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ObjectiveProsocial behavior has been linked to improved physical health, but the biological mechanisms involved remain unclear. This study tested whether a 4-week kindness intervention could reduce expression of a stress-related immune response gene signature known as the Conserved Transcriptional Response to Adversity (CTRA).MethodsIn a diverse sample of community adults (N = 182), study participants were randomly assigned to perform 3 kind acts for other people, to perform 3 kind acts for themselves, or to list daily activities (control), on one day per week over 4 weeks. CTRA gene expression was measured by RNA sequencing of dried blood spots (DBS) collected at baseline and 5 weeks later (1 week after completing study assignments). Participants' descriptions of their kind acts were coded for protocol adherence and act content.ResultsParticipants who were randomized to perform kind acts for others showed significant reductions in CTRA gene expression relative to controls. Participants who were randomized to perform kind acts for themselves also showed significant reductions in CTRA gene expression relative to controls, but this pattern emerged only for those who failed to perform the requested self-kind acts (protocol non-adherent). Those who fully adhered to the self-kindness protocol showed no change in CTRA gene expression and did not differ from controls. Act content analyses implicated self-stress-reducing behavior in the paradoxical effects of self-kindness and the physical presence of others in the effects of prosocial behavior.ConclusionsProsocial engagement-doing something kind for others rather than oneself-reduces CTRA gene expression. The nature of kind acts and their intended recipient plays a key role in shaping the genomic impact of kindness.

BackgroundSocial genomics has demonstrated altered inflammatory and type I interferon (IFN) gene expression among people experiencing chronic social adversity. Adverse social experiences such as discrimination and violence are linked to stimulant misuse and HIV, conditions that dysregulate inflammatory and innate antiviral responses, leading to increased HIV viral replication and risk of chronic diseases.PurposeWe aimed to determine whether methamphetamine (MA) use, unsuppressed HIV viral load (VL) (≥200 c/mL), and experienced intimate partner violence (IPV) (past 12 months) predicted inflammatory and type I IFN gene expression in HIV-positive Black and Latinx men who have sex with men (MSM).MethodsParticipants were 147 HIV-positive Black and Latinx MSM recruited from the mSTUDY, a cohort of 561 MSM aged 18-45 in Los Angeles, CA, of whom half are HIV-positive and substance-using. Transcriptomic measures of inflammatory and type I IFN activity were derived from RNA sequencing of peripheral blood mononuclear cells and matched to urine drug tests, VL, and survey data across two time points 12 months apart. Analysis used linear random intercept modeling of MA use, unsuppressed VL, and experienced IPV on inflammatory and type I IFN expression.ResultsIn adjusted models, MA use predicted 27% upregulated inflammatory and 31% upregulated type I IFN expression; unsuppressed VL predicted 84% upregulated type I IFN but not inflammatory expression; and experienced IPV predicted 31% upregulated inflammatory and 26% upregulated type I IFN expression.ConclusionsIn Black and Latinx MSM with HIV, MA use, unsuppressed VL, and experienced IPV predicted upregulated social genomic markers of immune functioning.

Survey-based studies suggest naturalistic psychedelic use provides mental health benefits similar to those observed in clinical trials. The current study sought to confirm these findings in a large group of psychedelic users and to conduct a novel examination of associations between amount of psychedelic use and behavioral outcomes, as well as frequency of harms ascribed to psychedelic use. A cross-sectional, online survey was completed by 2,510 adults reporting at least one lifetime psychedelic experience. Participants retrospectively completed a battery of instruments assessing depression, anxiety, and emotional well-being prior to and following psychedelic exposure. Participants also reported preferred psychedelic agent, number of uses, and harms attributed to psychedelic use. Psychedelic use was associated with significant improvements in depressive and anxious symptoms and with increased emotional well-being. These improvements increased in magnitude with increasing psychedelic exposure, with a ceiling effect. However, improvements were noted following a single lifetime use. Strong evidence for benefit of one preferred psychedelic agent over another was not observed, but enduring increases in factors related to mystical-experience and prosocial perspective taking associated with enhanced mental health. Thirteen percent of the survey sample (n = 330) endorsed at least one harm from psychedelic use, and these participants reported less mental health benefit. Results from the current study add to a growing database indicating that psychedelic use-even outside the context of clinical trials-may provide a wide range of mental health benefits, while also posing some risk for harm in a minority of individuals.

