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Past research has suggested that sexual and gender minorities experience elevated levels of systemic inflammation which in turn has been linked to worse mental health outcomes. Therefore, the goals of this work are to develop a better understanding of the relationship between mental health variables and inflammation among this high-risk population. Data were collected among a sample of young men who have sex with men and transgender women (YMSM/TGW,N= 685) aged 16–20 at the time of enrollment. Multiplex plasma cytokine and inflammatory biomarkers were quantified. Mental health variables were self-reported and included perceived stress, depression, and suicidal ideation. Latent profile analyses (i.e., latent class analyses intended for continuous variables) were utilized to identify four unique profiles of individuals with similar inflammatory markers followed by adjusted multinomial logistic regression to estimate the association between inflammatory profiles and mental health variables. Participants experienced moderate levels of perceived stress, normal levels of depression and ten percent reported suicidal ideation in the past 6 months. Multinomial regression models indicated that being in the highest inflammation profile, compared to the lowest inflammation profile, was significantly associated only with increased perceived stress and suicidal ideation. In sum, we observed significant relationships between inflammation and both perceived stress and suicidal ideation, but not between inflammation and depression. Future research should continue to assess these relationships using longitudinal data as they are intricate and likely bidirectional and may be key to reducing health disparities among this population.

INTRODUCTION: Non-Hispanic Black infants experience disproportionately high risks of low birth weight compared with non-Hispanic White infants, particularly among mothers with high educational attainment and greater socioeconomic advantage. This study investigates how maternal early-life disadvantage contributes to ongoing racial birth weight inequities among U.S. college-educated mothers, specifically declining birth weights with age among non-Hispanic Black mothers. METHODS: Study analyses used cohort data from the National Longitudinal Study of Adolescent to Adult Health. Racial inequities in birth weight by maternal age and early-life disadvantage were assessed using completed reproductive histories at age 33–44 years, collected in 2016–2018, and regression-based marginal standardization techniques. Early-life disadvantage was measured using a study-based composite measure of early-life concentrated poverty and social disadvantage in homes, neighborhoods, and schools, collected in prior waves. Primary analyses were completed in 2020–2021 among college-educated mothers. RESULTS: Among non-Hispanic Black mothers who experienced high early-life disadvantage, a 1-year increase in maternal age at delivery was associated with lower birth weight by 26.07 grams (95% CI= −48.74, −3.40). Similar declines were not found among non-Hispanic Black mothers with low early-life disadvantage. Non-Hispanic White mothers experienced increased birth weight with maternal age, 6.85 grams (95% CI= −1.12, 14.82) per year, which did not significantly vary by early-life disadvantage. CONCLUSIONS: Early-life disadvantage modifies whether and how college-educated mothers experience birth weight decline with older age. The effects of early-life contexts, and embedded racial inequities, on maternal health inequities and differential weathering warrant further public health attention.

Background/Objectives We evaluated potential socioeconomic contributors to variation in Andean adolescents’ growth between households within a peri-urban community undergoing rapid demographic and economic change, between different community types (rural, peri-urban, urban) and over time. Because growth monitoring is widely used for assessing community needs and progress, we compared the prevalences of stunting, underweight, and overweight estimated by three different growth references. Methods Anthropometrics of 101 El Alto, Bolivia, adolescents (Alteños), 11.0–14.9 years old in 2003, were compared between households (economic status assessed by parental occupations); to one urban and two rural samples collected in 1983/1998/1977, respectively; and to the WHO growth reference, a representative sample of Bolivian children (MESA), and a region-wide sample of high-altitude Peruvian children (Puno). Results Female Alteños’ growth was positively associated with household and maternal income indices. Alteños’ height averaged ∼0.8SD/∼0.6SD/∼2SDs greater than adolescents’ height in urban and rural communities measured in 1983/1998/1977, respectively. Overweight prevalence was comparable to the WHO, and lower than MESA and Puno, references. Stunting was 8.5/2.5/0.5 times WHO/MESA/Puno samples, respectively. Conclusions/Implications Both peri-urban conditions and temporal trends contributed to gains in Alteños’ growth. Rural out-migration can alleviate migrants’ poverty, partly because of more diverse economic options in urbanized communities, especially for women. Nonetheless, Alteños averaged below WHO and MESA height and weight medians. Evolved biological adaptations to environmental challenges, and the consequent variability in growth trajectories, favor using multiple growth references. Growth monitoring should be informed by community- and household-level studies to detect and understand local factors causing or alleviating health disparities.

Current evolutionary theory conceptualizes fathers' childcare as highly facultative and likely contingent on a variety of local socioecological predictors. Much of the evolutionarily-motivated work on the predictors of paternal care has focused on smaller-scale societies, while similar, potentially complementary research in larger-scale societies has focused on theoretical frameworks from (e.g.) economics and developmental psychology. Due to the different emphases, relatively few studies have incorporated information on variables known to predict paternal care in one context with those known to predict it in the other. Here, we assess whether paternal care conforms to predictions derived from the facultative fathering hypothesis and life history theory in Cebu, the Philippines. We evaluated which of 6 variables—hours worked outside the home, age and number of children, number of other caregivers, family residence pattern, and fathers' educational attainment—predicted the number of hours fathers reported spending on 12 common caregiving tasks. Consistent with the basic premise of facultative fathering, men who worked more spent less time on childcare. Additionally, the time fathers spent on different types of caregiving reflected changes in demand as children age. However, alloparental care appears to be a complement to, rather than a substitute for, paternal care in this context, in contrast to the predictions of the facultative fathering hypothesis. We also found that men with more education reported spending more time on childcare, consistent with a caregiving strategy that emphasizes heavy investment in embodied capital across generations. Our data illustrate the context-specific nature of ‘facultative’ caregiving in humans, and highlight the importance of considering locally-relevant predictors when testing predictions derived from evolutionary theory.

