Threats to social safety and neuro-inflammatory mechanisms underlying sexual orientation disparities in depression symptom severity: A prospective cohort study of young adults.

Sexual minority individuals have a markedly elevated risk of depression compared to heterosexuals. We examined early threats to social safety and chronically elevated inflammation as mechanisms contributing to this disparity in depression symptoms, and compared the relative strength of the co-occurrence between chronic inflammation and depression symptoms for sexual minorities versus heterosexuals. To do so, we analyzed data from a prospective cohort of sexual minority and heterosexual young adults (n = 595), recruited from a nationally representative sample, that included assessments of early threats to social safety in the form of adverse childhood interpersonal events, three biomarkers of inflammation (i.e., CRP, IL-6, TNF-α) measured at two time points, and depression symptoms over four years. In pre-registered analyses, we found that sexual minorities experienced more adverse childhood interpersonal events, were more likely to display chronically elevated inflammation, and reported more severe depression symptoms than heterosexuals. Adverse childhood interpersonal events and chronically elevated inflammation explained approximately 23 % of the total effect of the association between sexual orientation and depression symptom severity. Further, there was an increased coupling of chronically elevated inflammation and depression symptoms among sexual minorities compared to heterosexuals. These results provide novel longitudinal, population-based evidence for the role of chronically elevated inflammation in linking threats to social safety during childhood with depression symptom severity in young adulthood, consistent with the primary tenets of the social signal transduction theory of depression. Our study extends this theory to the population level by finding that members of a stigmatized population (i.e., sexual minorities) experience a greater risk of depression because of their greater exposure to adverse childhood interpersonal events and the subsequent link to chronic inflammation, highlighting potential biopsychosocial intervention targets.

Men's physical health and life history transitions in the Philippines: Evidence for 'marital selection' but not protective effects of partnering and fatherhood.

In Euro-American societies, married people typically have lower overall risks for total mortality and for certain chronic conditions compared to non-married people. However, people becoming partnered and parents also tend to gain weight in Euro-American settings. Few studies have tested whether links between physical health and life history status translate to other cultural contexts where the socio-ecological dynamics of family life may differ. This limits the application of these insights to men's well-being in global public health. To help address this gap, we drew on a large, long-running birth cohort study of Filipino men, using data collected at three waves between 2005 and 2014 when men were 21.5-30.5 years old (N = 607, obs. = 1760). We tested for the effects of the transition to partnering (marriage/cohabitation) and fatherhood on men's physical health (waist circumference, fat-free mass index, and grip strength). Men becoming partnered or partnered fathers (P/PF) had comparable longitudinal physical health trajectories to men remaining single non-fathers. However, men who became P/PF by their mid 20s had higher fat-free mass index values than single non-fathers at each wave, with the largest effect observed when all men were single non-fathers at baseline. Men who became P/PF by their early 30s were also stronger than the reference group at baseline. Thus, men who were more muscular and stronger at baseline were more likely to transition to P/PF status, consistent with a 'marital selection' model. In complementary analyses, men did not exhibit adverse health effects when they became partnered fathers as young adults or parents to infants, respectively. These findings suggest that links between health and life history transitions in this setting differ from those commonly observed in Euro-American societies. While transitions to marriage and fatherhood are promising windows for interventions to improve men's health, our results highlight the importance of tailoring such approaches to local dynamics.

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.

Implementation of a minimally invasive cell culture system to measure the regulation of inflammation in a school-based sample of adolescents.

Dysregulated inflammation underlies many human diseases, and measures of responsiveness to activation, and sensitivity to inhibition, provide important information beyond baseline assessments of chronic inflammation. This study implements a simplified cell culture protocol in a school-based setting, using finger stick capillary blood collected from 333 adolescents (age 11.4-15.6 years) incubated with lipopolysaccharide (LPS). Median cytokine responses for IL6, IL1ß, and TNFα were 61.9, 26.2, and 11.2 pg/mL, respectively. Samples were also incubated with LPS and glucocorticoid (GC) to measure GC sensitivity. Median responses were reduced in the presence of GC inhibition for IL6 (20.3 pg/mL), IL1ß (10.5 pg/mL), and TNFα (3.3 pg/mL). Minimally invasive cell culture protocols provide novel opportunities for measuring inflammatory phenotypes in a wide range of non-clinical settings.

