Epigenetic Effects of Social Stress and Epigenetic Inheritance

Öz

Social events that cause stress can cause epigenetic changes on living things. The study of the effects of social events experienced by an individual on epigenetic marks on the genome has created the field of social epigenetics. Social epigenetics examines the effects of psychosocial stress factors such as poverty, war trauma and childhood abuse on epigenetic mechanisms. Epigenetic mechanisms alter chemical markers in the genome structure without changing the DNA sequence. Among these mechanisms, DNA methylation in particular may have different phenotypic effects in response to stressors that may occur in the psychosocial environment. Post-traumatic stress disorder is one of the most significant proofs of the effects of epigenetic expressions altered due to traumatic events on the phenotype. The field of epigenetic inheritance has shown that epigenetic changes triggered by environmental influences can, in some cases, be transmitted through generations. This field provides a better understanding of the basis of many psychological disorders. This review provides an overview of social epigenetics, PTSD, and epigenetic inheritance.

Anahtar Kelimeler

• Social epigenetics
• stress
• DNA methylation
• post traumatic stress disorder
• epigenetic inheritance

Sosyal Stresin Epigenetik Etkileri ve Epigenetik Kalıtım

Öz

Stres oluşturan sosyal olaylar, canlı üzerinde epigenetik değişimlere sebep olabilmektedir. Bir bireyin sosyal açıdan yaşadığı olayların genom üzerindeki epigenetik işaretlere olan etkisinin incelenmesi, sosyal epigenetik alanını oluşturmuştur. Sosyal epigenetik; yoksulluk, savaş travması, çocukluk dönemi istismarı gibi psikososyal stres faktörlerinin epigenetik mekanizmalar üzerine etkisini incelemektedir. Epigenetik mekanizmalar DNA dizilimini değiştirmeden genom yapısındaki kimyasal işaretleri değiştirmektedir. Bu mekanizmalardan özellikle DNA metilasyonu, psikososyal ortamlarda oluşabilecek stres faktörlerine yanıt vererek farklı fenotipik etkiler meydana getirebilir. Travma sonrası stres bozukluğu (TSSB), travmatik olaylar sonucu değişen epigenetik ifadelerin fenotipteki etkilerinin en büyük kanıtlarından biridir. Epigenetik kalıtım alanı, çevresel etkilerin tetiklediği epigenetik değişimlerin bazı durumlarda nesiller boyu aktarılabildiği göstermiştir. Bu alan birçok psikolojik rahatsızlığın temelinin daha iyi anlaşılabilmesine olanak sağlamaktadır. Bu derlemede sosyal epigenetik, TSSB ve epigenetik kalıtım konularına genel bir bakış sunulmuştur.

Anahtar Kelimeler

• Sosyal epigenetik
• stres
• DNA metilasyonu
• travma sonrası stres bozukluğu
• epigenetik kalıtım

Kaynakça

1. Almli LM, Fani N, Smith, AK, Ressler KJ (2014) Genetic approaches to understanding post-traumatic stress disorder. The international journal of neuropsychopharmacology, 17(2):355–370. 
2. Bahari-Javan S, Sananbenesi F, Fischer A (2014) Histone-acetylation: a link between Alzheimer’s disease and post-traumatic stress disorder? Frontiers in Neuroscience, 8:160.
3. Bannister AJ, Kouzarides T. (2011) Regulation of chromatin by histone modifications. Cell Res, 21:381–395. 
4. Beck D, Sadler-Riggleman I, Skinner MK (2017) Generational comparisons (F1 versus F3) of vinclozolin induced epigenetic transgenerational inheritance of sperm differential DNA methylation regions (epimutations) using MeDIP-Seq. Environ Epigenet, 3:016.
5. Bisson JI, Cosgrove S, Lewis C, Roberts NP (2015) Post-traumatic stress disorder. BMJ, 351:h6161. 
6. Bohacek J, Mansuy I (2013) Epigenetic Inheritance of Disease and Disease Risk. Neuropsychopharmacol, 38:220–236. 
7. Bošković A, Rando OJ (2018) Transgenerational Epigenetic Inheritance. Annual Review of Genetics, 52:21-41.:21-41
8. Braithwaite EC, Kundakovic M, Ramchandani PG, Murphy SE, Champagne FA (2015) Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation. Epigenetics, 10:408–17.

