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Обозрение психиатрии и медицинской психологии имени В.М.Бехтерева

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Выявление биологических основ психических заболеваний: эпигенетические исследования как новое направление в диагностике и лечении

https://doi.org/10.31363/2313-7053-2021-56-3-19-31

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Аннотация

Резюме. Психические расстройства являются клинически неоднородными хроническими заболеваниями, возникающими в результате сложного взаимодействия между вариантами генотипа и факторами окружающей среды. Эпигенетические процессы, такие как метилирование ДНК и посттрансляционная модификация гистонов, определяют интерпретацию организмом на клеточном и тканевом уровне разнообразных факторов воздействия внешней среды. Учитывая, что эпигенетические модификации чувствительны к окружающей среде, стабильны и обратимы, эпигенетические исследования в области психиатрии могут быть многообещающим подходом к лучшему пониманию и лечению психических заболеваний. В настоящем обзоре обсуждаются клинические возможности и проблемы, возникающие в ходе эпигенетических исследований в психиатрии. Используя отдельные примеры, делаются основные выводы, подтверждающие роль неблагоприятных жизненных событий, отдельно или в сочетании с генетическим риском, в эпигенетическом программировании нервно-психиатрических систем. Дальнейшие эпигенетические исследования показывают обнадеживающие результаты в использовании изменений метилирования как диагностических маркеров проявлений заболевания и выявляют предиктивные инструменты оценки прогрессии и ответа на лечение. Далее обсуждается потенциал использования таргетной эпигенетической фармакотерапии, в сочетании с психосоциальными методами в контексте персонализированной медицины будущего в психиатрии. В заключении рассматриваются методологические ограничения, которые могут затруднять интерпретацию эпигенетических данных в психиатрии. В основном они возникают из-за гетерогенности индивидов как на уровне целого организма, так и на уровне тканей и требуют новых стратегий для лучшей оценки биологической значмости эпигенетических данных и их трансляционного использования в психиатрии. В целом, мы полагаем, что эпигенетика может обеспечить новые идеи и более всестороннее понимание этиологии и патогенеза психических заболеваний и должна в конечном итоге улучшить нозологию, лечение и профилактику психических расстройств.

Об авторах

С. Е. Хальчицкий
Национальный медицинский исследовательский центр детской травматологии и ортопедии им. Г.И.Турнера
Россия

Хальчицкий Сергей Егорович

Санкт-Петербург



М. В. Иванов
Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева
Россия

Иванов Михаил Владимирович

Санкт-Петербург



М. В. Согоян
Национальный медицинский исследовательский центр детской травматологии и ортопедии им. Г.И.Турнера
Россия

Согоян Марина Ваниковна

Санкт-Петербург



М. Г. Янушко
Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева
Россия

Янушко Мария Григорьевна

Санкт-Петербург



М. А. Тумова
Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева
Россия

Тумова Марианна Анатольевна

Санкт-Петербург



Л. М. Муслимова
Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева
Россия

Муслимова Лилия Мухаметшевна

Санкт-Петербург



В. В. Становая
Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева
Россия

Становая Виктория Владимировна

Санкт-Петербург



Ю. В. Хуторянская
Санкт-Петербургский государственный педиатрический медицинский университет
Россия

Хуторянская Юлия Валерьевна

Санкт-Петербург



С. В. Виссарионов
Национальный медицинский исследовательский центр детской травматологии и ортопедии им. Г.И.Турнера
Россия

Виссарионов Сергей Валентинович

Санкт-Петербург



Список литературы

1. Abdolmaleky HM, Cheng KH, Faraone SV, Wilcox M, Glatt SJ, Gao F, et al. Hypomethylation of MBCOMT promoter is a major risk factor for schizophrenia and bipolar disorder. Hum. Mol. Genet. 2006; 15:3132–3145. doi: 10.1093/hmg/ddl253.