Intimate partner violence, depression, and chronic low-grade inflammation among middle-aged women in Cebu, Philippines.

OBJECTIVES: Recent discussions in human biology have highlighted how local ecological contexts shape the relationship between social stressors and health across populations. Chronic low-grade inflammation has been proposed as a pathway linking social stressors to health, with evidence concentrated in high-income Western contexts. However, it remains unclear whether this is an important pathway in populations where prevalence is lower due to lower adiposity and greater infectious exposures. To investigate this further, we tested associations between multiple types of intimate partner violence (IPV), a highly prevalent stressor and health crisis globally, and C-reactive protein (CRP), a commonly used measure of chronic low-grade inflammation, in Cebu, Philippines. For reference, we compared results for CRP to depression, a well-established and consistently observed health outcome of IPV. METHODS: Data came from 1601 currently partnered women (ages 35-69 years) as part of the Cebu Longitudinal Health and Nutrition Survey. IPV exposures included physical, emotional, and controlling behavior. Depression scores were measured using a modified version of the Center for Epidemiologic Studies-Depression Scale for this population, whereas plasma CRP was measured from overnight-fasted morning blood samples. RESULTS: All three types of IPV were associated with a higher depression score. However, none of the IPV measures were associated with CRP. In a post hoc interaction test, emotional IPV became positively associated with CRP as waist circumference increased above the mean. CONCLUSIONS: Our results suggest a complex relationship between social stressors and chronic low-grade inflammation, which is likely dependent on the population-specific context of lifestyle and environmental factors.

Evaluation of a Photo Captioning Cognitive Empathy Intervention for Dementia Caregivers.

OBJECTIVES: The goal of this study was to develop and evaluate an intervention aimed at increasing cognitive empathy, improving mental health, and reducing inflammation in dementia caregivers, and to examine the relevant neural and psychological mechanisms. METHODS: Twenty dementia caregivers completed an intervention that involved taking 3-5 daily photographs of their person living with dementia (PLWD) over a period of 10 days and captioning those photos with descriptive text capturing the inner voice of the PLWD. Both before and after the intervention, participants completed questionnaires, provided a blood sample for measures of inflammation, and completed a neuroimaging session to measure their neural response to viewing photographs of their PLWD and others. RESULTS: 87% of enrolled caregivers completed the intervention. Caregivers experienced pre- to post-intervention increases in cognitive empathy (i.e. Perspective-Taking) and decreases in both burden and anxiety. These changes were paralleled by an increased neural response to photographs of their PLWD within brain regions implicated in cognitive empathy. CONCLUSION: These findings warrant a larger replication study that includes a control condition and follows participants to establish the duration of the intervention effects. CLINICAL IMPLICATIONS: Cognitive empathy interventions may improve caregiver mental health and are worthy of further investigation.

Infectious Illness Symptoms Are Associated with Elevated Anxiety in a Sample of Sexual and Gender Minority Young Adults During the COVID-19 Pandemic.

BACKGROUND: To evaluate whether infectious illness symptoms (IIS) are associated with generalized anxiety symptoms during the COVID-19 pandemic in sexual/gender (SGM) minority young adults assigned male at birth (AMAB). METHOD: Four hundred eighteen participants (median age = 25; range, 20-40) were recruited through RADAR, an ongoing Chicago-based cohort study of SGM-AMAB between September 2020 and February 2021. Participants completed online surveys. A subset (n = 145) provided dried blood spot samples to assess SARS-CoV-2 serostatus. RESULTS: One hundred twenty participants (28.7%) had GAD-7 scores of 10 or greater, which indicates generalized anxiety symptoms that may be clinically significant. In a binomial logistic regression model adjusting age, gender identity, race/ethnicity, substance use, and HIV status, the authors found that having a higher IIS count since March 1, 2020, was associated with greater odds of having a GAD-7 score of 10 or greater (OR = 1.14; 95% CI, 1.04, 1.25; P = 0.007). This effect was more pronounced in a binomial logistic regression model adjusting for the same covariates but using current IIS count as the independent variable (OR = 1.39; 95% CI, 1.13, 1.74; P = 0.002). CONCLUSION: Among SGM-AMAB young adults, those who experienced ISS reported higher scores on the GAD-7, a widely used and validated screening measure for generalized anxiety symptoms. These findings highlight the importance of screening for anxiety disorders when patients present with IIS in clinical settings and psychobehavioral health follow-ups when indicated.

