<?xml version='1.0' encoding='utf-8'?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd">
<article article-type="research-article" dtd-version="1.2" xml:lang="ru" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><front><journal-meta><journal-id journal-id-type="issn">2658-6533</journal-id><journal-title-group><journal-title>Research Results in Biomedicine</journal-title></journal-title-group><issn pub-type="epub">2658-6533</issn></journal-meta><article-meta><article-id pub-id-type="doi">10.18413/2658-6533-2022-8-1-0-2</article-id><article-id pub-id-type="publisher-id">2659</article-id><article-categories><subj-group subj-group-type="heading"><subject>Genetics</subject></subj-group></article-categories><title-group><article-title>&lt;strong&gt;Epigenetic and genomic mechanisms in the pathogenesis of posttraumatic stress disorder (review)&lt;/strong&gt;&lt;br /&gt;
&amp;nbsp;</article-title><trans-title-group xml:lang="en"><trans-title>&lt;strong&gt;Epigenetic and genomic mechanisms in the pathogenesis of posttraumatic stress disorder (review)&lt;/strong&gt;&lt;br /&gt;
&amp;nbsp;</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Faustova</surname><given-names>Anna G.</given-names></name><name xml:lang="en"><surname>Faustova</surname><given-names>Anna G.</given-names></name></name-alternatives><email>a.faustova@rzgmu.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Iourov</surname><given-names>Ivan Y.</given-names></name><name xml:lang="en"><surname>Iourov</surname><given-names>Ivan Y.</given-names></name></name-alternatives><email>ivan.iourov@gmail.com</email></contrib></contrib-group><pub-date pub-type="epub"><year>2022</year></pub-date><volume>8</volume><issue>1</issue><fpage>0</fpage><lpage>0</lpage><self-uri content-type="pdf" xlink:href="/media/medicine/2022/1/Биомедицинские_исследования-16-36.pdf" /><abstract xml:lang="ru"><p>Background:&amp;nbsp;Posttraumatic stress disorder is one of the most prominent examples of gene-environment interactions. Psychological traumatization is a dominant, but not the only etiological factor. Over the past 20 years, sufficient data have been accumulated to confirm the role of the hereditary component in the formation of the so-called &amp;quot;vulnerable phenotype&amp;rdquo;. Epigenetic modifications are considered as a mechanism for environmental (traumatic) exposure provoking changes in gene expression and genome stability, which can lead to specific symptoms. The aim of the study:&amp;nbsp;To summarize and to compare the essential results of studies of epigenetic mechanisms of genome regulation in posttraumatic stress disorder. Materials and methods:&amp;nbsp;A theoretical analysis of the published studies dedicated to epigenetic markers of posttraumatic stress disorder was carried out. The PubMed database was browsed in the aforementioned context. Results:&amp;nbsp;The studies published during the last decades have a number of common characteristics (reliance on retrospective data about a traumatic event obtained by the self-report method; use of available tissues for analysis; use of a retrospective cross-sectional design). The systematics of research is based on both the dominant methodology (search and study of candidate genes; methods of whole-genome or epigenome associations) and the analysis of DNA methylation, posttranslational modifications of histones, and chromatin structural organization. The pathogenesis of posttraumatic stress disorder is also explained in the context of cytogenomic hypothesis (changes in genome instability levels modulate behavior). The limitations and prospects of studying epigenetic mechanisms in the pathogenesis of posttraumatic stress disorder are outlined. Conclusion:&amp;nbsp;Epigenetic and genomic analyses of the molecular basis of PTSD offer the most holistic approach to understanding the interaction between genotype and environment presenting as a traumatic event. The study of epigenetic modifications and genome instability, which are potentially reversible, will contribute to the improvement of the prevention and the provision of clinical and psychological assistance to individuals who have experienced traumatic events.