2. Abdolmaleky HM, Zhou JR, Thiagalingam S. An update on the epigenetics of psychotic diseases and autism. Epigenomics. 2015; 7:427–449. doi: 10.2217/epi.14.85.

3. Adriani W, Romano E, Pucci M, Pascale E, Cerniglia L, Cimino S et al. Potential for diagnosis versus therapy monitoring of attention deficit hyperactivity disorder: A new epigenetic biomarker interacting with both genotype and auto-immunity. Eur. Child Adolesc. Psychiatry. 2018; 27(2):241-252. doi:10.1007/s00787-017-1040-9.

4. Andersen AM, Philibert RA, Gibbons FX, Simons RL, Long J. Accuracy and utility of an epigenetic biomarker for smoking in populations with varying rates of false self-report. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2017; 174:641–650. doi: 10.1002/ajmg.b.32555.

5. Bakulski KM, Halladay A, Hu VW, Mill J, Fallin MD. Epigenetic research in neuropsychiatric disorders: The «Tissue Issue.». Curr. Behav. Neurosci. Rep. 2016; 3:264–274. doi: 10.1007/s40473-016-0083-4.

6. Belsky J, Pluess M. Beyond diathesis stress: Differential susceptibility to environmental influences. Psychol. Bull. 2009; 135:885–908. doi: 10.1037/a0017376.

7. Birur B, Kraguljac NV, Shelton RC, Lahti AC. Brain structure, function, and neurochemistry in schizophrenia and bipolar disorder: A systematic review of the magnetic resonance neuroimaging literature. NPJ Schizophr. 2017; 3:15. doi: 10.1038/s41537-017-0013-9.

8. Busche S, Shao X, Caron M, Kwan T, Allum F, Cheung WA et al. Population whole-genome bisulfite sequencing across two tissues highlights the environment as the principal source of human methylome variation. Genome Biol. 2015; 16:290. doi: 10.1186/s13059-015-0856-1.

9. Campbell IC, Mill J, Uher R, Schmidt U. Eating disorders, gene-environment interactions and epigenetics. Neurosci. Biobehav. Rev. 2011; 35:784–793. doi: 10.1016/j.neubiorev.2010.09.012.

10. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington HL et al. Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science. 2003; 301: 386–389. doi: 10.1126/science.1083968.

11. Cecil CA, Smith RG, Walton E, Mill J, McCrory EJ, Viding E. Epigenetic signatures of childhood abuse and neglect: Implications for psychiatric vulnerability. J. Psychiatr. Res. 2016; 83:184–194. doi: 10.1016/j.jpsychires.2016.09.010.

12. Chen L, Ge B, Casale FP Vasquez L, Kwan T, Garrido-Martín D et al. Genetic drivers of epigenetic and transcriptional variation in human immune cells. Cell. 2016; 167:1398–1414. doi: 10.1016/j.cell.2016.10.026.

13. Clive ML, Boks MP, Vinkers CHm Osborne LM, Payne JL, Kerry Ressler J et al. Discovery and replication of a peripheral tissue DNA methylation biosignature to augment a suicide prediction model. Clin. Epigenetics. 2016; 8:113. doi: 10.1186/s13148-016-0279-1.

14. Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: A genome-wide analysis. Lancet. 2013; 381:1371–1379. doi: 10.1016/S0140-6736(12)62129-1.

15. D’Addario C, Micale V, Di Bartolomeo M, Stark T, Pucci M, Sulcova A et al. A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia. Schizophr. Res. 2017; 188:132–140. doi: 10.1016/j.schres.2017.01.022.

16. Daskalakis NP, Oitzl MS, Schachinger H, Champagne DL, de Kloet ER. Testing the cumulative stress and mismatch hypotheses of psychopathology in a rat model of early-life adversity. Physiol. Behav. 2012; 106:707–721. doi: 10.1016/j.physbeh.2012.01.015.

