The long-term impact of adverse caregiving environments on epigenetic modifications and telomeres

Frontiers in Behavioral Neuroscience

Volumn 9, Issue APR, 2015, Pages

  Blaze, Jennifer ^a   Asok, Arun ^a   Roth, Tania L ^a  

^a UNIVERSITY OF DELAWARE   (United States)

Author keywords

DNA methylation; Early life stress; Maltreatment; miRNAs; Telomeres

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; CORTICOTROPIN RELEASING FACTOR; DOPAMINE 1 RECEPTOR; DOPAMINE 2 RECEPTOR; GLUCOCORTICOID RECEPTOR; HISTONE DEACETYLASE; MICRORNA; MICRORNA 16; MICRORNA 504; MICRORNA LET 7A; SEROTONIN TRANSPORTER; TELOMERASE REVERSE TRANSCRIPTASE; TELOMERIC REPEAT BINDING FACTOR 1; TELOMERIC REPEAT BINDING FACTOR 2; UNCLASSIFIED DRUG;

5HTT GENE; BDNF GENE; CAREGIVER; DNA METHYLATION; EARLY LIFE STRESS; ENVIRONMENTAL FACTOR; EPIGENETICS; FKBP5 GENE; GENE; GENE EXPRESSION REGULATION; GENE FUNCTION; GENOTYPE ENVIRONMENT INTERACTION; GR GENE; HIPPOCAMPUS; HUMAN; MATERNAL DEPRIVATION; MENTAL HEALTH; NONHUMAN; NR3C1 GENE; NUCLEUS ACCUMBENS; PERIPHERAL NERVOUS SYSTEM; PREFRONTAL CORTEX; PROTEIN FUNCTION; REVIEW; RNA PROCESSING; TELOMERE; TELOMERE HOMEOSTASIS; TELOMERE SHORTENING; TRANSCRIPTION REGULATION; UPREGULATION;

EID: 84931067775     PISSN: 16625153     EISSN: None     Source Type: Journal    
DOI: 10.3389/fnbeh.2015.00079     Document Type: Review

References (123)

1. Adlakha, Y. K., and Saini, N. (2014). Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128. Mol. Cancer 13:33. doi: 10.1186/1476-4598-13-33
2. Ambros, V. (2004). The functions of animal microRNAs. Nature 431, 350-355. doi: 10.1038/nature02871
3. Anda, R. F., Felitti, V. J., Bremner, J. D., Walker, J. D., Whitfield, C., Perry, B. D., et al. (2006). The enduring effects of abuse and related adverse experiences in childhood. Eur. Arch. Psychiatry Clin. Neurosci. 256, 174-186. doi: 10.1007/s00406-005-0624-4
4. Asok, A., Bernard, K., Rosen, J. B., Dozier, M., and Roth, T. L. (2014). Infant-caregiver experiences alter telomere length in the brain. PLoS One 9:e101437. doi: 10.1371/journal.pone.0101437
5. Asok, A., Bernard, K., Roth, T. L., Rosen, J. B., and Dozier, M. (2013). Parental responsiveness moderates the association between early-life stress and reduced telomere length. Dev. Psychopathol. 25, 577-585. doi: 10.1017/s0954579413000011
6. Bai, M., Zhu, X., Zhang, Y., Zhang, S., Zhang, L., Xue, L., et al. (2012). Abnormal hippocampal BDNF and miR-16 expression is associated with depression-like behaviors induced by stress during early life. PLoS One 7:e46921. doi: 10.1371/journal.pone.0046921
7. Bai, M., Zhu, X.-Z., Zhang, Y., Zhang, S., Zhang, L., Xue, L., et al. (2014). Anhedonia was associated with the dysregulation of hippocampal HTR4 and microRNA Let-7a in rats. Physiol. Behav. 129, 135-141. doi: 10.1016/j.physbeh.2014.02.035
8. Barrett, E. L., and Richardson, D. S. (2011). Sex differences in telomeres and lifespan. Aging Cell 10, 913-921. doi: 10.1111/j.1474-9726.2011.00741.x
9. Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism and function. Cell 116, 281-297. doi: 10.1016/S0092-8674(04)00045-5
10. Baur, J. A., Zou, Y., Shay, J. W., and Wright, W. E. (2001). Telomere position effect in human cells. Science 292, 2075-2077. doi: 10.1126/science.1062329
11. Beach, S. R. H., Brody, G. H., Todorov, A. A., Gunter, T. D., and Philibert, R. A. (2010). 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, 710-713. doi: 10.1002/ajmg.b.31028
