SLC6A4 methylation as an epigenetic marker of life adversity exposures in humans: A systematic review of literature

Neuroscience and Biobehavioral Reviews

Volumn 71, Issue , 2016, Pages 7-20

  Provenzi, Livio ^a   Giorda, Roberto ^a   Beri, Silvana ^a   Montirosso, Rosario ^a  

^a SCIENTIFIC INSTITUTE   (Italy)

Author keywords

Early adversity; Epigenetics; Methylation; Serotonin transporter; SLC6A4; Stress; Systematic review

Indexed keywords

SEROTONIN TRANSPORTER; GENETIC MARKER;

BEHAVIOR GENETICS; CHILD ABUSE; DNA METHYLATION; EARLY LIFE STRESS; ENVIRONMENTAL STRESS; EPIGENETICS; GENETIC ASSOCIATION; GENETIC MARKER; HUMAN; OUTCOME ASSESSMENT; PERINATAL STRESS; PREGNANCY; PRENATAL EXPOSURE; PRIORITY JOURNAL; PSYCHOTRAUMA; PUERPERAL DEPRESSION; REVIEW; SLC6A4 GENE; SYSTEMATIC REVIEW; DEPRESSION; GENETIC EPIGENESIS; GENETICS;

DEPRESSION; DNA METHYLATION; EPIGENESIS, GENETIC; EPIGENOMICS; GENETIC MARKERS; HUMANS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS;

EID: 84984780842     PISSN: 01497634     EISSN: 18737528     Source Type: Journal    
DOI: 10.1016/j.neubiorev.2016.08.021     Document Type: Review

References (87)