Depression is a common, often recurrent disorder that causes substantial disease burden worldwide, and this is especially true for women following the pubertal transition. According to the Social Signal Transduction Theory of Depression, stressors involving social stress and rejection, which frequently precipitate major depressive episodes, induce depressive symptoms in vulnerable individuals in part by altering the activity and connectivity of stress-related neural pathways, and by upregulating components of the immune system involved in inflammation. To test this theory, we recruited adolescent females at high and low risk for depression and assessed their psychological, neural, inflammatory, and genomic responses to a brief (10 minute) social stress task, in addition to trait psychological and microbial factors affecting these responses. We then followed these adolescents longitudinally to investigate how their multi-level stress responses at baseline were related to their biological aging at baseline, and psychosocial and clinical functioning over one year. In this protocol paper, we describe the theoretical motivations for conducting this study as well as the sample, study design, procedures, and measures. Ultimately, our aim is to elucidate how social adversity influences the brain and immune system to cause depression, one of the most common and costly of all disorders.

Previous research has linked perceived social isolation (loneliness) to reduced antiviral immunity, but the immunologic effects of the objective social isolation imposed by pandemic "shelter in place" (SIP) policies is unknown. We assessed the immunologic impact of SIP by relocating 21 adult male rhesus macaques from 2,000-m2 field cage communities of 70 to 132 other macaques to 2 wk of individual housing in indoor shelters. SIP was associated with 30% to 50% reductions in all circulating immune cell populations (lymphocytes, monocytes, and granulocytes), down-regulation of Type I interferon (IFN) antiviral gene expression, and a relative up-regulation of CD16- classical monocytes. These effects emerged within the first 48 h of SIP, persisted for at least 2 wk, and abated within 4 wk of return to social housing. A subsequent round of SIP in the presence of a novel juvenile macaque showed comparable reductions in circulating immune cell populations but reversal of Type I IFN reductions and classical monocyte increases observed during individual SIP. Analyses of lymph node tissues showed parallel up-regulation of Type I IFN genes and enhanced control of viral gene expression during juvenile-partnered SIP compared to isolated SIP. These results identify a significant adverse effect of SIP social isolation on antiviral immune regulation in both circulating immune cells and lymphoid tissues, and they suggest a potential behavioral strategy for ameliorating gene regulatory impacts (but not immune cell declines) by promoting prosocial engagement during SIP.

ObjectiveTo determine the effects of ESRT (an iteratively adapted and tailored MBI) on perceived stress, executive cognitive function, psychosocial well-being (ie, burnout, mindfulness), and pro-inflammatory gene expression in surgical (ESRT-1) and mixed specialty (ESRT-2) PGY-1 volunteers.Summary of background and dataTailored MBIs have proven beneficial in multiple high-stress and high-performance populations. In surgeons, tailored MBIs have been shown to be feasible and potentially beneficial, but whether mindfulness-based cognitive training can improve perceived stress, executive function, well-being or physiological distress in surgical and nonsurgical trainees is unknown.MethodsIn 2 small single-institution randomized clinical trials, ESRT, a tailored mindfulness-based cognitive training program, was administered and iteratively adapted for first-year surgical (ESRT-1, 8 weekly, 2-hour classes, n = 44) and mixed specialty (ESRT-2, 6 weekly, 90-minute classes, n = 45) resident trainees. Primary and secondary outcomes were, respectively, perceived stress and executive function. Other prespecified outcomes were burnout (assessed via Maslach Burnout Inventory), mindfulness (assessed via Cognitive Affective Mindfulness Scale - Revised), and pro-inflammatory gene expression (assessed through the leukocyte transcriptome profile "conserved transcriptional response to adversity").ResultsNeither version of ESRT appeared to affect perceived stress. Higher executive function and mindfulness scores were seen in ESRT-1, and lower emotional exhaustion and depersonalization scores in ESRT-2, at pre-/postintervention and/or 50-week follow-up (ESRT-1) or at 32-week follow-up (ESRT-2), compared to controls. Pooled analysis of both trials found ESRT-treated participants had reduced pro-inflammatory RNA expression compared to controls.ConclusionsThis pilot work suggests ESRT can variably benefit executive function, burnout, and physiologic distress in PGY-1 trainees, with potential for tailoring to optimize effects.