Background Traumatic experiences are strongly predictive of adverse mental health outcomes. Experimental studies have demonstrated that systemic inflammation can increase reactivity to threatening stimuli. It is not known whether naturally occurring inflammation amplifies the impact of traumatic experiences on mental health. Here we test whether incident traumatic events are more predictive of adverse mental health outcomes for individuals with greater pre-trauma systemic inflammation in a racially and ethnically diverse cohort study of youth assigned male at birth who identify as sexual or gender minorities (ages 16–29, n = 518), a group at high risk for trauma exposure. Methods Measures of inflammation, depression symptom severity, and perceived stress were measured at baseline. One year later, depression symptom severity and perceived stress were measured again, and participants reported the traumatic events they had experienced in the intervening year. Results In a model adjusted for baseline depression symptom severity and other key covariates, we found that higher baseline levels of interleukin-1β amplified the effect of incident trauma exposure on depression symptom severity at follow-up (β = 0.234, SE = 0.080, P = 0.004). In a model adjusted for baseline perceived stress and other key covariates, we found that higher baseline scores on a multi-marker inflammatory index amplified the effect of incident trauma exposure on perceived stress at follow-up (β = 0.243, SE = 0.083, P = 0.003). Conclusions These findings suggest that greater pre-trauma inflammation may predict poorer mental health following trauma exposure. Understanding how inflammation interacts with trauma to shape mental health may generate novel insights for preventing and treating the debilitating psychological consequences of trauma.

We investigated whether the antibody response to coronavirus disease 2019 (COVID-19) mRNA vaccination is similar in women and men. In a community cohort without prior COVID-19, first vaccine dose produced higher immunoglobulin G (IgG) levels and percent inhibition of spike-ACE2 receptor binding, a surrogate measure of virus neutralization, in women compared to men (7.0 µg/mL, 51.6% vs 3.3 µg/mL, 36.4%). After 2 doses, IgG levels remained significantly higher for women (30.4 µg/mL) compared to men (20.6 µg/mL), while percent inhibition was similar (98.4% vs 97.7%). Sex-specific antibody response to mRNA vaccination informs future efforts to understand vaccine protection and side effects.

SARS-CoV-2 vaccines protect against symptomatic and severe COVID-19. The BNT162b2/Pfizer and mRNA-1273/Moderna vaccines represent new vaccine technology relying on administration of mRNA encoding SARS-CoV-2 viral spike protein encased in lipid nanoparticles. The vaccines are administered as two doses into muscle, which elicits a strong response, typically within 14 days after the second dose. Neuromuscular diseases are characterized by the progressive loss of muscle and are often treated with chronic glucocorticoid steroids, both of which may contribute to a blunted immune response to vaccination. Herein, we measured IgG antibody content and neutralizing antibody response after mRNA COVID-19 vaccination in non-ambulatory neuromuscular disease patients. After two doses of mRNA COVID-19 vaccine, median anti-receptor binding domain IgG and percent surrogate viral neutralization in non-ambulatory neuromuscular disease samples were significantly elevated similar to healthy vaccinated controls. As in healthy controls, COVID-19 vaccines produce greater antibody levels compared to those with a history of outpatient COVID-19 infection. This data documents that non-ambulatory neuromuscular disease patients respond well to two doses of mRNA COVID-19 vaccine despite low muscle mass and even chronic steroid use.

Shorter sleep duration and more sleep disturbances, in addition to greater night-to-night fluctuations in sleep (intraindividual variability; IIV), have been associated with elevated inflammation. However, these associations were only at the between-person level. The current study examined the within-person relationship between mean levels and IIV of sleep duration and sleep disturbances and C-reactive protein (CRP) in healthy, aging women.Participants ( N = 179) from a longitudinal study of activity and well-being in middle-aged and older women (mean age = 62 years; range = 50-75 years) completed a 7-day daily diary, every 3 months, for 2 years (up to nine bursts). Sleep was assessed each day asking participants how many hours of sleep they got the night before and with the four-item PROMIS Sleep Disturbance Short Form. Finger-stick dried blood spot samples were collected after each 7-day daily diary.In bursts when women experienced greater than average variability in sleep duration, they had higher CRP ( γ = 0.06, p = .004). Within-person changes in mean sleep duration were not associated with CRP. In addition, neither mean sleep disturbances nor sleep disturbance IIV were associated with CRP.This study is the first to show that within-person changes in variable sleep duration are related to changes in inflammation. Findings from the current study suggest that greater variability in sleep duration is related to higher CRP, which may increase risk for early morbidity and mortality. Future studies should investigate inflammation as a pathway linking sleep variability and health.

Purpose: Transgender and gender-nonconforming (TGNC) youth often report higher rates of chronic social stressors such as victimization, discrimination, and rejection. Some of these gender-based stressors may have long-range physical health consequences through inflammation pathways. This study evaluates the feasibility and acceptability of adding biological measures of inflammation to an ongoing prospective clinical study of TGNC youth (ages 9–20 years), initiating affirming medical therapy at a large, urban children's hospital (N=56). We also examine the relationship between gender-based sources of stress and support with inflammation. This is the first study to explore how gender identity, social stressors, and social supports may contribute to poorer health in TGNC youth through inflammation and immune dysregulation pathways. Methods: Between October 2016 and August 2018, the study team collected dried blood spot (DBS) samples and health measures during clinical visits. Participants also completed computer-assisted surveys assessing gender minority stress and support during these visits. We used regression analysis to evaluate differences in C-reactive protein (CRP) controlling for demographics, health, gender-based stress, and supports. Results: The results from this study indicate that adding DBS samples to assess inflammation was feasible and acceptable in a clinical sample of TGNC youth seeking affirming-medical interventions. We found an association between greater inflammation and the composite score for greater gender-based stressors and lower gender-based supports using the Gender Minority Stress and Resilience Tool (GMSR); however, we did not find statistically significant differences in CRP associated with any of the individual GMSR subscales assessing various types of gender-based supports or stressors. Conclusion: More research is necessary to evaluate how different sources of gender-based support and stress relate to inflammation with larger sample sizes.

