title: A functional genomic perspective on human well-being.
abstract: 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.
authors.affiliation: Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Fredrickson
authors.forename: Karen M
authors.initials: KM
authors.lastname: Grewen
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Coffey
authors.forename: Sara B
authors.initials: SB
authors.lastname: Algoe
authors.forename: Ann M
authors.initials: AM
authors.lastname: Firestine
authors.forename: Jesusa M G
authors.initials: JM
authors.lastname: Arevalo
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ma
authors.forename: Steven W
authors.initials: SW
authors.lastname: Cole
mesh_terms: D000328:Adult; D000906:Antibodies / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D053263:Gene Regulatory Networks / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006240:Happiness; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D008875:Middle Aged; D008960:Models, Psychological; D016328:NF-kappa B / Q000378:metabolism; D009657:North Carolina; D057181:Pleasure; D011788:Quality of Life / Q000523:psychology*; D011795:Surveys and Questionnaires; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D000906:Antibodies; D007370:Interferon Type I; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014157:Transcription Factors
keywords: gene regulation; social genomics
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