BackgroundExposure to adverse social factors has been associated with an altered inflammatory profile, a risk factor for several acute and chronic diseases. Differential gene expression may be a biological mediator in the relationship. In this study, associations between a range of social factors and expression of inflammation-related genes were investigated.MethodsSocial factor and gene expression data were collected from 1,264 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA). Inflammation-related genes were identified from the Gene Ontology database. The associations between social factors and gene expression were first assessed using the Global Analysis of Covariance (Global ANCOVA) gene set enrichment test. When the global test was significant, linear regression and elastic net penalized regression were employed to identify the individual gene transcripts within each gene set associated with the social factor.ResultsLoneliness (p = 0.003), chronic burden (p = 0.002), and major or lifetime discrimination (p = 0.045) were significantly associated with global expression of the chronic inflammatory gene set. Of the 20 transcripts that comprise this gene set, elastic net selected 12 transcripts for loneliness, 8 for chronic burden, and 3 for major or lifetime discrimination. Major or lifetime discrimination was also associated with the inflammatory response (p = 0.029), regulation of the inflammatory response (p = 0.041), and immune response (p = 0.025) gene sets in global analyses, and 53, 136, and 26 transcripts were selected via elastic net for these gene sets respectively. There were no significant associations in linear regression analyses after adjustment for multiple testing.ConclusionsThis study highlights gene expression as a biological mechanism through which social factors may affect inflammation.

Generativity, or concern for and contribution to the well-being of younger generations, plays an important role in successful aging. The purpose of this study was to develop a novel, writing-based intervention to increase feelings of generativity and test the effect of this intervention on well-being and inflammation in a sample of older women. Participants in this study (n = 73; mean age = 70.9 years, range 60-86 years) were randomly assigned to a 6-week generativity writing condition (writing about life experiences and sharing advice with others) or a control writing condition (neutral, descriptive writing). Self-reported measures of social well-being, mental health, and physical health, as well as objective measures of systemic and cellular levels of inflammation (plasma pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α; genome-wide RNA transcriptional profiling), were assessed pre- and post-intervention. The generativity intervention led to significant improvements across multiple domains, including increases in participation in social activities, decreases in psychological distress, more positive expectations regarding aging in the physical health domain, and decreases in pro-inflammatory gene expression. Thus, this study provides preliminary evidence for the ability of a novel, low-cost, low-effort intervention to favorably impact inflammation and well-being in older women.

Men who have sex with men (MSM) experience high rates of homophobic victimization, which is linked to myriad chronic physical and mental health disparities. Social adversity such as rejection, isolation, and racial discrimination can induce a conserved transcriptional response to adversity (CTRA) involving upregulation of proinflammatory genes and downregulation of type I interferon and antibody synthesis genes. This study specifically examines whether homophobic victimization is associated with expression of CTRA profiles in Black and Latino MSM living in Los Angeles. Analyses linked behavioral survey data with quantified RNA from leukocytes from blood samples of 70 participants over 12 months. CTRA gene expression was increased by 3.1-fold in MSM who experienced homophobic victimization while adjusting for major leukocyte subsets and sociodemographics. Accounting for all these factors, CTRA gene expression was significantly enhanced in MSM who identified as Black compared to Latino. Our findings identify experiences of homophobic victimization as drivers of inflammatory and type I interferon gene expression profiles, which can contribute to physical and mental health challenges in Black and Latino MSM.

