Epigenetics in posttraumatic stress disorder

Progress in Molecular Biology and Translational Science

Volumn 128, Issue C, 2014, Pages 29-50

  Rampp, Carina ^a   Binder, Elisabeth B ^a,b   Provençal, Nadine ^a  

^a MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

STRESS HORMONE;

ARTICLE; DNA METHYLATION; EPIGENETICS; GENETIC ASSOCIATION; GENOTYPE ENVIRONMENT INTERACTION; HUMAN; INJURY; NONHUMAN; POSTTRAUMATIC STRESS DISORDER; PREVALENCE; PRIORITY JOURNAL; REGULATORY MECHANISM; STRESS; TISSUE SPECIFICITY;

EID: 84927747322     PISSN: 18771173     EISSN: 18780814     Source Type: Book Series    
DOI: 10.1016/B978-0-12-800977-2.00002-4     Document Type: Chapter

References (132)

1. Breslau N, Kessler RC, Chilcoat HD, et al. Trauma and posttraumatic stress disorder in the community: the 1996 Detroit Area Survey of Trauma. Arch Gen Psychiatry. 1998;55:626-632.
2. Breslau N. The epidemiology of posttraumatic stress disorder: what is the extent of the problem? J Clin Psychiatry. 2001;62(suppl 17):16-22.
3. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995;52:1048-1060.
4. Gillespie CF, Phifer J, Bradley B, Ressler KJ. Risk and resilience: genetic and environmental influences on development of the stress response. Depress Anxiety. 2009;26:984-992.
5. Booij L, Wang D, Levesque ML, Tremblay RE, 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. 2013;368:20120251.
6. Mehta D, Binder EB. Gene-environment vulnerability factors for PTSD: the HPAaxis. Neuropharmacology. 2012;62:654-662.
7. Prigerson HG, Maciejewski PK, Rosenheck RA. Combat trauma: trauma with highest risk of delayed onset and unresolved posttraumatic stress disorder symptoms, unemployment, and abuse among men. J Nerv Ment Dis. 2001;189:99-108.
8. Galea S, Resnick H, Ahern J, et al. Posttraumatic stress disorder in Manhattan, New York City, after the September 11th terrorist attacks. J Urban Health. 2002;79:340-353.
9. Nemeroff CB, Bremner JD, Foa EB, et al. Posttraumatic stress disorder: a state-of-thescience review. J Psychiatr Res. 2006;40:1-21.
10. Yehuda R, Flory JD, Pratchett LC, et al. Putative biological mechanisms for the association between early life adversity and the subsequent development of PTSD. Psychopharmacology (Berl). 2010;212:405-417.
11. Widom CS. Posttraumatic stress disorder in abused and neglected children grown up. Am J Psychiatry. 1999;156:1223-1229.
12. Bremner JD, Southwick SM, Johnson DR, Yehuda R, Charney DS. Childhood physical abuse and combat-related posttraumatic stress disorder in Vietnam veterans. Am J Psychiatry. 1993;150:235-239.
13. Heim C, Nemeroff CB. The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry. 2001;49: 1023-1039.
14. Widom CS. The cycle of violence. Science. 1989;244:160-166.
15. Rutter M. Developmental catch-up, and deficit, following adoption after severe global early privation. English and Romanian Adoptees (ERA) Study Team. J Child Psychol Psychiatry. 1998;39:465-476.
16. Klengel T, Pape J, Binder EB, Mehta D. The role of DNA methylation in stress-related psychiatric disorders. Neuropharmacology. 2014;80:115-132.
17. Klengel T, Binder EB. Gene-environment interactions in major depressive disorder. Can J Psychiatry. 2013;58:76-83.
18. Wray NR, Pergadia ML, Blackwood DH, et al. Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned. Mol Psychiatry. 2012;17:36-48.
19. Hek K, Demirkan A, Lahti J, et al. A genome-wide association study of depressive symptoms. Biol Psychiatry. 2013;73:667-678.
20. Ripke S, O'Dushlaine C, Chambert K, et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet. 2013;45:1150-1159.
21. Meaney MJ. Epigenetics and the biological definition of gene-environment interactions. Child Dev. 2010;81:41-79.
22. Widom CS, DuMont K, Czaja SJ. A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up. Arch Gen Psychiatry. 2007;64:49-56.
23. Danese A, Moffitt TE, Harrington H, et al. Adverse childhood experiences and adult risk factors for age-related disease: depression, inflammation, and clustering of metabolic risk markers. Arch Pediatr Adolesc Med. 2009;163:1135-1143.
24. Stein MB, Jang KL, Taylor S, Vernon PA, Livesley WJ. Genetic and environmental influences on trauma exposure and posttraumatic stress disorder symptoms: a twin study. Am J Psychiatry. 2002;159:1675-1681.