</p></abstract><trans-abstract xml:lang="en"><p>Background:&amp;nbsp;Posttraumatic stress disorder is one of the most prominent examples of gene-environment interactions. Psychological traumatization is a dominant, but not the only etiological factor. Over the past 20 years, sufficient data have been accumulated to confirm the role of the hereditary component in the formation of the so-called &amp;quot;vulnerable phenotype&amp;rdquo;. Epigenetic modifications are considered as a mechanism for environmental (traumatic) exposure provoking changes in gene expression and genome stability, which can lead to specific symptoms. The aim of the study:&amp;nbsp;To summarize and to compare the essential results of studies of epigenetic mechanisms of genome regulation in posttraumatic stress disorder. Materials and methods:&amp;nbsp;A theoretical analysis of the published studies dedicated to epigenetic markers of posttraumatic stress disorder was carried out. The PubMed database was browsed in the aforementioned context. Results:&amp;nbsp;The studies published during the last decades have a number of common characteristics (reliance on retrospective data about a traumatic event obtained by the self-report method; use of available tissues for analysis; use of a retrospective cross-sectional design). The systematics of research is based on both the dominant methodology (search and study of candidate genes; methods of whole-genome or epigenome associations) and the analysis of DNA methylation, posttranslational modifications of histones, and chromatin structural organization. The pathogenesis of posttraumatic stress disorder is also explained in the context of cytogenomic hypothesis (changes in genome instability levels modulate behavior). The limitations and prospects of studying epigenetic mechanisms in the pathogenesis of posttraumatic stress disorder are outlined. Conclusion:&amp;nbsp;Epigenetic and genomic analyses of the molecular basis of PTSD offer the most holistic approach to understanding the interaction between genotype and environment presenting as a traumatic event. The study of epigenetic modifications and genome instability, which are potentially reversible, will contribute to the improvement of the prevention and the provision of clinical and psychological assistance to individuals who have experienced traumatic events.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>psychological trauma</kwd><kwd>posttraumatic stress disorder</kwd><kwd>PTSD</kwd><kwd>epigenomics</kwd><kwd>epigenome</kwd><kwd>DNA methylation</kwd></kwd-group><kwd-group xml:lang="en"><kwd>psychological trauma</kwd><kwd>posttraumatic stress disorder</kwd><kwd>PTSD</kwd><kwd>epigenomics</kwd><kwd>epigenome</kwd><kwd>DNA methylation</kwd></kwd-group></article-meta></front><back><ref-list><title>Список литературы</title><ref id="B1"><mixed-citation>1. Koenen KC, Ratanatharathorn A, Ng L, et al. Posttraumatic stress disorder in the World Mental Health Surveys. Psychological Medicine. 2017;47(13):2260-2274. DOI: https://doi.org/10.1017/S0033291717000708</mixed-citation></ref><ref id="B2"><mixed-citation>2. True WR, Rice J, Eisen SA, et al. A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms. Archives of General Psychiatry. 1993;50:257-264. DOI: https://doi.org/10.1001/archpsyc.1993.01820160019002</mixed-citation></ref><ref id="B3"><mixed-citation>3. Stein MB, Jang KL, Taylor S, et al. Genetic and environmental influences on trauma exposure and posttraumatic stress disorder symptoms: a twin study. American Journal of Psychiatry. 2002;159:1675-1681. DOI: https://doi.org/10.1176/appi.ajp.159.10.1675</mixed-citation></ref><ref id="B4"><mixed-citation>4. Sartor CE, McCutcheon VV, Pommer NE, et al. Common genetic and environmental contributions to post-traumatic stress disorder and alcohol dependence in young women. Psychological Medicine. 2011;41:1497-1505. DOI: https://doi.org/10.1017/S0033291710002072</mixed-citation></ref><ref id="B5"><mixed-citation>5. Zannas AS, Proven&amp;ccedil;al N, Binder EB. Epigenetics of posttraumatic stress disorder: current evidence, challenges, and future directions. Biological Psychiatry. 