Psychological well-being and the human conserved transcriptional response to adversity

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.

Fig 1. Well-being and CTRA gene expression.

(A) Relationship between MHC-SF hedonic and eudaimonic well-being domain scores (2-d representation). (B) Relationship between psychological well-being and social well-being scores (the 2-d eudaimonic domain within the 3-d well-being representation). (C) Point estimates of average association coefficients relating range-spanning variations in hedonic and eudaimonic well-being scores [-2 SD, +2 SD] to unstandardized (log₂ metric) gene expression values for 52 CTRA indicator genes (reverse scoring 34 inverse components) in the discovery study (n = 76) and confirmation study (n = 122). Log₂ association coefficients are transformed to % difference in average CTRA transcript abundance to facilitate interpretation.