25. True WR, Rice J, Eisen SA, et al. A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms. Arch Gen Psychiatry. 1993;50:257-264.
26. Razin A. CpG methylation, chromatin structure and gene silencing-a three-way connection. EMBO J. 1998;17:4905-4908.
27. Lister R, Pelizzola M, Dowen RH, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462:315-322.
28. Xie W, Barr CL, Kim A, et al. Base-resolution analyses of sequence and parent-oforigin dependent DNA methylation in the mouse genome. Cell. 2012;148:816-831.
29. Bird AP. CpG-rich islands and the function of DNA methylation. Nature. 1986;321:209-213.
30. Murgatroyd C, Spengler D. Histone tales: echoes from the past, prospects for the future. Genome Biol. 2010;11:105.
31. Ball MP, Li JB, Gao Y, et al. Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol. 2009;27:361-368.
32. Maunakea AK, Chepelev I, Zhao K. Epigenome mapping in normal and disease states. Circ Res. 2010;107:327-339.
33. Ogoshi K, Hashimoto S, Nakatani Y, et al. Genome-wide profiling of DNA methylation in human cancer cells. Genomics. 2011;98:280-287.
34. Jiang Y, Liu S, Chen X, Cao Y, Tao Y. Genome-wide distribution of DNA methylation and DNA demethylation and related chromatin regulators in cancer. Biochim Biophys Acta. 2013;1835:155-163.
35. Jjingo D, Conley AB, Yi SV, Lunyak VV, Jordan IK. On the presence and role of human gene-body DNA methylation. Oncotarget. 2012;3:462-474.
36. Mehta D, Raison CL, Woolwine BJ, et al. Transcriptional signatures related to glucose and lipid metabolism predict treatment response to the tumor necrosis factor antagonist infliximab in patients with treatment-resistant depression. Brain Behav Immun. 2013;31:205-215.
37. Provencal N, Suderman MJ, Caramaschi D, et al. Differential DNA methylation regions in cytokine and transcription factor genomic loci associate with childhood physical aggression. PLoS One. 2013;8:e71691.
38. Ando T, Nishimura M, Oka Y. Decitabine (5-aza-2 0 -deoxycytidine) decreased DNA methylation and expression of MDR-1 gene in K562/ADM cells. Leukemia. 2000;14:1915-1920.
39. Bartolomei MS. Genomic imprinting: employing and avoiding epigenetic processes. Genes Dev. 2009;23:2124-2133.
40. Jeltsch A. Reading and writing DNA methylation. Nat Struct Mol Biol. 2008;15: 1003-1004.
41. Ramchandani S, Bhattacharya SK, Cervoni N, Szyf M. DNA methylation is a reversible biological signal. Proc Natl Acad Sci USA. 1999;96:6107-6112.
42. Barreto G, Schafer A, Marhold J, et al. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature. 2007;445:671-675.
43. Ma DK, Guo JU, Ming GL, Song H. DNA excision repair proteins and Gadd45 as molecular players for active DNA demethylation. Cell Cycle. 2009;8:1526-1531.
44. Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK. Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming. J Biol Chem. 2004;279: 52353-52360.
45. Rai K, Huggins IJ, James SR, et al. DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell. 2008;135:1201-1212.
46. Schmitz KM, Schmitt N, Hoffmann-Rohrer U, et al. TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation. Mol Cell. 2009;33:344-353.
47. Guo JU, Su Y, Zhong C, Ming GL, Song H. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell. 2011;145: 423-434.
48. Darnaudery M, Maccari S. Epigenetic programming of the stress response in male and female rats by prenatal restraint stress. Brain Res Rev. 2008;57:571-585.
49. Gudsnuk K, Champagne FA. Epigenetic influence of stress and the social environment. ILAR J. 2012;53:279-288.
50. Jirtle RL, Skinner MK. Environmental epigenomics and disease susceptibility. Nat Rev Genet. 2007;8:253-262.
51. Mill J, Tang T, Kaminsky Z, et al. Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am J Hum Genet. 2008;82:696-711.
52. Sasaki A, de Vega WC, McGowan PO. Biological embedding in mental health: an epigenomic perspective. Biochem Cell Biol. 2013;91:14-21.
53. Szyf M. The early-life social environment and DNA methylation. Clin Genet. 2012;81:341-349.
54. Mill J, Petronis A. Pre- and peri-natal environmental risks for attention-deficit hyperactivity disorder (ADHD): the potential role of epigenetic processes in mediating susceptibility. J Child Psychol Psychiatry. 2008;49:1020-1030.
