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Epigenetic Biomarkers for Early-Life Adversity

  • Gustavo TureckiEmail author
Chapter
Part of the Epigenetics and Human Health book series (EHH)

Abstract

The early-life environment has important consequences on behavioral development. Specifically, the adversity experienced during sensitive developmental periods in childhood is associated with an increased risk for psychopathology in adulthood, such as mood disorders and mental illness. We have only recently started to uncover some of the mechanisms that may contribute to behavioral changes induced by early-life adversity. Epigenetics modifications regulate gene expression by changing the DNA’s or chromatin’s chemical composition or physical structure without altering its sequence. The epigenome is responsive to the environment, and landmark studies in rodents have shown that variations in early-life environment stably regulate the expression of key gene systems involved in behavioral and emotional responses through epigenetic processes. Early-life adversity could alter behavioral development and increase the vulnerability to psychopathology epigenetic regulation. This chapter will review the findings from human studies that support this hypothesis. We will describe epigenetic changes associated with early-life adversity and will discuss their potential as biomarkers for early-life adversity.

Keywords

Child abuse Epigenetics Biomarkers Psychopathology 

References

  1. Agid O, Shapira B, Zislin J et al (1999) Environment and vulnerability to major psychiatric illness: a case control study of early parental loss in major depression, bipolar disorder and schizophrenia. Mol Psychiatry 4:163–172CrossRefPubMedGoogle Scholar
  2. Appel K, Schwahn C, Mahler J et al (2011) Moderation of adult depression by a polymorphism in the FKBP5 gene and childhood physical abuse in the general population. Neuropsychopharmacology 36:1982–1991. doi: 10.1038/npp.2011.81 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Baker-Andresen D, Ratnu VS, Bredy TW (2013) Dynamic DNA methylation: a prime candidate for genomic metaplasticity and behavioral adaptation. Trends Neurosci 36:3–13. doi: 10.1016/j.tins.2012.09.003 CrossRefPubMedGoogle Scholar
  4. Beach SR, Brody GH, Todorov AA, Gunter TD, Philibert RA (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 PubMedPubMedCentralGoogle Scholar
  5. Beach SR, Brody GH, Todorov AA, Gunter TD, Philibert RA (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 CrossRefPubMedGoogle Scholar
  6. Bensley LS, Van Eenwyk J, Spieker SJ, Schoder J (1999) Self-reported abuse history and adolescent problem behaviors. I. Antisocial and suicidal behaviors. J Adolesc Health 24:163–172, doi: S1054139X98001116 [pii]CrossRefPubMedGoogle Scholar
  7. Binder EB, Bradley RG, Liu W et al (2008) Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 299:1291–1305. doi: 10.1001/jama.299.11.1291 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Bremner JD, Randall P, Vermetten E et al (1997) Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse--a preliminary report. Biol Psychiatry 41:23–32CrossRefPubMedPubMedCentralGoogle Scholar
  9. Bremner JD, Vythilingam M, Vermetten E et al (2003) MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder. Am J Psychiatry 160:924–932CrossRefPubMedGoogle Scholar
  10. Briere J, Elliott DM (2003) Prevalence and psychological sequelae of self-reported childhood physical and sexual abuse in a general population sample of men and women. Child Abuse Negl 27:1205–1222CrossRefPubMedGoogle Scholar
  11. Brown GW, Moran P (1994) Clinical and psychosocial origins of chronic depressive episodes. I: a community survey. Br J Psychiatry 165:447–456CrossRefPubMedGoogle Scholar
  12. Brunoni AR, Lopes M, Fregni F (2008) A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol 11:1169–1180, doi:S1461145708009309 [pii]  10.1017/S1461145708009309 CrossRefPubMedGoogle Scholar
