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01-12-2017 | ORIGINAL PAPER

Epigenetic Response to Mindfulness in Peripheral Blood Leukocytes Involves Genes Linked to Common Human Diseases

Auteurs: Javier García-Campayo, Marta Puebla-Guedea, Alberto Labarga, Amaya Urdánoz, Miren Roldán, Laura Pulido, Xabier Martínez de Morentin, Álvaro Perdones-Montero, Jesús Montero-Marín, Maite Mendioroz

Gepubliceerd in: Mindfulness | Uitgave 4/2018

Abstract

The benefits of mindfulness on human health are well-documented, but the mechanisms underlying these effects are not well-understood. Our aim was to identify molecular alterations related to mindfulness by profiling the epigenetic response in long-term meditators. We performed a genome-wide screen of DNA methylation by using the Illumina HumanMethylation450 platform in peripheral blood leukocytes from 17 long-term meditators and 17 matched controls. Top-ranked genes were validated by bisulfite cloning sequencing. Database for Annotation, Visualization, and Integrated Discovery and Ingenuity Pathways Analysis bioinformatic tools were used to characterize key processes underling the methylation changes. We found 64 differentially methylated regions (DMRs) in meditators compared to controls, corresponding to 43 genes. Most of the mindfulness-related DMRs (70.3%) were hypomethylated in meditators, and 23.4% of mindfulness-related DMRs clustered in telomeric chromosomal regions. Notably, almost half of the mindfulness-related DMRs (48.4%) involved genes linked to common human diseases, such as neurological and psychiatric disorders, cardiovascular diseases, and cancer. Lipid metabolism and atherosclerosis signaling pathway were significantly enriched in our set of DMRs. Functional in silico analysis also revealed tumor necrosis factor (TNF) and NF-κB signaling as crucial regulators of the mindfulness-related genes. Our study suggests that there is a consistent epigenetic response to long-term meditation practice in blood leukocytes with predominant loss of cytosine-phosphate-guanine methylation in distinct genomic regions, such as telomeres. Further research is warranted to confirm that the molecular response to mindfulness practice involves crucial transcriptional regulators related to a wide range of human common diseases, such as TNF and NF-κB.

vorige artikel Additive Effects of 3,4-Methylenedioxymethamphetamine (MDMA) and Compassionate Imagery on Self-Compassion in Recreational Users of Ecstasy

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Akbarian, S., Beeri, M. S., & Haroutunian, V. (2013). Epigenetic determinants of healthy and diseased brain aging and cognition. JAMA Neurology, 70, 711–718. CrossRefPubMed

Alda, M., Puebla-Guedea, M., Rodero, B., Demarzo, M., Montero-Marin, J., Roca, M., & Garcia-Campayo, J. (2016). Zen meditation, length of telomeres, and the role of experiential avoidance and compassion. Mindfulness, 7, 651–659. CrossRefPubMedPubMedCentral

Bergman, Y., & Cedar, H. (2013). DNA methylation dynamics in health and disease. Nature Structural & Molecular Biology, 20(3), 274–281. CrossRef

Bishop, S. R., Lau, M., Shapiro, S., Carlson, L., Anderson, N. D., Carmody, J., Segal, Z. V., Abbey, S., Speca, M., Velting, D., & Devins, G. (2004). Mindfulness: a proposed operational definition. Clinical Psychology: Science and Practice, 11(3), 230–241.

Black, D. S., & Slavich, G. M. (2016). Mindfulness meditation and the immune system: a systematic review of randomized controlled trials. Annals of the New York Academy of Sciences, 1373(1), 13–24. CrossRefPubMedPubMedCentral

Black, D. S., Cole, S. W., Irwin, M. R., Breen, E., Cyr, N. M. S., Nazarian, N., et al. (2013). Yogic meditation reverses NF-κB and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial. Psychoneuroendocrinology, 38(3), 348–355. CrossRefPubMed

Bock, C. (2012). Analysing and interpreting DNA methylation data. Nature reviews. Genetics, 13(10), 705–719. PubMed

Bower, J. E., Crosswell, A. D., Stanton, A. L., et al. (2015). Mindfulness meditation for younger breast cancer survivors: a randomized controlled trial. Cancer, 121(8), 1231–1240. CrossRefPubMed

Buervenich, S., Carmine, A., Arvidsson, M., Xiang, F., Zhang, Z., Sydow, O., et al. (2000). NURR1 mutations in cases of schizophrenia and manic-depressive disorder. American Journal of Medical Genetics, 96(6), 808–813. CrossRefPubMed

Chen, Y., Lemire, M., Choufani, S., Butcher, D. T., Grafodatskaya, D., Zanke, B. W., et al. (2013). Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 microarray. Epigenetics, 8(2), 203–209. CrossRefPubMedPubMedCentral