9. Brigadski T, Lessmann V (2014) BDNF: A regulator of learning and memory processes with clinical potential. e-Neuroforum, 5:1-11.
10. Brown AS (2012) Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism. Dev Neurobiol, 72(10):1272-6.
11. Bryant RA (2019) Post-traumatic stress disorder: a state-of-the-art review of evidence and challenges. World psychiatry Official Journal of the World Psychiatric Association (WPA), 18(3):259–269.
12. Burggren WW (2015) Dynamics of epigenetic phenomena: intergenerational and intragenerational phenotype “washout”. J. Exp. Biol, 218:80–87.
13. Burton NO ve Greer EL (2021) Multigenerational epigenetic inheritance: Transmitting information across generations. Seminars in Cell & Developmental Biology.
14. Cavalli G, Heard E (2019) Advances in epigenetics link genetics to the environment and disease. Nature, 571:489–499.
15. Champagne FA (2018) Social and Behavioral Epigenetics: Evolving Perspectives on Nature-Nurture Interplay, Plasticity, and Inheritance. The Palgrave Handbook of Biology and Society, 227–250.
16. Claudino FCA, Gonçalves L, Schuch FB, Martins HRS, Rocha NS (2020) The Effects of Individual Psychotherapy in BDNF Levels of Patients With Mental Disorders: A Systematic Review. Front. Psychiatry, 11:445.
17. Curley JP, Mashoodh R, Champagne FA (2011) Epigenetics and the origins of paternal effects. Hormones and behavior, 59(3), 306–314.
18. Daxinger L, Whitelaw E. (2012) Understanding transgenerational epigenetic inheritance via the gametes in mammals. Nature Reviews Genetics, 13(3), 153–162.
19. Fernandez-Twinn DS, Constância M, Ozanne SE (2015) Intergenerational epigenetic inheritance in models of developmental programming of adult disease: Seminars in Cell & Developmental Biology, 43: 85–95.
20. Fischer S, Schumacher T, Knaevelsrud C et al. (2021) Genes and hormones of the hypothalamic–pituitary–adrenal axis in post-traumatic stress disorder. What is their role in symptom expression and treatment response?. J Neural Transm, 128:1279–1286.
21. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien, F, Ballestar ML et al. (2005) From The Cover: Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences, 102(30):10604–10609.
22. Franklin TB, Russig H, Weiss IC, Gräff J, Linder N, Michalon A, Vizi S, Mansuy IM (2010) Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry, 1;68(5):408-15.
23. Glaser R, Kiecolt-Glaser JK (2005) Stress-induced immune dysfunction: implications for health. Nat Rev Immunol, 5:243–251.
24. Guerrero T, Fickel J, Benhaiem S, Weyrich A (2020) Epigenomics and gene regulation in mammalian social systems. Current Zoology, 66(3):307-319.
25. Gunnar M, Quevedo K (2007) The neurobiology of stress and development. Annu. Rev. Psychol, 58:145–73.
26. Harris A, Seckl J (2011) Glucocorticoids, prenatal stress and the programming of disease. Hormones and Behavior, 59(3):279–289.
27. Heard E, Martienssen RA (2014) Transgenerational Epigenetic Inheritance: Myths and Mechanisms. Cell, 157(1):95–109. 
28. Henigsberg N, Kalember P, Petrović ZK, Šečić A (2019) Neuroimaging research in posttraumatic stress disorder – Focus on amygdala, hippocampus and prefrontal cortex. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 90: 37–42.
29. Horsthemke B (2018) A critical view on transgenerational epigenetic inheritance in humans. Nature Communications, 9(1):2973.
30. Howie H, Rijal CM, Ressler KJ (2019) A review of epigenetic contributions
to post-traumatic stress disorder. Dialogues in clinical neuroscience, 21(4):417–428. 
31. Jawaid A, Roszkowski M, Mansuy IM (2018) Transgenerational Epigenetics of Traumatic Stress. Neuroepigenetics and Mental Illness, 158: 273-298.
32. Jenuwein T, Allis C (2001) Translating the Histone Code. Science, 10;293(5532):1074-80.
33. Jiang S, Postovit L, Cattaneo A, Binder EB, Aitchison KJ (2019) Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma. Frontiers in Psychiatry, 10.
34. Johansson A, Enroth S, Gyllensten U (2013) Continuous aging of the human DNA methylome throughout the human lifespan. PLOS ONE, 8(6): e67378.
35. Jones PA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet, 13:484–92.
