A functional genomic perspective on human well-being

Barbara L. Fredrickson1, Karen Grewen2, Kimberly A. Coffey1, Sara B. Algoe1, Ann M. Firestine1, Jesusa M.G. Arevalo3, Jeffrey Ma3, Steve W. Cole4,3
1Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
2Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599;
3University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095; and
4Jonsson Comprehensive Cancer Center, Norman Cousins Center for Psychoneuroimmunology, AIDS Institute, and Molecular Biology Institute, University of California, Los Angeles, CA 90095

Tóm tắt

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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Tài liệu tham khảo

JE Bower, ME Kemeny, SE Taylor, JL Fahey, Cognitive processing, discovery of meaning, CD4 decline, and AIDS-related mortality among bereaved HIV-seropositive men. J Consult Clin Psychol 66, 979–986 (1998).

S Cohen, CM Alper, WJ Doyle, JJ Treanor, RB Turner, Positive emotional style predicts resistance to illness after experimental exposure to rhinovirus or influenza a virus. Psychosom Med 68, 809–815 (2006).

Y Chida, A Steptoe, Positive psychological well-being and mortality: A quantitative review of prospective observational studies. Psychosom Med 70, 741–756 (2008).

M Koizumi, H Ito, Y Kaneko, Y Motohashi, Effect of having a sense of purpose in life on the risk of death from cardiovascular diseases. J Epidemiol 18, 191–196 (2008).

A Steptoe, J Wardle, Positive affect measured using ecological momentary assessment and survival in older men and women. Proc Natl Acad Sci USA 108, 18244–18248 (2011).

EM Friedman, Well-being, aging, and immunity. The Oxford Handbook of Psychoneuroimmunology, ed S Segerstrom (Oxford Univ Press, New York), pp. 37–62 (2012).

JT Moskowitz, Positive affect predicts lower risk of AIDS mortality. Psychosom Med 65, 620–626 (2003).

SD Pressman, S Cohen, Does positive affect influence health? Psychol Bull 131, 925–971 (2005).

JT Moskowitz, ES Epel, M Acree, Positive affect uniquely predicts lower risk of mortality in people with diabetes. Health Psychol 27, S73–S82 (2008).

PA Boyle, LL Barnes, AS Buchman, DA Bennett, Purpose in life is associated with mortality among community-dwelling older persons. Psychosom Med 71, 574–579 (2009).

N Krause, Meaning in life and mortality. J Gerontol B Psychol Sci Soc Sci 64, 517–527 (2009).

S Cole, Social regulation of gene expression in the immune system. The Oxford Handbook of Psychoneuroimmunology, ed S Segerstrom (Oxford Univ Press, New York), pp. 254–273 (2012).

CD Ryff, BH Singer, G Dienberg Love, Positive health: Connecting well-being with biology. Philos Trans R Soc Lond B Biol Sci 359, 1383–1394 (2004).

AS Waterman, Two conceptions of happiness: Contrasts of personal expressiveness (eudaimonia) and hedonic enjoyment. J Pers Soc Psychol 64, 678–691 (1993).

CD Ryff, B Singer, Psychological well-being: Meaning, measurement, and implications for psychotherapy research. Psychother Psychosom 65, 14–23 (1996).

RM Ryan, EL Deci, On happiness and human potentials: A review of research on hedonic and eudaimonic well-being. Annu Rev Psychol 52, 141–166 (2001).

BL Fredrickson, What good are positive emotions? Rev Gen Psychol 2, 300–319 (1998).

BL Fredrickson, The broaden-and-build theory of positive emotions. Philos Trans R Soc Lond B Biol Sci 359, 1367–1378 (2004).

RM Nesse, Natural selection and the elusiveness of happiness. Philos Trans R Soc Lond B Biol Sci 359, 1333–1347 (2004).

D Archontaki, GJ Lewis, TC Bates, Genetic influences on psychological well-being: A nationally representative twin study. J Pers 81, 221–230 (2013).

