Loneliness, eudaimonia, and the human conserved transcriptional response to adversity

Abstract

Background Chronic social adversity activates a conserved transcriptional response to adversity (CTRA) marked by increased expression of pro-inflammatory genes and decreased expression of antiviral- and antibody-related genes. Recent findings suggest that some psychological resilience factors may help buffer CTRA activation, but the relative impact of resilience and adversity factors remains poorly understood. Here we examined the relative strength of CTRA association for the two best-established psychological correlates of CTRA gene expression – the risk factor of perceived social isolation (loneliness) and the resilience factor of eudaimonic well-being (purpose and meaning in life). Methods Peripheral blood samples and validated measures of loneliness and eudaimonic well-being were analyzed in 108 community-dwelling older adults participating in the longitudinal US Health and Retirement Study (56% female, mean age 73). Mixed effect linear model analyses quantified the strength of association between CTRA gene expression and measures of loneliness and eudaimonic well-being in separate and joint analyses. Results As in previous studies, separate analyses found CTRA gene expression to be up-regulated in association with loneliness and down-regulated in association with eudaimonic well-being. In joint analyses, effects of loneliness were completely abrogated whereas eudaimonic well-being continued to associate with CTRA down-regulation. Similar eudaimonia-dominant effects were observed for positive and negative affect, optimism and pessimism, and anxiety symptoms. All results were independent of demographic and behavioral health risk factors. Conclusions Eudaimonic well-being may have the potential to compensate for the adverse impact of loneliness on CTRA gene expression. Findings suggest a novel approach to targeting the health risks associated with social isolation by promoting purpose and meaning in life.

Kindness in the blood: A randomized controlled trial of the gene regulatory impact of prosocial behavior

“…The leukocyte CTRA represents one molecular process that may potentially mediate the health effects of negative psychological processes and adverse social conditions (Cole et al, 2007(Cole et al, , 2011(Cole et al, , 2015a(Cole et al, , 2015b. Little is known about how positive psychological processes may impact the CTRA, although several studies have found down-regulation of the CTRA in people with high levels of eudaimonic well-being (a multi-faceted complex of self-transcendent aspects of well-being, including purpose in life, positive relations with others, and several other prosocial components; Cole et al, 2015b;Fredrickson et al 2013Fredrickson et al , 2015Kitayama et al 2016).…”

“…Little is known about how positive psychological processes may impact the CTRA, although several studies have found down-regulation of the CTRA in people with high levels of eudaimonic well-being (a multi-faceted complex of self-transcendent aspects of well-being, including purpose in life, positive relations with others, and several other prosocial components; Cole et al, 2015b;Fredrickson et al 2013Fredrickson et al , 2015Kitayama et al 2016). However, all of the results involving eudaimonic well-being come from cross-sectional studies, and it remains unclear whether there is any causal effect of eudaimonic well-being on CTRA gene expression or whether any such effects stem specifically from the prosocial components of eudaimonia.…”

“…Analyses focused on an a priori-defined set of 53 CTRA indicator genes used in previous studies (Cole et al, 2015b;Fredrickson et al, 2013Fredrickson et al, , 2015, 36 of which were reliably detectable across this study's DBS samples (i.e., quantified at above-background level in all valid samples by Illumina GenomeStudio software). (DBS samples yield small quantities of RNA, rendering it difficult to uniformly detect some genes that are expressed at relatively low levels or inconsistently across individuals; Kohrt et al, 2016;McDade et al, 2016.)…”

“…(The 17 genes unavailable for analysis due to missing values were FOSB, IFI16, IFI44, IFIT2, IFIT5, IFITM1, IFITM3, IFITM5, IFNB1, IGLL3, IL1B, IL6, IL8, JUND, MX2, OAS3, and PTGS1.) Genespecific z-score signs were reversed for the antiviral and antibodyrelated gene sets to reflect their inverse relationship to the overall CTRA profile (Cole et al, 2015b;Fredrickson et al, 2013Fredrickson et al, , 2015.…”

“…Prosocial behavior has been theorized to directly modulate several neural and endocrine signaling pathways that might potentially modulate CTRA gene expression (Brown and Brown, 2015;Eisenberger and Cole, 2012). Prosocial behavior may also affect CTRA gene expression indirectly by promoting other social or psychological factors that have previously been linked to CTRA regulation, such as social connection, eudaimonic well-being, or reduced negative affect (Fredrickson et al 2013(Fredrickson et al , 2015Cole et al, 2007Cole et al, , 2011Cole et al, , 2015aCole et al, , 2015bKitayama et al, 2016;Wingo and Gibson, 2015). In the present study, statistical control for differences in perceived connectedness and negative affect could not account for the effects of the kindness-to-others intervention on CTRA gene regulation.…”