17. Davies MN, Volta M, Pidsley R, Lunnon K, Dixit A, Lovestone S et al. Functional annotation of the human brain methylome identifies tissuespecific epigenetic variation across brain and blood. Genome Biol. 2012; 13:R43. doi: 10.1186/gb-2012-13-6-r43.

18. Doherty TS, Roth TL. Insight from animal models of environmentally driven epigenetic changes in the developing and adult brain. Dev. Psychopathol. 2016; 28:1229–1243. doi: 10.1017/S095457941600081X.

19. Fiori LM, Turecki G. Investigating epigenetic consequences of early-life adversity: Some methodological considerations. Eur. J. Psychotraumatol. 2016; 7:31593. doi: 10.3402/ejpt.v7.31593.

20. Fries GR, Li Q, McAlpin B, Rein T, Walss-Bass C, Jair C Soares JC et al. The role of DNA methylation in the pathophysiology and treatment of bipolar disorder. Neurosci. Biobehav. Rev. 2016; 68: 474–488. doi: 10.1016/j.neubiorev.2016.06.010.

21. Fuchikami M, Morinobu S, Segawa M, Okamoto Y, Yamawaki S, Ozaki N et al. DNA methylation profiles of the brain-derived neurotrophic factor (BDNF) gene as a potent diagnostic biomarker in major depression. PLoS ONE. 2011; 6:e23881. doi: 10.1371/journal.pone.0023881.

22. Fuchikami M, Yamamoto S, Morinobu S, Okada S, Yamawaki Y, Yamawaki S. The potential use of histone deacetylase inhibitors in the treatment of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2016; 64:320–324. doi: 10.1016/j.pnpbp.2015.03.010.

23. Gagliano SA. It’s all in the brain: A review of available functional genomic annotations. Biol. Psychiatry. 2017; 81:478–483. doi: 10.1016/j.biopsych.2016.08.011.

24. Gao X, Jia M, Zhang Y, Breitling LP, Brenner H. DNA methylation changes of whole blood cells in response to active smoking exposure in adults: A systematic review of DNA methylation studies. Clin. Epigenetics. 2015; 7:113. doi: 10.1186/s13148-015-0148-3.

25. Gao S, Cheng J, Li G et al. Catechol-O-methyltransferase gene promoter methylation as a peripheral biomarker in male schizophrenia. Eur. Psychiatry. 2017; 44:39–46. doi: 10.1016/j.eurpsy.2017.03.002.

26. Giri AK, Bharadwaj S, Banerjee P, Shraddha Chakraborty S, Parekatt V, Rajashekar D et al. DNA methylation profiling reveals the presence of population-specific signatures correlating with phenotypic characteristics. Mol. Genet. Genomics. 2017; 292:655–662. doi: 10.1007/s00438-017-1298-0.

27. Guidotti A, Grayson DR. DNA methylation and demethylation as targets for antipsychotic therapy. Dialogues Clin. Neurosci. 2014; 16:419–429.

28. Guintivano J, Aryee MJ, Kaminsky ZA. A cell epigenotype specific model for the correction of brain cellular heterogeneity bias and its application to age, brain region and major depression. Epigenetics. 2013; 8:290–302. doi: 10.4161/epi.23924.

29. Halldorsdottir T, Binder EB. Gene x environment interactions: From molecular mechanisms to behavior. Annu. Rev. Psychol. 2017; 68:215–241. doi: 10.1146/annurev-psych-010416-044053.

30. Hannon E, Dempster E, Viana J, Burrage J, Smith AR, Macdonald R et al. An integrated genetic-epigenetic analysis of schizophrenia: Evidence for co-localization of genetic associations and differential DNA methylation. Genome Biol. 2016; 17: 176. doi: 10.1186/s13059-016-1041-x.

31. Hannon E, Spiers H, Viana J, Pidsley R, Burrage J, Murphy TM et al. Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci. Nat. Neurosci. 2016; 19:48–54. doi: 10.1038/nn.4182.

32. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013; 14:R115. doi: 10.1186/gb-2013-14-10-r115.