2015;78(5):327-335. DOI: https://doi.org/10.1016/j.biopsych.2015.04.003</mixed-citation></ref><ref id="B6"><mixed-citation>6. Proven&amp;ccedil;al N, Binder EB. The effects of early life stress on the epigenome: From the womb to adulthood and even before. Experimental Neurology. 2015;268:10-20. DOI: https://doi.org/10.1016/j.expneurol.2014.09.001</mixed-citation></ref><ref id="B7"><mixed-citation>7. Yehuda R, Lehrner R. Межпоколенческая передача травматических эффектов: предполагаемая роль эпигенетических механизмов. World Psychiatry. 2018;17(3):243-257. DOI: https://doi.org/10.1002/wps.20568</mixed-citation></ref><ref id="B8"><mixed-citation>8. Howie H, Rijal CM, Ressler KJ. A review of epigenetic contributions to posttraumatic stress disorder. Dialogues in Clinical Neuroscience. 2019;21(4):417-428. DOI: https://doi.org/10.31887/DCNS.2019.21.4/kressler</mixed-citation></ref><ref id="B9"><mixed-citation>9. Guljaeva NV. Stress Neurochemistry: The Chemistry of Stress Reactivity and Stress Sensitivity. Neurochemistry. 2018;35(2):111-114. Russian. DOI: https://doi.org/10.7868/S1027813318020012</mixed-citation></ref><ref id="B10"><mixed-citation>10. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington (VA): American Psychiatric Association; 2013.</mixed-citation></ref><ref id="B11"><mixed-citation>11. Kostiuk GP, editor. ICD-11. Chapter 6. Mental and behavioral disorders and disorders of neurocognitive development. Statistical classification. Moscow: &amp;ldquo;KDU&amp;rdquo;, &amp;ldquo;Universitetskaya kniga&amp;rdquo;; 2021. Russian.</mixed-citation></ref><ref id="B12"><mixed-citation>12. Miller MW, Sadeh N. Traumatic stress, oxidative stress and post-traumatic stress disorder: neurodegeneration and the accelerated-aging hypothesis. Molecular Psychiatry. 2014;19:1156-1162.&amp;nbsp; DOI: https://doi.org/10.1038/mp.2014.111</mixed-citation></ref><ref id="B13"><mixed-citation>13. Roberts AL, Agnew-Blais JC, Spiegelman D, et al. Posttraumatic stress disorder and incidence of type 2 diabetes mellitus in a sample of women: a 22-year longitudinal study. JAMA Psychiatry. 2015;72:203-210. DOI: https://doi.org/10.1001/jamapsychiatry.2014.2632</mixed-citation></ref><ref id="B14"><mixed-citation>14. Berens AE, Jensen SKG, Nelson CA 3rd. Biological embedding of childhood adversity: from physiological mechanisms to clinical implications. BMC Medicine. 2017;15(1):135. DOI: https://doi.org/10.1186/s12916-017-0895-4</mixed-citation></ref><ref id="B15"><mixed-citation>15. Brewin CR, Andrews B, Valentine JD. Meta-analysis of risk factors for posttraumatic stress disorder in trauma exposed adults. Journal of Consulting and Clinical Psychology. 2000;68:748-766. DOI: https://doi.org/10.1037//0022-006x.68.5.748</mixed-citation></ref><ref id="B16"><mixed-citation>16. Duncan LE, Cooper BN, Shen H. Robust findings from 25 years of PTSD genetics research. Current Psychiatry Reports. 2018;20(12):115. DOI: https://doi.org/10.1007/s11920-018-0980-1</mixed-citation></ref><ref id="B17"><mixed-citation>17. Caspi A, Houts RM, Belsky DW, et al. The p factor: one general psychopathology factor in the structure of psychiatric disorders? Clinical Psychological Science. 2014;2(2):119-137. DOI: https://doi.org/10.1177/2167702613497473</mixed-citation></ref><ref id="B18"><mixed-citation>18. Heim C, Binder EB. Current research trends in early life stress and depression: review of human studies on sensitive periods, gene-environment interactions, and epigenetics. Experimental Neurology. 2012;233:102-111. DOI: https://doi.org/10.1016/j.expneurol.2011.10.032</mixed-citation></ref><ref id="B19"><mixed-citation>19. Seckl JR. Glucocorticoids, developmental &amp;ldquo;programming&amp;rdquo; and the risk of affective dysfunction. Progress in Brain Research. 2008;167:17-34. DOI: https://doi.org/10.1016/S0079-6123(07)67002-2</mixed-citation></ref><ref id="B20"><mixed-citation>20. Mehta D, Klengel T, Conneely KN, et al. Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(20):8302-8307. DOI: https://doi.org/10.1073/pnas.1217750110</mixed-citation></ref><ref id="B21"><mixed-citation>21. Liu H, Petukhova MV, Sampson NA, et al. Association of DSM-IV posttraumatic stress disorder with traumatic experience type and history in the World Health Organization World Mental Health Surveys. JAMA Psychiatry. 2017;74:270-281. DOI: https://doi.org/10.1001/jamapsychiatry.2016.3783</mixed-citation></ref><ref id="B22"><mixed-citation>22. Checknita D, Ekstr&amp;ouml;m TJ, Comasco E, et al. Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women. Journal of Neural Transmission. 2018;125(7):1053-1064. DOI: https://doi.org/10.1007/s00702-018-1875-3</mixed-citation></ref><ref id="B23"><mixed-citation>23. Marzi SJ, Sugden K, Arseneault L, et al. Analysis of DNA methylation in young people: limited evidence for an association between victimization stress and epigenetic variation in blood. American Journal of Psychiatry. 2018;175(6):517-529. DOI: https://doi.org/10.1176/appi.ajp.2017.17060693</mixed-citation></ref><ref id="B24"><mixed-citation>24. Leen-Feldner EW, Feldner MT, Knapp A, et al. Offspring psychological and biological correlates of parental posttraumatic stress: review of the literature and research agenda. Clinical Psychology Review. 2013;33(8):1106-1133. DOI: https://doi.org/10.1016/j.cpr.2013.09.001</mixed-citation></ref><ref id="B25"><mixed-citation>25. Lambert JE, Holzer J, Hasbun A. Association between parents&amp;rsquo; PTSD severity and children&amp;rsquo;s psychological distress: a meta-analysis. Journal of Traumatic Stress. 2014;27(1):9-17. DOI: https://doi.org/10.1002/jts.21891</mixed-citation></ref><ref id="B26"><mixed-citation>26. 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. American Journal of Psychiatry. 2014;171:872-880. DOI: https://doi.org/10.1176/appi.ajp.2014.13121571</mixed-citation></ref><ref id="B27"><mixed-citation>27. Rodgers AB, Bale TL. Germ cell origins of posttraumatic stress disorder risk: the transgenerational impact of parental stress experience. Biological Psychiatry. 2015;78:307-314. DOI: https://doi.org/10.1016/j.biopsych.2015.03.018</mixed-citation></ref><ref id="B28"><mixed-citation>28. Moog NK, Buss C, Entringer S, et al. Maternal exposure to childhood trauma is associated during pregnancy with placental-fetal stress physiology. Biological Psychiatry. 2016;79:831-839. DOI: https://doi.org/10.1016/j.biopsych.2015.08.032</mixed-citation></ref><ref id="B29"><mixed-citation>29. Buss C, Entringer S, Moog NK, et al. Intergenerational transmission of maternal childhood maltreatment exposure: implications for fetal brain development. Journal of the American Academy of Child and Adolescent Psychiatry. 2017;56:373-382. DOI: https://doi.org/10.1016/j.jaac.2017.03.001</mixed-citation></ref><ref id="B30"><mixed-citation>30. Cecil CAM, Zhang Y, Nolte T. Childhood maltreatment and DNA methylation: a systematic review. Neuroscience and Biobehavioral Reviews. 2020;112:392-409. DOI: https://doi.org/10.1016/j.neubiorev.2020.02.019</mixed-citation></ref><ref id="B31"><mixed-citation>31. Nievergelt CM, Ashley-Koch AE, Dalvie S, et al. Genomic Approaches to Posttraumatic Stress Disorder: The Psychiatric Genomic Consortium Initiative. Biological Psychiatry. 2018;83(10):831-839. DOI: https://doi.org/10.1016/j.biopsych.2018.01.020</mixed-citation></ref><ref id="B32"><mixed-citation>32. Murgatroyd C, Patchev AV, Wu Y, et al. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nature Neuroscience. 2009;12:1559-1566. DOI: https://doi.org/10.1038/nn.2436</mixed-citation></ref><ref id="B33"><mixed-citation>33. Vijayendran M, Beach SR, Plume JM, et al. Effects of genotype and child abuse on DNA methylation and gene expression at the serotonin transporter. Frontiers in Psychiatry. 2012;3:55. DOI: https://doi.org/10.3389/fpsyt.2012.00055</mixed-citation></ref><ref id="B34"><mixed-citation>34. Haramati S, Navon I, Issler O, et al. MicroRNA as repressors of stress-induced anxiety: the case of amygdalar miR-34. The Journal of Neuroscience. 2011;31(40):14191-14203. DOI: https://doi.org/10.1523/JNEUROSCI.1673-11.2011</mixed-citation></ref><ref id="B35"><mixed-citation>35. Bam M, Yang X, Zumbrun EE, et al. Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation. Scientific Reports. 