Socioeconomic status is negatively associated with immunosenescence but positively associated with inflammation among middle-aged women in Cebu, Philippines.

BACKGROUND: Socioeconomic status (SES) gradients in health are well-documented, and while biological pathways are incompletely understood, chronic inflammation and accelerated immune aging (immunosenescence) among lower SES individuals have been implicated. However, previous findings have come from samples in higher income countries, and it is unclear how generalizable they are to lower- and middle-income countries (LMIC) with different infectious exposures and where adiposity-an important contributor to chronic inflammation-might show different SES patterning. To address this gap, we explored associations between SES and inflammation and immunosenescence in a sample of women in Cebu, Philippines. METHODS: Data came from the mothers of the Cebu Longitudinal Health and Nutrition Survey birth cohort (mean age: 47.7, range: 35-69 years). SES was measured as a combination of annual household income, education level, and assets. Chronic inflammation was measured using C-reactive protein (CRP) in plasma samples from 1,834 women. Immunosenescence was measured by the abundance of exhausted CD8T (CD8 + CD28-CD45RA-) and naïve CD8T and CD4T cells, estimated from DNA methylation in whole blood in a random subsample of 1,028. Possible mediators included waist circumference and a collection of proxy measures of pathogen exposure. RESULTS: SES was negatively associated with the measures of immunosenescence, with slight evidence for mediation by a proxy measure for pathogen exposure from the household's drinking water source. In contrast, SES was positively associated with CRP, which was explained by the positive association with waist circumference. CONCLUSIONS: Similar to higher income populations, in Cebu there is an SES-gradient in pathogen exposures and immunosenescence. However, lifestyle changes occurring more rapidly among higher SES individuals is contributing to a positive association between SES and adiposity and inflammation. Our results suggest more studies are needed to clarify the relationship between SES and inflammation and immunosenescence across LMIC.

Three common assumptions about inflammation, aging, and health that are probably wrong.

Chronic inflammation contributes to the onset and progression of cardiovascular disease and other degenerative diseases of aging. But does it have to? This article considers the associations among inflammation, aging, and health through the lens of human population biology and suggests that chronic inflammation is not a normal nor inevitable component of aging. It is commonly assumed that conclusions drawn from research in affluent, industrialized countries can be applied globally; that aging processes leading to morbidity and mortality begin in middle age; and that inflammation is pathological. These foundational assumptions have shifted focus away from inflammation as a beneficial response to infection or injury and toward an understanding of inflammation as chronic, dysregulated, and dangerous. Findings from community-based studies around the world-many conducted in areas with relatively high burdens of infectious disease-challenge these assumptions by documenting substantial variation in levels of inflammation and patterns of association with disease. They also indicate that nutritional, microbial, and psychosocial environments in infancy and childhood play important roles in shaping inflammatory phenotypes and their contributions to diseases of aging. A comparative, developmental, and ecological approach has the potential to generate novel insights into the regulation of inflammation and how it relates to human health over the life course.

Employee Cardiometabolic Risk Following a Cluster-Randomized Workplace Intervention From the Work, Family and Health Network, 2009-2013.