Across vertebrates, testosterone is an important mediator of reproductive trade-offs, shaping how energy and time are devoted to parenting versus mating/competition. Based on early environments, organisms often calibrate adult hormone production to adjust reproductive strategies. For example, favorable early nutrition predicts higher adult male testosterone in humans, and animal models show that developmental social environments can affect adult testosterone. In humans, fathers’ testosterone often declines with caregiving, yet these patterns vary within and across populations. This may partially trace to early social environments, including caregiving styles and family relationships, which could have formative effects on testosterone production and parenting behaviors. Using data from a multidecade study in the Philippines (n = 966), we tested whether sons’ developmental experiences with their fathers predicted their adult testosterone profiles, including after they became fathers themselves. Sons had lower testosterone as parents if their own fathers lived with them and were involved in childcare during adolescence. We also found a contributing role for adolescent father–son relationships: sons had lower waking testosterone, before and after becoming fathers, if they credited their own fathers with their upbringing and resided with them as adolescents. These findings were not accounted for by the sons’ own parenting and partnering behaviors, which could influence their testosterone. These effects were limited to adolescence: sons’ infancy or childhood experiences did not predict their testosterone as fathers. Our findings link adolescent family experiences to adult testosterone, pointing to a potential pathway related to the intergenerational transmission of biological and behavioral components of reproductive strategies.

We followed a fully-vaccinated (two mRNA vaccine doses) community cohort (n=41) without prior COVID-19 diagnosis from September 2021 through March 2022 through the Omicron wave following a booster mRNA vaccination. 19.5% of participants reported a known SARS-CoV-2 infection during the Omicron wave, which was confirmed by anti-nucleocapsid IgG. An additional 36.5% also developed anti-nucleocapsid IgG after the boost, consistent with unknown, asymptomatic SARS-CoV-2 infection during this period. Infection defined by anti-nucleocapsid IgG, whether known to participant or not, increased anti-spike IgG levels, relative to those lacking anti-nucleocapsid IgG, at 120 days post-booster.

African American adults suffer disproportionately from several non-communicable and infectious diseases. Among numerous contributing factors, perceived discrimination is considered a stressor for members of historically marginalized groups that contributes to health risk, although biological pathways are incompletely understood. Previous studies have reported associations between stress and both an up-regulation of non-specific (innate) inflammation and down-regulation of specific (adaptive) immunity. While associations between perceived discrimination and markers of inflammation have been explored, it is unclear if this is part of an overall shift that also includes down-regulated adaptive immunity. Relying on a large cross-section of African American adults (n = 3,319) from the Jackson Heart Study (JHS) in Jackson, Mississippi, we tested whether perceived everyday and lifetime discrimination as well as perceived burden from lifetime discrimination were associated with counts of neutrophils (innate), monocytes (innate), lymphocytes (adaptive), and the neutrophil-to-lymphocyte ratio (NLR), derived from complete white blood cell counts with differential. In addition, DNA methylation (DNAm) was measured on the EPIC array in a sub-sample (n = 1,023) of participants, allowing estimation of CD4T, CD8T and B lymphocyte proportions. Unexpectedly, high lifetime discrimination compared to low was significantly associated with lower neutrophils (b : -0.14, [95% CI: -0.24, -0.04]) and a lower NLR (b : -0.15, [95% CI: -0.25, -0.05]) after controlling for confounders. However, high perceived burden from lifetime discrimination was significantly associated with higher neutrophils (b : 0.17, [95% CI: 0.05, 0.30]) and a higher NLR (b : 0.16, [95% CI: 0.03, 0.29]). High perceived burden was also associated with lower lymphocytes among older men, which our analysis suggested might have been attributable to differences in CD4T cells. These findings highlight immune function as a potentially important pathway linking perceived discrimination to health outcomes.

By tracking a group of individuals through time, cohort studies provide fundamental insights into the developmental time course and causes of health and disease. Evolutionary life history theory seeks to explain patterns of growth, development, reproduction and senescence, and inspires a range of hypotheses that are testable using the longitudinal data from cohort studies. Here we review two decades of life history theory-motivated work conducted in collaboration with the Cebu Longitudinal Health and Nutrition Survey (CLHNS), a birth cohort study that enrolled more than 3000 pregnant women in the Philippines in 1983 and has since followed these women, their offspring and grandoffspring. This work has provided evidence that reproduction carries "costs" to cellular maintenance functions, potentially speeding senescence, and revealed an unusual form of genetic plasticity in which the length of telomeres inherited across generations is influenced by reproductive timing in paternal ancestors. Men in Cebu experience hormonal and behavioural changes in conjunction with changes in relationship and fatherhood status that are consistent with predictions based upon other species that practice bi-parental care. The theoretical expectation that early life cues of mortality or environmental unpredictability will motivate a "fast" life history strategy are confirmed for behavioural components of reproductive decision making, but not for maturational tempo, while our work points to a broader capacity for early life developmental calibration of systems like immunity, reproductive biology and metabolism. Our CLHNS findings illustrate the power of life history theory as an integrative, lifecourse framework to guide longitudinal studies of human populations.