12. Beach, S. R., Brody, G. H., Todorov, A. A., Gunter, T. D., and Philibert, R. A. (2011). 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, 83-87. doi: 10.1097/psy.0b013e3181fdd074
13. Beach, S. R., Lei, M. K., Brody, G. H., Yu, T., and Philibert, R. A. (2014). Nonsupportive parenting affects telomere length in young adulthood among African Americans: Mediation through substance use. J. Fam. Psychol. 28, 967-972. doi: 10.1037/fam0000039
14. Beery, A. K., Lin, J., Biddle, J. S., Francis, D. D., Blackburn, E. H., and Epel, E. S. (2012). Chronic stress elevates telomerase activity in rats. Biol. Lett. 8, 1063-1066. doi: 10.1098/rsbl.2012.0747
15. Benetti, R., García-Cao, M., and Blasco, M. A. (2007). Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nat. Genet. 39, 243-250. doi: 10.1038/ng1952
16. Blackburn, E. H. (1991). Structure and function of telomeres. Nature 350, 569-573. doi: 10.1038/350569a0
17. Blasco, M. A. (2007). The epigenetic regulation of mammalian telomeres. Nat. Rev. Genet. 8, 299-309. doi: 10.1038/nrg2047
18. Blaze, J., and Roth, T. L. (2012). Epigenetic mechanisms in learning and memory. Wiley Interdiscip. Rev. Cogn. Sci.4, 105-115. doi: 10.1002/wcs.1205
19. Blaze, J., and Roth, T. L. (2013). Exposure to caregiver maltreatment alters expression levels of epigenetic regulators in the medial prefrontal cortex. Int. J. Dev. Neurosci. 31, 804-810. doi: 10.1016/j.ijdevneu.2013.10.001
20. Blaze, J., Scheuing, L., and Roth, T. L. (2013). Differential methylation of genes in the medial prefrontal cortex of developing and adult rats following exposure to maltreatment or nurturing care during infancy. Dev. Neurosci. 35, 306-316. doi: 10.1159/000350716
21. Botha, M., Grace, L., Bugarith, K., Russell, V. A., Kidd, M., Seedat, S., et al. (2012). The impact of voluntary exercise on relative telomere length in a rat model of developmental stress. BMC Res. Notes 5:697. doi: 10.1186/1756-0500-5-697
22. Brazauskas, P., and Kriaucionis, S. (2014). DNA modifications: another stable base in DNA. Nat. Chem. 6, 1031-1033. doi: 10.1038/nchem.2115
23. Buxton, J. L., Suderman, M., Pappas, J. J., Borghol, N., Mcardle, W., Blakemore, A. I., et al. (2014). Human leukocyte telomere length is associated with DNA methylation levels in multiple subtelomeric and imprinted loci.Sci. Rep. 4:4954. doi: 10.1038/srep04954
24. Caldji, C., Tannenbaum, B., Sharma, S., Francis, D., Plotsky, P. M., and Meaney, M. J. (1998). Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proc. Natl. Acad. Sci. U S A 95, 5335-5340. doi: 10.1073/pnas.95.9.5335
25. Celli, G. B., and de Lange, T. (2005). DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat. Cell Biol. 7, 712-718. doi: 10.1038/ncb1275
26. Cesare, A. J., and Reddel, R. R. (2010). Alternative lengthening of telomeres: models, mechanisms and implications. Nat. Rev. Genet. 11, 319-330. doi: 10.1038/nrg2763
27. Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T., Qin, J., et al. (2008). MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320, 1224-1229. doi: 10.1126/science.1153252
28. Chen, L. H., Chiou, G. Y., Chen, Y. W., Li, H. Y., and Chiou, S. H. (2010). MicroRNA and aging: a novel modulator in regulating the aging network. Ageing Res. Rev. 9(Suppl. 1), S59-S66. doi: 10.1016/j.arr.2010.08.002