36. Kanherkar RR, Bhatia-Dey N, Csoka AB. (2014) Epigenetics across the human lifespan. Frontiers in Cell and Developmental Biology, 2:49.
37. Kanwal R, Gupta S (2012) Epigenetic modifications in cancer. Clin Genet, 81(4):303-11.
38. Kapoor A, Matthews SG (2005) Short periods of prenatal stress affect growth, behaviour and hypothalamo-pituitary-adrenal axis activity in male guinea pig offspring. J Physiol, 1;566(Pt 3):967-77.
39. Kertes DA, Kamin HS, Hughes DA, Rodney NC, Bhatt S, Mulligan CJ (2016) Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo. Child Dev, 87(1):61-72.
40. Kim GS, Smith AK, Nievergelt CM, Uddin M (2018) Neuroepigenetics of Post-Traumatic Stress Disorder. Neuroepigenetics and Mental Illness, 158:227–253.
41. Klengel T, Dias BG, Ressler KJ (2016) Models of Intergenerational and Transgenerational Transmission of Risk for Psychopathology in Mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology,41(1): 219–231.
42. Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC, Pariante CM, Bradley B (2013) Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nature Neuroscience, 16(1):33–41.
43. Klose RJ, Bird AP (2006) Genomic DNA methylation: the mark and its mediators. Trends Biochem. Sci, 31:89–97.
44. Kouzarides T (2007) Chromatin modifications and their function. Cell, 128:693–705.
45. Kubsad D, Nilsson EE, King SE, Sadler-Riggleman I, Beck D et al. (2019) Assessment of glyphosate induced epigenetic transgenerational inheritance of pathologies and sperm epimutations: generational toxicology. Sci Rep, 9:1–17.
46. Kürekçi̇ GK, Bunsuz M, Önal G, Di̇nçer PR (2017) Inheritance of acquired epigenetic modifications and its role in disease susceptibility. Journal of Istanbul Faculty of Medicine, 80 (1):45-53.
47. Lacal I, Ventura R (2018) Epigenetic Inheritance: Concepts, Mechanisms and Perspectives. Frontiers in Molecular Neuroscience, 11.
48. Landecker H, Panofsky A (2013) From Social Structure to Gene Regulation, and Back: A Critical Introduction to Environmental Epigenetics for Sociology. Annual Review of Sociology, 39:1,333-357
49. Lehrner A, Yehuda, R (2018) Cultural trauma and epigenetic inheritance. Development and Psychopathology, 30(5):1763-1777.
50. Maeng LY, Milad MR (2017) Post-Traumatic Stress Disorder: The Relationship Between the Fear Response and Chronic Stress. Chronic stress (Thousand Oaks, Calif.), 1:2470547017713297.
51. McCormick C, Mathews I (2010) Adolescent development, hypothalamic-pituitary-adrenal function, and programming of adult learning and memory. Progress In Neuro-Psychopharmacology And Biological Psychiatry, 34(5):756-765.
52. McGrath J, Solter D (1984) Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell, 37:179–183.
53. McNerney MW, Sheng T, Nechvatal JM, Lee AG, Lyons DM, Soman S et al. (2018) Integration of neural and epigenetic contributions to posttraumatic stress symptoms: The role of hippocampal volume and glucocorticoid receptor gene methylation. PLOS ONE, 13(2): e0192222.
54. Mehta D, Pelzer ES, Bruenig D, Lawford B, McLeay S, Morris CP et al (2019). DNA methylation from germline cells in veterans with PTSD. Journal of Psychiatric Research, 116:42–50. 
55. Meyer U, Feldon J, Dammann O (2011) Schizophrenia and autism: both shared and disorder-specific pathogenesis via perinatal inflammation? Pediatr Res, 69(5 Pt 2):26R-33R.
56. Mulligan C (2016) Early Environments, Stress, and the Epigenetics of Human Health. Annual Review of Anthropology, 45(1):233-249.
57. Murgatroyd C, Spengler D (2011) Epigenetics of early child development. Front Psychiatry, 2:16.
58. Murray SL, Holton KF (2021) Post-traumatic stress disorder may set the neurobiological stage for eating disorders: A focus on glutamatergic dysfunction. Appetite, 167:105599.
59. Neylan TC (1998) Hans Selye and the Field of Stress Research. The Journal of Neuropsychiatry and Clinical Neurosciences, 10(2):230–230.
60. Oberlander TF, Weinberg J, Papsdorf M, Grunau R, Misri S, Devlin AM (2008) Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics, 3:97–106.
61. Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell, 99:247-257.