Alloparental caregiving is key to humans’ highly flexible reproductive strategies. Across species and across societies, alloparental care is more common in harsh and/or unpredictable environments (HUEs). Currently, however, it is unclear whether HUEs predict intra-population variation in alloparental care, or whether early life HUEs might predict later alloparental care use in adulthood, consistent with adaptive developmental plasticity. We test whether harshness measures (socioeconomic status (SES), environmental hygiene, crowding) and unpredictability measures (parental unemployment, paternal absence, household moves) predicted how much alloparental assistance families in Cebu, Philippines received, in a multigenerational study with data collected across four decades. Though worse environmental hygiene predicted more concurrent alloparental care in 1994, we found little evidence that HUEs predict within-population variation in alloparental care in this large-scale, industrialized society. Indeed, less-crowded conditions and higher SES predicted more alloparental care, not less, in the 1980s and in 2014 respectively, while paternal absence in middle childhood predicted less reliance on alloparental care in adulthood. In this cultural context, our results generally do not provide support for the translation of interspecific or intersocietal patterns linking HUEs and alloparental care to intra-population variation in alloparental care, nor for the idea that a reproductive strategy emphasizing alloparental care use may be preceded by early life HUEs.

A new generation of community- and population-based research is combining measures of social context, experience, and behavior with direct measures of physiology, gene sequence and function, and health. Studies drawing on models and methods from the social and biological sciences have the potential to illuminate the multilevel mechanisms through which experience becomes biology, and to move past decontextualized and reductionistic approaches to human development, behavior, and health. In this perspective we highlight challenges and opportunities at the biosocial interface, and briefly discuss COVID-19 as a case study demonstrating the importance of linking across levels of analysis.

We evaluated potential socioeconomic contributors to variation in Andean adolescents' growth between households within a peri-urban community undergoing rapid demographic and economic change, between different community types (rural, peri-urban, urban) and over time. Because growth monitoring is widely used for assessing community needs and progress, we compared the prevalences of stunting, underweight, and overweight estimated by three different growth references.Anthropometrics of 101 El Alto, Bolivia, adolescents (Alteños), 11.0-14.9 years old in 2003, were compared between households (economic status assessed by parental occupations); to one urban and two rural samples collected in 1983/1998/1977, respectively; and to the WHO growth reference, a representative sample of Bolivian children (MESA), and a region-wide sample of high-altitude Peruvian children (Puno).Female Alteños' growth was positively associated with household and maternal income indices. Alteños' height averaged ∼0.8SD/∼0.6SD/∼2SDs greater than adolescents' height in urban and rural communities measured in 1983/1998/1977, respectively. Overweight prevalence was comparable to the WHO, and lower than MESA and Puno, references. Stunting was 8.5/2.5/0.5 times WHO/MESA/Puno samples, respectively.Both peri-urban conditions and temporal trends contributed to gains in Alteños' growth. Rural out-migration can alleviate migrants' poverty, partly because of more diverse economic options in urbanized communities, especially for women. Nonetheless, Alteños averaged below WHO and MESA height and weight medians. Evolved biological adaptations to environmental challenges, and the consequent variability in growth trajectories, favor using multiple growth references. Growth monitoring should be informed by community- and household-level studies to detect and understand local factors causing or alleviating health disparities.

This was a secondary analysis of a pilot randomized controlled trial (RCT) of mindfulness-based stress reduction (MBSR) among young adult (YA) survivors of cancer, which showed preliminary evidence for improving psychosocial outcomes. Secondary outcomes assessed were the feasibility of collecting biological data from YAs and preliminary effects of MBSR on markers of inflammation and cardiovascular function.Participants were randomized to 8-week MBSR or a waitlist control condition. Participants provided whole blood spot samples for analysis of C-reactive protein (CRP) and interleukin (IL)-6 as well as blood pressure data in-person at baseline and 16-week follow-up. Feasibility was assessed with rates of providing biological data. Linear mixed effects modeling was used to evaluate preliminary effects of MBSR on inflammatory markers and blood pressure over time.Of 126 total participants enrolled, 77% provided biological data at baseline (n = 48/67 MBSR, n = 49/59 control). At 16 weeks, 97% of the 76 retained participants provided follow-up biological data (n = 34/35 MBSR, n = 40/41 control). Relative to the control group, MBSR was associated with decreased systolic blood pressure (p = 0.042, effect sizes (ES) = 0.45) and decreased diastolic blood pressure (p = 0.017, ES = 0.64). There were no changes in CRP or IL-6.This was the first study to explore the feasibility of collecting biological data from YA survivors of cancer and assess preliminary effects of MBSR on inflammatory and cardiovascular markers in an RCT. Minimally invasive biological data collection methods were feasible. Results provide preliminary evidence for the role of MBSR in improving cardiovascular outcomes in this population, and results should be replicated.

Background Confidence in natural immunity after infection with severe acute respiratory syndrome coronavirus 2 is one reason for vaccine hesitancy. Methods We measured antibody-mediated neutralization of spike protein-ACE2 receptor binding in a large community-based sample of seropositive individuals who differed in severity of infection (N = 790). Results A total of 39.8% of infections were asymptomatic, 46.5% were symptomatic with no clinical care, 13.8% were symptomatic with clinical care, and 3.7% required hospitalization. Moderate/high neutralizing activity was present after 41.3% of clinically managed infections, in comparison with 7.9% of symptomatic and 1.9% of asymptomatic infections. Conclusions Prior coronavirus disease 2019 infection does not guarantee a high level of antibody-mediated protection against reinfection in the general population.

The COVID-19 pandemic has left many individuals suffering from “connection deficit disorder” given changes to the way we work, go to school, socialize, and engage in daily activities. Young adults affected by cancer between the ages of 18–39 have known this connection deficit long before the pandemic. Being diagnosed and treated for cancer during this time can significantly disrupt engagement in important educational, career, social, and reproductive pursuits, and contribute to increased stress, anxiety, depression, and other negative outcomes. Experiencing meaningful connection—with nature, with peers who understand, and with oneself, may help assuage this adverse effect of disconnect. A single arm within-subjects program evaluation was conducted to examine outcomes following participation in immersive, multi-night, mindfulness-based treks in nature in a sample of young adults (n = 157) and caregivers (n = 50) affected by cancer from 2016–2021. Pre to post-trek changes included significant (p < 0.001) self-reported improvements in feeling connected to nature (d = 0.93–0.95), peers (d = 1.1–1.3), and oneself (d = 0.57–1.5); significant (p < 0.001) improvements on PROMIS Anxiety (d = 0.62–0.78), Depression (d = 0.87–0.89), and Sleep Disturbance (d = 0.37–0.48) short forms; and significant (p < 0.05) changes in pro-inflammatory biomarkers (d = 0.55–0.82). Connection-promoting experiences like this have the potential to improve health and wellbeing in this population and serve as a model for others.