  13. Capitanio JP, Mendoza SP, Mason WA, Maninger N (2005) Rearing environment and hypothalamic-pituitary-adrenal regulation in young rhesus monkeys (Macaca mulatta). Dev Psychobiol 46:318–330. doi: 10.1002/dev.20067 CrossRefPubMedGoogle Scholar
  14. Carpenter LL, Tyrka AR, McDougle CJ, Malison RT, Owens MJ, Nemeroff CB, Price LH (2004) Cerebrospinal fluid corticotropin-releasing factor and perceived early-life stress in depressed patients and healthy control subjects. Neuropsychopharmacology 29:777–784. doi: 10.1038/sj.npp.1300375 CrossRefPubMedGoogle Scholar
  15. Carrion VG, Weems CF, Eliez S, Patwardhan A, Brown W, Ray RD, Reiss AL (2001) Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder. Biol Psychiatry 50:943–951CrossRefPubMedGoogle Scholar
  16. Caspi A, Sugden K, Moffitt TE et al (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389. doi: 10.1126/science.1083968 CrossRefPubMedGoogle Scholar
  17. Chen ES, Ernst C, Turecki G (2011) The epigenetic effects of antidepressant treatment on human prefrontal cortex BDNF expression. Int J Neuropsychopharmacol 14:427–429. doi: 10.1017/S1461145710001422 CrossRefPubMedGoogle Scholar
  18. Davies MN, Volta M, Pidsley R et al (2012) Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biol 13:R43. doi: 10.1186/gb-2012-13-6-r43 CrossRefPubMedPubMedCentralGoogle Scholar
  19. De Bellis MD, Keshavan MS, Frustaci K, Shifflett H, Iyengar S, Beers SR, Hall J (2002) Superior temporal gyrus volumes in maltreated children and adolescents with PTSD. Biol Psychiatry 51:544–552CrossRefPubMedGoogle Scholar
  20. Dempster EL, Pidsley R, Schalkwyk LC et al (2011) Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Hum Mol Genet 20:4786–4796. doi: 10.1093/hmg/ddr416 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Dinwiddie S, Heath AC, Dunne MP et al (2000) Early sexual abuse and lifetime psychopathology: a co-twin-control study. Psychol Med 30:41–52CrossRefPubMedGoogle Scholar
  22. Driessen M, Herrmann J, Stahl K et al (2000) Magnetic resonance imaging volumes of the hippocampus and the amygdala in women with borderline personality disorder and early traumatization. Arch Gen Psychiatry 57:1115–1122CrossRefPubMedGoogle Scholar
  23. Dwivedi Y, Rizavi HS, Conley RR, Roberts RC, Tamminga CA, Pandey GN (2003) Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatry 60:804–815 doi: 10.1001/archpsyc.60.8.804 [doi] 60/8/804 [pii]CrossRefPubMedGoogle Scholar
  24. Evans E, Hawton K, Rodham K (2005) Suicidal phenomena and abuse in adolescents: a review of epidemiological studies. Child Abuse Negl 29:45–58. doi: 10.1016/j.chiabu.2004.06.014 CrossRefPubMedGoogle Scholar
  25. Fergusson DM, Horwood LJ, Lynskey MT (1996) Childhood sexual abuse and psychiatric disorder in young adulthood: II. Psychiatric outcomes of childhood sexual abuse. J Am Acad Child Adolesc Psychiatry 35:1365–1374CrossRefPubMedGoogle Scholar
  26. Francis D, Diorio J, Liu D, Meaney MJ (1999) Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286:1155–1158CrossRefPubMedGoogle Scholar
  27. Gilbert R, Widom CS, Browne K, Fergusson D, Webb E, Janson S (2009) Burden and consequences of child maltreatment in high-income countries. Lancet 373:68–81. doi: 10.1016/S0140-6736(08)61706-7 CrossRefPubMedGoogle Scholar
  28. Gladstone GL, Parker GB, Mitchell PB, Malhi GS, Wilhelm K, Austin MP (2004) Implications of childhood trauma for depressed women: an analysis of pathways from childhood sexual abuse to deliberate self-harm and revictimization. Am J Psychiatry 161:1417–1425, doi: 10.1176/appi.ajp.161.8.1417 [doi] 161/8/1417 [pii]CrossRefPubMedGoogle Scholar
  29. Gorey KM, Leslie DR (1997) The prevalence of child sexual abuse: integrative review adjustment for potential response and measurement biases. Child Abuse Negl 21:391–398CrossRefPubMedGoogle Scholar
  30. Heim C, Nemeroff CB (2001) The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry 49:1023–1039CrossRefPubMedGoogle Scholar
  31. Heim C, Newport DJ, Heit S et al (2000) Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA 284:592–597, doi: joc92111 [pii]CrossRefPubMedGoogle Scholar