2016;6:31209. DOI: https://doi.org/10.1038/srep31209</mixed-citation></ref><ref id="B36"><mixed-citation>36. Wingo AP, Almli LM, Stevens JJ, et al. DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression. Nature communications. 2015;6:10106. DOI: https://doi.org/10.1038/ncomms10106</mixed-citation></ref><ref id="B37"><mixed-citation>37. Guffanti G, Galea S, Yan L, et al. Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women. Psychoneuroendocrinology. 2013;38(12):3029-3038. DOI: https://doi.org/10.1016/j.psyneuen.2013.08.014</mixed-citation></ref><ref id="B38"><mixed-citation>38. Yehuda R, Daskalakis NP, Desarnaud F, et al. Epigenetic biomarkers as predictors and correlates of symptom improvement following psychotherapy in combat veterans with PTSD. Frontiers in Psychiatry. 2013;4:118. DOI: https://doi.org/10.3389/fpsyt.2013.00118</mixed-citation></ref><ref id="B39"><mixed-citation>39. Labonte B, Azoulay N, Yerko V, et al. Epigenetic modulation of glucocorticoid receptors in posttraumatic stress disorder. Translational Psychiatry. 2014;4:e368. DOI: https://doi.org/10.1038/tp.2014.3</mixed-citation></ref><ref id="B40"><mixed-citation>40. Radtke KM, Ruf M, Gunter HM, et al. Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Translational Psychiatry. 2011;1:e21. DOI: https://doi.org/10.1038/tp.2011.21</mixed-citation></ref><ref id="B41"><mixed-citation>41. Labonte B, Yerko V, Gross J, et al. Differential glucocorticoid receptor exon 1(B), 1(C), and 1(H) expression and methylation in suicide completers with a history of childhood abuse. Biological Psychiatry. 2012;72:41-48. DOI: https://doi.org/10.1016/j.biopsych.2012.01.034</mixed-citation></ref><ref id="B42"><mixed-citation>42. Turecki G, Meaney MJ. Effects of the social environment and stress on glucocorticoid receptor gene methylation: a systematic review. Biological Psychiatry. 2016;79(2):87-96. DOI: https://doi.org/10.1016/j.biopsych.2014.11.022</mixed-citation></ref><ref id="B43"><mixed-citation>43. Wang Q, Shelton RC, Dwivedi Y. Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: a systematic review and meta-analysis. Journal of Affective Disorders. 2018;118(24):6072-6078. DOI: https://doi.org/10.1002/cncr.27633</mixed-citation></ref><ref id="B44"><mixed-citation>44. Klengel T, Mehta D, Anacker C, et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nature Neuroscience. 2013;16:33-41. DOI: https://doi.org/10.1038/nn.3275</mixed-citation></ref><ref id="B45"><mixed-citation>45. McNerney MW, Sheng T, Nechvatal JM, et al. Integration of neural and epigenetic contributions to posttraumatic stress symptoms: the role of hippocampal volume and glucocorticoid receptor gene methylation. PLoS ONE. 2018;13:e0192222. DOI: https://doi.org/10.1371/journal.pone.0192222</mixed-citation></ref><ref id="B46"><mixed-citation>46. Zannas AS, Arloth J, Carrillo-Roa T, et al. Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling. Genome Biology. 2015;16:266. DOI: https://doi.org/10.1186/s13059-015-0828-5</mixed-citation></ref><ref id="B47"><mixed-citation>47. Iourov IY, Vorsanova SG, Kurinnaia OS, et al. Causes and Consequences of Genome Instability in Psychiatric and Neurodegenerative Diseases. Molecular Biolology. 2021;55:37-46. DOI: https://doi.org/10.1134/S0026893321010155</mixed-citation></ref><ref id="B48"><mixed-citation>48. Iourov IY, Yurov YB, Vorsanova SG, et al. Chromosome Instability, Aging and Brain Diseases. Cells. 2021;10(5):1256. DOI: https://doi.org/10.3390/cells10051256</mixed-citation></ref><ref id="B49"><mixed-citation>49. Vorsanova SG, Yurov YB, Iourov IY. Dynamic nature of somatic chromosomal mosaicism, genetic-environmental interactions and therapeutic opportunities in disease and aging. Molecular Cytogenetics. 2020;13:16. DOI: https://doi.org/10.1186/s13039-020-00488-0</mixed-citation></ref><ref id="B50"><mixed-citation>50. Heng HH, Regan S, Ye CJ. Genotype, environment, and evolutionary mechanism of diseases. Environmental Disease. 2016;1:14-23.</mixed-citation></ref><ref id="B51"><mixed-citation>51. Ramikie TS, Ressler KJ. Stress-related disorders, pituitary adenylate cyclase-activating peptide (PACAP)ergic system, and sex differences. Dialogues in Clinical Neuroscience. 