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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]
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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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“As first observed by Chaussabel and colleagues [23, 51], covariance contained within these axes is perturbed in a variety of immune diseases, and similarly Cole and colleagues have defined a conserved transcriptional response to adversity that is also related to the axes and associates with multiple aspects of mental…”
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“…effects of social disadvantage, such as HI and economic strain (131); empirical evidence shows perceived control is a buffer between economic hardships and psychological and physical health (131, 132); and may be among eudaimonic wellbeing factors associated with CTRA down-regulation (53, 133).”
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“This study focuses on eudaimonic well-being in both private and community life and thus utilized the approach of previous studies by combining the psychological and social well-being subscales into a single scale of eudaimonic well-being (11 items total) [26, 65].”
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“In this perspective, researchers believe the functions of eudaimonic wellbeing are richer and more positive than their hedonic wellbeing equivalents (Bauer & McAdams, 2010; Fredrickson et al., 2013).”
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“Based on extant research, hedonic well-being may be more protective for disability over time compared to eudaimonic well-being (Fredrickson et al., 2013; Ryff, 2014).”
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The buzz trap: Speeded-up lives, distractedness, impulsiveness and decreasing empathy
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“I wonder if there is a clue in a recent piece of research outlining two very different kinds of happiness, both of which have very different effects on our health and well-being (Fredrickson et al., 2013).”
BackgroundNew Movement in Neuroscience: A Purpose-Driven Life.
Kaplin, A. I., & Anzaldi, L. J. (2015) · Europe PMC (PubMed Central) · Cited by 8
Compassion as the Highest Ethic
Kirby, J. N., Steindl, S. R., & Doty, J. R. (2017) · Mindfulness in behavioral health · doi:10.1007/978-3-319-64924-5_10 · Cited by 9
Eudaimonie statt Hedonismus: das Glück als aktive und kreative Lebensaufgabe
Lelkes, O. (2017) · Zeitschrift für Psychodrama und Soziometrie · doi:10.1007/s11620-017-0424-7 · Cited by 8
Chrisinger, B. W., & Rich, T. (2020) · Frontiers in Public Health · doi:10.3389/fpubh.2020.00031 · Cited by 8
Muennig, P. A., Vail, D. G., & Hakes, J. K. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-037051 · Cited by 9
Working with psychology journal editors to correct problems in the scientific literature.
Friedman, H. L., MacDonald, D. A., & Coyne, J. C. (2020) · Canadian Psychology/Psychologie canadienne · doi:10.1037/cap0000248 · Cited by 8
Towards an operational measurement of socio-ecological performancePreprint
Kettner, C., Köppl, A., & Stagl, S. (2014) · RePEc: Research Papers in Economics · doi:10.57938/c8de251e-fd4b-42a5-98f8-fad5f0c2a714 · Cited by 8
Awopeju, O., Oninla, O., Olowookere, S., Ogunnaike-quaye, M., & Erhabor, G. (2022) · Journal of HIV/AIDS & Social Services · doi:10.1080/15381501.2022.2038759 · Cited by 6
“Genetically, a gene transcriptional profiles study reported that eudaimonic well-being (an overarching umbrella term that includes purpose) was linked with enhanced expression of antiviral response genes and reduced expression of proinflammatory genes (Fredrickson et al., 2013).”
BackgroundMurakami, Y., Goto, D., Tsukamoto, H., Yamaura, K., & Hashimoto, T. (2025) · Brain and Behavior · doi:10.1002/brb3.70284 · Cited by 7
“…by the upregulation of genes involved in inflammation and the downregulation of genes involved in antiviral defenses (Cole et al. 2015; Fredrickson et al. 2013) (Tracey 2002), it has been suggested that HRV affects the expression of genes such as CTRA, and there could be mutual…”
Wirga, M., DeBernardi, M., Wirga, A., Wirga, M. L., Banout, M., & Gulyayeva, O. (2020) · Journal of Rational-Emotive & Cognitive-Behavior Therapy · doi:10.1007/s10942-020-00341-8 · Cited by 7
Nielsen, T. W., & Ma, J. S. (2021) · Multicultural Education Review · doi:10.1080/2005615x.2021.1919964 · Cited by 7
“Moreover, having meaning in one’s life can help to buffer against depression, anxiety and other mental and physical health issues, and foster generosity and compassion towards others (Fredrickson et al., 2013; Mariano & Vaillant, 2012; Post, 2005, 2011; Ryff, 2014).”
