Steven W. Cole

Objective: Sexual minority populations are growing, experience elevated physical and mental health risks, and have unique stressor exposures. However, biopsychosocial research on sexual minority individuals at the population level remains limited. Addressing this gap, we launched the National Couples’ Health and Time Stress Biology Study (NCHAT-BIO), the first US-based study focused on stress biology within a large, diverse sample of married/cohabiting sexual minority and heterosexual adults. NCHAT-BIO capitalized on the unique opportunity of NCHAT, a population-representative US sample which intentionally oversampled sexual minority respondents. Methods: NCHAT-BIO was approved by The Ohio State University and Gallup Institutional Review Boards. A total of 950 participants completed at-home dried blood spot (DBS) collection with return by mail. After exclusions, 787 respondent samples were assayed: 44.5% sexual minority, 56.9% assigned female at birth, 55.3% who identified as women, 25% with non-White racial identity, and mean age=42.69 (SD=10.19). Samples were analyzed for interleukin-6 (IL-6), C-reactive protein (CRP), and Epstein Barr Virus (EBV) antibodies. Final analytic samples were: IL-6 (n=452), CRP (n=663), EBV (n=647, including n=84 EBV negative). These biomarker data can be merged with rich NCHAT survey responses, time diaries with an embedded Experience Sampling Method (ESM) component, and contextual state- and county-level indicators. Dissemination: Wave 1 NCHAT-BIO data have been deposited at ICPSR for public release; the current report should be cited in future empirical manuscripts using these data. Wave 1 NCHAT survey data are also at ICPSR, and the two archives will be linked to facilitate integrated use. Future Directions: Whole blood data collection from Wave 3 NCHAT participants will begin in 2026. Planned assays, which will also become publicly available, include IL-6, CRP, and epigenetic aging (per DNA methylation).

Background: Research supports immune pathways of depression characterized by sickness-like symptoms (e.g., appetite changes, low energy, sleep disturbance, difficulty initiating activity, concentration difficulties), with limited evidence for negative affect symptoms (e.g., depressed mood, feeling of failure). However, most findings come from otherwise healthy individuals, limiting generalizability to medical populations. This study leveraged breast cancer as a disease context, given the lasting cancer- and treatment-related effects on immune function, to examine the hypothesis that proinflammatory gene expression relates more strongly to sickness-like than negative affect symptoms. Methods: Data were drawn from 175 women with Stage 0-III breast cancer (M _age= 55.3 years) assessed at five time points from diagnosis through 18 months post-treatment. Depressive symptom dimensions were assessed using the Center for Epidemiologic Studies Depression Scale. Peripheral blood mononuclear cell gene expression was assessed using RNA sequencing-based transcriptional profiling. Primary analyses focused on proinflammatory gene expression. Exploratory analyses examined Type-I interferon gene expression and transcript-derived cell-type composition (myeloid-to-lymphoid and classical-to-non-classical monocyte ratios). Results: Longitudinal mixed-effects models across repeated assessment revealed that greater sickness-like symptom severity was associated with elevated proinflammatory gene expression (p<.001), Type-I Interferon antiviral gene expression (p<.001), myeloid cell abundance (p<.001), and particularly non-classical monocytes (p=.002). By contrast, negative affect symptoms showed weaker, null, or opposite associations. Conclusions: Sickness-like and negative affect symptoms show divergent associations with innate immune system activation and myeloid lineage bias. Results may inform more targeted interventions for both physical/energetic and psychological symptoms in breast cancer survivors, and may be relevant to other depression and medical contexts.

Introduction: Depression is common among people receiving haemodialysis and is associated with adverse outcomes, but the biological pathways underlying this relationship remain uncertain. We examined associations between depressive symptoms, mortality, immune–metabolic markers and stress-related transcriptional profiles, including potential sex differences in routine biomarkers. Methods: We studied 297 adults receiving maintenance haemodialysis across North and East London and Essex. Moderate/severe depressive symptoms were defined as a 17-item Hamilton Depression Rating Scale score >18. Cox regression examined all-cause mortality from enrolment until death or administrative censoring on 24 March 2026. Linear regression assessed associations between depressive-symptom severity and routinely measured immune–metabolic markers, overall and by sex. In a laboratory subset, inflammatory proteins and transcriptional profiles were examined overall only. Results: Moderate/severe depressive symptoms were associated with higher mortality in the adjusted model, although the association was attenuated after full adjustment (hazard ratio, 1.49; 95% confidence interval, 1.00–2.23; P=0.052). Higher white-cell count was associated with greater depressive-symptom severity before, but not after, adjustment for body mass index. Diastolic blood pressure was the only routine marker showing evidence that its association with depressive symptoms differed by sex (interaction P=0.022). Exploratory analyses did not provide convincing evidence that the measured biomarkers accounted for the depression–mortality association. In the laboratory subset, no inflammatory protein or transcriptional measure was significantly associated with depressive symptoms in fully adjusted analyses. Conclusion: Depression may identify a clinically relevant risk state among people receiving haemodialysis. The exploratory biological findings require validation in larger, prospectively sampled cohorts.