29. Chen, S. H., Epel, E. S., Mellon, S. H., Lin, J., Reus, V. I., Rosser, R., et al. (2014). Adverse childhood experiences and leukocyte telomere maintenance in depressed and healthy adults. J. Affect. Disord. 169, 86-90. doi: 10.1016/j.jad.2014.07.035
30. Chen, J., Evans, A. N., Liu, Y., Honda, M., Saavedra, J. M., and Aguilera, G. (2012). Maternal deprivation in rats is associated with corticotrophin-releasing hormone (CRH) promoter hypomethylation and enhances CRH transcriptional responses to stress in adulthood. J. Neuroendocrinol. 24, 1055-1064. doi: 10.1111/j.1365-2826.2012.02306.x
31. Cherif, H., Tarry, J. L., Ozanne, S. E., and Hales, C. N. (2003). Ageing and telomeres: a study into organ- and gender-specific telomere shortening. Nucleic Acids Res. 31, 1576-1583. doi: 10.1093/nar/gkg208
32. Chilton, W. L., Marques, F. Z., West, J., Kannourakis, G., Berzins, S. P., O'brien, B. J., et al. (2014). Acute exercise leads to regulation of telomere-associated genes and microRNA expression in immune cells. PLoS One 9:e92088. doi: 10.1371/journal.pone.0092088
33. Cicchetti, D., and Toth, S. L. (2005). Child maltreatment. Annu. Rev. Clin. Psychol. 1, 409-438. doi: 10.1146/annurev.clinpsy.1.102803.144029
34. Dabouras, V., Rothermel, A., Reininger-Mack, A., Wien, S. L., Layer, P. G., and Robitzki, A. A. (2004). Exogenous application of glucose induces aging in rat cerebral oligodendrocytes as revealed by alteration in telomere length.Neurosci. Lett. 368, 68-72. doi: 10.1016/j.neulet.2004.06.066
35. D'Addario, C., Dell'osso, B., Palazzo, M. C., Benatti, B., Lietti, L., Cattaneo, E., et al. (2012). Selective DNA methylation of BDNF promoter in bipolar disorder: differences among patients with BDI and BDII.Neuropsychopharmacology 37, 1647-1655. doi: 10.1038/npp.2012.10
36. de Lange, T., Lundbald, V., and Blackburn, E. (eds) (2006). Telomeres. 2nd Edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
37. Dinami, R., Ercolani, C., Petti, E., Piazza, S., Ciani, Y., Sestito, R., et al. (2014). miR-155 drives telomere fragility in human breast cancer by targeting TRF1. Cancer Res. 74, 4145-4156. doi: 10.1158/0008-5472.can-13-2038
38. Drury, S. S., Esteves, K., Hatch, V., Woodbury, M., Borne, S., Adamski, A., et al. (2015). Setting the trajectory: racial disparities in newborn telomere length. J. Pediatr. doi: 10.1016/j.jpeds.2015.01.003. [Epub ahead of print].
39. Drury, S. S., Mabile, E., Brett, Z. H., Esteves, K., Jones, E., Shirtcliff, E. A., et al. (2014). The association of telomere length with family violence and disruption. Pediatrics 134, e128-e137. doi: 10.1542/peds.2013-3415
40. Drury, S. S., Theall, K., Gleason, M. M., Smyke, A. T., De Vivo, I., Wong, J. Y., et al. (2012). Telomere length and early severe social deprivation: linking early adversity and cellular aging. Mol. Psychiatry 17, 719-727. doi: 10.1038/mp.2011.53
41. Edwards, V. J., Holden, G. W., Felitti, V. J., and Anda, R. F. (2003). Relationship between multiple forms of childhood maltreatment and adult mental health in community respondents: results from the adverse childhood experiences study. Am. J. Psychiatry 160, 1453-1460. doi: 10.1176/appi.ajp.160.8.1453
42. Eitan, E., Hutchison, E. R., and Mattson, M. P. (2014). Telomere shortening in neurological disorders: an abundance of unanswered questions. Trends Neurosci. 37, 256-263. doi: 10.1016/j.tins.2014.02.010
43. Enokido, M., Suzuki, A., Sadahiro, R., Matsumoto, Y., Kuwahata, F., Takahashi, N., et al. (2014). Parental care influences leukocyte telomere length with gender specificity in parents and offsprings. BMC Psychiatry 14:277. doi: 10.1186/s12888-014-0277-9