1. Alasaari, J.S., Lagus, M., Ollila, H.M., Toivola, A., Kivimaki, M., Vahtera, J., et al. Environmental stress affects DNA methylation of a CpG rich promoter region of serotonin transporter gene in a nurse cohort. PLoS One, 7(9), 2012, e45813.
2. Alexander, N., Wankerl, M., Hennig, J., Miller, R., Zankert, S., Steudte-Schmiedgen, S., et al. DNA methylation profiles within the serotonin transporter gene moderate the association of 5-HTTLPR and cortisol stress reactivity. Transl. Psychiatry, 4, 2014, e443.
3. Avila, L., Yuen, R.K., Diego-Alvarez, D., Peñaherrera, M.S., Jiang, R., Robinson, W.P., Evaluating DNA methylation and gene expression variability in the human term placenta. Placenta 31:12 (2010), 1070–1077.
4. Barry, R.A., Kochanska, G., Philibert, R.A., G × E interaction in the organization of attachment: mothers’ responsiveness as a moderator of children's genotypes. J. Child Psychol. Psychiatry 49:12 (2008), 1313–1320.
5. Beach, S.R.H., Brody, G.H., Todorov, A.A., Gunter, T.D., Philibert, R.A., Methylation at SLC6A4 is linked to family history of child abuse: an examination of the Iowa Adoptee sample. Am. J. Med. Genet. B Neuropsychiatr. Genet. 153B:2 (2010), 710–713.
6. Beach, S.R., Brody, G.H., Todorov, A.A., Gunter, T.D., Philibert, R.A., Methylation at 5HTT mediates the impact of child sex abuse on women's antisocial behavior: an examination of the Iowa adoptee sample. Psychosom. Med. 73:1 (2011), 83–87.
7. Beach, S.R., Dogan, M.V., Brody, G.H., Philibert, R.A., Differential impact of cumulative SES risk on methylation of protein-protein interaction pathways as a function of SLC6A4 genetic variation in African American young adults. Biol. Psychol. 96 (2014), 28–34.
8. Bennett, A.J., Lesch, K.P., Heils, A., Long, J.C., Lorenz, J.G., Shoaf, S.E., et al. Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol. Psychiatry 7:1 (2002), 118–122.
9. Bertolino, A., Arciero, G., Rubino, V., Latorre, V., De Candia, M., Mazzola, V., et al. Variation of human amygdala response during threatening stimuli as a function of 5′HTTLPR genotype and personality style. Biol. Psychiatry 57:12 (2005), 1517–1525.
10. Bird, A., DNA methylation patterns and epigenetic memory DNA methylation patterns and epigenetic memory?. Genes Dev. 16:1 (2002), 6–21.
11. Booij, L., Wang, D., Levesque, M.L., Tremblay, R.E., Szyf, M., Looking beyond the DNA sequence: the relevance of DNA methylation processes for the stress-diathesis model of depression. Philos. Trans. R. Soc. Lond. B Biol. Sci., 368(1615), 2013, 20120251.
12. Booij, L., Szyf, M., Carballedo, A., Frey, E.M., Morris, D., Dymov, S., et al. DNA methylation of the serotonin transporter gene in peripheral cells and stress-related changes in hippocampal volume: a study in depressed patients and healthy controls. PLoS One, 10(3), 2015, e0119061.
13. Canli, T., Lesch, K.P., Long story short: the serotonin transporter in emotion regulation and social cognition. Nat. Neurosci. 10:9 (2007), 1103–1109.
14. Canli, T., Qiu, M., Omura, K., Congdon, E., Haas, B.W., Amin, Z., et al. Neural correlates of epigenesis. Proc. Natl. Acad. Sci. U. S. A. 103:43 (2006), 16033–16038.
15. Caspi, A., Sugden, K., Moffitt, T.E., Taylor, A., Craig, I.W., Harrington, H., et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:5631 (2003), 386–389.
16. Champagne, F.A., Curley, J.P., Epigenetic mechanisms mediating the long-term effects of maternal care on development. Neurosci. Biobehav. Rev. 33:4 (2009), 593–600.
17. Val158Met genotype in relation to serotonin transporter (SLC6A4) promoter methylation in very preterm children at school age. Front. Behav. Neurosci., 8, 2014, 409.
18. Conradt, E., Hawes, K., Guerin, D., Armstrong, D.A., Marsit, C.J., Tronick, E., et al. The contributions of maternal sensitivity and maternal depressive symptoms to epigenetic processes and neuroendocrine functioning. Child Dev. 87:1 (2016), 73–85.
19. Devlin, A.M., Brain, U., Austin, J., Oberlander, T.F., Prenatal exposure to maternal depressed mood and the MTHFR C677T variant affect SLC6A4 methylation in infants at birth. PLoS One, 5(8), 2010, e12201.
20. Duman, E.A., Canli, T., Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males. Biol. Mood Anxiety Disord., 5(1), 2015, 2.
