Abstract
Research in human social genomics has identified a conserved transcriptional response to adversity (CTRA) characterized by up-regulated expression of pro-inflammatory genes and down-regulated expression of Type I interferon- and antibody-related genes. This report seeks to identify the specific aspects of positive psychological well-being that oppose such effects and predict reduced CTRA gene expression. In a new confirmation study of 122 healthy adults that replicated the approach of a previously reported discovery study, mixed effect linear model analyses identified a significant inverse association between expression of CTRA indicator genes and a summary measure of eudaimonic well-being from the Mental Health Continuum – Short Form. Analyses of a 2- representation of eudaimonia converged in finding correlated psychological and social subdomains of eudaimonic well-being to be the primary carriers of CTRA associations. Hedonic well-being showed no consistent CTRA association independent of eudaimonic well-being, and summary measures integrating hedonic and eudaimonic well-being showed less stable CTRA associations than did focal measures of eudaimonia (psychological and social well-being). Similar results emerged from analyses of pooled discovery and confirmation samples (n = 198). Similar results also emerged from analyses of a second new generalization study of 107 healthy adults that included the more detailed Ryff Scales of Psychological Well-being and found this more robust measure of eudaimonic well-being to also associate with reduced CTRA gene expression. Five of the 6 major sub-domains of psychological well-being predicted reduced CTRA gene expression when analyzed separately, and 3 remained distinctively prognostic in mutually adjusted analyses. All associations were independent of demographic characteristics, health-related confounders, and RNA indicators of leukocyte subset distribution. These results identify specific sub-dimensions of eudaimonic well-being as promising targets for future interventions to mitigate CTRA gene expression, and provide no support for any independent favorable contribution from hedonic well-being.
Highlights
Research in human social genomics has linked adverse social and psychological conditions to increased immune cell expression of a “conserved transcriptional response to adversity” (CTRA) characterized by up-regulated expression of pro-inflammatory genes (e.g., IL1B, IL8, PTGS2, TNF) and down-regulated expression of genes involved in Type I interferon innate antiviral responses (e.g., IFI, ISG, MX, and OAS-family genes) and antibody synthesis (e.g., IGJ) [1,2,3]
Fredrickson et al [11] found that a composite score of MHC-SF items tapping social and psychological dimensions of eudaimonic well-being was associated with down-regulated expression of the CTRA transcriptome profile in peripheral blood mononuclear cells (PBMC)
All associations are adjusted for age, sex, race, BMI, smoking, alcohol consumption, illness symptoms, and gene transcript covariates marking major leukocyte subsets
Summary
Research in human social genomics has linked adverse social and psychological conditions to increased immune cell expression of a “conserved transcriptional response to adversity” (CTRA) characterized by up-regulated expression of pro-inflammatory genes (e.g., IL1B, IL8, PTGS2, TNF) and down-regulated expression of genes involved in Type I interferon innate antiviral responses (e.g., IFI-, ISG-, MX-, and OAS-family genes) and antibody synthesis (e.g., IGJ) [1,2,3]. In an initial study of the transcriptomic correlates of positive psychological states, Fredrickson et al [11] reported an association between reduced CTRA gene expression and scores in one domain of an established summary measure of well-being known as the Mental Health Continuum—Short Form (MHC-SF, known as the Short Flourishing Scale) [12,13,14,15]. Brown and colleagues [18] questioned the integration of psychological and social well-being into a single integrated measure of eudaimonia, suggested the use of mixed effect linear models to address the issue of correlated residuals in pooled association analyses involving multiple CTRA indicator genes, and concluded that the initial results were “spurious” and “the chances of a successful reproduction . Results from the confirmation study, a pooled analysis of the discovery and confirmation samples, and a separate generalization study using more robust measures of psychological well-being (Ryff Scales for Psychological Well-Being; Ryff-PWB) all find an inverse association between CTRA gene expression and eudaimonic well-being and converge in identifying psychological well-being as a key carrier of that relationship
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