44. Epel, E. S., Blackburn, E. H., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., et al. (2004). Accelerated telomere shortening in response to life stress. Proc. Natl. Acad. Sci. U S A 101, 17312-17315. doi: 10.1073/pnas.0407162101
45. Essex, M. J., Boyce, W. T., Hertzman, C., Lam, L. L., Armstrong, J. M., Neumann, S. M. A., et al. (2013). Epigenetic vestiges of early developmental adversity: childhood stress exposure and DNA methylation in adolescence. Child Dev. 84, 58-75. doi: 10.1111/j.1467-8624.2011.01641.x
46. Fossel, M. (2012). Use of telomere length as a biomarker for aging and age-related disease. Curr. Transl. Geriatr. Exp. Gerontol. Rep. 1, 121-127. doi: 10.1007/s13670-012-0013-6
47. Franklin, T. B., Russig, H., Weiss, I. C., Gräff, J., Linder, N., Michalon, A., et al. (2010). Epigenetic transmission of the impact of early stress across generations. Biol. Psychiatry 68, 408-415. doi: 10.1016/j.biopsych.2010.05.036
48. Fuchikami, M., Morinobu, S., Segawa, M., Okamoto, Y., Yamawaki, S., Ozaki, N., et al. (2011). DNA methylation profiles of the Brain-Derived Neurotrophic Factor (BDNF) gene as a potent diagnostic biomarker in major depression. PLoS One 6:e23881. doi: 10.1371/journal.pone.0023881
49. Galati, A., Micheli, E., and Cacchione, S. (2013). Chromatin structure in telomere dynamics. Front. Oncol. 3:46. doi: 10.3389/fonc.2013.00046
50. Garcia-Cao, M., O'sullivan, R., Peters, A. H., Jenuwein, T., and Blasco, M. A. (2004). Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat. Genet. 36, 94-99. doi: 10.1038/ng1278
51. Gonzalo, S., Jaco, I., Fraga, M. F., Chen, T., Li, E., Esteller, M., et al. (2006). DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat. Cell Biol. 8, 416-424. doi: 10.1038/ncb1386
52. Guintivano, J., Brown, T., Newcomer, A., Jones, M., Cox, O., Maher, B. S., et al. (2014). Identification and replication of a combined epigenetic and genetic biomarker predicting suicide and suicidal behaviors. Am. J. Psychiatry 171, 1287-1296. doi: 10.1176/appi.ajp.2014.14010008
53. Gunnar, M. R. (1998). Quality of early care and buffering of neuroendocrine stress reactions: potential effects on the developing human brain. Prev. Med. 27, 208-211. doi: 10.1006/pmed.1998.0276
54. Hao, Y., Huang, W., Nielsen, D. A., and Kosten, T. A. (2011). Litter gender composition and sex affect maternal behavior and DNA methylation levels of the oprm1 gene in rat offspring. Front. Psychiatry 2:21. doi: 10.3389/fpsyt.2011.00021
55. Kaffman, A., and Meaney, M. J. (2007). Neurodevelopmental sequelae of postnatal maternal care in rodents: clinical and research implications of molecular insights. J. Child Psychol. Psychiatry 48, 224-244. doi: 10.1111/j.1469-7610.2007.01730.x
56. Kananen, L., Surakka, I., Pirkola, S., Suvisaari, J., Lönnqvist, J., Peltonen, L., et al. (2010). Childhood adversities are associated with shorter telomere length at adult age both in individuals with an anxiety disorder and controls.PLoS One 5:e10826. doi: 10.1371/journal.pone.0010826
57. Karlseder, J., Kachatrian, L., Takai, H., Mercer, M., Hingorani, S., Jacks, T., et al. (2003). Targeted deletion reveals an essential function for the telomere length regulator Trf1. Mol. Cell Biol. 23, 6533-6541. doi: 10.1128/mcb.23.18.6533-6541.2003