Creswell, J. D., Myers, H. F., Cole, S. W., & Irwin, M. R. (2009). Mindfulness meditation training effects on CD4+ T lymphocytes in HIV-1 infected adults: a small randomized controlled trial. Brain Behavior and Immunity, 23(2), 184–188. CrossRef

Creswell, J. D., Irwin, M. R., Burklund, L. J., Lieberman, M. D., Arevalo, J. M. G., Ma, J., et al. (2012). Mindfulness-based stress reduction training reduces loneliness and pro-inflammatory gene expression in older adults: a small randomized controlled trial. Brain, Behavior, and Immunity, 26(7), 1095–1101. CrossRefPubMedPubMedCentral

Dahl, C. J., Lutz, A., & Davidson, R. J. (2015). Reconstructing and deconstructing the self: cognitive mechanisms in meditation practice. Trends in Cognitive Sciences, 19(9), 515–523. CrossRefPubMedPubMedCentral

De Jager, P., Srivastava, G., Lunnon, K., Burgess, J., Schalkwyk, L., Yu, L., et al. (2014). Alzheimer’s disease pathology is associated with early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nature Neuroscience, 17(9), 1156–1163. CrossRefPubMedPubMedCentral

Do, C., Lang, C. F., Lin, J., Darbary, H., Krupska, I., Gaba, A., et al. (2016). Mechanisms and disease associations of haplotype-dependent allele-specific DNA methylation. American Journal of Human Genetics, 98(5), 934–955. CrossRefPubMedPubMedCentral

Domcke, S., Bardet, A. F., Ginno, P. A., Hartl, D., Burger, L., & Schübeler, D. (2015). Competition between DNA methylation and transcription factors determines binding of NRF1. Nature, 528(7583), 575–579. CrossRefPubMed

Elsenbruch, S., Langhorst, J., Popkirowa, K., et al. (2005). Effects of mind-body therapy on quality of life and neuroendocrine and cellular immune functions in patients with ulcerative colitis. Psychotherapy and Psychosomatics, 74(5), 277–287. CrossRefPubMed

Fayed, N., Lopez del Hoyo, Y., Andres, E., Serrano-Blanco, A., Bellón, J., Aguilar, K., et al. (2013). Brain changes in long-term Zen meditators using proton magnetic resonance spectroscopy and diffusion tensor imaging: a controlled study. PLoS One, 8(3), e58476. CrossRefPubMedPubMedCentral

Fox, K. C., Nijeboer, S., Dixon, M. L., Floman, J. L., Ellamil, M., Rumak, S. P., et al. (2014). Is meditation associated with altered brain structure? A systematic review and meta-analysis of morphometric neuroimaging in meditation practitioners. Neuroscience & Biobehavioral Reviews, 43, 48–73. CrossRef

Fung, H. C., Scholz, S., Matarin, M., Simón-Sánchez, J., Hernandez, D., Britton, A., et al. (2006). Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data. The Lancet Neurology, 5(11), 911–916. CrossRefPubMed

Graves, M. C., Benton, M., Lea, R. A., Boyle, M., Tajouri, L., MacArtney-Coxson, D., et al. (2014). Methylation differences at the HLA-DRB1 locus in CD4+ T-cells are associated with multiple sclerosis. Multiple Sclerosis Journal, 20(8), 1033–1041. CrossRefPubMed

Grossman, P., Niemann, L., Schmidt, S., & Walach, H. (2004). Mindfulness-based stress reduction and health benefits: a meta-analysis. Journal of Psychosomatic Research, 57(1), 35–43. CrossRefPubMed

Hernández, S. E., Suero, J., Barros, A., González-Mora, J. L., & Rubia, K. (2016). Increased grey matter associated with long-term Sahaja yoga meditation: a voxel-based morphometry study. PLoS One, 11(3), e0150757. CrossRefPubMedPubMedCentral

Heyn, H., & Esteller, M. (2012). DNA methylation profiling in the clinic: applications and challenges. Nature reviews. Genetics, 13(10), 679–692. PubMed

Horvath, S., Zhang, Y., Langfelder, P., Kahn, R. S., Boks, M. P., van Eijk, K., et al. (2012). Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biology, 13(10), R97. CrossRefPubMedPubMedCentral

Huang, F., Shang, Y., Luo, Y., Wu, P., Huang, X., Tan, X., et al. (2016). Lower prevalence of Alzheimer’s disease among Tibetans: association with religious and genetic factors. Journal of Alzheimer's Disease, 50(3), 659–667. CrossRefPubMed

Jaffe, A. E., Murakami, P., Lee, H., Leek, J. T., Fallin, M. D., Feinberg, A. P., & Irizarry, R. A. (2012). Bump hunting to identify differentially methylated regions in epigenetic epidemiology studies. International Journal of Epidemiology, 41(1), 200–209. CrossRefPubMedPubMedCentral