  32. Heim C, Mletzko T, Purselle D, Musselman DL, Nemeroff CB (2008a) The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma. Biol Psychiatry 63:398–405, doi:S0006-3223(07)00640-3 [pii]  10.1016/j.biopsych.2007.07.002 CrossRefPubMedGoogle Scholar
  33. Heim C, Newport DJ, Mletzko T, Miller AH, Nemeroff CB (2008b) The link between childhood trauma and depression: insights from HPA axis studies in humans. Psychoneuroendocrinology 33:693–710, doi:S0306-4530(08)00069-3 [pii]  10.1016/j.psyneuen.2008.03.008 CrossRefPubMedGoogle Scholar
  34. Heim C, Shugart M, Craighead WE, Nemeroff CB (2010) Neurobiological and psychiatric consequences of child abuse and neglect. Dev Psychobiol 52:671–690. doi: 10.1002/dev.20494 CrossRefPubMedGoogle Scholar
  35. Hertzman C (2012) Putting the concept of biological embedding in historical perspective. Proc Natl Acad Sci USA 109(Suppl 2):17160–17167. doi: 10.1073/pnas.1202203109 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Higley JD, Hasert MF, Suomi SJ, Linnoila M (1991) Nonhuman primate model of alcohol abuse: effects of early experience, personality, and stress on alcohol consumption. Proc Natl Acad Sci USA 88:7261–7265CrossRefPubMedPubMedCentralGoogle Scholar
  37. Horvath S, Zhang Y, Langfelder P et al (2012) Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol 13:R97. doi: 10.1186/gb-2012-13-10-r97 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Issler O, Haramati S, Paul ED et al (2014) MicroRNA 135 is essential for chronic stress resiliency, antidepressant efficacy, and intact serotonergic activity. Neuron 83:344–360. doi: 10.1016/j.neuron.2014.05.042 CrossRefPubMedGoogle Scholar
  39. Jaffee SR, Moffitt TE, Caspi A, Fombonne E, Poulton R, Martin J (2002) Differences in early childhood risk factors for juvenile-onset and adult-onset depression. Arch Gen Psychiatry 59:215–222, doi: yoa10107 [pii]CrossRefPubMedGoogle Scholar
  40. Kang HJ, Kim JM, Stewart R et al (2013) Association of SLC6A4 methylation with early adversity, characteristics and outcomes in depression. Prog Neuropsychopharmacol Biol Psychiatry 44:23–28. doi: 10.1016/j.pnpbp.2013.01.006 CrossRefPubMedGoogle Scholar
  41. Kaplan MJ, Klinetob NA (2000) Childhood emotional trauma and chronic posttraumatic stress disorder in adult outpatients with treatment-resistant depression. J Nerv Ment Dis 188:596–601CrossRefPubMedGoogle Scholar
  42. Kendler KS, Bulik CM, Silberg J, Hettema JM, Myers J, Prescott CA (2000) Childhood sexual abuse and adult psychiatric and substance use disorders in women: an epidemiological and cotwin control analysis. Arch Gen Psychiatry 57:953–959CrossRefPubMedGoogle Scholar
  43. Kendler KS, Kuhn JW, Prescott CA (2004) Childhood sexual abuse, stressful life events and risk for major depression in women. Psychol Med 34:1475–1482CrossRefPubMedGoogle Scholar
  44. Klengel T, Mehta D, Anacker C et al (2013) Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci 16:33–41. doi: 10.1038/nn.3275 CrossRefPubMedGoogle Scholar
  45. Labonte B, Suderman M, Maussion G et al (2012a) Genome-wide epigenetic regulation by early-life trauma. Arch Gen Psychiatry 69:722–731. doi: 10.1001/archgenpsychiatry.2011.2287 CrossRefPubMedGoogle Scholar
  46. Labonte B, Yerko V, Gross J, Mechawar N, Meaney MJ, Szyf M, Turecki G (2012b) Differential glucocorticoid receptor exon 1(B), 1(C), and 1(H) expression and methylation in suicide completers with a history of childhood abuse. Biol Psychiatry 72:41–48. doi: 10.1016/j.biopsych.2012.01.034 CrossRefPubMedGoogle Scholar
  47. Levine A, Cohen D, Zadik Z (1994) Urinary free cortisol values in children under stress. J Pediatr 125:853–857CrossRefPubMedGoogle Scholar
  48. Liang P, Song F, Ghosh S et al (2011) Genome-wide survey reveals dynamic widespread tissue-specific changes in DNA methylation during development. BMC Genomics 12:231. doi: 10.1186/1471-2164-12-231 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Lister R, Mukamel EA, Nery JR et al (2013) Global epigenomic reconfiguration during mammalian brain development. Science 341:1237905. doi: 10.1126/science.1237905 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Liu D, Diorio J, Tannenbaum B et al (1997) Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 277:1659–1662CrossRefPubMedGoogle Scholar