58. Kenna, G. A., Roder-Hanna, N., Leggio, L., Zywiak, W. H., Clifford, J., Edwards, S., et al. (2012). Association of the 5-HTT gene-linked promoter region (5-HTTLPR) polymorphism with psychiatric disorders: review of psychopathology and pharmacotherapy. Pharmgenomics. Pers. Med. 5, 19-35. doi: 10.2147/pgpm.s23462
59. Khulan, B., Manning, J. R., Dunbar, D. R., Seckl, J. R., Raikkonen, K., Eriksson, J. G., et al. (2014). Epigenomic profiling of men exposed to early-life stress reveals DNA methylation differences in association with current mental state. Transl. Psychiatry 4:e448. doi: 10.1038/tp.2014.94
60. Kiecolt-Glaser, J. K., Gouin, J. P., Weng, N. P., Malarkey, W. B., Beversdorf, D. Q., and Glaser, R. (2011). Childhood adversity heightens the impact of later-life caregiving stress on telomere length and inflammation. Psychosom. Med. 73, 16-22. doi: 10.1097/PSY.0b013e31820573b6
61. Kim, S.-H., Beausejour, C., Davalos, A. R., Kaminker, P., Heo, S.-J., and Campisi, J. (2004). TIN2 mediates functions of TRF2 at human telomeres. J. Biol. Chem. 279, 43799-43804. doi: 10.1074/jbc.m408650200
62. Kinnally, E. L., Capitanio, J. P., Leibel, R., Deng, L., LeDuc, C., Haghighi, F., et al. (2010). Epigenetic regulation of serotonin transporter expression and behavior in infant rhesus macaques. Genes Brain Behav. 9, 575-582. doi: 10.1111/j.1601-183x.2010.00588.x
63. Klengel, T., Mehta, D., Anacker, C., Rex-Haffner, M., Pruessner, J. C., Pariante, C. M., et al. (2013). Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat. Neurosci. 16, 33-41. doi: 10.1038/nn.3275
64. Kosten, T. A., Huang, W., and Nielsen, D. A. (2014). Sex and litter effects on anxiety and DNA methylation levels of stress and neurotrophin genes in adolescent rats. Dev. Psychobiol. 56, 392-406. doi: 10.1002/dev.21106
65. Labonté, B., Suderman, M., Maussion, G., Navaro, L., Yerko, V., Mahar, I., et al. (2012). Genome-wide epigenetic regulation by early-life trauma. Arch. Gen. Psychiatry 69, 722-731. doi: 10.1001/archgenpsychiatry.2011.2287
66. Lei, M., Podell, E. R., and Cech, T. R. (2004). Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat. Struct. Mol. Biol. 11, 1223-1229. doi: 10.1038/nsmb867
67. Li, X., Wei, W., Ratnu, V. S., and Bredy, T. W. (2013). On the potential role of active DNA demethylation in establishing epigenetic states associated with neural plasticity and memory. Neurobiol. Learn. Mem. 105, 125-132. doi: 10.1016/j.nlm.2013.06.009
68. Li, X., Wei, W., Zhao, Q.-Y., Widagdo, J., Baker-Andresen, D., Flavell, C. R., et al. (2014). Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation. Proc. Natl. Acad. Sci. U S A 111, 7120-7125. doi: 10.1073/pnas.1318906111
69. Liu, D., Diorio, J., Day, J. C., Francis, D. D., and Meaney, M. J. (2000). Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat. Neurosci. 3, 799-806. doi: 10.1038/77702
70. Liu, D., Diorio, J., Tannenbaum, B., Caldji, C., Francis, D., Freedman, A., et al. (1997). Maternal care, hippocampal glucocorticoid receptors and hypothalamic-pituitary-adrenal responses to stress. Science 277, 1659-1662. doi: 10.1126/science.277.5332.1659
71. Lupien, S. J., McEwen, B. S., Gunnar, M. R., and Heim, C. (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat. Rev. Neurosci. 10, 434-445. doi: 10.1038/nrn2639
72. Ma, D. K., Guo, J. U., Ming, G. L., and Song, H. (2009a). DNA excision repair proteins and Gadd45 as molecular players for active DNA demethylation. Cell Cycle 8, 1526-1531. doi: 10.4161/cc.8.10.8500