33. Houseman EA, Molitor J, Marsit CJ. Reference-free cell mixture adjustments in analysis of DNA methylation data. Bioinformatics. 2014; 30:1431–1439. doi: 10.1093/bioinformatics/btu029.

34. Ibi D, Gonzalez-Maeso J. Epigenetic signaling in schizophrenia. Cell. Signal. 2015; 27:2131–2136. doi: 10.1016/j.cellsig.2015.06.003.

35. Iwamoto K, Bundo M, Ueda J, Oldham MC, Ukai W, Hashimoto E et al. Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons. Genome Res. 2011; 21:688–696. doi: 10.1101/gr.112755.110.

36. Jaffe AE, Irizarry RA. Accounting for cellular heterogeneity is critical in epigenome-wide association studies. Genome Biol. 2014; 15: R31. doi: 10.1186/gb-2014-15-2-r31.

37. Kang HJ, Kim JM, Lee JY, Kim SY, Bae KY, Kim SW et al. BDNF promoter methylation and suicidal behavior in depressive patients. J. Affect. Disord. 2013; 151:679–685. doi: 10.1016/j.jad.2013.08.001.

38. Karg K, Burmeister M, Shedden K, Sen S. The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: Evidence of genetic moderation. Arch. Gen. Psychiatry. 2011; 68:444–454. doi: 10.1001/archgenpsychiatry.2010.189.

39. Karsli-Ceppioglu S. Epigenetic mechanisms in psychiatric diseases and epigenetic therapy. Drug Dev. Res. 2016; 77: 407–413. doi: 10.1002/ddr.21340.

40. Kebir O, Chaumette B, Rivollier F, Miozzo F, Lemieux Perreault LP, Barhdadi A et al. Methylomic changes during conversion to psychosis. Mol. Psychiatry. 2017; 22:512–518. doi: 10.1038/mp.2016.53.

41. Kozlenkov A, Wang M, Roussos P, Rudchenko S, Barbu M, Bibikova M et al. Substantial DNA methylation differences between two major neuronal subtypes in human brain. Nucleic Acids Res. 2016; 44:2593–2612. doi: 10.1093/nar/gkv1304.

42. Latvala A, Ollikainen M. Mendelian randomization in (epi)genetic epidemiology: An effective tool to be handled with care. Genome Biol. 2016;17:156. doi: 10.1186/s13059-016-1018-9.

43. Li E, Zhang Y. DNA methylation in mammals. Cold Spring Harb. Perspect. Biol. 2014; 6:a019133. doi: 10.1101/cshperspect.a019133.

44. Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: A population-based study. Lancet. 2009; 373:234–239. doi: 10.1016/S0140-6736(09)60072-6.

45. Lisoway AJ, Zai CC, Tiwari AK, Kennedy JL. DNA methylation and clinical response to antidepressant medication in major depressive disorder: A review and recommendations. Neurosci. Lett. 2018; 16;669:14-23. doi: 10.1016/j.neulet.2016.12.071

46. Liu Y, Aryee MJ, Padyukov L, Fallin MD, Hesselberg E, Runarsson A, et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat. Biotechnol. 2013; 31:142–147. doi: 10.1038/nbt.2487.

47. Liu XS, Wu H, Ji X, Stelzer Y, Wu X, Czauderna S et al. Editing DNA methylation in the mammalian genome. Cell. 2016; 167:233–247. doi: 10.1016/j.cell.2016.08.056.

48. Lu CT, Zhao YZ, Wong HL, Cai J, Peng L, Tian XQ. Current approaches to enhance CNS delivery of drugs across the brain barriers. Int. J. Nanomedicine. 2014; 9:2241–2257. doi: 10.2147/IJN.S61288.