Objectives. To examine whether workplace interventions to increase workplace flexibility and supervisor support and decrease work-family conflict can reduce cardiometabolic risk. Methods. We randomly assigned employees from information technology (n = 555) and long-term care (n = 973) industries in the United States to the Work, Family and Health Network intervention or usual practice (we collected the data 2009-2013). We calculated a validated cardiometabolic risk score (CRS) based on resting blood pressure, HbA1c (glycated hemoglobin), HDL (high-density lipoprotein) and total cholesterol, height and weight (body mass index), and tobacco consumption. We compared changes in baseline CRS to 12-month follow-up. Results. There was no significant main effect on CRS associated with the intervention in either industry. However, significant interaction effects revealed that the intervention improved CRS at the 12-month follow-up among intervention participants in both industries with a higher baseline CRS. Age also moderated intervention effects: older employees had significantly larger reductions in CRS at 12 months than did younger employees. Conclusions. The intervention benefited employee health by reducing CRS equivalent to 5 to 10 years of age-related changes for those with a higher baseline CRS and for older employees. Trial Registration. ClinicalTrials.gov Identifier: NCT02050204. (Am J Public Health. 2023;113(12):1322-1331. https://doi.org/10.2105/AJPH.2023.307413).

Inflammation Assessed by Latent Profiling is Associated with Stress and Suicidality but not Depression: Findings from the RADAR Cohort Study.

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 six 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.

Association between infectious exposures in infancy and epigenetic age acceleration in young adulthood in metropolitan Cebu, Philippines.

OBJECTIVES: The drivers of human life expectancy gains over the past 200 years are not well-established, with a potential role for historical reductions in infectious disease. We investigate whether infectious exposures in infancy predict biological aging using DNA methylation-based markers that forecast patterns of morbidity and mortality later in life. METHODS: N = 1450 participants from the Cebu Longitudinal Health and Nutrition Survey-a prospective birth cohort initiated in 1983-provided complete data for the analyses. Mean chronological age was 20.9 years when venous whole blood samples were drawn for DNA extraction and methylation analysis, with subsequent calculation of three epigenetic age markers: Horvath, GrimAge, and DunedinPACE. Unadjusted and adjusted least squares regression models were evaluated to test the hypothesis that infectious exposures in infancy are associated with epigenetic age. RESULTS: Birth in the dry season, a proxy measure for increased infectious exposure in the first year of life, as well as the number of symptomatic infections in the first year of infancy, predicted lower epigenetic age. Infectious exposures were associated with the distribution of white blood cells in adulthood, which were also associated with measures of epigenetic age. CONCLUSIONS: We document negative associations between measures of infectious exposure in infancy and DNA methylation-based measures of aging. Additional research, across a wider range of epidemiological settings, is needed to clarify the role of infectious disease in shaping immunophenotypes and trajectories of biological aging and human life expectancy.

Trauma History Predicts Decoupling of C-Reactive Protein and Somatic Symptoms: Results From a Cohort Study of Sexual and Gender Minority Youth.

OBJECTIVE: Systemic inflammation can induce somatic symptoms (e.g., pain, nausea, fatigue) through neuroimmune signaling pathways. Previous research suggests that early-life adversity amplifies signaling between peripheral inflammation and the brain. We therefore hypothesized that greater lifetime trauma exposure at baseline would predict stronger associations between systemic inflammation and somatic symptoms at 2.5-year follow-up in a cohort study of sexual and gender minority youth assigned male at birth ( n = 694). METHODS: We measured prior trauma exposure (lifetime count of traumatic event types reported at baseline), somatic symptoms (Brief Symptom Inventory somatization score), and systemic inflammation (C-reactive protein, interleukin 6, interleukin 1ß, and tumor necrosis factor α). All models included age, gender, education, recent trauma exposure, substance use, body mass index, and HIV status as covariates. RESULTS: Higher C-reactive protein concentrations were associated with greater somatic symptoms in the main effects model ( ß = 0.019, 95% confidence interval [CI] = 0.006 to 0.031). Contrary to our hypothesis, we observed a negative interaction between prior trauma exposure and C-reactive protein levels in predicting somatic symptoms ( ß = -0.017, 95% CI = -0.030 to -0.004). Higher C-reactive protein was associated with greater somatic symptoms only in participants without prior trauma exposure at baseline ( ß = 0.044, 95% CI = 0.026 to 0.062). Specificity analyses revealed similar patterns when nonsomatic depressive symptoms were used as the outcome variable. CONCLUSIONS: These results suggest that sexual and gender minority youth assigned male at birth who have a history of prior trauma exposure may experience decoupling of systemic inflammation and somatic symptoms. The absence of inflammation-related symptoms may prevent individuals from seeking necessary medical care by reducing interoceptive awareness of pathological states.