73. Ma, D. K., Jang, M. H., Guo, J. U., Kitabatake, Y., Chang, M. L., Pow-Anpongkul, N., et al. (2009b). Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323, 1074-1077. doi: 10.1126/science.1166859
74. Martinez, P., Thanasoula, M., Carlos, A. R., Gómez-López, G., Tejera, A. M., Schoeftner, S., et al. (2010). Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites. Nat. Cell Biol. 12, 768-780. doi: 10.1038/ncb2081
75. Martinowich, K., Manji, H., and Lu, B. (2007). New insights into BDNF function in depression and anxiety. Nat. Neurosci. 10, 1089-1093. doi: 10.1038/nn1971
76. Mather, K. A., Jorm, A. F., Parslow, R. A., and Christensen, H. (2011). Is telomere length a biomarker of aging? A review. J. Gerontol. A Biol. Sci. Med. Sci. 66, 202-213. doi: 10.1093/gerona/glq180
77. McCord, R. A., and Broccoli, D. (2008). Telomeric chromatin: roles in aging, cancer and hereditary disease. Mutat. Res. 647, 86-93. doi: 10.1016/j.mrfmmm.2008.08.005
78. McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., et al. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat. Neurosci. 12, 342-348. doi: 10.1038/nn.2270
79. McGowan, P. O., Suderman, M., Sasaki, A., Huang, T. C., Hallett, M., Meaney, M. J., et al. (2011). Broad epigenetic signature of maternal care in the brain of adult rats. PLoS One 6:e14739. doi: 10.1371/journal.pone.0014739
80. Meaney, M. J., Diorio, J., Francis, D., Widdowson, J., LaPlante, P., Caldji, C., et al. (1996). Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress. Dev. Neurosci. 18, 49-72. doi: 10.1159/000111396
81. Mitomo, S., Maesawa, C., Ogasawara, S., Iwaya, T., Shibazaki, M., Yashima-Abo, A., et al. (2008). Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines. Cancer Sci. 99, 280-286. doi: 10.1111/j.1349-7006.2007.00666.x
82. Moore, L. D., Le, T., and Fan, G. (2013). DNA methylation and its basic function. Neuropsychopharmacology 38, 23-38. doi: 10.1038/npp.2012.112
83. Murgatroyd, C., Patchev, A. V., Wu, Y., Micale, V., Bockmühl, Y., Fischer, D., et al. (2009). Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat. Neurosci. 12, 1559-1566. doi: 10.1038/nn.2436
84. Murgatroyd, C., and Spengler, D. (2014). Polycomb binding precedes early-life stress responsive DNA methylation at the AVP enhancer. PLoS One 9:e90277. doi: 10.1371/journal.pone.0090277
85. Murphy, T. M., Mullins, N., Ryan, M., Foster, T., Kelly, C., McClelland, R., et al. (2013). Genetic variation in DNMT3B and increased global DNA methylation is associated with suicide attempts in psychiatric patients. Genes Brain Behav. 12, 125-132. doi: 10.1111/j.1601-183x.2012.00865.x
86. Naumova, O. Y., Lee, M., Koposov, R., Szyf, M., Dozier, M., and Grigorenko, E. L. (2012). Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents. Dev. Psychopathol. 24, 143-155. doi: 10.1017/s0954579411000605
87. Oberlander, T. F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S., and Devlin, A. M. (2008). Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 3, 97-106. doi: 10.4161/epi.3.2.6034
88. O'Donovan, A., Epel, E., Lin, J., Wolkowitz, O., Cohen, B., Maguen, S., et al. (2011). Childhood trauma associated with short leukocyte telomere length in posttraumatic stress disorder. Biol. Psychiatry 70, 465-471. doi: 10.1016/j.biopsych.2011.01.035
89. Okuda, K., Bardeguez, A., Gardner, J. P., Rodriguez, P., Ganesh, V., Kimura, M., et al. (2002). Telomere length in the newborn. Pediatr. Res. 52, 377-381. doi: 10.1203/01.pdr.0000022341.72856.72
