phenotypes 20 years later.

Although the biological embedding model of adversity proposes that stressful experiences in childhood create a durable proinflammatory phenotype in immune cells, research to date has relied on study designs that limit our ability to make conclusions about whether the phenotype is long-lasting. The present study leverages an ongoing 20-year investigation of African American youth to test research questions about the extent to which stressors measured in childhood forecast a proinflammatory phenotype in adulthood, as indicated by exaggerated cytokine responses to bacterial stimuli, monocyte insensitivity to inhibitory signals from hydrocortisone, and low-grade inflammation. Parents reported on their depressive symptoms and unsupportive parenting tendencies across youths' adolescence. At age 31, youth participants (now adults) completed a fasting blood draw. Samples were incubated with lipopolysaccharide and doses of hydrocortisone to evaluate proinflammatory processes. Additionally, blood samples were tested for indicators of low-grade inflammation, including IL-6, IL-8, IL-10, and TNF-α, and soluble urokinase plasminogen activator receptor. Analyses revealed that parental depression across youths' adolescence prospectively predicted indicators of proinflammatory phenotypes at age 31. Follow-up analyses suggested that unsupportive parenting mediated these associations. These findings suggest that exposure to parental depression in adolescence leaves an imprint on inflammatory activity that can be observed 20 years later.

Socioeconomic disadvantage and high-effort coping in childhood: evidence of skin-deep resilience.

BACKGROUND: Low socioeconomic status (SES) is a risk factor for poor outcomes across development. Recent evidence suggests that, although psychosocial resilience among youth living in low-SES households is common, such expressions of resilience may not extend to physical health. Questions remain about when these diverging mental and physical health trajectories emerge. The current study hypothesized that skin-deep resilience - a pattern wherein socioeconomic disadvantage is linked to better mental health but worse physical health for individuals with John Henryism high-effort coping - is already present in childhood. METHODS: Analyses focus on 165 Black and Latinx children (Mage = 11.5) who were free of chronic disease and able to complete study procedures. Guardians provided information about their SES. Children reported on their John Henryism high-effort coping behaviors. They also provided reports of their depressed and anxious mood, which were combined into a composite of internalizing symptoms. Children's cardiometabolic risk was captured as a composite reflecting high levels of systolic or diastolic blood pressure, waist circumference, HbA1c, triglycerides, and low high-density lipoprotein cholesterol. RESULTS: Among youth who reported using John Henryism high-effort coping, SES risk was unrelated to internalizing symptoms and was positively associated with cardiometabolic risk. In contrast, for youth who did not engage in high-effort coping, SES risk was positively associated with internalizing symptoms and was unrelated to cardiometabolic risk. CONCLUSIONS: For youth with high-effort coping tendencies, socioeconomic disadvantage is linked to cardiometabolic risk. Public health efforts to support at-risk youth must consider both mental and physical health consequences associated with striving in challenging contexts.

Skin-deep Resilience and Early Adolescence: Neighborhood Disadvantage, Executive Functioning, and Pubertal Development in Minority Youth.

Skin-deep resilience, in which youth overcome adversity and achieve success in psychological and academic domains but at a cost to their physiological well-being, has been documented in late adolescence and adulthood. However, its potential to emerge at earlier developmental stages is unknown. To address this gap, secondary data analyses were executed using waves 1 and 2 of the Adolescent Brain Cognitive Development study (n = 7712; ages 9-10 years at baseline [mean: 9.92; SD = 0.63]; 47.1% female; 66.1% White, 13.4% Black, and 20.6% Hispanic). The results indicated high levels of executive functioning were associated with improved psychological and behavioral outcomes at one-year follow-up. However, for racial and ethnic minority (i.e., Black or Hispanic) youth from disadvantaged neighborhoods, high levels of executive functioning were also associated with accelerated pubertal development. No significant interaction was observed among White youth. The findings suggest the skin-deep resilience pattern may be evident in early adolescence.