49. Massart R, Nemoda Z, Suderman MJ, Sutti S, Ruggiero AM, Dettmer AM et al. Early life adversity alters normal sex-dependent developmental dynamics of DNA methylation. Dev. Psychopathol. 2016; 28:1259–1272. doi: 10.1017/S0954579416000833

50. Mastrototaro G, Zaghi M, Sessa A. Epigenetic mistakes in neurodevelopmental disorders. J. Mol. Neurosci. 2017; 61:590–602. doi: 10.1007/s12031-017-0900-6.

51. McEwen BS. Mood disorders and allostatic load. Biol. Psychiatry. 2003; 54:200–207. doi: 10.1016/s0006-3223(03)00177-x.

52. McGuffin P, Katz R, Watkins S, Rutherford J. A hospitalbased twin register of the heritability of DSM-IV unipolar depression. Arch. Gen. Psychiatry. 1996; 53:129–136. doi: 10.1001/archpsyc.1996.01830020047006.

53. Melas PA, Rogdaki M, Osby U, Schalling M, Lavebratt C, Ekstrom TJ. Epigenetic aberrations in leukocytes of patients with schizophrenia: Association of global DNA methylation with antipsychotic drug treatment and disease onset. FASEB J. 2012; 26:2712–2718. doi: 10.1096/fj.11-202069.

54. Murer MG, Yan Q, Raisman-Vozari R. Brainderived neurotrophic factor in the control human brain, and in Alzheimer’s disease and Parkinson’s disease. Prog. Neurobiol. 2001; 63:71–124. doi: 10.1016/s0301-0082(00)00014-9.

55. Nagy J, Kobolak J, Berzsenyi S, Ábrahám Z, Avci HX, Bock I et al. Altered neurite morphology and cholinergic function of induced pluripotent stem cell-derived neurons from a patient with Kleefstra syndrome and autism. Transl. Psychiatry. 2017; 7:e1179. doi: 10.1038/tp.2017.144.

56. Nagy C, Torres-Platas SG, Mechawar N, Turecki G. Repression of astrocytic connexins in cortical and subcortical brain regions and prefrontal enrichment of H3K9me3 in depression and suicide. Int. J. Neuropsychopharmacol. 2017; 20:50–57. doi: 10.1093/ijnp/pyw071.

57. Ng B, White CC, Klein HU, Sieberts SK, McCabe C, Patrick E et al. An xQTL map integrates the genetic architecture of the human brain’s transcriptome and epigenome. Nat. Neurosci. 2017; 20:1418–1426. doi: 10.1038/nn.4632.

58. Nissen JB, Hansen CS, Starnawska A, Mattheisen M, Børglum AD, Buttenschøn HN and Hollegaard M. DNA methylation at the neonatal state and at the time of diagnosis: Preliminary support for an association with the estrogen receptor 1, gammaaminobutyric acid B receptor 1, and myelin oligodendrocyte glycoprotein in female adolescent patients with OCD. Front. Psychiatry. 2016; 7:35. doi: 10.3389/fpsyt.2016.00035.

59. Palma-Gudiel H, Fañanás L. An integrative review of methylation at the serotonin transporter gene and its dialogue with environmental risk factors, psychopathology and 5-HTTLPR. Neurosci. Biobehav. Rev. 2017; 72:190–209. doi: 10.1016/j.neubiorev.2016.11.011.

60. Perroud N, Paoloni-Giacobino A, Prada P, Olié E, Salzmann A, Nicastro R et al. 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. 2011; 1:e59. doi: 10.1038/tp.2011.60.

61. Perroud N, Salzmann A, Prada P, Nicastro R, Hoeppli ME, Furrer S et al. Response to psychotherapy in borderline personality disorder and methylation status of the BDNF gene. Transl. Psychiatry. 2013; 3:e207. doi: 10.1038/tp.2012.140.

62. Perroud N, Rutembesa E, Paoloni-Giacobino A, Mutabaruka J, Mutesa L, Stenz L 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. doi: 10.3109/15622975.2013.866693.

63. Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J. Biol. Chem. 2001; 276:36734–36741. doi: 10.1074/jbc.M101287200.

64. Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J et al. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: A meta-analysis. JAMA. 2009; 301:2462–2471. doi: 10.1001/jama.2009.878.

65. Roth TL, Zoladz PR, Sweatt JD, Diamond DM. Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder. J. Psychiatr. Res. 2011; 45:919–926. doi: 10.1016/j.jpsychires.2011.01.013.

66. Roy B, Dwivedi Y. Understanding epigenetic architecture of suicide neurobiology: A critical perspective. Neurosci. Biobehav. Rev. 2017; 72:10–27. doi: 10.1016/j.neubiorev.2016.10.031.

67. Rutter M, Moffitt TE, Caspi A. Gene-environment interplay and psychopathology: Multiple varieties but real effects. J. Child Psychol. Psychiatry. 2006; 47:226–261. doi: 10.1111/j.1469-7610.2005.01557.x.

68. Saavedra K, Molina-Marquez AM, Saavedra N, Zambrano T, Salazar LA. Epigenetic modifications of major depressive disorder. Int. J. Mol. Sci. 2016;17:pii: E1279. doi: 10.3390/ijms17081279.

69. Santarelli S, Lesuis SL, Wang XD, Wagner KV, Hartmann J, Labermaier C et al. Evidence supporting the match/mismatch hypothesis of psychiatric disorders. Eur. Neuropsychopharmacol. 2014; 24:907–918. doi: 10.1016/j.euroneuro.2014.02.002.

70. Santarelli S, Zimmermann C, Kalideris G, Lesuis SL, Arloth J, Uribe A et al. An adverse early life environment can enhance stress resilience in adulthood. Psychoneuroendocrinology 2017; 78:213–221. doi: 10.1016/j.psyneuen.2017.01.021.

71. Shi Y, Li M, Song C, Xu Q, Huo R, Shen L et al. Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients. Transl. Psychiatry. 2017; 7:e1170. doi: 10.1038/tp.2017.143.

72. Singh-Taylor A, Molet J, Jiang S, Korosi A, Bolton JL, Noam Y et al. NRSF-dependent epigenetic mechanisms contribute to programming of stresssensitive neurons by neonatal experience, promoting resilience. Mol. Psychiatry. 2018; 23(3):648-657. doi: 10.1038/mp.2016.240.

73. Stenz L, Zewdie S, Laforge-Escarra T, Prados J, La Harpe R, Dayer A et al. BDNF promoter I methylation correlates between post-mortem human peripheral and brain tissues. Neurosci. Res. 2015; 91:1–7. doi: 10.1016/j.neures.2014.10.003

74. Suderman M, McGowan PO, Sasaki A, Huang TCT, Hallett MT, Meaney MJ et al. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus. Proc. Natl. Acad. Sci. U. S. A. 2012;109(Suppl 2):17266–17272. doi: 10.1073/pnas.1121260109.

75. Thakore PI, D’Ippolito AM, Song L, Safi A, Shivakumar NK, Kabadi AM et al. Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements. Nat. Methods. 2015; 12:1143–1149. doi: 10.1038/nmeth.3630.

76. Thomassin H, Flavin M, Espinas ML, Grange T. Glucocorticoid-induced DNA demethylation and gene memory during development. EMBO J. 2001; 20:1974–1983.

77. Turecki G, Meaney MJ. Effects of the social environment and stress on glucocorticoid receptor gene methylation: A systematic review. Biol. Psychiatry. 2016; 79:87–96. doi: 10.1016/j.biopsych.2014.11.022.

78. Uher R. Gene-environment interactions in severe mental illness. Front. Psychiatry. 2014; 5:48. doi: 10.3389/fpsyt.2014.00048.

79. Unternaehrer E, Meyer AH, Burkhardt SC, Emma Dempster E, Simon Staehli S, Theill N et al. Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral blood cells in adult men and women. Stress. 2015; 18:451–461. doi: 10.3109/10253890.2015.1038992.