Two-dose messenger RNA vaccines (BNT162b2/Pfizer and mRNA-1273/Moderna) against SARS-CoV-2 were rolled out in the US in December 2020, and provide protection against hospitalization and death from COVID-19 for at least six months. Breakthrough infections have increased with waning immunity and the spread of the B.1.617.2 (Delta) variant in summer 2021, prompting approval of boosters for all adults over 18. We measured anti-receptor binding domain (RBD) IgG and surrogate virus neutralization of the interaction between SARS-CoV-2 spike protein and the human angiotensin-converting enzyme (ACE2) receptor, before and after boosters in N=33 healthy adults. We document large antibody responses 6-10 days after booster, with antibody levels that exceed levels documented after natural infection with COVID-19, after two doses of vaccine, or after both natural infection and vaccination. Surrogate neutralization of B.1.617.2 is high but reduced in comparison with wild-type SARS-CoV-2. These data support the use of boosters to prevent breakthrough infections and suggest that antibody-mediated immunity may last longer than after the second vaccine dose.

Serological testing for SARS-CoV-2 IgG antibodies is used to assess their presence in blood samples from exposed individuals and provides a measure of the magnitude of immune response to infection. The measurement of neutralizing antibodies (NAbs) in particular provides information about the severity of prior infection and level of protective immunity against re-infection. Much of the work investigating the association between prior infection severity and NAb levels has been conducted among clinical populations, and less is known about this relationship in the general population. Accordingly, we utilize data from a large (n = 790) community-based cohort of unvaccinated, seropositive participants. We analyzed the association between NAb response, measured via surrogate virus neutralization assay, with patterns of symptoms and household exposure. Our results indicate no detectable NAb activity in 63.8% of the seropositive participants (n = 504). Those with detectable NAb levels demonstrated a positive relationship between NAb activity and both self-reported previous symptom severity and household exposure. These findings are significant in light of recent concerns about degree of protective immunity conferred by prior infection or vaccination, and we highlight the value of community-based research for investigating variation in immune response.

Scholarship linking social contextual measures to health outcomes has grown in recent decades, but the role of individuals' intersecting identities in structuring social contexts to influence health remains unclear. Building on an existing intersectionality framework, we conceptualize how this may occur through social relationships. Then, we apply this framework to analyze whether adolescent peer social contextual disadvantage influences life-course obesity heterogeneously by individual gender, race, and early-life income. We take a life course approach as adolescence is a sensitive period for both social development and adult obesity development. In our analysis, we use cohort data from the National Longitudinal Study of Adolescent to Adult Health and leverage quasi-experimental variation in adolescent peers to addresses common sources of bias in prior observational studies. We find that among Black men from lower-income households in adolescence, there is a strong negative relationship between adolescent peer economic disadvantage and adult obesity that strengthens over time. By contrast, among Black women across adolescent household income levels, we find a strong positive relationship between adolescent peer economic disadvantage and obesity that emerges as women leave high school and endures into mid-adulthood. Among non-Black women, a more modest positive relationship appears between peer disadvantage and obesity. Among non-Black men, we find no relationship. These diverging patterns suggest that the pathways through which adolescent peer economic disadvantage influences health may differ or produce differential effects based on intersecting race, gender, and socioeconomic identities. Such heterogenous effects offer new insights, and future directions, for better understanding social life-course determinants of adult health and addressing inequities.

BACKGROUND: Cannabis use has been linked to lower systemic inflammation, but the pathways connecting cannabis use and systemic inflammation are unclear. Here we investigate whether body mass index (BMI) accounts for the association between cannabis use and systemic inflammation in a cohort of sexual and gender minority youth assigned male at birth (n=712). METHODS: Substance use was assessed across six biannual visits. Cannabis use was measured using the Cannabis Use Disorders Identification Test-Revised (CUDIT-R) and urine screening for tetrahydrocannabinol (THC). At the final visit, BMI was measured, and a plasma sample was collected to measure biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6, interleukin-1β, and tumor necrosis factor-α. Inflammatory markers were log(2)-transformed. Age, gender, race/ethnicity, education, HIV status, cigarette use, alcohol use, and polydrug use were included as covariates. RESULTS: In models including all covariates except BMI, greater cumulative CUDIT-R score was associated with lower CRP (β=−0.14; 95% CI: −0.22,−0.05) and lower interleukin-6 (β=−0.12; 95% CI: −0.21,−0.04). These associations were attenuated when BMI was added to the model. Mediation analyses revealed an indirect effect of cumulative CUDIT-R score on CRP (β=−0.08; 95% CI: −0.12,−0.05) and interleukin-6 (β=−0.08; 95% CI: −0.12,−0.05), mediated by BMI. Models using urine THC or self-reported frequency to operationalize cannabis use produced similar results. We found no clear evidence that HIV status moderates these associations. CONCLUSIONS: These results suggest that BMI may partially account for the apparent anti-inflammatory effects of cannabis use. Research on the mechanisms linking cannabis use, adiposity, and inflammation may uncover promising intervention targets.