62. Palma-Gudiel H, Córdova-Palomera A, Leza JC, Fañanás L (2015b) Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: a critical review. Neurosci. Biobehav. Rev, 55: 520–35.
63. Prakash, J, Saha A, Das RC, Srivastava, K, Shashikumar R (2016) Post traumatic stress disorder. Medical journal, Armed Forces India, 72(2):189–191. 
64. Qi W, Gevonden M, Shalev A (2016) Prevention of Post-Traumatic Stress Disorder After Trauma: Current Evidence and Future Directions. Current psychiatry reports, 18(2): 20.
65. Radtke KM, Ruf M, Gunter HM, Dohrmann K, Schauer M, Meyer A et al. (2011) Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Transl. Psychiatry, 1:e21.  Rodney NC, Mulligan CJ (2014) A biocultural study of the effects of maternal stress on mother and newborn health in the Democratic Republic of Congo. Am. J. Phys. Anthropol, 155: 200-9.
66. Roth TL, Lubin FD, Funk AJ, Sweatt JD (2009) Lasting epigenetic influence of early-life adversity on the BDNF gene. Biological Psychiatry, 65(9):760–769.
67. Sarkies P (2019) Molecular mechanisms of epigenetic inheritance: Possible evolutionary implications. Semin Cell Dev Biol, 97:106-115.
68. Schneiderman N, Ironson G, Siegel SD (2005) Stress and Health: Psychological, Behavioral, and Biological Determinants. Annual Review of Clinical Psychology, 1(1):607–628.
69. Schnurr PP, Friedman MJ, Bernardy NC (2002) Research on posttraumatic stress disorder: epidemiology, pathophysiology, and assessment. Journal of clinical psychology, 58(8):877–889. 
70. Shin LM, Shin PS, Heckers S, Krangel TS, Macklin ML, Orr SP et al. (2004) Hippocampal function in posttraumatic stress disorder. Hippocampus, 14(3):292–300.
71. Smith AK, Conneely KN, Kilaru V, Mercer KB, Weiss TE, Bradley B et al. (2011) Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 156B(6):700–708. 
72. Spencer K (2017) Developmental stress and social phenotypes: integrating neuroendocrine, behavioural and evolutionary perspectives. Philosophical Transactions Of The Royal Society B: Biological Sciences, 372(1727):20160242. 
73. Takei S, Morinobu S, Yamamoto S, Fuchikami M, Matsumoto T, Yamawaki S (2011) Enhanced hippocampal BDNF/TrkB signaling in response to fear conditioning in an animal model of posttraumatic stress disorder. Journal of Psychiatric Research, 45(4):460-468.
74. Turecki G, Meaney MJ (2016) Effects of the social environment and stress on glucocorticoid receptor gene methylation: a systematic review. Biol. Psychiatry, 79:87–96.
75. van Otterdijk SD, Michels KB (2016) Transgenerational epigenetic inheritance in mammals: how good is the evidence? The FASEB Journal, 30(7):2457–2465.
76. Vukojevic V, Kolassa IT, Fastenrath M, Gschwind L, Spalek K, Milnik A et al. (2014) Epigenetic modification of the glucocorticoid receptor gene is linked to traumatic memory and post-traumatic stress disorder risk in genocide survivors. J Neurosci, 30;34(31):10274-84.
77. Waterland RA, Michels KB (2007) Epigenetic epidemiology of the developmental origins hypothesis. Annu. Rev. Nutr, 27:363–88.
78. Weaver IC, Cervoni N, Champagne FA, D'Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (2004) Epigenetic programming by maternal behavior. Nat Neurosci, 7(8):847-54.
79. Weinstock M. (2001) Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Prog Neurobiol, 65(5):427-51.
80. Wingfield, JC, Romero LM (2011) Adrenocortical Responses to Stress and Their Modulation in Free‐Living Vertebrates. Comprehensive Physiology, 211-234.
81. Xu L, Sun Y, Gao L, Cai YY, Shi SX (2014) Prenatal restraint stress is associated with demethylation of corticotrophin releasing hormone (CRH) promoter and enhances CRH transcriptional responses to stress in adolescent rats. Neurochemical Research, 39(7):1192–1198.
82. Yurdakök K, Çelik M (2019) Çocuk istismarı ve ihmalinin epigenetik etkileri. Çocuk Sağlığı ve Hastalıkları Dergisi, 62: 17-30.
83. Zhao M, Wang W, Jiang Z, Zhu Z, Liu D, Pan F (2020) Long-Term Effect of Post-traumatic Stress in Adolescence on Dendrite Development and H3K9me2/BDNF Expression in Male Rat Hippocampus and Prefrontal Cortex. Frontiers in Cell and Developmental Biology, 8.