55. Szyf M. DNA methylation, the early-life social environment and behavioral disorders. J Neurodev Disord. 2011;3:238-249.
56. Weaver IC, Diorio J, Seckl JR, Szyf M, Meaney MJ. Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites. Ann NY Acad Sci. 2004;1024:182-212.
57. Murgatroyd C, Patchev AV, Wu Y, et al. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci. 2009;12:1559-1566.
58. Roth TL, Lubin FD, Funk AJ, Sweatt JD. Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry. 2009;65:760-769.
59. McGowan PO, Sasaki A, D'Alessio AC, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009;12:342-348.
60. McGowan PO, Sasaki A, Huang TC, et al. Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS One. 2008;3:e2085.
61. Weder N, Zhang H, Jensen K, et al. Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry. J Am Acad Child Adolesc Psychiatry. 2014;53(4):417-424.e5. http://dx.doi.org/10.1016/j.jaac.2013.12.025. Epub 2014 Jan 27.
62. Suderman M, McGowan PO, Sasaki A, et al. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus. Proc Natl Acad Sci USA. 2012;109(suppl 2):17266-17272.
63. Labonte B, Suderman M, Maussion G, et al. Genome-wide epigenetic regulation by early-life trauma. Arch Gen Psychiatry. 2012;69:722-731.
64. Chen Y, Sharples TJ, Phillips KG, et al. The nicotinic alpha 4 beta 2 receptor selective agonist, TC-2559, increases dopamine neuronal activity in the ventral tegmental area of rat midbrain slices. Neuropharmacology. 2003;45:334-344.
65. Martinowich K, Hattori D, Wu H, et al. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science. 2003;302:890-893.
66. Weaver IC, D'Alessio AC, Brown SE, et al. The transcription factor nerve growth factor-inducible protein a mediates epigenetic programming: altering epigenetic marks by immediate-early genes. J Neurosci. 2007;27:1756-1768.
67. Kress C, Thomassin H, Grange T. Active cytosine demethylation triggered by a nuclear receptor involves DNA strand breaks. Proc Natl Acad Sci USA. 2006;103: 11112-11117.
68. Thomassin H, Flavin M, Espinas ML, Grange T. Glucocorticoid-induced DNA demethylation and gene memory during development. EMBO J. 2001;20:1974-1983.
69. Darnaudery M, Maccari S. Epigenetic programming of the stress response in male and female rats by prenatal restraint stress. Brain Res Rev. 2008;57:571-585.
70. Gudsnuk K, Champagne FA. Epigenetic influence of stress and the social environment. ILAR J. 2012;53:279-288.
71. Jirtle RL, Skinner MK. Environmental epigenomics and disease susceptibility. Nat Rev Genet. 2007;8:253-262.
72. Mill J, Tang T, Kaminsky Z, et al. Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am J Hum Genet. 2008;82:696-711.
73. Sasaki A, de Vega WC, McGowan PO. Biological embedding in mental health: an epigenomic perspective. Biochem Cell Biol. 2013;91:14-21.
74. Szyf M. The early-life social environment and DNA methylation. Clin Genet. 2012;81:341-349.
75. Mill J, Petronis A. Pre- and peri-natal environmental risks for attention-deficit hyperactivity disorder (ADHD): the potential role of epigenetic processes in mediating susceptibility. J Child Psychol Psychiatry. 2008;49:1020-1030.
76. Szyf M. DNA methylation, the early-life social environment and behavioral disorders. J Neurodev Disord. 2011;3:238-249.
77. Weaver IC, Diorio J, Seckl JR, Szyf M, Meaney MJ. Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites. Ann NY Acad Sci. 2004;1024:182-212.
78. Murgatroyd C, Patchev AV, Wu Y, et al. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci. 2009;12:1559-1566.
79. Roth TL, Lubin FD, Funk AJ, Sweatt JD. Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry. 2009;65:760-769.
80. McGowan PO, Sasaki A, D'Alessio AC, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009;12:342-348.
81. McGowan PO, Sasaki A, Huang TC, et al. Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS One. 2008;3:e2085.
82. Weder N, Zhang H, Jensen K, et al. Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry. J Am Acad Child Adolesc Psychiatry. 2014;53(4):417-424.e5. http://dx.doi.org/10.1016/j.jaac.2013.12.025. Epub 2014 Jan 27.
