Changes in the expression of inflammatory and epigenetic-modulatory genes after an intensive meditation retreat

María Jesús Álvarez-López, Quinn A Conklin, Marta Cosín-Tomás, Grant S Shields, Brandon G King, Anthony P Zanesco, Perla Kaliman, Clifford D Saron, María Jesús Álvarez-López, Quinn A Conklin, Marta Cosín-Tomás, Grant S Shields, Brandon G King, Anthony P Zanesco, Perla Kaliman, Clifford D Saron

Abstract

Background: Meditation retreats are characterized by intensive or concentrated periods of meditation practice, commonly undertaken in a residential setting. Although research indicates that meditation training can positively influence physical and mental health outcomes, the biological consequences of meditation retreat interventions are relatively understudied. In this study, we examined the influence of a month-long, silent meditation retreat on the expression of genes involved in epigenetic modulation and immune processes.

Method: We assessed gene expression changes in experienced meditators attending a month-long Insight meditation retreat (n = 28), as compared to a community control group (n = 34) of experienced practitioners living their everyday lives. Blood samples were collected on day two of the retreat (Time 1) and again 3 weeks later (Time 2). Control participants were also assessed across a 3-week interval, during which they maintained their regular daily routines.

Results: As compared to controls, retreat participants showed differential changes in the expression of several genes involved in chromatin modulation and inflammation. The most substantive finding was downregulation of the TNF pathway in retreat participants, which was not observed in controls.

Conclusions: These findings indicate that meditation retreat participation may influence some of the inflammatory mechanisms involved in the development of chronic diseases, and that this style of psychosocial intervention may have therapeutic potential, particularly in experienced practitioners.

Keywords: Cytokines; Epigenetics; Gene expression; Meditation; Mindfulness; Retreat.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

© 2022 The Authors. Published by Elsevier Ltd.

Figures

Fig. 1
Fig. 1
A)Dendrograms and heatmaps depicting relations between genes across participants at each time point. The dendrograms drawn to the left show the hierarchical clustering between genes. In the heat maps, the red end of the gradient indicates lower gene expression while blue indicates greater expression. Each column represents the gene expression profile for one participant, with retreat participants plotted to the left of the black line and controls plotted to the right. B) Gene expression heatmaps by Group and Time. Each row represents an individual participant; columns represent individual genes. Here, the most notable differences between groups lie in COX2, IL8 and IL1β, which are lower in the retreat group at Time 1 as shown in the upper left panel. There is also a visible pattern of upregulation in CCR3, CXCR2, and GADD45G across groups at Time 2, shown in the panels on the right. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
Fig. 2
Fig. 2
Significant Group effects that survived False Discovery Rate correction. Expression values were log transformed. Error bars represent standard errors of the mean. Group differences at Time 1 or Time 2 are indicated: ns = not significant, *p < .05, **p < .01, ***p < .001.
Fig. 3
Fig. 3
Significant Group × Time effects that survived False Discovery Rate correction. Gene expression values were log transformed. Error bars represent standard errors of the mean. Group differences at Time 1 or Time 2 are indicated: ns = not significant, *p < .05, **p < .01, ***p < .001.