Prenatal household size and composition are associated with infant fecal bacterial diversity in Cebu, Philippines.

OBJECTIVES: The gut microbiome (GM) connects physical and social environments to infant health. Since the infant GM affects immune system development, there is interest in understanding how infants acquire microbes from mothers and other household members. MATERIALS AND METHODS: As a part of the Cebu Longitudinal Health and Nutrition Survey (CLHNS), we paired fecal samples (proxy for the GM) collected from infants living in Metro Cebu, Philippines at 2 weeks (N = 39) and 6 months (N = 36) with maternal interviews about prenatal household composition. We hypothesized that relationships between prenatal household size and composition and infant GM bacterial diversity (as measured in fecal samples) would vary by infant age, as well as by household member age and sex. We also hypothesized that infant GM bacterial abundances would differ by prenatal household size and composition. RESULTS: Data from 16 S rRNA bacterial gene sequencing show that prenatal household size was the most precise estimator of infant GM bacterial diversity, and that the direction of the association between this variable and infant GM bacterial diversity changed between the two time points. The abundances of bacterial families in the infant GM varied by prenatal household variables. CONCLUSIONS: Results highlight the contributions of various household sources to the bacterial diversity of the infant GM, and suggest that prenatal household size is a useful measure for estimating infant GM bacterial diversity in this cohort. Future research should measure the effect of specific sources of household bacterial exposures, including social interactions with caregivers, on the infant GM.

Structural racism in school contexts and adolescent depression: Development of new indices for the National Longitudinal Study of Adolescent to Adult Health and beyond.

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.

Socioeconomic impacts on Andean adolescents' growth: Variation between households, between communities and over time.

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.

Sleep Variability and Inflammation in Midlife and Older Women.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

COVID-19 symptom severity predicts neutralizing antibody activity in a community-based serological study.

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.

Birth weight and maternal energy status during pregnancy as predictors of epigenetic age acceleration in young adults from metropolitan Cebu, Philippines.

Epigenetic clocks quantify regular changes in DNA methylation that occur with age, or in relation to biomarkers of ageing, and are strong predictors of morbidity and mortality. Here, we assess whether measures of fetal nutrition and growth that predict adult chronic disease also predict accelerated biological ageing in young adulthood using a suite of commonly used epigenetic clocks. Data come from the Cebu Longitudinal Health and Nutrition Survey (CLHNS), a long-running cohort followed since birth in metropolitan Cebu, Philippines. Past work has shown that birth weight (BW) and the mother's arm fat during pregnancy (a measure of pregnancy energy status) relate inversely to health outcomes in the CLHNS but primarily in males. Genome-wide DNA methylation was assessed in whole blood using the Infinium EPIC array. Participants included males (n=895) and females (n=803) measured in 2005 (20.8-22.5 years). Clocks included the Hannum and Horvath clocks trained on chronological age, the DNAmPhenoAge and DNAmGrimAge clocks trained on clinical biomarkers, the Dunedin pace of ageing (DunedinPACE) clock trained on longitudinal changes in ageing biomarkers, and the DNAmTL clock trained on leukocyte telomere length. In males, lower BW predicted advanced biological ageing using the Hannum, DNAmPhenoAge, DunedinPoAm, and DNAmTL clocks. In contrast, BW did not predict any clock in female participants. Participants' mothers' pregnancy arm fat only predicted DNAmTL in males. These findings suggest that epigenetic clocks are a useful tool for gauging long-term outcomes predicted by fetal growth, and add to existing evidence in the CLHNS for sex differences in these relationships.