  51. Lopez JP, Mamdani F, Labonte B et al (2013) Epigenetic regulation of BDNF expression according to antidepressant response. Mol Psychiatry 18:398–399. doi: 10.1038/mp.2012.38 CrossRefPubMedGoogle Scholar
  52. Lopez JP, Lim R, Cruceanu C et al (2014) miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment. Nat Med 20:764–768. doi: 10.1038/nm.3582 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 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 8:1030–1038. doi: 10.4161/epi.25865 CrossRefPubMedPubMedCentralGoogle Scholar
  54. McCauley J, Kern DE, Kolodner K et al (1997) Clinical characteristics of women with a history of childhood abuse: unhealed wounds. JAMA 277:1362–1368CrossRefPubMedGoogle Scholar
  55. McGowan P, Sasaki A, D’Alessio A 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 CrossRefPubMedPubMedCentralGoogle Scholar
  56. Meaney MJ (2001) Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 24:1161–1192. doi: 10.1146/annurev.neuro.24.1.1161 CrossRefPubMedGoogle Scholar
  57. Mehta D, Klengel T, Conneely KN et al (2013) Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proc Natl Acad Sci USA 110:8302–8307. doi: 10.1073/pnas.1217750110 CrossRefPubMedPubMedCentralGoogle Scholar
  58. Meissner A, Mikkelsen TS, Gu H et al (2008) Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454:766–770. doi: 10.1038/nature07107 PubMedPubMedCentralGoogle Scholar
  59. Mikkelsen TS, Ku M, Jaffe DB et al (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448:553–560. doi: 10.1038/nature06008 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Molnar BE, Berkman LF, Buka SL (2001) Psychopathology, childhood sexual abuse and other childhood adversities: relative links to subsequent suicidal behaviour in the US. Psychol Med 31:965–977CrossRefPubMedGoogle Scholar
  61. Nagy C, Turecki G (2012) Sensitive periods in epigenetics: bringing us closer to complex behavioral phenotypes. Epigenomics 4:445–457. doi: 10.2217/epi.12.37 CrossRefPubMedGoogle Scholar
  62. Pandey GN, Ren X, Rizavi HS, Conley RR, Roberts RC, Dwivedi Y (2008) Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims. Int J Neuropsychopharmacol 11:1047–1061, doi:S1461145708009000 [pii]  10.1017/S1461145708009000 CrossRefPubMedGoogle Scholar
  63. Pappas TC, Bader AG, Andruss BF, Brown D, Ford LP (2008) Applying small RNA molecules to the directed treatment of human diseases: realizing the potential. Expert Opin Ther Targets 12:115–127. doi: 10.1517/14728222.12.1.115 CrossRefPubMedGoogle Scholar
  64. Perroud N, Paoloni-Giacobino A, Prada P 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 CrossRefPubMedPubMedCentralGoogle Scholar
  65. Perroud N, Salzmann A, Prada P et al (2013) Response to psychotherapy in borderline personality disorder and methylation status of the BDNF gene. Transl Psychiatry 3, e207. doi: 10.1038/tp.2012.140 CrossRefPubMedPubMedCentralGoogle Scholar
  66. Pruunsild P, Kazantseva A, Aid T, Palm K, Timmusk T (2007) Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters. Genomics 90:397–406. doi: 10.1016/j.ygeno.2007.05.004 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Radtke KM, Ruf M, Gunter HM, Dohrmann K, Schauer M, Meyer A, Elbert T (2011) Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Transl Psychiatry 1:1–6CrossRefGoogle Scholar
  68. Roth TL, Lubin FD, Funk AJ, Sweatt JD (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 CrossRefPubMedPubMedCentralGoogle Scholar
  69. Roy A, Gorodetsky E, Yuan Q, Goldman D, Enoch MA (2010) Interaction of FKBP5, a stress-related gene, with childhood trauma increases the risk for attempting suicide. Neuropsychopharmacology 35:1674–1683. doi: 10.1038/npp.2009.236 PubMedPubMedCentralGoogle Scholar
  70. Santa Mina EE, Gallop RM (1998) Childhood sexual and physical abuse and adult self-harm and suicidal behaviour: a literature review. Can J Psychiatry 43:793–800PubMedGoogle Scholar
