Social connection has been linked to reduced disease risk and enhanced antiviral immunity, but it is unclear whether online social connections have similar effects to those previously documented for ...in-person/offline social relationships, or whether online connections can substitute for in-person social relations when the latter are restricted. We examined this question in the context of the COVID-19 pandemic, focusing specifically on an immune system gene regulation profile known as the conserved transcriptional response to adversity (CTRA), which is characterized by up-regulation of proinflammatory genes and down-regulation of genes linked to innate antiviral responses and antibody production.
We analyzed CTRA RNA profiles in blood samples from 142 healthy young adults (69% female, 87% white) during the “social distancing” period of the COVID-19 pandemic. Mixed effect linear models quantified the relation of CTRA gene expression to measures of in-person social connection (number of friends, social eudaimonia, loneliness) and online psychosocial connection (online loneliness, perceived social value in online leisure and educational contexts, and internet use) while controlling for demographic and health factors.
Multiple indicators of in-person and generalized social connection were associated with lower CTRA gene expression, whereas no measure of online social connection showed any significant association with CTRA gene expression.
Experiences of in-person social connection are associated with reduced CTRA gene expression during a period of restricted social interaction. In contrast, online social relationships show no such association. Digitally mediated social relations do not appear to substantially offset the absence of in-person/offline social connection in the context of immune cell gene regulation.
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•Study of immune biology (CTRA) during the COVID-19 pandemic social distancing period.•In-person/ offline social connection indicators are associated with improved CTRA.•Online sociality is not predictive of immune biology gene expression.•Digital social ties do not offset CTRA immune biology altered by social distancing.
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-m
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.
•Examined effects of a novel, writing-based generativity intervention in older women.•Generativity intervention led to improvements in multiple domains of well-being.•Generativity intervention led to ...decreases in inflammation.•Suggests a low-cost, low effort intervention to improve well-being in older adults.
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.
Adverse social conditions have been linked to a conserved transcriptional response to adversity (CTRA) in circulating leukocytes that may contribute to social gradients in disease. However, the CNS ...mechanisms involved remain obscure, in part because CTRA gene-expression profiles often track external social–environmental variables more closely than they do self-reported internal affective states such as stress, depression, or anxiety. This study examined the possibility that variations in patterns of natural language use might provide more sensitive indicators of the automatic threat-detection and -response systems that proximally regulate autonomic induction of the CTRA. In 22,627 audio samples of natural speech sampled from the daily interactions of 143 healthy adults, both total language output and patterns of function-word use covaried with CTRA gene expression. These language features predicted CTRA gene expression substantially better than did conventional self-report measures of stress, depression, and anxiety and did so independently of demographic and behavioral factors (age, sex, race, smoking, body mass index) and leukocyte subset distributions. This predictive relationship held when language and gene expression were sampled more than a week apart, suggesting that associations reflect stable individual differences or chronic life circumstances. Given the observed relationship between personal expression and gene expression, patterns of natural language use may provide a useful behavioral indicator of nonconsciously evaluated well-being (implicit safety vs. threat) that is distinct from conscious affective experience and more closely tracks the neurobiological processes involved in peripheral gene regulation.
The authors tested the evolutionary genetic hypothesis that the functional form of an asymmetrically risky Gene x Environment interaction will differ as a function of age-related antagonistic ...pleiotropy (i.e., show opposite effects in young vs. old individuals). Previous studies have identified a polymorphism in the human "IL6" promoter (rs1800795; "IL6" -174 G/C) that interacts with adverse socioenvironmental conditions to promote chronic inflammation in older adults (elevated C-reactive protein). This study identifies a protective effect of the same polymorphism in 17- to 19-year-old adolescents confronting socioeconomic adversity. Over 60% of the environmental risk contribution to the "IL6" x Socioeconomic Status interaction could be accounted for by interpersonal stress and adult role burden. Thus, the "IL6" -174G allele does not represent an undifferentiated risk factor but instead sensitizes inflammatory biology to socioenvironmental conditions, conferring either genetic vulnerability or resilience depending on the developmental "somatic environment" that interacts with social conditions to influence gene expression. (Contains 4 tables.)
•Higher gamer eudaimonia links to less genomic dysregulation of immune function (CTRA).•Social well-being is particularly strongly associated with reduced expression of CTRA.•The eudaimonia CTRA ...association is strongest among the most highly involved players.•Play may damp CTRA expression among persons already above a well-being threshold.•The study is the first to link internet-related wellness to immune system regulation.
Previous research has identified a link between experiencing life as meaningful and purposeful—what is referred to as “eudaimonia”—and reduced expression of a stress-induced gene profile known as the “conserved transcriptional response to adversity” (CTRA). In the current study, we examine whether similar links between eudaimonic well-being and CTRA reduction occur in a sample of 56 individuals with a particularly strong engagement with virtual worlds: avid online videogame players. Results consistently linked higher eudaimonic well-being, and more specifically the social well-being subdomain of eudaimonia, to lower levels of CTRA gene expression. That favorable psychobiological relationship between eudaimonia and CTRA appeared most strongly among individuals reporting high levels of positive psychosocial involvement with gaming. Findings are consistent with the hypothesis that committed social/recreational activity may help damp CTRA expression especially among persons who are already experiencing some kind of threshold of positive eudaimonic experience.
Aim
There are marked socioeconomic disparities in pediatric asthma control, but the molecular origins of these disparities are not well understood. To fill this gap, we performed genome‐wide ...expression profiling of monocytes and T‐helper cells from pediatric asthma patients of lower and higher socioeconomic status (SES).
Method
Ninety‐nine children with asthma participated in a cross‐sectional assessment. Out of which 87% were atopic, and most had disease of mild (54%) or moderate (29%) severity. Children were from lower‐SES (n = 49; household income <$50 000) or higher‐SES (n = 50; household income >$140 000) families. Peripheral blood monocytes and T‐helper cells were isolated for genome‐wide expression profiling of mRNA.
Results
Lower‐SES children had worse asthma quality of life relative to higher‐SES children, by both their own and their parents’ reports. Although the groups had similar disease severity and potential confounds were controlled, their transcriptional profiles differed notably. The monocytes of lower‐SES children showed transcriptional indications of up‐regulated anti‐microbial and pro‐inflammatory activity. The T‐helper cells of lower‐SES children also had comparatively reduced expression of genes encoding γ‐interferon and tumor necrosis factor‐α, cytokines that orchestrate Type 1 responses. They also showed up‐regulated activity of transcription factors that polarize cells towards Type 2 responses and promote Th17 cell maturation.
Conclusion
Collectively, these patterns implicate pro‐inflammatory monocytes and Type 2 cytokine activity as mechanisms contributing to worse asthma control among lower‐SES children.
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.
Increased adrenergic signaling facilitates tumor progression, but the underlying mechanisms remain poorly understood. We examined factors responsible for stress-mediated effects on ...monocyte/macrophage recruitment into the tumor microenvironment, and the resultant effects on tumor growth. In vitro, MCP1 was significantly increased after catecholamine exposure, which was mediated by cAMP and PKA. Tumor samples from mice subjected to daily restraint stress had elevated MCP1 gene and protein levels, increased CD14+ cells, and increased infiltration of CD68+ cells. hMCP1 siRNA-DOPC nanoparticles significantly abrogated daily restraint stress-induced tumor growth and inhibited infiltration of CD68+ and F4/80+ cells. In ovarian cancer patients, elevated peripheral blood monocytes and tumoral macrophages were associated with worse overall survival. Collectively, we demonstrate that increased adrenergic signaling is associated with macrophage infiltration and mediated by tumor cell-derived MCP1 production.
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