83. Suderman M, McGowan PO, Sasaki A, et al. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus. Proc Natl Acad Sci USA. 2012;109(suppl 2):17266-17272.
84. Labonte B, Suderman M, Maussion G, et al. Genome-wide epigenetic regulation by early-life trauma. Arch Gen Psychiatry. 2012;69:722-731.
85. Chen Y, Sharples TJ, Phillips KG, et al. The nicotinic alpha 4 beta 2 receptor selective agonist, TC-2559, increases dopamine neuronal activity in the ventral tegmental area of rat midbrain slices. Neuropharmacology. 2003;45:334-344.
86. Martinowich K, Hattori D, Wu H, et al. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science. 2003;302:890-893.
87. Weaver IC, D'Alessio AC, Brown SE, et al. The transcription factor nerve growth factor-inducible protein a mediates epigenetic programming: altering epigenetic marks by immediate-early genes. J Neurosci. 2007;27:1756-1768.
88. Kress C, Thomassin H, Grange T. Active cytosine demethylation triggered by a nuclear receptor involves DNA strand breaks. Proc Natl Acad Sci USA. 2006;103: 11112-11117.
89. Thomassin H, Flavin M, Espinas ML, Grange T. Glucocorticoid-induced DNA demethylation and gene memory during development. EMBO J. 2001;20:1974-1983.
90. Yehuda R, Flory JD, Bierer LM, et al. Lower methylation of glucocorticoid receptor gene promoter 1 in peripheral blood of veterans with posttraumatic stress disorder. Biol Psychiatry. 2014, in press. pii: S0006-3223(14)00100-0. http://dx.doi.org/10.1016/j.biopsych.2014.02.006. [Epub ahead of print].
91. Yehuda R, Daskalakis NP, Desarnaud F, et al. Epigenetic biomarkers as predictors and correlates of symptom improvement following psychotherapy in combat veterans with PTSD. Front Psychiatry. 2013;4:118.
92. Perroud N, Rutembesa E, Paoloni-Giacobino A, et al. The Tutsi genocide and transgenerational transmission of maternal stress: epigenetics and biology of the HPA axis. World J Biol Psychiatry. 2014;15:334-345.
93. Yehuda R, Daskalakis NP, Lehrner A, et al. Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in holocaust survivor offspring. Am J Psychiatry. 2014;171(8):872-880.
94. Ressler KJ, Mercer KB, Bradley B, et al. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature. 2011;470:492-497.
95. Koenen KC, Uddin M, Chang SC, et al. SLC6A4 methylation modifies the effect of the number of traumatic events on risk for posttraumatic stress disorder. Depress Anxiety. 2011;28:639-647.
96. van IMH, Caspers K, Bakermans-Kranenburg MJ, Beach SR, Philibert R. Methylation matters: interaction between methylation density and serotonin transporter genotype predicts unresolved loss or trauma. Biol Psychiatry. 2010;68: 405-407.
97. Beach SR, Brody GH, Todorov AA, Gunter TD, Philibert RA. Methylation at 5HTT mediates the impact of child sex abuse on women's antisocial behavior: an examination of the Iowa adoptee sample. Psychosom Med. 2011;73:83-87.
98. Vijayendran M, Beach SR, Plume JM, Brody GH, Philibert RA. Effects of genotype and child abuse on DNA methylation and gene expression at the serotonin transporter. Front Psychiatry. 2012;3:55.
99. Chang SC, Koenen KC, Galea S, et al. Molecular variation at the SLC6A3 locus predicts lifetime risk of PTSD in the Detroit Neighborhood Health Study. PLoS One. 2012;7:e39184.
100. Clark R, DeYoung CG, Sponheim SR, et al. Predicting post-traumatic stress disorder in veterans: interaction of traumatic load with COMT gene variation. J Psychiatr Res. 2013;47:1849-1856.
101. Norrholm SD, Jovanovic T, Smith AK, et al. Differential genetic and epigenetic regulation of catechol-O-methyltransferase is associated with impaired fear inhibition in posttraumatic stress disorder. Front Behav Neurosci. 2013;7:30.
102. Wong CM. Post-traumatic stress disorder: advances in psychoneuroimmunology. Psychiatr Clin North Am. 2002;25:369-383, vii.
103. Uddin M, Aiello AE, Wildman DE, et al. Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proc Natl Acad Sci USA. 2010;107: 9470-9475.
104. Newton-Cheh C, Hirschhorn JN. Genetic association studies of complex traits: design and analysis issues. Mutat Res. 2005;573:54-69.
105. Clarke MC, Tanskanen A, Huttunen M, Whittaker JC, Cannon M. Evidence for an interaction between familial liability and prenatal exposure to infection in the causation of schizophrenia. Am J Psychiatry. 2009;166:1025-1030.