  71. Scammell JG, Denny WB, Valentine DL, Smith DF (2001) Overexpression of the FK506-binding immunophilin FKBP51 is the common cause of glucocorticoid resistance in three New World primates. Gen Comp Endocrinol 124:152–165. doi: 10.1006/gcen.2001.7696 CrossRefPubMedGoogle Scholar
  72. Scher CD, Forde DR, McQuaid JR, Stein MB (2004) Prevalence and demographic correlates of childhood maltreatment in an adult community sample. Child Abuse Negl 28:167–180. doi: 10.1016/j.chiabu.2003.09.012 CrossRefPubMedGoogle Scholar
  73. Stein MB, Koverola C, Hanna C, Torchia MG, McClarty B (1997) Hippocampal volume in women victimized by childhood sexual abuse. Psychol Med 27:951–959CrossRefPubMedGoogle Scholar
  74. Suderman M, Borghol N, Pappas JJ et al (2014) Childhood abuse is associated with methylation of multiple loci in adult DNA. BMC Med Genomics 7:13. doi: 10.1186/1755-8794-7-13 CrossRefPubMedPubMedCentralGoogle Scholar
  75. Tanskanen A, Hintikka J, Honkalampi K, Haatainen K, Koivumaa-Honkanen H, Viinamaki H (2004) Impact of multiple traumatic experiences on the persistence of depressive symptoms--a population-based study. Nord J Psychiatry 58:459–464. doi: 10.1080/08039480410011687 CrossRefPubMedGoogle Scholar
  76. Turner JD, Muller CP (2005) Structure of the glucocorticoid receptor (NR3C1) gene 5′ untranslated region: identification, and tissue distribution of multiple new human exon 1. J Mol Endocrinol 35:283–292. doi: 10.1677/jme.1.01822 CrossRefPubMedGoogle Scholar
  77. Tyrka AR, Price LH, Marsit C, Walters OC, Carpenter LL (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 CrossRefPubMedPubMedCentralGoogle Scholar
  78. U.S. Department of Health and Human Services AfCaF, Administration on Children, Youth and Families, Children’s Bureau (2015) Child Maltreatment 2013. U.S. Department of Health and Human ServiceGoogle Scholar
  79. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659. doi: 10.1038/ncb1596 CrossRefPubMedGoogle Scholar
  80. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT (2011) MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 13:423–433. doi: 10.1038/ncb2210 CrossRefPubMedPubMedCentralGoogle Scholar
  81. Vijayendran M, Beach SR, Plume JM, Brody GH, Philibert RA (2012) Effects of genotype and child abuse on DNA methylation and gene expression at the serotonin transporter. Front Psychiatry 3:55. doi: 10.3389/fpsyt.2012.00055 CrossRefPubMedPubMedCentralGoogle Scholar
  82. Wankerl M, Miller R, Kirschbaum C, Hennig J, Stalder T, Alexander N (2014) Effects of genetic and early environmental risk factors for depression on serotonin transporter expression and methylation profiles. Transl Psychiatry 4, e402. doi: 10.1038/tp.2014.37 CrossRefPubMedPubMedCentralGoogle Scholar
  83. Weaver IC, Cervoni N, Champagne FA et al (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854. doi: 10.1038/nn1276 CrossRefPubMedGoogle Scholar
  84. Wochnik GM, Ruegg J, Abel GA, Schmidt U, Holsboer F, Rein T (2005) FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. J Biol Chem 280:4609–4616. doi: 10.1074/jbc.M407498200 CrossRefPubMedGoogle Scholar
  85. Xin Y, Chanrion B, Liu MM et al (2010) Genome-wide divergence of DNA methylation marks in cerebral and cerebellar cortices. PLoS ONE 5, e11357. doi: 10.1371/journal.pone.0011357 CrossRefPubMedPubMedCentralGoogle Scholar
  86. Xin Y, O’Donnell AH, Ge Y et al (2011) Role of CpG context and content in evolutionary signatures of brain DNA methylation. Epigenetics 6:1308–1318. doi: 10.4161/epi.6.11.17876 CrossRefPubMedPubMedCentralGoogle Scholar
  87. Yang BZ, Zhang H, Ge W et al (2013) Child abuse and epigenetic mechanisms of disease risk. Am J Prev Med 44:101–107. doi: 10.1016/j.amepre.2012.10.012 CrossRefPubMedPubMedCentralGoogle Scholar
  88. Zlotnick C, Mattia J, Zimmerman M (2001) Clinical features of survivors of sexual abuse with major depression. Child Abuse Negl 25:357–367, doi:S0145-2134(00)00251-9 [pii]CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.McGill Group for Suicide Studies, Douglas Mental Health University Institute, Department of PsychiatryMcGill UniversityMontrealCanada

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