21. Evans, G.W., Cohen, S., Environmental stress. Stokols, D., Altman, I., (eds.) Handbook of Environmental Psychology, vol. 1, 1978, John Wiley & Sons, New York.
22. Fallgatter, A.J., Bartsch, A.J., Herrmann, M.J., Electrophysiological measurements of anterior cingulate function. J. Neural. Transm. 109:5–6 (2002), 977–988.
23. Frodl, T., Szyf, M., Carballedo, A., Ly, V., Dymov, S., Vaisheva, F., et al. DNA methylation of the serotonin transporter gene (SLC6A4) is associated with brain function involved in processing emotional stimuli. J. Psychiatry Neurosci. 40:5 (2015), 296–305.
24. Gaspar, P., Cases, O., Maroteaux, L., The developmental role of serotonin: news from mouse molecular genetics. Nat. Rev. Neurosci. 4:12 (2003), 1002–1012.
25. Griffiths, B.B., Hunter, R.G., Neuroepigenetics of stress. Neuroscience 275 (2014), 420–435.
26. Gutierrez-Mecinas, M., Trollope, A., Collins, A., Morfett, H., Hesketh, S., Kersante, F., et al. Long-lasting behavioral responses to stress involve a direct interaction of glucocorticoid receptors with ERK1/2-MSK1-Elk-1 signaling. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 13806–13811.
27. Hariri, A.R., Mattay, V.S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., et al. Serotonin transporter genetic variation and the response of the human amygdala. Science 297:5580 (2002), 400–403.
28. Heils, A., Teufel, A., Petri, S., Seemann, M., Bengel, D., Balling, U., et al. Functional promoter and polyadenylation site mapping of the human serotonin (5-HT) transporter gene. J. Neural Transm. 102:3 (1995), 247–254.
29. Hermann, A., Goyal, R., Jeltsch, A., The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites. J. Biol. Chem. 279:46 (2004), 48350–48359.
30. Homberg, J.R., Schubert, D., Gaspar, P., New perspectives on the neurodevelopmental effects of SSRIs. Trends Pharmacol. Sci. 31:2 (2010), 60–65.
31. Hood, S.D., Hince, D.A., Robinson, H., Cirillo, M., Christmas, D., Kaye, J.M., Serotonin regulation of the human stress response. Psychoneuroendocrinology 31:9 (2006), 1087–1097.
32. Horvath, S., Zhang, Y., Langfelder, P., Kahn, R.S., Boks, M.P.M., van Eijk, K., et al. Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol., 13(10), 2012, R97.
33. Hyman, S.E., How adversity gets under the skin. Nat. Neurosci. 12:3 (2009), 241–243.
34. Jaenisch, R., Bird, A., Epigenetic regulation of gene expression: how the genome integrates intrinsic and envirnomental signals. Nat. Genet. 33 (2003), 245–254.
35. Jones, A.L., Thomas, C.K., Maule, A.J., De novo methylation and co-suppression induced by a cytoplasmically replicating plant RNA virus. EMBO J. 17:21 (1998), 6385–6393.
36. Jung, M., Pfeifer, G.P., Aging and DNA methylation. BMC Biol., 13, 2015, 7.
37. Kang, H.J., Kim, J.M., Stewart, R., Kim, S.Y., Bae, K.Y., Kim, S.W., et al. Association of SLC6A4 methylation with early adversity, characteristics and outcomes in depression. Prog. Neurospychopharmacol. Biol. Psychiatry 44 (2013), 23–28.
38. Kinnally, E.L., Lyons, L.A., Abel, K., Mendoza, S., Capitanio, J.P., The effects of experience and genotype on serotonin transporter gene expression in response to maternal separation in infant rhesus macaques. Genes Brain Behav. 7 (2008), 481–486.
39. Kinnally, E.L., Tarara, E.R., Abel, K., Mendoza, S.P., Lyons, L.A., Mason, W.A., et al. Serotonin transporter expression is influenced by early life stress and predicts disinhibited behavior in infant rhesus macaques. Genes Brain Behav. 9 (2009), 45–52.
40. Kinnally, E.L., Capitatnio, J.P., Leibel, R., Deng, L., LeDuc, C., Haghighi, F., et al. Epigenetic regulation of serotonin transporter expression and behavior in infant rhesus macaques. Genes Brain Behav. 9 (2010), 575–582.
41. Koenen, K.C., Uddin, M., Chang, S.C., Aiello, A.E., Wildman, D.E., Goldmann, E., Galea, S., SLC6A4 methylation modifies the effect of the number of traumatic events on risk for posttraumatic stress disorder. Depress. Anxiety 28:8 (2011), 639–647.
42. Lesch, K.P., Heils, A., Riederer, P., The role of neurotransporters in excitotoxicity, neuronal cell death, and other neurodegenerative processes. J. Mol. Med. 74:7 (1996), 365–378.
43. Lesch, K.P., When the serotonin transporter gene meets adversity: the contribution of animal models to understanding epigenetic mechanisms in affective disorders and resilience. Curr. Top. Behav. Neurosci. 7 (2011), 251–280.