80. Vogel Ciernia A, LaSalle J. The landscape of DNA methylation amid a perfect storm of autism aetiologies. Nat. Rev. Neurosci. 2016; 17:411–423. doi: 10.1038/nrn.2016.41.

81. Vojta A, Dobrinic P, Tadic V, Bočkor L, Korać P, Julg B et al. Repurposing the CRISPR-Cas9 system for targeted DNA methylation. Nucleic Acids Res. 2016; 44:5615–5628. doi: 10.1093/nar/gkw159.

82. Walton E, Cecil CAM, Suderman M, Jingyu Liu J, Turner JA, Calhoun V et al. Longitudinal epigenetic predictors of amygdala: hippocampus volume ratio. J. Child Psychol. Psychiatry. 2017; 58:1341–1350. doi: 10.1111/jcpp.12740.

83. Wang Y, Wang X, Li R, Yang ZF, Wang YZ, Gong XL, Wang XM. A DNA methyltransferase inhibitor, and upregulates Parkinson’s disease-related genes in dopaminergic neurons. CNS Neurosci. Ther. 2013; 19:183-190. doi: 10.1111/cns.12059.

84. Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR et al. Epigenetic programming by maternal behavior. Nat. Neurosci. 2004; 7:847–854. doi: 10.1038/nn1276.

85. Weaver IC. Epigenetic programming by maternal behavior and pharmacological intervention. Nature versus nurture: Let’s call the whole thing off. Epigenetics 2007; 2:22–28. doi: 10.4161/epi.2.1.3881.

86. Weaver IC. Integrating early life experience, gene expression, brain development, and emergent phenotypes: Unraveling the thread of nature via nurture. Adv. Genet. 2014; 86:277–307. doi: 10.1016/B978-0-12-800222-3.00011-5.

87. Yehuda R, Daskalakis NP, Desarnaud F, Makotkine I, Lehrner AL, Koch E et al. Epigenetic biomarkers as predictors and correlates of symptom improvement following psychotherapy in combat veterans with PTSD. Front. Psychiatry. 2013; 4:118. doi: 10.3389/fpsyt.2013.00118.

88. Yousefi P, Huen K, Dave V, Barcellos L, Eskenazi B, Holland N. Sex differences in DNA methylation assessed by 450 K BeadChip in newborns. BMC Genomics. 2015; 16:911. doi: 10.1186/s12864-015-2034-y.

89. Zannas AS, Wiechmann T, Gassen NC, Binder EB. Gene-stress-epigenetic regulation of FKBP5: Clinical and translational implications. Neuropsychopharmacology 2016; 41:261–274. doi: 10.1038/npp.2015.235.

90. Zong L, Zhou L, Hou Y, Zhang L, Jiang W, Zhang W et al. Genetic and epigenetic regulation on the transcription of GABRB2: Genotypedependent hydroxymethylation and methylation alterations in schizophrenia. J. Psychiatr. Res. 2017; 88:9–17. doi: 10.1016/j.jpsychires.2016.12.019.


Для цитирования:


Хальчицкий С.Е., Иванов М.В., Согоян М.В., Янушко М.Г., Тумова М.А., Муслимова Л.М., Становая В.В., Хуторянская Ю.В., Виссарионов С.В. Выявление биологических основ психических заболеваний: эпигенетические исследования как новое направление в диагностике и лечении. Обозрение психиатрии и медицинской психологии имени В.М.Бехтерева. 2021;56(3):19-31. https://doi.org/10.31363/2313-7053-2021-56-3-19-31

For citation:


Khalchitsky S.E., Ivanov M.V., Sogoyan M.V., Yanushko M.G., Tumova M.A., Muslimova L.M., Stanovaya V.V., Khutoryanskaya J.V., Vissarionov S.V. Revealing the biological basis of mental illness: epigenetic research as a new direction in diagnosis and treatment. V.M. BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY. 2021;56(3):19-31. (In Russ.) https://doi.org/10.31363/2313-7053-2021-56-3-19-31

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