Racial discrimination is an important predictor of racial inequities in mental and physical health. Scholars have made progress conceptualizing and measuring structural forms of racism, yet, little work has focused on measuring structural racism in social contexts, which are especially relevant for studying the life course consequences of racism for health. Using the National Longitudinal Study of Adolescent to Adult Health, we take a biosocial, life course approach and develop two life stage-specific indices measuring manifestations of structural racism in school contexts in adolescence, a sensitive period of development. The first is a school contextual disadvantage index (CDI), which captures differences in resources and opportunities across schools that have been partly determined by socio-historic structural racism that has sorted Black students into more disadvantaged schools. The second is a school structural racism index (SRI), which measures differences in resources and opportunities between Black and white students within schools. Then, we relate these indices to adolescent depressive symptoms. We find that among both Black and white students of both genders, higher CDI levels are associated with more depressive symptoms. However, Black students are twice as likely to be in schools with a CDI above the median compared to white students. We also find that, controlling for the CDI, the SRI is positively associated with depressive symptoms among Black boys and girls only. Finally, the CDI and the SRI interact to produce a pattern where the likelihood of depressive symptoms increases as the SRI increases, but only among Black boys and girls in low-disadvantage schools. These findings underscore the importance of measuring structural racism in social contexts in multifaceted ways to study life course health inequities.

Two-dose messenger RNA vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective in preventing symptomatic COVID-19 infection. However, the durability of protection is not known, nor is the effectiveness against emerging viral variants. Additionally, vaccine responses may differ based on prior SARS-CoV-2 exposure history. To investigate protection against SARS-CoV-2 variants we measured binding and neutralizing antibody responses following both vaccine doses. We document significant declines in antibody levels three months post-vaccination, and reduced neutralization of emerging variants, highlighting the need to identify correlates of clinical protection to inform the timing of and indications for booster vaccination.

BackgroundThe spike protein of SARS-CoV-2 engages the human angiotensin-converting enzyme 2 (ACE2) receptor to enter host cells, and neutralizing antibodies are effective at blocking this interaction to prevent infection. Widespread application of this important marker of protective immunity is limited by logistical and technical challenges associated with live virus methods and venous blood collection. To address this gap, we validated an immunoassay-based method for quantifying neutralization of the spike-ACE2 interaction in a single drop of capillary whole blood, collected on filter paper as a dried blood spot (DBS) sample.MethodsSamples are eluted overnight and incubated in the presence of spike antigen and ACE2 in a 96-well solid phase plate. Competitive immunoassay with electrochemiluminescent label is used to quantify neutralizing activity. The following measures of assay performance were evaluated: dilution series of confirmed positive and negative samples, agreement with results from matched DBS-serum samples, analysis of results from DBS samples with known COVID-19 status, and precision (intra-assay percent coefficient of variation; %CV) and reliability (inter-assay; %CV).ResultsDilution series produced the expected pattern of dose-response. Agreement between results from serum and DBS samples was high, with concordance correlation = 0.991. Analysis of three control samples across the measurement range indicated acceptable levels of precision and reliability. Median % neutralization was 46.9 for PCR confirmed convalescent COVID-19 samples and 0.1 for negative samples.ConclusionsLarge-scale testing is important for quantifying neutralizing antibodies that can provide protection against COVID-19 in order to estimate the level of immunity in the general population. DBS provides a minimally-invasive, low cost alternative to venous blood collection, and this scalable immunoassay-based method for quantifying neutralization of the spike-ACE2 interaction can be used as a surrogate for virus-based assays to expand testing across a wide range of settings and populations.

Background Consistent with evolutionarily theorized costs of reproduction (CoR), reproductive history in women is associated with life expectancy and susceptibility to certain cancers, autoimmune disorders and metabolic disease. Immunological changes originating during reproduction may help explain some of these relationships. Methodology To explore the potential role of the immune system in female CoR, we characterized leukocyte composition and regulatory processes using DNA methylation (DNAm) in a cross-sectional cohort of young (20–22 years old) women differing in reproductive status. Results Compared to nulliparity, pregnancy was characterized by differential methylation at 828 sites, 96% of which were hypomethylated and enriched for genes associated with T-cell activation, innate immunity, pre-eclampsia and neoplasia. Breastfeeding was associated with differential methylation at 1107 sites (71% hypermethylated), enriched for genes involved in metabolism, immune self-recognition and neurogenesis. There were no significant differences in DNAm between nulliparous and parous women. However, compared to nullipara, pregnant women had lower proportions of B, CD4T, CD8T and natural killer (NK) cells, and higher proportions of granulocytes and monocytes. Monocyte counts were lower and NK counts higher among breastfeeding women, and remained so among parous women. Implications Our findings point to widespread differences in DNAm during pregnancy and lactation. These effects appear largely transient, but may accumulate with gravidity become detectable as women age. Nulliparous and parous women differed in leukocyte composition, consistent with more persistent effects of reproduction on cell type. These findings support transient (leukocyte DNAm) and persistent (cell composition) changes associated with reproduction in women, illuminating potential pathways contributing to CoR. Lay Summary: Evolutionary theory and epidemiology support costs of reproduction (CoR) to women’s health that may involve changes in immune function. We report differences in immune cell composition and gene regulation during pregnancy and breastfeeding. While many of these differences appear transient, immune cell composition may remain, suggesting mechanisms for female CoR.

In a community-based sample of seropositive adults (n = 1101), we found that seropositive individuals who lived with a known coronavirus disease 2019 (COVID-19) case exhibited higher blood anti–severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain immunoglobulin G concentrations and greater symptom severity compared to seropositive individuals who did not live with a known COVID-19 case.

The number of US adults identifying as lesbian, gay, bisexual, transgender, or a different sexual identity has doubled since 2008, and about 40 % of the sexual and gender minority population identify as people of color. Minority stress theory posits that sexual and gender minorities are at particular risk for stress via stigma and discrimination at the structural, interpersonal, and individual levels. This stress, in turn, elevates the risk of adverse health outcomes across several domains. However, there remains a conspicuously limited amount of research on the psychoneuroimmunology of stress among sexual and gender minorities. We developed the Biopsychosocial Minority Stress Framework which posits that sexual minority status leads to unique experiences of minority stress which results in adverse health behavioral factors, elevated psychological distress and sleep disturbance, and immune dysregulation. Moderators in the model include both individual differences and intersectional identities. There is a crucial need to understand the biological-psychological axis of stress among the increasingly visible sexual and gender minority population to increase their health, longevity, and quality of life.