Jankovic, J., Chen, S., & Le, W. D. (2005). The role of Nurr1 in the development of dopaminergic neurons and Parkinson’s disease. Progress in Neurobiology, 77(1–2), 128–138. CrossRefPubMed

Jo, B. S., Koh, I. U., Bae, J. B., Yu, H. Y., Jeon, E. S., Lee, H. Y., et al. (2016). Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy. Genomics, 108(2), 84–92. CrossRefPubMed

Kaliman, P., Álvarez-López, M. J., Cosín-Tomás, M., Rosenkranz, M. A., Lutz, A., & Davidson, R. J. (2014). Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators. Psychoneuroendocrinology, 40, 96–107. CrossRefPubMed

Kang, D. H., Jo, H. J., Jung, W. H., Kim, S. H., Jung, Y. H., Choi, C. H., et al. (2013). The effect of meditation on brain structure: cortical thickness mapping and diffusion tensor imaging. Social Cognitive and Affective Neuroscience, 8(1), 27–33. CrossRefPubMed

Keng, S. L., Smoski, M. J., & Robins, C. J. (2011). Effects of mindfulness on psychological health: a review of empirical studies. Clinical Psychology Review, 31(6), 1041–1056. CrossRefPubMedPubMedCentral

Kumaki, Y., Oda, M., & Okano, M. (2008). QUMA: quantification tool for methylation analysis. Nucleic Acids Research, 36(Web Server issue), W170–W175.

Li, L. C., & Dahiya, R. (2002). MethPrimer: designing primers for methylation PCRs. Bioinformatics, 18(11), 1427–1431. CrossRefPubMed

Lippelt, D. P., Hommel, B., & Colzato, L. S. (2014). Focused attention, open monitoring and loving kindness meditation: Effects on attention, conflict monitoring, and creativity—a review. Frontiers in Psychology, 5, 1083. CrossRefPubMedPubMedCentral

Liu, H., Fu, Y., Ren, J., Yu, S., Liu, H., Jiang, P., et al. (2015). Association between NR4A2 genetic variation and schizophrenia: a comprehensive systematic review and meta-analysis. Neuroscience Letters, 598, 85–90. CrossRefPubMed

Luders, E., Thompson, P. M., Kurth, F., Hong, J. Y., Phillips, O. R., Wang, Y., et al. (2013). Global and regional alterations of hippocampal anatomy in long-term meditation practitioners. Human Brain Mapping, 34(12), 3369–3375. CrossRefPubMed

Masliah, E., Dumaop, W., Galasko, D., & Desplats, P. (2013). Distinctive patterns of DNA methylation associated with Parkinson disease: identification of concordant epigenetic changes in brain and peripheral blood leukocytes. Epigenetics, 8(10), 1030–1038. CrossRefPubMedPubMedCentral

Melé, M., Ferreira, P. G., Reverter, F., DeLuca, D. S., Monlong, J., Sammeth, M., et al. (2015). The human transcriptome across tissues and individuals. Science, 348(6235), 660–665. CrossRefPubMedPubMedCentral

Miller, S. A., Dykes, D. D., & Polesky, H. F. (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Research, 16(3), 1215. CrossRefPubMedPubMedCentral

Panday, A., Inda, M. E., Bagam, P., Sahoo, M. K., Osorio, D., & Batra, S. (2016). Transcription factor NF-κB: an update on intervention strategies. Archivum Immunologiae et Therapiae Experimentalis, 64(6), 463–483. CrossRefPubMed

Peters, T. J., Buckley, M. J., Statham, A. L., Pidsley, R., Samaras, K., Lord, R. V., Clark, S. J., & Molloy, P. L. (2015). De novo identification of differentially methylated regions in the human genome. Epigenetics & Chromatin, 8, 6.

Pickut, B. A., Van Hecke, W., Kerckhofs, E., Mariën, P., Vanneste, S., Cras, P., & Parizel, P. M. (2013). Mindfulness based intervention in Parkinson's disease leads to structural brain changes on MRI: a randomized controlled longitudinal trial. Clinical Neurology and Neurosurgery, 115(12), 2419–2425. CrossRefPubMed

Pidsley, R., Y Wong, C. C., Volta, M., Lunnon, K., Mill, J., & Schalkwyk, L. C. (2013). A data-driven approach to preprocessing Illumina 450K methylation array data. BMC Genomics, 14, 293. CrossRefPubMedPubMedCentral

Price, E. M., Cotton, A. M., Lam, L. L., Farré, P., Emberly, E., Brown, C. J., et al. (2013). Additional annotation enhances potential for biologically-relevant analysis of the Illumina Infinium HumanMethylation450 BeadChip array. Epigenetics & Chromatin, 6, 4. CrossRef