106. van Os J, Rutten BP, Poulton R. Gene-environment interactions in schizophrenia: review of epidemiological findings and future directions. Schizophr Bull. 2008;34: 1066-1082.
107. Binder EB, Bradley RG, Liu W, et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA. 2008;299:1291-1305.
108. Klengel T, Mehta D, Anacker C, et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci. 2013;16:33-41.
109. Binder EB, Salyakina D, Lichtner P, et al. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet. 2004;36:1319-1325.
110. Binder EB. The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology. 2009;34(suppl 1):S186-S195.
111. Jaaskelainen T, Makkonen H, Palvimo JJ. Steroid up-regulation of FKBP51 and its role in hormone signaling. Curr Opin Pharmacol. 2011;11:326-331.
112. Vermeer H, Hendriks-Stegeman BI, van der Burg B, van Buul-Offers SC, Jansen M. Glucocorticoid-induced increase in lymphocytic FKBP51 messenger ribonucleic acid expression: a potential marker for glucocorticoid sensitivity, potency, and bioavailability. J Clin Endocrinol Metab. 2003;88:277-284.
113. Ising M, Depping AM, Siebertz A, et al. Polymorphisms in the FKBP5 gene region modulate recovery from psychosocial stress in healthy controls. Eur J Neurosci. 2008;28:389-398.
114. Buchmann AF, Holz N, Boecker R, et al. Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood. Eur Neuropsychopharmacol. 2014;24:837-845.
115. Fani N, Gutman D, Tone EB, et al. FKBP5 and attention bias for threat: associations with hippocampal function and shape. JAMA Psychiatry. 2013;70:392-400.
116. Holz NE, Buchmann AF, Boecker R, et al. Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume. Brain Struct Funct. 2014, in press.
117. White MG, Bogdan R, Fisher PM, et al. FKBP5 and emotional neglect interact to predict individual differences in amygdala reactivity. Genes Brain Behav. 2012;11:869-878.
118. Zannas AS, Binder EB. Gene-environment interactions at the FKBP5 locus: sensitive periods, mechanisms and pleiotropism. Genes Brain Behav. 2014;13:25-37.
119. Menke A, Klengel T, Rubel J, et al. Genetic variation in FKBP5 associated with the extent of stress hormone dysregulation in major depression. Genes Brain Behav. 2013;12:289-296.
120. Mehta D, Gonik M, Klengel T, et al. Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: evidence from endocrine and gene expression studies. Arch Gen Psychiatry. 2011;68:901-910.
121. Franz MR, Wolf EJ, MacDonald HZ, et al. Relationships among predeployment risk factors, warzone-threat appraisal, and postdeployment PTSD symptoms. J Trauma Stress. 2013;26:498-506.
122. Szyf M. Early life, the epigenome and human health. Acta Paediatr. 2009;98:1082-1084.
123. Szyf M, Bick J. DNA methylation: a mechanism for embedding early life experiences in the genome. Child Dev. 2013;84:49-57.
124. Uddin M, Aiello AE, Wildman DE, et al. Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proc Natl Acad Sci USA. 2011;107: 9470-9475.
125. Pace TW, Wingenfeld K, Schmidt I, et al. Increased peripheral NF-kappaB pathway activity in women with childhood abuse-related posttraumatic stress disorder. Brain Behav Immun. 2012;26:13-17.
126. Spitzer C, Wibisono D, Terfehr K, et al. C-reactive protein, pre- and postdexamethasone cortisol levels in post-traumatic stress disorder. Nord J Psychiatry. 2014;68:296-299.
127. Szyf M, Weaver I, Meaney M. Maternal care, the epigenome and phenotypic differences in behavior. Reprod Toxicol. 2007;24:9-19.
128. Zovkic IB, Sweatt JD. Epigenetic mechanisms in learned fear: implications for PTSD. Neuropsychopharmacology. 2013;38:77-93.
129. Levenson JM, Roth TL, Lubin FD, et al. Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus. J Biol Chem. 2006;281: 15763-15773.
130. Monsey MS, Ota KT, Akingbade IF, Hong ES, Schafe GE. Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala. PLoS One. 2011;6:e19958.
131. Rogan MT, Staubli UV, LeDoux JE. Fear conditioning induces associative long-term potentiation in the amygdala. Nature. 1997;390:604-607.
132. Koshibu K, Graff J, Mansuy IM. Nuclear protein phosphatase-1: an epigenetic regulator of fear memory and amygdala long-term potentiation. Neuroscience. 2011;173:30-36.