OBJECTIVE: Children exposed to institutional rearing often exhibit problems across a broad array of developmental domains. We compared the consequences of long-term high-quality foster care versus standard institution-based care which began in early childhood on cardiometabolic and immune markers assessed at the time of adolescence. METHODS: The Bucharest Early Intervention Project is a longitudinal investigation of children institutionalized during early childhood (ages 6 to 30 months at baseline) who were subsequently randomized to either high-quality foster care or continued institutional care. At age 16, 127 respondents participated in a biomarker collection protocol, including 44 institutionalized children randomly assigned to receive care as usual, 41 institutionalized children randomized to be removed from institutional care and placed in high-quality foster care in infancy, and a control group of 42 demographically-matched children raised in biological families. Outcomes included body mass index (BMI), systolic and diastolic blood pressure, C-reactive protein, interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α, glycosylated hemoglobin A1c, and Epstein Barr virus antibody titers. RESULTS: Early institutional rearing was not associated with differences in cardiometabolic or immune markers. Randomization to foster care and age of placement into foster care were also unrelated to these markers, with the exception of BMI z-score, where children assigned to care as usual had lower BMI z-scores relative to children assigned to foster care (−0.23 vs 0.08, p=0.06), and older age at placement was associated with lower BMI (β=−0.07, p=0.03). CONCLUSIONS: The impact of institutional rearing on measures of cardiometabolic health and immune system functioning is either absent, or not evident until later in development. These findings provide new insights into the biological embedding of adversity and how it varies developmentally and across regulatory systems and adversity type. CLINICAL TRIAL REGISTRATION: NCT00747396

Sociosexuality is defined as an individual's interest in uncommitted sexual activity and can be measured in terms of both psychological orientations and behavioral expression. In socio-ecological contexts in which adults monogamously partner and cooperate to raise children, individuals with unrestricted sociosexuality are likely to prioritize mating/competition over committed partnering and parenting. Given the importance of mother-father cooperation in the evolutionary past, humans may have the capacity to facultatively and opportunistically downregulate sociosexuality to focus on priorities related to invested partnering and parenting. To date, no prior studies have used longitudinal data to track within-individuals changes in sociosexuality as it relates to such life history transitions. Given the lack of prior longitudinal research in this area, it is likewise unknown what physiological mechanisms might mediate within-individual changes in sociosexuality through time but testosterone is a plausible candidate. To explore these questions, we drew on a large, long-running study of Filipino men (n = 288), who were single non-fathers at 25.9 years of age and were followed up 4–5 years later. We found that men with more unrestricted sociosexuality at baseline were more likely to experience relationship dissolution by follow-up, consistent with past work. Compared to men who remained single non-fathers at follow-up, men who became married residential fathers showed shifts towards more restricted global sociosexuality as well as sociosexual behavior. Relative to their own baseline values, married residential fathers also had more restricted sociosexuality in all domains at follow-up. They were the only group for whom this was found. We found theoretically-consistent but modest support for positive correlations between men's testosterone and their sociosexuality, but no evidence that the two change in tandem together through time. Our results suggest that some amount of between-individual differences in sociosexuality are not stable and can facultatively shift alongside other aspects of male reproductive effort.

Objectives Socioeconomic status (SES) is a powerful determinant of health, but the underlying biological mechanisms are poorly understood. This study investigates whether levels of DNA methylation at CpG sites across the genome are associated with SES in a cohort of young adults in the Philippines. Methods DNA methylation was assayed with the Illumina HumanMethylation450 Bead Chip, in leukocytes from 489 participants in the Cebu Longitudinal Health and Nutrition Survey (mean age = 20.9 years). SES was measured in infancy/childhood and adulthood, and was based on composite measures of income, assets, and education. Genome-wide analysis of variable probes identified CpG sites significantly associated with SES after adjustment for multiple comparisons. Functional enrichment analysis was used to identify biological pathways associated with these sites. Results A total of 2,546 CpG sites, across 1,537 annotated genes, were differentially methylated in association with SES. In comparison with high SES, low SES was associated with increased methylation at 1,777 sites, and decreased methylation at 769 sites. Functional enrichment analysis identified over-representation of biological pathways related to immune function, skeletal development, and development of the nervous system. Conclusions Socioeconomic status predicts DNA methylation at a large number of CpG sites across the genome. The scope of these associations is commensurate with the wide range of biological systems and health outcomes that are shaped by SES, and these findings suggest that DNA methylation may play an important role.

BackgroundEstimates of seroprevalence to SARS-CoV-2 vary widely and may influence vaccination response. We ascertained IgG levels across a single US metropolitan site, Chicago, from June 2020 through December 2020.MethodsParticipants (n=7935) were recruited through electronic advertising and received materials for a self-sampled dried blood spot assay through the mail or a minimal contact in person method. IgG to the receptor binding domain of SARS-CoV-2 was measured using an established highly sensitive and highly specific assay.ResultsOverall seroprevalence was 17.9%, with no significant difference between method of contact. Only 2.5% of participants reported having had a diagnosis of COVID-19 based on virus detection, consistent with a 7-fold greater exposure to SARS-CoV-2 measured by serology than detected by viral testing. The range of IgG level observed in seropositive participants from this community survey overlapped with the range of IgG levels associated with COVID-19 cases having a documented positive PCR positive test. From a subset of those who participated in repeat testing, half of seropositive individuals retained detectable antibodies for 3-4 months.ConclusionsQuantitative IgG measurements with a highly specific and sensitive assay indicate more widespread exposure to SARS-CoV-2 than observed by viral testing. The range of IgG concentration produced from these asymptomatic exposures is similar to IgG levels occurring after documented non-hospitalized COVID-19, which is considerably lower than that produced from hospitalized COVID-19 cases. The differing ranges of IgG response, coupled with the rate of decay of antibodies, may influence response to subsequent viral exposure and vaccine.Graphical Abstract