A Gigantesco, et al., Psychological well-being (PWB): a natural life outlook? An Italian twin study on heritability of PWB in young adults. Psychol Med June 14, 1–13 (2011).

JH Stubbe, D Posthuma, DI Boomsma, EJ De Geus, Heritability of life satisfaction in adults: A twin-family study. Psychol Med 35, 1581–1588 (2005).

CL Keyes, JM Myers, KS Kendler, The structure of the genetic and environmental influences on mental well-being. Am J Public Health 100, 2379–2384 (2010).

CA Rietveld, et al., Molecular genetics and subjective well-being. Proc Natl Acad Sci USA 110, 9692–9697 (2013).

RF Baumeister, KD Vohs, JL Aaker, EN Garbinsky, Some key differences between a happy life and a meaningful life. J Posit Psychol, in press. (2013).

BL Fredrickson, Positive emotions broaden and build. Advances in Experimental Social Psychology, eds EA Plant, PG Devine (Elsevier, Amsterdam) Vol 47, 1–53 (2013).

CL Keyes, D Shmotkin, CD Ryff, Optimizing well-being: The empirical encounter of two traditions. J Pers Soc Psychol 82, 1007–1022 (2002).

TB Kashdan, R Biswas-Diener, LA King, Reconsidering happiness: The costs of distinguishing between hedonics and eudaimonia. J Posit Psychol 3, 219–233 (2008).

LA King, JA Hicks, Positive affect and meaning in life: The intersection of hedonism and eudaimonia. The Human Quest for Meaning, ed PT Wong (Routledge, New York), pp. 125–142 (2012).

CD Ryff, et al., Psychological well-being and ill-being: Do they have distinct or mirrored biological correlates? Psychother Psychosom 75, 85–95 (2006).

EM Friedman, M Hayney, GD Love, BH Singer, CD Ryff, Plasma interleukin-6 and soluble IL-6 receptors are associated with psychological well-being in aging women. Health Psychol 26, 305–313 (2007).

E Fox Keller, Genes, genomes, and genomics. Biol Theory 6, 132–140 (2012).

MR Irwin, SW Cole, Reciprocal regulation of the neural and innate immune systems. Nat Rev Immunol 11, 625–632 (2011).

MH Antoni, et al., Transcriptional modulation of human leukocytes by cognitive-behavioral stress management in women undergoing treatment for breast cancer. Biol Psychiatry 71, 366–372 (2012).

SW Cole, et al., Transcriptional modulation of the developing immune system by early life social adversity. Proc Natl Acad Sci USA 109, 20578–20583 (2012).

SW Cole, LC Hawkley, JM Arevalo, JT Cacioppo, Transcript origin analysis identifies antigen-presenting cells as primary targets of socially regulated gene expression in leukocytes. Proc Natl Acad Sci USA 108, 3080–3085 (2011).

CE Finch The Biology of Human Longevity: Inflammation, Nutrition, and Aging in the Evolution of Lifespans (Academic, Burlington, MA, 2007).

SM Lamers, GJ Westerhof, ET Bohlmeijer, PM ten Klooster, CL Keyes, Evaluating the psychometric properties of the Mental Health Continuum-Short Form (MHC-SF). J Clin Psychol 67, 99–110 (2011).

F Mosteller, J Tukey Data Analysis and Regression (Addison-Wesley, New York, 1977).

SW Cole, W Yan, Z Galic, J Arevalo, JA Zack, Expression-based monitoring of transcription factor activity: The TELiS database. Bioinformatics 21, 803–810 (2005).

GE Miller, et al., A functional genomic fingerprint of chronic stress in humans: Blunted glucocorticoid and increased NF-kappaB signaling. Biol Psychiatry 64, 266–272 (2008).

A O’Donovan, et al., Transcriptional control of monocyte gene expression in post-traumatic stress disorder. Dis Markers 30, 123–132 (2011).