Ravnik-Glavač, M., Hrašovec, S., Bon, J., Dreu, J., & Glavač, D. (2012). Genome-wide expression changes in a higher state of consciousness. Consciousness and Cognition, 21(3), 1322–1344. CrossRefPubMed

Reitz, C. (2013). Dyslipidemia and the risk of Alzheimer’s disease. Current Atherosclerosis Reports, 15(3), 307. CrossRefPubMedPubMedCentral

Rhead, B., Holingue, C., Cole, M., Shao, X., Quach, H. L., Quach, D., et al. (2017). Rheumatoid arthritis naive T cells share hypermethylation sites with synoviocytes. Arthritis & Rheumatology (Hoboken, N.j.), 69(3), 550–559. CrossRef

Rosenkranz, M. A., Davidson, R. J., Maccoon, D. G., Sheridan, J. F., Kalin, N. H., & Lutz, A. (2013). A comparison of mindfulness-based stress reduction and an active control in modulation of neurogenic inflammation. Brain, Behavior and Immunity, 27(1), 174–184. CrossRef

Saatcioglu, F. (2013). Regulation of gene expression by yoga, meditation and related practices: a review of recent studies. Asian Journal of Psychiatry, 6(1), 74–77. CrossRefPubMed

Saini, A., Mahajan, S., & Gupta, P. (2016). Nuclear receptor expression atlas in BMDCs: Nr4a2 restricts immunogenicity of BMDCs and impedes EAE. European Journal of Immunology, 46(8), 1842–1853. CrossRefPubMed

Sandoval, J., Heyn, H., Moran, S., Serra-Musach, J., Pujana, M. A., Bibikova, M., & Esteller, M. (2011). Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome. Epigenetics, 6(6), 692–702. CrossRefPubMed

Segal, Z. V., Williams, J. M. G., & Teasdale, J. D. (2002). Mindfulness-based cognitive therapy for depression: a new approach to preventing relapse. New York: Guilford.

Shapiro, S. L., & Schwartz, G. E. (2000). Intentional systemic mindfulness: an integrative model for self-regulation and health. Advances in Mind-Body Medicine, 16(2), 128–134. PubMed

Sleiman, P. M. A., Healy, D. G., Muqit, M. M. K., Yang, Y. X., Van Der Brug, M., Holton, J. L., et al. (2009). Characterisation of a novel NR4A2 mutation in Parkinson’s disease brain. Neuroscience Letters, 457(2), 75–79. CrossRefPubMedPubMedCentral

Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., et al. (2005). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences of the United States of America, 102(43), 15545–15550. CrossRefPubMedPubMedCentral

Suzuki, M. M., & Bird, A. (2008). DNA methylation landscapes: provocative insights from epigenomics. Nature Reviews Genetics, 9(6), 465–476. CrossRefPubMed

Tang, Y. Y., Hölzel, B. K., & Posner, M. I. (2015). The neuroscience of mindfulness meditation. Nature Reviews. Neuroscience, 16(4), 213–225. PubMed

Urdinguio, R. G., Bayón, G. F., Dmitrijeva, M., Toraño, E. G., Bravo, C., Fraga, M. F., et al. (2015). Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility. Human Reproduction, 30(5), 1014–1028. CrossRefPubMed

Walsh, E., Eisenlohr-Moul, T., & Baer, R. (2016). Brief mindfulness training reduces salivary IL-6 and TNF-α in young women with depressive symptomatology. Journal of Consulting and Clinical Psychology, 84(10), 887–897. CrossRefPubMedPubMedCentral

Won, H. Y., & Hwang, E. S. (2016). Transcriptional modulation of regulatory T cell development by novel regulators NR4As. Archives of Pharmacal Research, 39(11), 1530–1536. CrossRefPubMed

Yan, L., Ma, C., Wang, D., Hu, Q., Qin, M., Conroy, J. M., et al. (2012). OSAT: a tool for sample-to-batch allocations in genomics experiments. BMC Genomics, 13, 689. CrossRefPubMedPubMedCentral

Titel: Epigenetic Response to Mindfulness in Peripheral Blood Leukocytes Involves Genes Linked to Common Human Diseases
Auteurs: Javier García-Campayo
Marta Puebla-Guedea
Alberto Labarga
Amaya Urdánoz
Miren Roldán
Laura Pulido
Xabier Martínez de Morentin
Álvaro Perdones-Montero
Jesús Montero-Marín
Maite Mendioroz
Publicatiedatum: 01-12-2017
Uitgeverij: Springer US
Gepubliceerd in: Mindfulness / Uitgave 4/2018
Print ISSN: 1868-8527
Elektronisch ISSN: 1868-8535
DOI: https://doi.org/10.1007/s12671-017-0851-6

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