The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
A functional genomic perspective on human well-being
Open accessAbstract
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.
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“The CTRA can also be activated by modernday social, symbolic, anticipated, and imagined threats, however, leading to increased risk for several inflammation-related conditions, including depression”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Fredrickson et al., 2013
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“they can also be separated in that they seem to correlate with different neurobiological systems (Fredrickson et al., 2013).”
From Blended care in the treatment of subthreshold symptoms of depression and psychosis in emerging adults: A randomised controlled trial of Acceptance and Commitment Therapy in Daily-Life (ACT-DL) (2020) · cites this paper as Fredrickson et al., 2013
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“Finally, a small study analyzed leukocyte basal gene expression profiles and reported distinct gene expression profiles for hedonic (positive affect) versus eudaimonic (striving, purpose) wellbeing (Fredrickson et al. 2013)”
From Genetics of Wellbeing and Its Components Satisfaction with Life, Happiness, and Quality of Life: A Review and Meta-analysis of Heritability Studies (2015) · cites this paper as Fredrickson et al. 2013
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“Additionally, a study that examined gene transcriptional profiles found that eudaimonic well-being (an overarching umbrella term that includes purpose) was associated with enhanced expression of antiviral response genes and reduced expression of proinflammatory genes (31).”
From Purpose in life and use of preventive health care services (2014) · cites this paper as [31]
In the citing paper
“Fredrickson and colleagues found that high levels of eudaimonic well-being were associated with significantly lower levels of CTRA-related gene expression (i.e., a more favorable, or less threatened, molecular profile) [54].”
From Human Social Genomics (2014) · cites this paper as [54]
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“In contrast, people who showed comparatively high levels of hedonic well-being relative to their level of eudaimonic well-being showed significantly elevated CTRA gene expression (above and beyond any effects of hedonistic behavioral factors such as smoking, alcohol consumption, or adiposity).”
From Human Social Genomics (2014) · cites this paper as [54]
In the citing paper
“the conserved transcriptional response to adversity (CTRA), and is characterized by increased proinflammatory and reduced antiviral skewing of the basal gene expression profile”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Fredrickson et al, 2013
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“which increases an individual's risk for both viral infection and inflammation-related disease”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Fredrickson et al, 2013
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“The impetus for this research was inspired by a wealth of research showing e that developing caring and compassion-focused motives for self and others has a range of benefits: on genetic expression [14, 31, 109], physiological processes [9, 68, 71, 73, 107, 108], psychological processes [63, 64, 66, 108], and social relationships [16, 18, 100].”
From The development of compassionate engagement and action scales for self and others (2017) · cites this paper as [31]
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Citations
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Zhang, J., Li, C., Shi, B., Keeley, A. R., & Managi, S. (2026) · Research Square · doi:10.21203/rs.3.rs-8160157/v1
Geyton, T. A., & Cole, S. W. (2026) · SSM - Mental Health · doi:10.1016/j.ssmmh.2026.100654
“Social genomics research suggests that prosocial behaviors, well-being, and optimism may be associated with reduced CTRA expression, whereas social isolation and chronic threat may be associated with increased CTRA expression (Fredrickson et al., 2013; Moieni et al., 2020).”
Self-citationPositive psychological well-being and inflammatory biomarkers IL-6 and CRP: A narrative review
Zuccarella‐Hackl, C., & von Känel, R. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-28842-5.00013-2
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Jach, E. A., & Armah, Y. E. (2026) · Oxford University Press eBooks · doi:10.1093/9780197759424.003.0017
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Wan, Y., Ghani, M. S. A., Daud, M. N., & Bao, X. (2026) · Child Indicators Research · doi:10.1007/s12187-026-10439-7
“Furthermore, evidence suggests that low levels of PWB heighten susceptibility to depression (Wood & Joseph, 2010), whereas high levels of PWB mitigate stress through the regulation of gene expression, exerting a positive impact on physical and mental health (Fredrickson et al., 2013 , 2015).”
Horwitz, R. I., Conroy, A. H., Cullen, M. R., Matory, A., & Sim, I. (2026) · The American Journal of Medicine · doi:10.1016/j.amjmed.2026.08.023
Schall, M. (2015) · KOPS (University of Konstanz)
Metadata
- Authors
- Fredrickson, B. L., Grewen, K. M., Coffey, K. A., Algoe, S. B., Firestine, A. M., Arevalo, J. M. G., Ma, J., & Cole, S. W.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of California, Los Angeles (US)
- University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095; and
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-07-29
- Volume
- 110
- Issue
- 33
- Pages
- 13684-13689
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3746929
- OpenAlex
- W2155399165
- Cited by
- 512
- References
- 72
- Citations by year
- 2026: 17 · 2025: 32 · 2024: 16 · 2023: 36 · 2022: 37 · 2021: 36 · 2020: 47 · 2019: 38 · 2018: 76 · 2017: 48 · 2016: 59 · 2015: 34 · 2014: 28 · 2013: 7
- FWCI
- 63.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health
- National Institute on Aging (P30AG107265, P30AG017265)
- NIH Office of the Director (R01NR012899)
- National Cancer Institute (R01CA116778)
- National Institute of Nursing Research (R01NR012899)
- Common Fund
- Topics
- Social Sciences › Psychology › Social Psychology › Psychological Well-being and Life Satisfaction
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- psychological well-being, hedonic well-being, eudaimonic well-being, leukocyte gene expression, peripheral blood mononuclear cells, conserved transcriptional response to adversity, pro-inflammatory genes, type I interferon response, NF-κB signaling, AP-1 signaling, transcription factor activity, monocytes, plasmacytoid dendritic cells, B cells, depressive symptoms, stress response
- MeSH terms
- Adult, Antibodies, Happiness, Humans, Interferon Type I, Leukocytes, Mononuclear, Middle Aged, Models, Psychological, North Carolina, Quality of Life, Surveys and Questionnaires, Transcription Factors, Genome, Human, NF-kappa B, Transcription Factor AP-1, Computational Biology, Gene Regulatory Networks, Pleasure, Transcriptome
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