Responsive parental support buffers the link between chronic stress and cardiometabolic risk among adolescents.

Youth exposed to chronic stress exhibit increased cardiometabolic risk which parental social support may attenuate. Notably, theories emphasize that support should be delivered responsively for it to exert buffering effects, but this has not been thoroughly tested empirically. This study examined whether timing of support is an important but unrecognized element of responsiveness during adolescence in buffering the link between chronic stress and cardiometabolic risk. Participants were 242 adolescents aged 15 years (63 % female, 38 % Black). Adolescents completed assessments of chronic stress (Life Stress Interview), and trained personnel collected anthropometric measures and blood samples to assess cardiometabolic risk (reflected in low-grade inflammation and metabolic syndrome). Adolescents also completed an eight-day diary assessment to report daily stressor exposure and parental support. Using the diary data, responsiveness of parental support was operationalized as the within-individual difference in parental support received on stressor (vs. non-stressor) days, such that increased parental support on stressor days reflected more timely support. Results suggest that responsive parental support buffered the link between chronic stress and cardiovascular risk. Specifically, chronic stress was associated with greater risk only when parental support was not temporally aligned with stress exposure, but this association was not observed among adolescents who received timely parental support. These findings shed light on why parental support may not always exert buffering effects during adolescence, highlighting the importance of taking a developmental approach to understanding protective effects.

Peer support as moderator of association between socioeconomic status and low-grade inflammation in adolescents.

OBJECTIVE: Individuals who grow up in low-socioeconomic status (SES) families are at an increased risk of health problems across the lifespan. Although supportive social relationships are postulated to be a protective factor for the health of these individuals, the role of friend support in adolescence is not well understood. Given that low-grade inflammation is one key biological mechanism proposed to explain links between family SES and health outcomes, we examined whether adolescents' friend support buffers the association between family SES and low-grade inflammation among adolescents. METHOD: 277 dyads of adolescents (63.5% female; 39.4% White, 38.3% Black, and 32.1% Hispanic; Mage = 13.92 years) and one of their parents participated in this longitudinal study (two waves approximately 2 years apart). Parents reported family objective SES (i.e., income, savings, and education) and family subjective SES (i.e., subjective social status). Adolescents reported perceived friend support. Fasting antecubital blood was drawn from adolescents at both visits. Low-grade inflammatory activity was represented by a composite of inflammatory biomarkers and numbers of classical monocytes. RESULTS: Adolescents' friend support moderated the associations of family subjective SES with both the inflammation composite and classical monocyte counts across cross-sectional, longitudinal, and prospective change (only significant for the inflammation composite) analyses. Specifically, lower family subjective SES was associated with higher levels of low-grade inflammation only among adolescents lower, but not higher, in friend support. No moderation was observed for objective SES. CONCLUSION: Supportive peer relationships buffer the link between family subjective, but not objective, SES and low-grade inflammation in adolescence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Social and psychological adversity are associated with distinct mother and infant gut microbiome variations.

Health disparities are driven by underlying social disadvantage and psychosocial stressors. However, how social disadvantage and psychosocial stressors lead to adverse health outcomes is unclear, particularly when exposure begins prenatally. Variations in the gut microbiome and circulating proinflammatory cytokines offer potential mechanistic pathways. Here, we interrogate the gut microbiome of mother-child dyads to compare high-versus-low prenatal social disadvantage, psychosocial stressors and maternal circulating cytokine cohorts (prospective case-control study design using gut microbiomes from 121 dyads profiled with 16 S rRNA sequencing and 89 dyads with shotgun metagenomic sequencing). Gut microbiome characteristics significantly predictive of social disadvantage and psychosocial stressors in the mothers and children indicate that different discriminatory taxa and related pathways are involved, including many species of Bifidobacterium and related pathways across several comparisons. The lowest inter-individual gut microbiome similarity was observed among high-social disadvantage/high-psychosocial stressors mothers, suggesting distinct environmental exposures driving a diverging gut microbiome assembly compared to low-social disadvantage/low-psychosocial stressors controls (P = 3.5 × 10-5 for social disadvantage, P = 2.7 × 10-15 for psychosocial stressors). Children's gut metagenome profiles at 4 months also significantly predicted high/low maternal prenatal IL-6 (P = 0.029), with many bacterial species overlapping those identified by social disadvantage and psychosocial stressors. These differences, based on maternal social and psychological status during a critical developmental window early in life, offer potentially modifiable targets to mitigate health inequities.