90. Perroud, N., Paoloni-Giacobino, A., Prada, P., Olié, E., Salzmann, A., Nicastro, R., et al. (2011). Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Transl. Psychiatry 1:e59. doi: 10.1038/tp.2011.60
91. Perroud, N., Salzmann, A., Prada, P., Nicastro, R., Hoeppli, M. E., Furrer, S., et al. (2013). Response to psychotherapy in borderline personality disorder and methylation status of the BDNF gene. Transl. Psychiatry3:e207. doi: 10.1038/tp.2012.140
92. Price, L. H., Kao, H. T., Burgers, D. E., Carpenter, L. L., and Tyrka, A. R. (2013). Telomeres and early-life stress: an overview. Biol. Psychiatry 73, 15-23. doi: 10.1016/j.biopsych.2012.06.025
93. Provençal, N., Suderman, M. J., Guillemin, C., Massart, R., Ruggiero, A., Wang, D., et al. (2012). The signature of maternal rearing in the methylome in rhesus macaque prefrontal cortex and T cells. J. Neurosci. 32, 15626-15642. doi: 10.1523/JNEUROSCI.1470-12.2012
94. Riethman, H., Ambrosini, A., Castaneda, C., Finklestein, J., Hu, X.-L., Mudunuri, U., et al. (2004). Mapping and initial analysis of human subtelomeric sequence assemblies. Genome Res. 14, 18-28. doi: 10.1101/gr.1245004
95. Roth, T. L., Lubin, F. D., Funk, A. J., and Sweatt, J. D. (2009). Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol. Psychiatry 65, 760-769. doi: 10.1016/j.biopsych.2008.11.028
96. Roth, T. L., Matt, S., Chen, K., and Blaze, J. (2014). Bdnf DNA methylation modifications in the hippocampus and amygdala of male and female rats exposed to different caregiving environments outside the homecage. Dev. Psychobiol. 56, 1755-1763. doi: 10.1002/dev.21218
97. Roth, T. L., and Sullivan, R. M. (2005). Memory of early maltreatment: neonatal behavioral and neural correlates of maternal maltreatment within the context of classical conditioning. Biol. Psychiatry 57, 823-831. doi: 10.1016/j.biopsych.2005.01.032
98. Samassekou, O., Gadji, M., Drouin, R., and Yan, J. (2010). Sizing the ends: normal length of human telomeres. Ann. Anat. 192, 284-291. doi: 10.1016/j.aanat.2010.07.005
99. Sanchez, M. M. (2006). The impact of early adverse care on HPA axis development: nonhuman primate models.Horm. Behav. 50, 623-631. doi: 10.1016/j.yhbeh.2006.06.012
100. Santambrogio, F., Gandellini, P., Cimino-Reale, G., Zaffaroni, N., and Folini, M. (2014). MicroRNA-dependent regulation of telomere maintenance mechanisms: a field as much unexplored as potentially promising. Curr. Pharm. Des. 20, 6404-6421. doi: 10.2174/1381612820666140630095918
101. Shalev, I. (2012). Early life stress and telomere length: investigating the connection and possible mechanisms.Bioessays 34, 943-952. doi: 10.1002/bies.201200084
102. Shalev, I., Moffitt, T. E., Braithwaite, A. W., Danese, A., Fleming, N. I., Goldman-Mellor, S., et al. (2014). Internalizing disorders and leukocyte telomere erosion: a prospective study of depression, generalized anxiety disorder and post-traumatic stress disorder. Mol. Psychiatry 19, 1163-1170. doi: 10.1038/mp.2013.183
103. Shalev, I., Moffitt, T., Sugden, K., Williams, B., Houts, R. M., Danese, A., et al. (2013). Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study. Mol. Psychiatry 18, 576-581. doi: 10.1038/mp.2012.32
104. Slagboom, P. E., Droog, S., and Boomsma, D. I. (1994). Genetic determination of telomere size in humans: a twin study of three age groups. Am. J. Hum. Genet. 55, 876-882.