References

    1. Dantzer R., Kelley K.W. Twenty years of research on cytokine-induced sickness behavior. Brain Behav. Immun. 2007;21:153–160. doi: 10.1016/j.bbi.2006.09.006.
    1. Segerstrom G.E. Suzanne C.; miller, psychological stress and the human immune system: a meta-analytic study of 30 Years of inquiry. Psychol. Bull. 2004;130:601–630. doi: 10.1037/0033-2909.130.4.601.
    1. Slavich G.M. Understanding inflammation, its regulation, and relevance for health: a top scientific and public priority. Brain Behav. Immun. 2015;45:13–14. doi: 10.1016/j.bbi.2014.10.012.
    1. Black D.S., Christodoulou G., Cole S. Mindfulness meditation and gene expression: a hypothesis-generating framework. Curr. Opin. Psychol. 2019;28:302–306. doi: 10.1016/j.copsyc.2019.06.004.
    1. Black D.S., Slavich G.M. Mindfulness meditation and the immune system: a systematic review of randomized controlled trials. Ann. N. Y. Acad. Sci. 2016;1373:13–24. doi: 10.1111/nyas.12998.
    1. Kaliman P. Epigenetics and meditation. Curr. Opin. Psychol. 2019;28:76–80. doi: 10.1016/j.copsyc.2018.11.010.
    1. Kaliman P., Alvarez-López M.J., Cosín-Tomás M., a Rosenkranz M., Lutz A., Davidson R.J. Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators. Psychoneuroendocrinology. 2014;40:96–107. doi: 10.1016/j.psyneuen.2013.11.004.
    1. Cole S.W., Conti G., Arevalo J.M.G., Ruggiero A.M., Heckman J.J., Suomi S.J. Transcriptional modulation of the developing immune system by early life social adversity. Proc. Natl. Acad. Sci. USA. 2012;109:20578–20583. doi: 10.1073/pnas.1218253109.
    1. Slavich G.M., Cole S.W. The emerging field of human social genomics. Clin. Psychol. Sci. 2013;1:331–348. doi: 10.1177/2167702613478594.
    1. Buric I., Farias M., Jong J., Mee C., Brazil I.A. What is the molecular signature of mind–body interventions? A systematic review of gene expression changes induced by meditation and related practices. Front. Immunol. 2017;8:670. doi: 10.3389/fimmu.2017.00670.
    1. O'Donovan A., Tomiyama A.J., Lin J., Puterman E., Adler N.E., Kemeny M., Wolkowitz O.M., Blackburn E.H., Epel E.S. Stress appraisals and cellular aging: a key role for anticipatory threat in the relationship between psychological stress and telomere length. Brain Behav. Immun. 2012;26:573–579. doi: 10.1016/j.bbi.2012.01.007.
    1. Slavich G., Irwin M. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol. Bull. 2014;140:774–815. doi: 10.1037/a0035302.
    1. Palin K., Bluthé R.-M., McCusker R.H., Levade T., Moos F., Dantzer R., Kelley K.W. The type 1 TNF receptor and its associated adapter protein, FAN, are required for TNFα-induced sickness behavior. Psychopharmacology (Berl) 2009;201:549–556. doi: 10.1007/s00213-008-1331-4.
    1. Kappelmann N., Lewis G., Dantzer R., Jones P.B., Khandaker G.M. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol. Psychiatr. 2018;23:335–343. doi: 10.1038/mp.2016.167.
    1. Bower J.E., Irwin M.R. Mind–body therapies and control of inflammatory biology: a descriptive review. Brain Behav. Immun. 2016;51:1–11. doi: 10.1016/j.bbi.2015.06.012.
    1. Conklin Q.A., Crosswell A.D., Saron C.D., Epel E.S. Meditation, stress processes, and telomere biology. Curr. Opin. Psychol. 2019;28:92–101. doi: 10.1016/j.copsyc.2018.11.009.
    1. Creswell J.D., Lindsay E.K. How does mindfulness training affect health? A mindfulness stress buffering account. Curr. Dir. Psychol. Sci. 2014;23:401–407. doi: 10.1177/0963721414547415.
    1. Chaix R., Fagny M., Cosin-Tomás M., Alvarez-López M., Lemee L., Regnault B., Davidson R.J., Lutz A., Kaliman P. Differential DNA methylation in experienced meditators after an intensive day of mindfulness-based practice: implications for immune-related pathways. Brain Behav. Immun. 2020;84:36–44. doi: 10.1016/j.bbi.2019.11.003.
    1. García-Campayo J., Puebla-Guedea M., Labarga A., Urdánoz A., Roldán M., Pulido L., de Morentin X.M., Perdones-Montero Á., Montero-Marín J., Mendioroz M. Epigenetic response to mindfulness in peripheral blood leukocytes involves genes linked to common human diseases. Mindfulness (N. Y). 2018;9:1146–1159. doi: 10.1007/s12671-017-0851-6.