Resilience in children with chronic illness: Tests of the shift-and-persist and skin-deep resilience theories.

This study investigated, and discusses the integration of, the shift-and-persist (SAP) and skin-deep resilience (SDR) theories. The SAP theory states that the combination of shifting (adjusting oneself to stressful situations through strategies like emotion regulation) and persisting (enduring adversity with strength by finding meaning and maintaining optimism) will be beneficial to physical health in children experiencing adversity. The SDR theory states that high striving/self-control will be beneficial to mental health but detrimental to physical health among those confronting adversity. This study investigated 308 children ages 8-17 experiencing the adversity of a chronic illness (asthma). SAP and SDR (striving/self-control) were assessed via questionnaires, and physical health (asthma symptoms, inflammatory profiles), mental health (anxiety/depression, emotional functioning), and behavioral (medication adherence, activity limitations, collaborative relationships with providers) outcomes were measured cross-sectionally. SAP was associated with better physical health, whereas SDR was associated with worse physical health. Both were associated with better mental health. Only SDR was associated with better behavioral outcomes. Implications of findings and discussion of how to integrate these theories are provided. We suggest that future interventions might seek to cultivate both SAP and SDR to promote overall better health and well-being across multiple domains in children experiencing adversity.

Discrimination and Inflammation in Adolescents of Color.

Background: This study examined how experiences with discrimination relate to inflammation, a key biological pathway in mental and physical illnesses, and whether associations are moderated by gender across two samples of adolescents of color. Methods: Study 1 was a longitudinal study of 419 African American adolescents assessed on discrimination (ages 19-20), with trajectories of biomarkers of low-grade inflammation (C-reactive protein and soluble urokinase plasminogen activator receptor) measured from ages 25 to 29. Study 2 was a cross-sectional study of 201 eighth graders of color assessed on discrimination and mechanistic indicators of a proinflammatory phenotype: 1) in vitro studies of immune cells' inflammatory cytokine responses to stimuli; 2) in vitro studies of cells' sensitivity to anti-inflammatory agents; 3) circulating numbers of classical monocytes, key cellular drivers of low-grade inflammation; and 4) a composite of six biomarkers of low-grade inflammation. Results: Interactions of discrimination by gender were found across both studies. In study 1, African American males experiencing high discrimination showed increasing trajectories of soluble urokinase plasminogen activator receptor over time (p < .001). In study 2, adolescent boys of color experiencing greater discrimination evinced a more proinflammatory phenotype: larger cytokine responses to stimuli (p = .003), lower sensitivity to anti-inflammatory agents (p = .003), higher numbers of classical monocytes (p = .008), and more low-grade inflammation (p = .003). No such associations were found in females. Conclusions: Discrimination is a pressing societal issue that will need to be addressed in efforts to promote health equity. This study suggests that adolescent males of color may be particularly vulnerable to its effects on mental health-relevant inflammatory processes.

Longitudinal links between early adolescent temperament and inflammation among young black adults.