Although there has been much interest in understanding the effect of gratitude on health-related outcomes, this remains an understudied area of research, particularly regarding mechanisms and measurement of biological outcomes. The present study explored whether a gratitude intervention could reduce inflammatory outcomes and whether this occurred through increased support-giving. Healthy women (n = 76) were randomly assigned to a 6-week gratitude intervention (i.e., writing on topics intended to induce gratitude) or a control condition (i.e., neutral writing). Support-giving and markers of inflammation were measured pre- and postintervention. Those in the gratitude intervention (vs. control) reported higher postintervention levels of support-giving. Moreover, those with lower levels of psychological distress gave more support as a function of the gratitude intervention. Regarding inflammatory outcomes, although there was no effect of the gratitude intervention on postintervention inflammatory markers, increases in support-giving across the entire sample were related to decreases in inflammatory markers. These results, along with a scarcity of work in this area, suggest that further work is needed to more fully understand the relationships between gratitude and biological markers relevant to health. Finally, these novel findings linking support-giving and decreases in inflammation also indicate that the mammalian caregiving system, associated with enhanced support-giving and reduced physiological stress responding, is a mechanism worth further examination to elucidate the links between social support and health. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Loneliness, or perceived social isolation, may be evident in any group-living species, although its assessment in nonhumans provides some measurement challenges. It is well-known that loneliness in humans confers significant risk for morbidity and mortality, although mechanisms remain unclear. The authors describe a naturally-occurring model of loneliness in adult male rhesus monkeys that shows many parallels with the phenomenon in humans. Lonely monkeys (those that display high frequencies of social initiations but low frequencies of complex interaction) show elevated sympathetic nervous system activity and down regulated Type I interferon responses. Analysis of data from simian immunodeficiency virus-infected monkeys indicates that these physiological changes have functional consequences. Use of this animal model can help identify mechanisms by which loneliness impacts health.

Low socioeconomic status (SES) is a risk factor for mortality and immune dysfunction across a wide range of diseases, including cancer. However, cancer is distinct in the use of allogeneic hematopoietic cell transplantation (HCT) as a treatment for hematologic malignancies to transfer healthy hematopoietic cells from one person to another. This raises the question of whether social disadvantage of an HCT cell donor, as assessed by low SES, might impact the subsequent health outcomes of the HCT recipient. To evaluate the cellular transplantability of SES-associated health risk, we analyzed the health outcomes of 2,005 HCT recipients who were transplanted for hematologic malignancy at 125 United States transplant centers and tested whether their outcomes differed as a function of their cell donor's SES (controlling for other known HCT-related risk factors). Recipients transplanted with cells from donors in the lowest quartile of SES experienced a 9.7% reduction in overall survival (P = 0.001) and 6.6% increase in treatment-related mortality within 3 y (P = 0.008) compared to those transplanted from donors in the highest SES quartile. These results are consistent with previous research linking socioeconomic disadvantage to altered immune cell function and hematopoiesis, and they reveal an unanticipated persistence of those effects after cells are transferred into a new host environment. These SES-related disparities in health outcomes underscore the need to map the biological mechanisms involved in the social determinants of health and develop interventions to block those effects and enhance the health of both HCT donors and recipients. [ABSTRACT FROM AUTHOR]

High conflict and low warmth in families may contribute to immune cells developing a tendency to respond to threats with exaggerated inflammation that is insensitive to inhibitory signaling. We tested associations between family environments and expression of genes bearing response elements for transcription factors that regulate inflammation: nuclear factor kappa B (NF-κB) and glucocorticoid receptor. The overall sample (47 families) completed interviews, questionnaires, and 8-week daily diary assessments of conflict and warmth, which were used to create composite family conflict and warmth scores. The diaries assessed upper respiratory infection (URI) symptoms, and URI episodes were clinically verified. Leukocyte RNA was extracted from whole blood samples provided by a subsample of 42 children (8-13 years of age) and 73 parents. In children, higher conflict and lower warmth were related to greater expression of genes bearing response elements for the proinflammatory transcription factor NF-κB, and more severe URI symptoms. In parents, higher conflict and lower warmth were also related to greater NF-κB-associated gene expression. Monocytes and dendritic cells were implicated as primary cellular sources of differential gene expression in the sample. Consistent with existing conceptual frameworks, stressful family environments were related to a proinflammatory phenotype at the level of the circulating leukocyte transcriptome.