BackgroundSelf-citationHwa, Y. L., Lacy, M. Q., Gertz, M. A., Kumar, S. K., Muchtar, E., Buadi, F. K., Dingli, D., Leung, N., Kapoor, P., Go, R. S., et al. (2020) · European Journal Of Haematology · doi:10.1111/ejh.13559 · Cited by 7
“There were no statistically significant differences in year of diagnosis, sex, performance score, number of prior line therapies and presence of high-risk FISH features at diagnosis (deletion 17p, t(14; 16), t(14; 20), t(4; 14) or 1q gain) between BB intake and no BB intake groups.”
BackgroundBuilding a Resilient Workforce: Promoting Joy in Clinical Care
West, P., & Gee, P. M. (2018) · Frontiers of Health Services Management · doi:10.1097/hap.0000000000000044 · Cited by 7
“• Resilience can be increased or modified in individuals, so we can build a more resilient workforce (Fredrickson et al. 2013).”
BackgroundThe Search for Purpose in Life: An Exploration of Purpose, the Search Process, and Purpose Anxiety
Rainey, L. (2014) · Scholarly Commons (University of Pennsylvania) · Cited by 7
Stevens, S. M., Gustavson, D. E., Fang, B., Tu, X. M., Logue, M. W., Lyons, M. J., Reynolds, C. A., Kremen, W. S., & Franz, C. E. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17124554 · Cited by 7
“Better HRQOL is linked to health, good immune function, happiness, longevity, and lower health care costs in aging adults [92,93].”
BackgroundPremji, S., Lalani, S. B., Ghani, F., Nausheen, S., Forcheh, N., Omuse, G., Letourneau, N. L., Babar, N., Sulaiman, S., Wangira, M., et al. (2024) · Psychopathology · doi:10.1159/000540579 · Cited by 7
Gene Expression of Inflammation Markers in Depression
Ciobanu, L. G., & Baune, B. T. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811073-7.00011-8 · Cited by 6
Social network position and the Conserved Transcriptional Response to Adversity in older Koreans
Lee, S., Cole, S. W., Choi, I., Sung, K., Kim, S., Youm, Y., & Chey, J. (2023) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106342 · Cited by 7
Self-citationReceptor regulation of senile phenoptosis
Skulachev, M. V., Severin, F. F., & Skulachev, V. P. (2014) · Biochemistry (Moscow) · doi:10.1134/s0006297914100022 · Cited by 6
Kariyawasam, L., Ononaiye, M. S. P., Irons, C., & Kirby, S. E. (2022) · Mindfulness · doi:10.1007/s12671-022-02041-z · Cited by 9
“Practicing compassion has been found to produce various physiological (Fredrickson et al., 2013), psychological (e.”
BackgroundPosttraumatic growth, purpose, and trauma in university survivors of sexual assault
Damiani, T., Sharkey, J. D., Consoli, M. L. M., & Mullin, A. C. (2023) · Journal of American College Health · doi:10.1080/07448481.2023.2208233 · Cited by 6
“12 Having purpose in life is associated with numerous aspects of positive psychological and physical well-being such as greater optimism, 13 enhanced work performance, 14 resilience, 15 and a stronger immune system.”