105. Teicher, M. H., Andersen, S. L., Polcari, A., Anderson, C. M., Navalta, C. P., and Kim, D. M. (2003). The neurobiological consequences of early stress and childhood maltreatment. Neurosci. Biobehav. Rev. 27, 33-44. doi: 10.1016/s0149-7634(03)00007-1
106. Theall, K. P., Brett, Z. H., Shirtcliff, E. A., Dunn, E. C., and Drury, S. S. (2013). Neighborhood disorder and telomeres: connecting children's exposure to community level stress and cellular response. Soc. Sci. Med. 85, 50-58. doi: 10.1016/j.socscimed.2013.02.030
107. Thomas, P., O' Callaghan, N. J., and Fenech, M. (2008). Telomere length in white blood cells, buccal cells and brain tissue and its variation with ageing and Alzheimer's disease. Mech. Ageing Dev. 129, 183-190. doi: 10.1016/j.mad.2007.12.004
108. Toth, S. L., Gravener-Davis, J. A., Guild, D. J., and Cicchetti, D. (2013). Relational interventions for child maltreatment: past, present and future perspectives. Dev. Psychopathol. 25, 1601-1617. doi: 10.1017/s0954579413000795
109. Tottenham, N. (2014). The importance of early environments for neuro-affective development. Curr. Top. Behav. Neurosci. 16, 109-129. doi: 10.1007/7854_2013_254
110. Tyrka, A. R., Price, L. H., Kao, H. T., Porton, B., Marsella, S. A., and Carpenter, L. L. (2010). Childhood maltreatment and telomere shortening: preliminary support for an effect of early stress on cellular aging. Biol. Psychiatry 67, 531-534. doi: 10.1016/j.biopsych.2009.08.014
111. Tyrka, A. R., Price, L. H., Marsit, C., Walters, O. C., and Carpenter, L. L. (2012). Childhood adversity and epigenetic modulation of the leukocyte glucocorticoid receptor: preliminary findings in healthy adults. PLoS One 7:e30148. doi: 10.1371/journal.pone.0030148
112. Uchida, S., Hara, K., Kobayashi, A., Funato, H., Hobara, T., Otsuki, K., et al. (2010). Early life stress enhances behavioral vulnerability to stress through the activation of REST4-mediated gene transcription in the medial prefrontal cortex of rodents. J. Neurosci. 30, 15007-15018. doi: 10.1523/jneurosci.1436-10.2010
113. von Zglinicki, T., and Martin-Ruiz, C. M. (2005). Telomeres as biomarkers for ageing and age-related diseases. Curr. Mol. Med. 5, 197-203. doi: 10.2174/1566524053586545
114. Wang, A., Nie, W., Li, H., Hou, Y., Yu, Z., Fan, Q., et al. (2014). Epigenetic upregulation of corticotrophin-releasing hormone mediates postnatal maternal separation-induced memory deficiency. PLoS One 9:e94394. doi: 10.1371/journal.pone.0094394
115. Weaver, I. C., Cervoni, N., Champagne, F. A., D'alessio, A. C., Sharma, S., Seckl, J. R., et al. (2004). Epigenetic programming by maternal behavior. Nat. Neurosci. 7, 847-854. doi: 10.1038/nn1276
116. Winter, J., Jung, S., Keller, S., Gregory, R. I., and Diederichs, S. (2009). Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat. Cell Biol. 11, 228-234. doi: 10.1038/ncb0309-228
117. Wu, Y., Patchev, A. V., Daniel, G., Almeida, O. F. X., and Spengler, D. (2014). Early-life stress reduces DNA methylation of the Pomc gene in male mice. Endocrinology 155, 1751-1762. doi: 10.1210/en.2013-1868
118. Ye, J. Z.-S., Donigian, J. R., Van Overbeek, M., Loayza, D., Luo, Y., Krutchinsky, A. N., et al. (2004). TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres. J. Biol. Chem. 279, 47264-47271. doi: 10.1074/jbc.m409047200
119. Zalli, A., Carvalho, L. A., Lin, J., Hamer, M., Erusalimsky, J. D., Blackburn, E. H., et al. (2014). Shorter telomeres with high telomerase activity are associated with raised allostatic load and impoverished psychosocial resources.Proc. Natl. Acad. Sci. U S A 111, 4519-4524. doi: 10.1073/pnas.1322145111
120. Zeichner, S. L., Palumbo, P., Feng, Y., Xiao, X., Gee, D., Sleasman, J., et al. (1999). Rapid telomere shortening in children. Blood 93, 2824-2830.
121. Zhang, Y., Zhu, X., Bai, M., Zhang, L., Xue, L., and Yi, J. (2013). Maternal deprivation enhances behavioral vulnerability to stress associated with miR-504 expression in nucleus accumbens of rats. PLoS One 8:e69934. doi: 10.1371/journal.pone.0069934
122. Zhou, Q. G., Hu, Y., Wu, D. L., Zhu, L. J., Chen, C., Jin, X., et al. (2011). Hippocampal telomerase is involved in the modulation of depressive behaviors. J. Neurosci. 31, 12258-12269. doi: 10.1523/jneurosci.0805-11.2011
123. Zhu, H., Wang, X., Gutin, B., Davis, C. L., Keeton, D., Thomas, J., et al. (2011). Leukocyte telomere length in healthy Caucasian and African-American adolescents: relationships with race, sex, adiposity, adipokines and physical activity. J. Pediatr. 158, 215-220. doi: 10.1016/j.jpeds.2010.08.007