A large body of research demonstrates that inflammation is involved in physical health problems that cause substantial morbidity and early mortality. Given inflammation's role in the etiology of chronic diseases, pediatric scientists have begun to study childhood factors that presage elevation of inflammatory biomarkers later in life. The purpose of this study was to test hypotheses designed to determine whether early adolescent emotionally intense and low attention temperaments forecast (a) inflammation at ages 25 and 29 years and (b) worsening levels of inflammation between these two data points. Toward this end, 307 Black children from the rural southeastern United States participated in an 18-year longitudinal study (mean age at baseline, 11.2 years) to determine whether and how early adolescent's behavioral styles or emotionally intense and low attention temperaments may be associated with absolute and worsening levels of inflammation in young adulthood. When children were 11-13 years of age, different teachers at each age provided assessments of emotionally intense and low attention temperaments. Thus, multiple measures of the same temperament constructs were obtained across 3 years for each participant. At age 25, participants provided data on their self-regulation abilities. Peripheral blood was collected at ages 25 and 29 years from which inflammation was quantified, using soluble urokinase plasminogen activator (suPAR), the proinflammatory cytokines interleukin (IL) IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α). Covariates associated with inflammation in prior studies were also assessed; these included socioeconomic risk, gender, cigarette smoking, body mass index (BMI), adverse childhood experiences (ACEs), depressive symptoms, and medication use. An early adolescent emotionally intense temperament was associated directly with higher suPAR and cytokine levels at age 29, and with worsening cytokine levels between ages 25 and 29. A low attention temperament was associated with suPAR levels at age 29. Collectively, these observations highlight pathways that could underlie health risks associated with early adolescent temperaments. The findings suggest that emotionally intense and low-attention early adolescent temperaments forecast higher and worsening inflammation levels across young adulthood.

A multilevel framework to investigate cardiovascular health disparities among South Asian immigrants in the United States.

PURPOSE: Prior studies of cardiovascular health (CVH) disparities among immigrants of South Asian origin in the United States have examined South Asians as one homogenous group, focused primarily on Indian-origin immigrants, and examined risk at the individual level. METHODS: We present current knowledge and evidence gaps about CVH in the three largest South Asian-origin populations in the United States-Bangladeshi, Indian, and Pakistani-and draw on socioecological and lifecourse frameworks to propose a conceptual framework for investigating multilevel risk and protective factors of CVH across these groups. RESULTS: The central hypothesis is that CVH disparities among South Asian populations exist due to differences in structural and social determinants, including lived experiences like discrimination, and that acculturation strategies and resilience resources (e.g., neighborhood environment, education, religiosity, social support) ameliorate stressors to act as health protective factors. RESULTS: Conclusions: Our framework advances conceptualization of the heterogeneity and drivers of cardiovascular disparities in diverse South Asian-origin populations. We present specific recommendations to inform the design of future epidemiologic studies on South Asian immigrant health and the development of multilevel interventions to reduce CVH disparities and promote well-being.

Racial Disparities in School Belonging and Prospective Associations With Diabetes and Metabolic Syndrome.

Importance: School belonging has important implications for academic, psychological, and health outcomes, but the associations between racial disparities in school belonging and health have not been explored to date. Objective: To examine associations between school-level racial disparities in belonging and cardiometabolic health into adulthood in a national sample of Black and White children, adolescents, and young adults. Design, Setting, and Participants: Prospective cohort study of a US national sample of 4830 Black and White students (National Longitudinal Study of Adolescent Health) followed up for 13 years. The study was conducted from 1994 to 1995 for wave 1 and in 2008 for wave 4. Data were analyzed from June 14 to August 13, 2021. Main Outcomes and Measures: School-level racial disparities in belonging at baseline were calculated as the mean level of school belonging for Black students minus the mean level of school belonging for White students at the school that they attended when they were aged 12 to 20 years. Diabetes and metabolic syndrome were measured as outcomes for these same participants at 24 to 32 years of age. Results: The study included 4830 students. For wave 1, mean (SD) age was 16.1 (1.7) years, and for wave 4, 29.0 (1.7) years. A total of 2614 (54.1%) were female, 2219 were non-Hispanic Black (45.9%), and 2611 were non-Hispanic White (54.1%). Among Black students, attending a school with a greater Black-White disparity in school belonging (more negative scores) was associated with an increased risk for diabetes (odds ratio, 0.66 [95% CI, 0.46-0.95]) and more risk factors for metabolic syndrome (rate ratio, 0.95 [95% CI, 0.90-1.00]) in adulthood 13 years later. These associations persisted above individual-level controls (age, sex, and body mass index) and school-level controls (school size, percentage of Black students, and percentage of Black teachers) and were not explained by either an individual's own perception of school belonging or the mean level of belonging across the whole school. Conclusions and Relevance: In this prospective cohort study of US students, racial disparities in school belonging were associated with risks for diabetes and metabolic syndrome in Black students. Among students, fostering a more equal sense of school belonging across racial groups may have implications for health disparities in the cardiometabolic domain into adulthood.