44. Lesseur, C., Paquette, A.G., Marsit, C.J., Epigenetic regulation of infant neurobehavioral outcomes. Med. Epigenet. 2:2 (2014), 71–79.
45. Lester, B.M., Tronick, E., Nestler, E., Abel, T., Kosofsky, B., Kuzawa, C.W., et al. Behavioral epigenetics. Ann. N. Y. Acad. Sci. 1226 (2011), 14–33.
46. Lester, B.M., Marsit, C.J., Giarraputo, J., Hawes, K., LaGasse, L.L., Padbury, J.F., Neurobehavior related to epigenetic differences in preterm infants. Epigenomics 7:7 (2015), 1123–1136.
47. Lester, B.M., Conradt, E., Marsit, C., Introduction to the special section on epigenetics. Child Dev. 87:1 (2016), 29–37.
48. Lomelin, D., Jorgenson, E., Risch, N., Human genetic variation recognizes functional elements in noncoding sequence. Genome Res. 20:3 (2010), 311–319.
49. Maze, I., Russo, S.J., Transcriptional mechanisms: underlying addiction-related structural plasticity. Mol. Interv. 10:4 (2010), 219–230.
50. Meaney, M.J., Szyf, M., Maternal care as a model for experience-dependent chromatin plasticity?. Trends Neurosci. 28:9 (2005), 456–463.
51. Meyer-Lindenberg, A., Weinberger, D.R., Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat. Rev. Neurosci. 7:10 (2006), 818–827.
52. Miller, C.A., Sweatt, J.D., Covalent modification of DNA regulates memory formation. Neuron 53:6 (2007), 857–869.
53. Mohammad-Zadeh, L.F., Moses, L., Gwaltney-Brant, S.M., Serotonin: a review. J. Vet. Pharmacol. Ther. 31:3 (2008), 187–199.
54. Montirosso, R., Provenzi, L., Implications of epigenetics and stress regulation on research and developmental care of preterm infants. J. Obstet. Gynecol. Neonatal Nurs. 44:2 (2015), 174–182.
55. Montirosso, R., Provenzi, L., Tavian, D., Morandi, F., Bonanomi, A., Missaglia, S., et al. Social stress regulation in 4-month-old infants: contribution of maternal social engagement and infants’ 5-HTTLPR genotype. Early Hum. Dev. 91:3 (2015), 173–179.
56. Montirosso, R., Provenzi, L., Fumagalli, M., Sirgiovanni, I., Giorda, R., Pozzoli, U., et al. Serotonin transporter gene (SLC6A4) methylation associates with Neonatal Intensive Care Unit stay and 3-month-old temperament in preterm infants. Child Dev. 87:1 (2016), 38–48.
57. Montirosso, R., Provenzi, L., Giorda, R., Fumagalli, M., Morandi, F., Sirgiovanni, I., et al. SLC6A4 promoter region methylation and socio-emotional stress response in very preterm and full-term infants. Epigenomics 8:7 (2016), 895–907.
58. Nan, X., Cross, S., Bird, A., Gene silencing by methyl-CpG-binding proteins. Novartis Found. Symp. 214 (1998), 6–16.
59. Nikolova, Y.S., Koenen, K.C., Galea, S., Wang, C.M., Seney, M.L., Sibille, E., et al. Beyond genotype: serotonin transporter epigenetic modification predicts human brain function. Nat. Neurosci. 17:9 (2014), 1153–1155.
60. Oberlander, T.F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S., Devlin, A.M., Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 3:2 (2008), 97–106.
61. Okano, M., Bell, D.W., Haber, D.A., Li, E., DNA methyltransferases DNMT3a and NDMT3b are essential for de novo methylation and mammalian development. Cell 99:3 (1999), 247–257.
62. Olsson, C.A., Foley, D.L., Parkinson-Bates, M., Byrnes, G., McKenzie, M., Patton, G.C., et al. Prospects for epigenetic research within cohort studies of psychological disorder: a pilot investigation of a peripheral cell marker of epigenetic risk for depression. Biol. Psychol. 83 (2010), 159–165.
63. Ouellet-Morin, I., Wong, C.C., Danese, A., Pariante, C.M., Papadopoulos, A.S., Mill, J., Arseneault, L., Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins. Psychol. Med. 43:9 (2013), 1813–1823.
64. Pauli-Pott, U., Friedl, S., Hinney, A., Hebebrand, J., Serotonin transporter gene polymorphism (5-HTTLPR), environmental conditions, and developing negative emotionality and fear in early childhood. J. Neural Transm. 116:4 (2009), 503–512.
65. Pezawas, L., Meyer-Lindenberg, A., Drabant, E.M., Verchinski, B.A., Munoz, K.E., Kolachana, B.S., et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat. Neurosci. 8:6 (2005), 828–834.
66. Philibert, R., Madan, A., Andersen, A., Cadoret, R., Packer, H., Sandhu, H., Serotonin transporter mRNA levels are associated with the methylation of an upstream CpG island. Am. J. Med. Genet. B Neuropsychiatr. Genet. 144B:1 (2007), 101–105.
