To identify molecular mechanisms underlying the prospective health advantages associated with psychological well-being, we analyzed leukocyte basal gene expression profiles in 80 healthy adults who were assessed for hedonic and eudaimonic well-being, as well as potentially confounded negative psychological and behavioral factors. Hedonic and eudaimonic well-being showed similar affective correlates but highly divergent transcriptome profiles. Peripheral blood mononuclear cells from people with high levels of hedonic well-being showed up-regulated expression of a stress-related conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes and decreased expression of genes involved in antibody synthesis and type I IFN response. In contrast, high levels of eudaimonic well-being were associated with CTRA down-regulation. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity in structuring the observed differences in gene expression associated with eudaimonic well-being (reduced NF-κB and AP-1 signaling and increased IRF and STAT signaling). Transcript origin analysis identified monocytes, plasmacytoid dendritic cells, and B lymphocytes as primary cellular mediators of these dynamics. The finding that hedonic and eudaimonic well-being engage distinct gene regulatory programs despite their similar effects on total well-being and depressive symptoms implies that the human genome may be more sensitive to qualitative variations in well-being than are our conscious affective experiences.
social genomics gene regulation
Psychological well-being has been shown to forecast future physical health above and beyond its association with current physical health (1⇓⇓⇓⇓–6), and above and beyond its association with reduced levels of stress, depression, and other negative affective states (2, 3, 5⇓⇓⇓⇓⇓–11). However, the biological basis for this relationship remains poorly understood, in part because of a paucity of information regarding the molecular signaling pathways that transduce positive psychological states into somatic physiology (12), and in part because of the multidimensional nature of human well-being (6, 13).
Philosophers have long distinguished two basic forms of well-being: a “hedonic” form representing the sum of an individual’s positive affective experiences, and a deeper “eudaimonic” form that results from striving toward meaning and a noble purpose beyond simple self-gratification (6, 13⇓⇓–16). Both dimensions of well-being are...