LA King, JA Hicks, JL Krull, AK Del Gaiso, Positive affect and the experience of meaning in life. J Pers Soc Psychol 90, 179–196 (2006).

BL Fredrickson, MA Cohn, KA Coffey, J Pek, SM Finkel, Open hearts build lives: Positive emotions, induced through loving-kindness meditation, build consequential personal resources. Journal of Personality and Social Psychology 95, 1045–1062 (2008).

K Yamasaki, K Uchida, R Katsuma, An intervention study of the effects of the coping strategy of “finding positive meaning” on positive affect and health. Int J Psychol 44, 249–256 (2009).

R Dantzer, JC O’Connor, GG Freund, RW Johnson, KW Kelley, From inflammation to sickness and depression: When the immune system subjugates the brain. Nat Rev Neurosci 9, 46–56 (2008).

NI Eisenberger, et al., Inflammation-induced anhedonia: Endotoxin reduces ventral striatum responses to reward. Biol Psychiatry 68, 748–754 (2010).

RJ Davidson, et al., Alterations in brain and immune function produced by mindfulness meditation. Psychosom Med 65, 564–570 (2003).

AL Marsland, S Cohen, BS Rabin, SB Manuck, Trait positive affect and antibody response to hepatitis B vaccination. Brain Behav Immun 20, 261–269 (2006).

A Steptoe, J Wardle, M Marmot, Positive affect and health-related neuroendocrine, cardiovascular, and inflammatory processes. Proc Natl Acad Sci USA 102, 6508–6512 (2005).

EM Friedman, et al., Social relationships, sleep quality, and interleukin-6 in aging women. Proc Natl Acad Sci USA 102, 18757–18762 (2005).

C Keyes The Mental Health Continuum-Short Form (MHC-SF) for adults. Available at http://calmhsa.org/wp-content/uploads/2013/06/MHC-SFEnglish.pdf. Accessed July 12 2013. (2006).

CD Ryff, Happiness is everything, or is it? Explorations on the meaning of psychological well-being. J Pers Soc Psychol 57, 1069–1081 (1989).

CD Ryff, BH Singer, Know thyself and become what you are: A eudaimonic approach to psychological well-being. J Happiness Stud 9, 13–39 (2008).

P Sterling, Principles of allostasis: Optimal design, predictive regulation, pathophysiology and rational therapeutics. Allostasis, Homeostasis, and the Costs of Physiological Adaptation, ed J Schulkin (Cambridge Univ Press, Cambridge, 2004).

BS McEwen, PJ Gianaros, Central role of the brain in stress and adaptation: Links to socioeconomic status, health, and disease. Ann N Y Acad Sci 1186, 190–222 (2010).

PS Churchland Braintrust: What Neuroscience Tells Us About Morality (Princeton Univ Press, Princeton, 2011).

His Holiness the Dalai Lama Gyatso T (2011) Beyond Religion: Ethics for a Whole World (Houghton Mifflin Harcourt New York).

EO Wilson The Social Conquest of Earth (W. W. Norton, New York, 2012).

LS Radloff, The CES-D scale: A self-report depression scale for research in the general population. Appl Psychol Meas 1, 386–401 (1977).

CE McCulloch, SR Searle, JM Neuhaus Generalized, Linear, and Mixed Models (Wiley, Hoboken, NJ, 2008).

SW Cole, et al., Computational identification of gene-social environment interaction at the human IL6 locus. Proc Natl Acad Sci USA 107, 5681–5686 (2010).

SW Cole, Elevating the perspective on human stress genomics. Psychoneuroendocrinology 35, 955–962 (2010).

SW Cole, et al., Social regulation of gene expression in human leukocytes. Genome Biol 8, R189 (2007).

GE Miller, et al., Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Proc Natl Acad Sci USA 106, 14716–14721 (2009).