Immigrants comprise approximately 14% of the U.S. population and experience increasing rates of chronic disease after migration that are not wholly attributable to behavioral acculturation. The present study examined whether social stressors commonly experienced by immigrants (e.g., acculturative stress, discrimination) are associated with proinflammatory gene expression in a sample of Chinese immigrants residing in the United States. Participants (n = 216) in an observational study completed assessments of acculturative stress, perceived discrimination, and social isolation. Participant weight and height were measured during an in-person exam, and fasting blood samples were collected and assayed for inflammatory gene expression. Greater perceived discrimination was significantly associated with higher levels of inflammatory gene expression controlling for age, sex, body mass index, smoking status, and other demographic variables. Neither acculturative stress nor social isolation was associated with inflammatory gene expression profiles. This is one of the first studies to examine social stressors in relation to biologic pathways that may underlie the increase in chronic disease risk observed among foreign-born populations. These findings contribute to a more comprehensive understanding of how social experiences may impact immigrant health. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Objective: To examine differences in social support, loneliness, and immune function by sexual orientation and to explore whether social support and loneliness mediate immune outcomes. Methods: Participants (394 heterosexual, 144 gay/lesbian, 144 plurisexual) completed the Perceived Social Support Questionnaire and the UCLA Loneliness short-form and provided dried blood spot samples to index i mmune markers (Epstein-Barr virus [EBV] titers, C-reactive protein [CRP], interleukin-6 [IL-6]) between September 2020 and November 2021. Results: Plurisexual (Cohen’s d=−0.80) and heterosexual (d=−0.64) males had lower friend support than gay males (ps < 0.0015), plurisexual (d=−0.42) and gay/lesbian (d=−0.40) adults reported lower family support than their heterosexual peers (ps < 0.001), and plurisexual people had higher CRP levels compared to gay/lesbian (d=0.37) and heterosexual people (d=0.22) (ps < 0.039). Loneliness and lower social support did not explain plurisexual adults’ higher inflammation, but BMI partially explained plurisexual adults’ higher IL-6 [indirect effect: 0.15 (0.04 – 0.26)] and CRP [indirect effect: 0.21 (0.04– 0.38)], compared to heterosexual adults. Conclusions: Partnered plurisexual individuals face disproportionate loneliness, lower social support, and greater inflammation—suggesting that partnered status alone does not ensure health equity. These findings underscore the need to better understand and address the unique social and biological vulnerabilities of plurisexual people. BMI may partially explain plurisexuals’ higher inflammation, but further longitudinal research is warranted.

Cellular epigenetic aging has become an important marker of healthy or unhealthy aging. The current study examined whether lifelong cumulative stressors across multiple domains were linked with epigenetic age acceleration (EAA; i.e., epigenetic age greater than chronological age) and whether psychological factors moderated this association. Dimensions of psychological well-being were hypothesized as protective factors, while neuroticism was posited as a vulnerability factor. Data from the Midlife in the United States (MIDUS) Genomics Project (N = 1,006) were used, which include deoxyribonucleic acid methylation data from a subset of participants in MIDUS Core Wave 2 and MIDUS Refresher Wave 1. Epigenetic aging values were calculated using the deoxyribonucleic acid methylation profiles at cytosine-phosphate-guanine sites. Cumulative stressors and psychological factors were assessed using the survey data at MIDUS Core Wave 2 and MIDUS Refresher Wave 1. The results revealed that cumulative stressors were not directly associated with EAA but were contingent on the levels of psychological well-being and neuroticism. Specifically, higher levels of cumulative stressors were significantly linked to EAA, measured by GrimAge2, among those who had lower levels of psychological well-being (β = -.23 to -.36, SE = .12 to .13, p = .04 to < .01) or higher neuroticism (β = .26, SE = .12, p = .03). Conversely, EAA in individuals who had higher levels of psychological well-being or lower neuroticism was not impacted by the levels of cumulative stressors. The findings underscore the importance of considering individual psychological assets and vulnerabilities in the pathways linking cumulative stressors to epigenetic aging. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Objective: Diagnosis with breast cancer is a profound stressor associated with increases in depression and inflammation. However, considerable variability in these outcomes is currently unexplained. We examined risk and resilience factors that may influence depressive symptoms and inflammatory markers in recently diagnosed breast cancer patients, including lifetime stressor exposure and psychological and behavioral resources. We focused on modifiable resources—sleep, physical activity, and coping resources—that can be leveraged to enhance women’s recovery. Methods: Women with stage 0-IIIA breast cancer (N = 180) were assessed before radiation, chemotherapy, or endocrine therapy. The Stress and Adversity Inventory (STRAIN) was administered to measure total count and severity of lifetime stressors. Blood samples assessed plasma protein markers of inflammation (TNF-α, IL-6, and CRP) that were combined into a composite score. Self-report questionnaires evaluated depressive symptoms, sleep, physical activity, social support, self-esteem, optimism, and mastery. Results: Total lifetime stressor count (β = 0.30, p < .0001) and severity (β = 0.12, p < .0001) were positively associated with depressive symptoms. Total lifetime stressor count (β = 0.01, p = .04), but not severity (β = 0.001, p = .17), was associated with higher inflammation. Sleep quality, social support, optimism, and mastery buffered the negative effects of lifetime stressor severity on depressive symptoms; social support and optimism also buffered stressor count on depressive symptoms (p < .04). None of the moderators influenced the stress-inflammation association (all ps > .20). Conclusions: Lifetime stressor exposure is associated with inflammation and depression in breast cancer patients. Interventions enhancing sleep quality, social support, optimism, and mastery may help prevent depression in this vulnerable group.