2016;18(4):403-413. DOI: https://doi.org/10.31887/DCNS.2016.18.4/kressler</mixed-citation></ref><ref id="B52"><mixed-citation>52. Lind MJ, Marraccini ME, Sheerin CM, et al. Association of Posttraumatic Stress Disorder With rs2267735 in the ADCYAP1R1 Gene: A Meta-Analysis. Journal of Traumatic Stress. 2017;30(4):389-398. DOI: https://doi.org/10.1002/jts.22211</mixed-citation></ref><ref id="B53"><mixed-citation>53. Maddox SA, Kilaru V, Shin J, et al. Estrogen-dependent association of HDAC4 with fear in female mice and women with PTSD. Molecular Psychiatry. 2018;23(3):658-665. DOI: https://doi.org/10.1038/mp.2016.250</mixed-citation></ref><ref id="B54"><mixed-citation>54. Uddin M, Aiello AE, Wildman DE, et al. Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(20):9470-9475. DOI: https://doi.org/10.1073/pnas.0910794107</mixed-citation></ref><ref id="B55"><mixed-citation>55. Smith AK, Conneely KN, Kilaru V, et al. Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2011;156B(6):700-708. DOI: https://doi.org/10.1002/ajmg.b.31212</mixed-citation></ref><ref id="B56"><mixed-citation>56. Bam M, Yang X, Zhou J, et al. Evidence for epigenetic regulation of pro-inflammatory cytokines, interleukin-12 and interferon gamma, in peripheral blood mononuclear cells from PTSD patients. Journal of Neuroimmune Pharmacology. 2016;11(1):168-181. DOI: https://doi.org/10.1007/s11481-015-9643-8</mixed-citation></ref><ref id="B57"><mixed-citation>57. Iourov IY, Vorsanova SG, Yurov YB, et al. Ontogenetic and Pathogenetic Views on Somatic Chromosomal Mosaicism. Genes. 2019;10(5):379. DOI: https://doi.org/10.3390/genes10050379</mixed-citation></ref><ref id="B58"><mixed-citation>58. Vorsanova SG, Zelenova MA, Yurov YB, et al. Behavioral Variability and Somatic Mosaicism: A Cytogenomic Hypothesis. Current Genomics. 2018;19(3):158-162. DOI: https://doi.org/10.2174/1389202918666170719165339</mixed-citation></ref><ref id="B59"><mixed-citation>59. Iourov IY, Vorsanova SG, Yurov YB, et al. The Cytogenomic &amp;ldquo;Theory of Everything&amp;rdquo;: Chromohelkosis May Underlie Chromosomal Instability and Mosaicism in Disease and Aging. International Journal of Molecular Sciences. 2020;21(21):8328. DOI: https://doi.org/10.3390/ijms21218328</mixed-citation></ref><ref id="B60"><mixed-citation>60. Liu G, Ye CJ, Chowdhury SK, et al. Detecting chromosome condensation defects in gulf war illness patients. Current Genomics. 2018;19:200-206. DOI: https://doi.org/10.2174/1389202918666170705150819</mixed-citation></ref><ref id="B61"><mixed-citation>61. Mehta D, Bruenig D, Carrillo-Roa T, et al. Genome-wide DNA methylation analysis in combat veterans reveals a novel locus for PTSD. Acta Psychiatrica Scandinavica. 2017;136(5):493-505. DOI: https://doi.org/10.1111/acps.12778</mixed-citation></ref><ref id="B62"><mixed-citation>62. Rutten BPF, Vermetten E, Vinkers CH, et al. Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder. Molecular Psychiatry. 2018;23(5):1145-1156. DOI: https://doi.org/10.1038/mp.2017.120</mixed-citation></ref><ref id="B63"><mixed-citation>63. Uddin M, Ratanatharathorn A, Armstrong D, et al. Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder. Epigenomics. 2018;10(12):1585-1601. DOI: https://doi.org/10.2217/epi-2018-0049</mixed-citation></ref><ref id="B64"><mixed-citation>64. de Lange GM. Understanding the cellular and molecular alterations in PTSD brains: the necessity of post-mortem brain tissue. European Journal of Psychotraumatology. 2017;8(1):1341824. DOI: https://doi.org/10.1080/20008198.2017.1341824</mixed-citation></ref><ref id="B65"><mixed-citation>65. Bhatt S, Hillmer AT, Girgenti MJ, et al. PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies. Nature Communications. 2020;11:2360. DOI: https://doi.org/10.1038/s41467-020-15930-5</mixed-citation></ref><ref id="B66"><mixed-citation>66. Wolf EJ, Logue MW, Hayes JP, et al. Accelerated DNA methylation age: associations with PTSD and neural integrity. Psychoneuroendocrinology. 2016;63:155-162. DOI: https://doi.org/10.1016/j.psyneuen.2015.09.020</mixed-citation></ref></ref-list></back></article>