Objectives Chronic inflammation is a potentially important mechanism through which social inequalities may contribute to health inequalities over the life course. Excess body fat contributes to chronic inflammation, and younger adults in the US have come of age during a pronounced secular increase in body mass index (BMI). We aim to document levels of chronic inflammation in a nationally representative sample of 33-to-44 year-old adults in the US, and to describe associations with BMI, race/ethnicity, and education. Methods High sensitivity C-reactive protein (CRP) was measured in Wave V (2016–18) of the National Longitudinal Study of Adolescent to Adult Health, with complete data available for 4349 participants. Sex-stratified weighted regression models were implemented to investigate CRP in association with education, race/ethnicity, and BMI. Results Geometric mean CRP was 1.9 mg/L, and 35.4% of the sample had CRP >3 mg/L. Females had significantly higher CRP than males. Body mass index was a strong positive predictor of CRP, and education level was negatively associated with CRP. Associations between education and CRP were substantially attenuated after adjusting for BMI. High risk CRP increased linearly with BMI even among the obese: 87.0 percent of females and 74.1 percent of males with class 3 obesity (BMI ≥40) were predicted to have high risk CRP > 3 mg/L. Conclusions The obesity epidemic is producing an epidemic of chronic inflammation in early mid-adulthood in the US. Strong associations between BMI and chronic inflammation portend high risk for future disease—and inequitable distribution of disease—as the cohort ages.

The degree of protective humoral immunity after mild or asymptomatic SARS-CoV-2 infection is not known. We measured antibody-mediated neutralization of spike protein-ACE2 receptor binding—a surrogate measure of protection against SARS-CoV-2 infection—in a large and diverse community-based seroprevalence study. Comparisons were made across three groups of seropositive participants that differed in the severity of infection and engagement with clinical care (N=790). The clinical group was seropositive for prior infection, symptomatic, and diagnosed with COVID-19 by a healthcare provider. The symptomatic group was seropositive and reported one or more symptoms of infection but received no clinical care. The asymptomatic group was seropositive but reported no symptoms. 86.2% of all infections were mild or asymptomatic; 13.8% received clinical care. Of the clinical cases, 96.3% were outpatient; only 3.7% required hospitalization. Moderate or high levels of neutralizing activity were detected following 27.5% of clinical infections, in comparison with 5.4% of symptomatic and 1.5% of asymptomatic infections. The majority of infections in the general population are mild or asymptomatic and likely result in low levels of antibody-mediated protective immunity.

In a community-based sample of seropositive adults (n = 1101), we found that seropositive individuals who lived with a known coronavirus disease 2019 (COVID-19) case exhibited higher blood anti–severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain immunoglobulin G concentrations and greater symptom severity compared to seropositive individuals who did not live with a known COVID-19 case., Exposure intensity may contribute to severity of SARS-CoV-2 infection. Seropositive participants who had lived with a known COVID-19 case had higher antibody concentrations and greater symptom severity compared to seropositive participants who had not lived with a known COVID-19 case.

To date, COVID-19 case rates are disproportionately higher in Black and Latinx communities across the U.S., leading to more hospitalizations and deaths in those communities. These differences in case rates are evident in comparisons of Chicago neighborhoods with differing race/ethnicities of their residents. Disparities could be due to neighborhoods with more adverse health outcomes associated with poverty and other social determinants of health experiencing higher prevalence of SARS-CoV-2 infection or due to greater morbidity and mortality resulting from equivalent SARS-CoV-2 infection prevalence. We surveyed five pairs of adjacent ZIP codes in Chicago with disparate COVID-19 case rates for highly specific and quantitative serological evidence of any prior infection by SARS-CoV-2 to compare with their disparate COVID-19 case rates. Dried blood spot samples were self-collected at home by internet-recruited participants in summer 2020, shortly after Chicago’s first wave of the COVID-19 pandemic. Pairs of neighboring ZIP codes with very different COVID-19 case rates had similar seropositivity rates for anti-SARS-CoV-2 receptor binding domain IgG antibodies. Overall, these findings of comparable exposure to SARS-CoV-2 across neighborhoods with very disparate COVID-19 case rates are consistent with social determinants of health, and the comorbidities related to them, driving differences in COVID-19 rates across neighborhoods.

Field-based research on inflammation and health is typically limited to baseline measures of circulating cytokines or acute-phase proteins, whereas laboratory-based studies can pursue a more dynamic approach with ex vivo cell culture methods. The laboratory infrastructure required for culturing leukocytes limits application in community-based settings, which in turn limits scientific understandings of how psychosocial, behavioral, and contextual factors influence the regulation of inflammation. We aim to address this gap by validating two "field-friendly" cell culture protocols, one using a small volume of venous whole blood and another using finger-stick capillary whole blood.We evaluated the performance of both protocols against a standard laboratory-based protocol using matched venous and capillary blood samples collected from young adults (n = 24). Samples were incubated with lipopolysaccharide and hydrocortisone, and the production of proinflammatory cytokines interleukin 1β, interleukin 6, and tumor necrosis factor α was measured in response.Comparisons indicate a high level of agreement in responses across the protocols and culture conditions. The overall correlation in results was 0.88 between the standard and small-volume protocols and 0.86 between the standard and capillary blood protocols. Repeatability for the small-volume and capillary blood protocols was high, with mean coefficients of variation across five replicates of 6.2% and 5.4%, respectively.These results demonstrate the feasibility of culturing cells and quantifying the inflammatory response to challenge outside the laboratory, with a wide range of potential applications in biobehavioral research in community-based and remote field settings.