    1. King B.G., Conklin Q.A., Zanesco A.P., Saron C.D. Residential meditation retreats: their role in contemplative practice and significance for psychological research. Curr. Opin. Psychol. 2019;28:238–244. doi: 10.1016/j.copsyc.2018.12.021.
    1. Conklin Q.A., King B.G., Zanesco A.P., Lin J., Hamidi A.B., Pokorny J.J., Álvarez-López M.J., Cosín-Tomás M., Huang C., Kaliman P., Epel E.S., Saron C.D. Insight meditation and telomere biology: the effects of intensive retreat and the moderating role of personality. Brain Behav. Immun. 2018;70:233–245. doi: 10.1016/j.bbi.2018.03.003.
    1. Goldstein J., Kornfield J. Shambhala Publications; Boston, MA: 2001. Seeking the Heart of Wisdom: the Path of Insight Meditation.
    1. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–408. doi: 10.1006/meth.2001.1262.
    1. McArtor D.B., Lubke G.H., Bergeman C.S. Extending multivariate distance matrix regression with an effect size measure and the asymptotic null distribution of the test statistic. Psychometrika. 2017;82:1052–1077. doi: 10.1007/s11336-016-9527-8.
    1. Zapala M.A., Schork N.J. Multivariate regression analysis of distance matrices for testing associations between gene expression patterns and related variables. Proc. Natl. Acad. Sci. U.S.A. 2006;103:19430–19435. doi: 10.1073/pnas.0609333103.
    1. Steeland S., Libert C., Vandenbroucke R.E. A new venue of TNF targeting. Int. J. Mol. Sci. 2018;19 doi: 10.3390/ijms19051442.
    1. O'Donovan A., Pantell M.S., Puterman E., Dhabhar F.S., Blackburn E.H., Yaffe K., Cawthon R.M., Opresko P.L., Hsueh W.-C., Satterfield S., Newman A.B., Ayonayon H.N., Rubin S.M., Harris T.B., Epel E.S. Cumulative inflammatory load is associated with short leukocyte telomere length in the Health, Aging and Body Composition Study. PLoS One. 2011;6 doi: 10.1371/journal.pone.0019687.
    1. Calabrese F., Rossetti A.C., Racagni G., Gass P., Riva M.A., Molteni R. Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity. Front. Cell. Neurosci. 2014;8:1–7. doi: 10.3389/fncel.2014.00430.
    1. Epel E.S., Puterman E., Lin J., Blackburn E.H., Lum P.Y., Beckmann N.D., Zhu J., Lee E., Gilbert A., Rissman R.A., Tanzi R.E., Schadt E.E. Meditation and vacation effects have an impact on disease-associated molecular phenotypes. Transl. Psychiatry. 2016;6 doi: 10.1038/tp.2016.164.
    1. Audet M.C., Anisman H. Interplay between pro-inflammatory cytokines and growth factors in depressive illnesses. Front. Cell. Neurosci. 2013:68. doi: 10.3389/fncel.2013.00068.
    1. Ja W.K., Duman R.S. IL-1 beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc. Natl. Acad. Sci. U.S.A. 2008;105:751–756. doi: 10.1073/PNAS.0708092105.
    1. Harada A., Sekido N., Akahoshi T., Wada T., Mukaida N., Matsushima K. Essential involvement of interleukin-8 (IL-8) in acute inflammation. J. Leukoc. Biol. 1994;56:559–564. doi: 10.1002/JLB.56.5.559.
    1. Penna G., Mondaini N., Amuchastegui S., Degli Innocenti S., Carini M., Giubilei G., Fibbi B., Colli E., Maggi M., Adorini L. Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia. Eur. Urol. 2007;51:524–533. doi: 10.1016/J.EURURO.2006.07.016.
    1. Cui G.B., An J.Z., Zhang N., Zhao M.G., Liu S.B., Yi J. Elevated interleukin-8 enhances prefrontal synaptic transmission in mice with persistent inflammatory pain. Mol. Pain. 2012;8 doi: 10.1186/1744-8069-8-11.
    1. Creswell J.D., Irwin M.R., Burklund L.J., Lieberman M.D., Arevalo J.M.G., Ma J., Crabb Breen E., Cole S.W. Mindfulness-Based Stress Reduction training reduces loneliness and pro-inflammatory gene expression in older adults: a small randomized controlled trial. Brain Behav. Immun. 2012;26(7):1095–1101. doi: 10.1016/j.bbi.2012.07.006.
    1. Black D.S., Cole S.W., Irwin M.R., Breen E., Cyr N.M. St, Nazarian N., Khalsa D.S., Lavretsky H. Yogic meditation reverses NF-κB and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial. Psychoneuroendocrinology. 2013;38:348–355. doi: 10.1016/j.psyneuen.2012.06.011.