67. Pluess, M., Velders, F.P., Belsky, J., Van IJzendoorn, M.H., Bakermans-Kranenburg, M.J., Jaddoe, V.W.V., et al. Serotonin transporter polymorphism moderates effects of prenatal maternal anxiety on infant negative emotionality. Biol. Psychiatry 69:6 (2011), 520–525.
68. Provenzi, L., Barello, S., Beavioral epigenetics of family-centered care in the neonatal intensive care unit. JAMA Pediatr. 169:7 (2015), 697–698.
69. Provenzi, L., Montirosso, R., Epigenethics in the neonatal intensive care unit: conveying complexity in health care for preterm children?. JAMA Pediatr. 169:7 (2015), 617–618.
70. Provenzi, L., Fumagalli, M., Sirgiovanni, I., Giorda, R., Pozzoli, U., Morandi, F., et al. Pain-related stress during the Neonatal Intensive Care Unit stay and SLC6A4 methylation in very preterm infants. Front. Behav. Neurosci., 9, 2015, 99.
71. Rausch, J.L., Johnson, M.E., Li, J., Hutcheson, J., Carr, B.M., Corley, K.M., et al. Serotonin transport kinetics correlated between human platelets and brain synaptosomes. Psychopharmacology (Berl.) 180:3 (2005), 391–398.
72. Richardson, S.S., Daniels, C.R., Gillman, M.W., Golden, J.L., Kukla, R., Kuzawa, C., Rich-Edwards, J., Don't blame the mothers. Nature 512 (2014), 131–132.
73. Sirota, L.A., Greenberg, B.D., Murphy, D.L., Hamer, D.H., Non-linear association between the serotonin transporter promoter polymorphism and neuroticism: a caution against using extreme samples to identify quantitative trait loci. Psychiatr. Genet. 9:1 (1999), 35–38.
74. Stankiewicz, A.M., Swiergiel, A.H., Lisowski, P., Epigenetics of stress adaptation in the brain. Brain Res. Bull. 98 (2013), 76–92.
75. Stroud, L.R., Papandonatos, G.D., Salisbury, A.L., Phipps, M.G., Huestis, M.A., Niaura, R., et al. Epigenetic regulation of placental NR3C1: mechanism underlying prenatal programming of infant neurobehavior by maternal smoking?. Child Dev. 87:1 (2016), 49–60.
76. Sugawara, H., Bundo, M., Ishigooka, J., Iwamoto, K., Kato, T., Epigenetic regulation of serotonin transporter in psychiatric disorders. J. Genet. Genomics 40:7 (2013), 325–329.
77. Szyf, M., The implications of a life-long dynamic epigenome. Epigenomics 1:1 (2009), 9–12.
78. Thompson, T.M., Sharfi, D., Lee, M., Yrigollen, C.M., Naumova, O.Y., Grigorenko, E.L., Comparison of whole-genome DNA methylation patterns in whole blood, saliva, and lymphoblastoid cell lines. Behav. Genet. 43:2 (2013), 168–176.
79. Torres, G.E., Gainetdinov, R.R., Caron, M.G., Plasma membrane monoamine transporters: structure, regulation and function. Nat. Rev. Neurosci. 4:1 (2003), 13–25.
80. Tronick, E., Als, H., Adamson, L., Wise, S., Brazelton, T.B., The infant's response to entrapment between contradictory messages in face-to-face interaction. J. Am. Acad. Child Psychiatry 17:1 (1978), 1–13.
81. Tsankova, N., Renthal, W., Kumar, A., Nestler, E.J., Epigenetic regulation in psychaitric disorders. Nat. Rev. Neurosci. 8 (2007), 355–367.
82. Uebelhack, R., Franke, L., Herold, N., Plotkin, M., Amthauer, H., Felix, R., Brain and platelet serotonin transporter in humans-correlation between [123I]-ADAM SPECT and serotonergic measurements in platelets. Neurosci. Lett. 406:3 (2006), 153–158.
83. van der Knaap, L.J., Riese, H., Hudziak, J.J., Verbiest, M.M.P.J., Verhulst, F.C., Oldehinkel, A.J., van Oort, F.V.A., Adverse life events and allele-specific methylation of the serotonin transporter gene (SLC6A4) in adolescents. Psychosom. Med. 77:3 (2015), 246–255.
84. Vijayendran, M., Beach, S.R., Plume, J.M., Brody, G.H., Philibert, R.A., Effects of genotype and child abuse on DNA methylation and gene expression at the serotonin transporter. Front. Psychiatry, 3, 2012, 55.
85. Wang, D., Liu, X., Zhou, Y., Xie, H., Hong, X., Tsai, H.J., et al. Individual variation and longitudinal pattern of genome-wide DNA methylation from birth to the first two years of life. Epigenetics 7:6 (2012), 594–605.
86. Wankerl, M., Miller, R., Kirschbaum, C., Hennig, J., Stalder, T., Alexander, N., Effects of genetic and early environmental risk factors for depression on serotonin transporter expression and methylation profiles. Transl. Psychiatry, 4, 2014, e402.
87. Weaver, I.C.G., Cervoni, N., Champagne, F.A., D'Alessio, A.C., Sharma, S., Seckl, J.R., et al. Epigenetic programming by maternal behavior. Nat. Neurosci. 7:8 (2004), 847–854.