Properties of the Shift and Persist Questionnaire in adolescent and young adult cancer patients and survivors: Validity, consistency, and interpretability.

PURPOSE: The Shift and Persist model provides an informative framework to understand how adolescent and young adult (AYA) cancer patients and survivors (ages 15-39) may withstand stress and thrive despite adversity. The goal of the present study was to examine the psychometric properties of the Shift and Persist Questionnaire (SPQ) in this population and provide guidelines for interpretation. METHODS: AYA cancer patients and survivors were recruited via an online research panel. Participants reported demographics and health history and completed the SPQ and Patient-Reported Outcome Measurement Information System 29-item profile (PROMIS®-29). We evaluated the structural validity, internal consistency, and construct validity of the SPQ. Minimally important differences (MIDs) were estimated to inform SPQ score interpretation. RESULTS: 572 eligible individuals completed the survey. On average, participants were aged 24 (SD = 7) at evaluation. Of the participants, 43.5% were female, 77.1% were white, and 17.5% were Hispanic (across races). The two-factor structure of the SPQ demonstrated very good structural validity (CFI > 0.95, SRMR < 0.08), and construct validity with PROMIS-29® domains (convergent Rs = 0.17 to 0.43, divergent Rs = - 0.11 to - 0.51). Internal consistency was adequate (ω = 0.76-0.83). Recommended MIDs were 1 point for the Shift subscale, 1-2 point(s) for the Persist subscale, and 2-3 points for the total SPQ score. CONCLUSION: The SPQ is a psychometrically sound measure of skills that contribute to resilience in AYA cancer patients and survivors. MID recommendations enhance the interpretability of the SPQ in this population. Future studies examining shifting and persisting in this population may benefit from administering the SPQ.

Socioeconomic disadvantage, chronic stress, and proinflammatory phenotype: an integrative data analysis across the lifecourse.

Socioeconomic disadvantage confers risk for many chronic illnesses, and theories have highlighted chronic psychological stress and alterations to inflammatory processes as key pathways. Specifically, disadvantage can heighten chronic stress, which may promote a proinflammatory phenotype characterized by immune cells mounting exaggerated cytokine responses to challenge and being less sensitive to inhibitory signals. Importantly, lifecourse perspectives emphasize that such immune alterations should be more potent earlier in life during a sensitive period when bodily tissues are highly plastic to environmental inputs. However, examining these propositions is resource intensive, as they require cell-culturing approaches to model functional inflammatory activities, a wide age range, and longitudinal data. Here, we integrated data from five independent studies to create a diverse sample of 1,607 individuals (960 with longitudinal data; 8 to 64 years old; 359 Asian, 205 Black, and 151 Latino/a). Leveraging the resulting lifecourse data, rich interview assessments of disadvantage and stress, and ex vivo assessments of inflammation, we examined two questions: (1) Does chronic stress account for the link between disadvantage and proinflammatory phenotype? (2) Is there a developmental period during which inflammatory responses are more sensitive to disadvantage and chronic stress? Disadvantage was associated with higher chronic stress, which was linked with a proinflammatory phenotype cross-sectionally, longitudinally, and in terms of prospective change across 1.5 to 2 years. Consistent with the sensitive period hypothesis, the magnitude of these indirect associations was strongest in earlier decades and declined across the lifecourse. These findings highlight the importance of taking a lifecourse perspective in examining health disparities.