Sherry, D. D. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-24145-8.00052-1 · Cited by 6
The Psychology of Positivity at Work
Green, S., McQuaid, M., Purtell, A., & Dulagil, A. (2016) · doi:10.1002/9781118977620.ch2 · Cited by 6
Manohar, P. (2013) · Ancient Science of Life · doi:10.4103/0257-7941.139246 · Cited by 6
Yamada, H. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27041908 · Cited by 6
“…hedonic well-being and eudaimonic well-being (sense of purpose) reveals that eudaimonia is associated with the downregulation of the Conserved Transcriptional Response to Adver-sity (CTRA)—a gene expression profile characterized by pro-inflammatory signaling and reduced antiviral responses [69].”
Psychological well‐being and salivary markers of inflammation: The moderating effect of age
Lee, S., Chey, J., Ahn, W., Woo, C., Youm, Y., Kim, H., Oh, N., Park, H.-Y., Gim, S., Lee, E., et al. (2022) · Applied Psychology Health and Well-Being · doi:10.1111/aphw.12389 · Cited by 5
The Integrative Science of Eudaimonic Wellbeing
Ryff, C. D. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780197567579.003.0002 · Cited by 7
Ohnishi, J., Ayuzawa, S., Nakamura, S., Sakamoto, S., Hori, M., Sasaoka, T., Takimoto‐Ohnishi, E., Tanatsugu, M., & Murakami, K. (2017) · Human Genomics · doi:10.1186/s40246-017-0117-3 · Cited by 5
“Notably, C17orf97 is also downregulated in the hedonic well-being status [13].”
BackgroundThe Early Life Course of Body Weight and Gene Expression Signatures for Disease
Potente, C., Harris, K. M., Chumbley, J. R., Cole, S. W., Gaydosh, L. M., Xu, W., Levitt, B. E., & Shanahan, M. J. (2021) · American Journal of Epidemiology · doi:10.1093/aje/kwab049 · Cited by 5
Self-citationAssociations between psychosocial factors and circulating cytokines in breast cancer survivors
Leschak, C. J., Dutcher, J. M., Haltom, K. E. B., Breen, E. C., Bower, J. E., & Eisenberger, N. I. (2021) · Psychology and Health · doi:10.1080/08870446.2021.2003797 · Cited by 5
“…is associated with the downregulation of antiviral genes and upregulation of proinflammatory genes (Cole et al., 2015), whereas eudaimonic well-being is associated with the opposite pattern—upregulation of antiviral genes and downregulation of proinflammatory genes (Fredrickson et al., 2013).”
BackgroundWang, Z., Zhang, Y., Li, Q., Zou, Q., & Liu, Q. (2022) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2022.105286 · Cited by 5
Brooks, J. L., Berry, D. C., Currin, E. G., Ledford, A., Knafl, G. J., Fredrickson, B. L., Beeber, L. S., Peden, D. B., & Corbie-Smith, G. M. (2019) · Research in Nursing & Health · doi:10.1002/nur.21944 · Cited by 5
“Following Fredrickson and colleagues, we aggregate the items for psychological well-being and social well-being to create an index of eudaimonic well-being, whereas the emotional well-being subscale is taken as one index of hedonic well-being (Fredrickson et al., 2013; Fredrickson et al., 2015).”
BackgroundMethodSelf-citationThe Pursuit of National Wellbeing Policies Across the GCC: The What, How, and Why?
Lambert, L., Mulay-Shah, A., Warren, M. A., & Younis, Y. (2019) · Springer eBooks · doi:10.1007/978-3-030-13921-6_2 · Cited by 4
McEwen, B. S. (2016) · Neuropsychoanalysis · doi:10.1080/15294145.2016.1149686 · Cited by 5
“It should be noted that many of these interventions that are intended to promote plasticity and slow decline with age, such as physical activity and positive social interactions that give meaning and purpose, are also useful for promoting “positive health” and “eudamonia” (Fredrickson et al., 2013; Ryff & Singer, 1998…”
BackgroundFadiji, A. W., Meiring, L., & Wissing, M. P. (2020) · Applied Research in Quality of Life · doi:10.1007/s11482-020-09819-0 · Cited by 5
Behavioural economics and the COVID-induced education crisis
Biddle, N. (2021) · OECD education working papers · doi:10.1787/eba2b867-en · Cited by 9
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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