    1. Sharma H., Datta P., Singh A., Sen S., Bhardwaj N.K., Kochupillai V., Singh N. Gene expression profiling in practitioners of Sudarshan Kriya. J. Psychosom. Res. 2008;64:213–218. doi: 10.1016/J.JPSYCHORES.2007.07.003.
    1. Zannas A.S., Wiechmann T., Gassen N.C., Binder E.B. Gene–stress–epigenetic regulation of FKBP5: clinical and translational implications. Neuropsychopharmacology. 2015;411(41):261–274. doi: 10.1038/npp.2015.235. 2016.
    1. Bishop J.R., Lee A.M., Mills L.J., Thuras P.D., Eum S., Clancy D., Erbes C.R., Polusny M.A., Lamberty G.J., Lim K.O. Methylation of FKBP5 and SLC6A4 in relation to treatment response to mindfulness based stress reduction for posttraumatic stress disorder. Front. Psychiatr. 2018;9 doi: 10.3389/fpsyt.2018.00418.
    1. Bishop J.R., Lee A.M., Mills L.J., Thuras P.D., Eum S., Clancy D., Erbes C.R., Polusny M.A., Lamberty G.J., Lim K.O. Corrigendum: methylation of FKBP5 and SLC6A4 in relation to treatment response to mindfulness based stress reduction for posttraumatic stress disorder. Front. Psychiatr. 2021 doi: 10.3389/fpsyt.2021.642245.
    1. Tsutsui T., Fukasawa R., Shinmyouzu K., Nakagawa R., Tobe K., Tanaka A., Ohkuma Y. Mediator complex recruits epigenetic regulators via its two cyclin-dependent kinase subunits to repress transcription of immune response genes. J. Biol. Chem. 2013;288:20955–20965. doi: 10.1074/jbc.M113.486746.
    1. Li H., Rauch T., Chen Z.X., Szabó P.E., Riggs A.D., Pfeifer G.P. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J. Biol. Chem. 2006;281:19489–19500. doi: 10.1074/jbc.M513249200.
    1. Fuks F., Burgers W.A., Godin N., Kasai M., Kouzarides T. Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription. EMBO J. 2001;20:2536–2544. doi: 10.1093/emboj/20.10.2536.
    1. Wang X., Zhu K., Li S., Liao Y., Du R., Zhang X., Shu H.-B., Guo A.-Y., Li L., Wu M. MLL1, a H3K4 methyltransferase, regulates the TNFα-stimulated activation of genes downstream of NF-κB. J. Cell Sci. 2012;125:4058–4066. doi: 10.1242/jcs.103531.
    1. Fraga M.F., Ballestar E., Villar-Garea A., Boix-Chornet M., Espada J., Schotta G., Bonaldi T., Haydon C., Ropero S., Petrie K., Iyer N.G., Pérez-Rosado A., Calvo E., Lopez J.A., Cano A., Calasanz M.J., Colomer D., Piris M.Á., Ahn N., Imhof A., Caldas C., Jenuwein T., Esteller M. Loss of acetylation at Lys 16 and trimethylation at Lys 20 of histone H4 is a common hallmark of human cancer. Nat. Genet. 2005;37:391–400. doi: 10.1038/ng1531.
    1. Fraga M.F., Agrelo R., Esteller M. Cross-talk between aging and cancer: the epigenetic language. Ann. N. Y. Acad. Sci. 2007:60–74. doi: 10.1196/annals.1395.005. Blackwell Publishing Inc.
    1. Champagne N., Bertos N.R., Pelletier N., Wang A.H., Vezmar M., Yang Y., Heng H.H., Yang X.J. Identification of a human histone acetyltransferase related to monocytic leukemia zinc finger protein. J. Biol. Chem. 1999;274:28528–28536. doi: 10.1074/JBC.274.40.28528.
    1. Sun J., Sun J., Ming G.L., Song H. Epigenetic regulation of neurogenesis in the adult mammalian brain. Eur. J. Neurosci. 2011;33:1087–1093. doi: 10.1111/j.1460-9568.2011.07607.x.
    1. Rosenkranz M.A., Dunne J.D., Davidson R.J. The next generation of mindfulness-based intervention research: what have we learned and where are we headed? Curr. Opin. Psychol. 2019;28:179–183. doi: 10.1016/j.copsyc.2018.12.022.
    1. Dopico X.C., Evangelou M., Ferreira R.C., Guo H., Pekalski M.L., Smyth D.J., Cooper N., Burren O.S., Fulford A.J., Hennig B.J., Prentice A.M., Ziegler A.-G., Bonifacio E., Wallace C., Todd J.a. Widespread seasonal gene expression reveals annual differences in human immunity and physiology. Nat. Commun. 2015;6:7000. doi: 10.1038/ncomms8000.
    1. Furman D., Campisi J., Verdin E., Carrera-Bastos P., Targ S., Franceschi C., Ferrucci L., Gilroy D.W., Fasano A., Miller G.W., Miller A.H., Mantovani A., Weyand C.M., Barzilai N., Goronzy J.J., Rando T.A., Effros R.B., Lucia A., Kleinstreuer N., Slavich G.M. Chronic inflammation in the etiology of disease across the life span. Nat. Med. 2019;2512(25):1822–1832. doi: 10.1038/s41591-019-0675-0. 2019.

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