bekhterevОбозрение психиатрии и медицинской психологии имени В.М.БехтереваV.M. BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY2313-70532713-055XV. M. BEKHTEREV NATIONAL RESEARCH MEDICAL CENTER FOR PSYCHIATRY AND NEUROLOGY OF THE RUSSIAN FEDERATION MINISTRY OF HEALTH10.31363/2313-7053-2021-56-3-19-31bekhterev-582Research ArticleПРОБЛЕМНЫЕ СТАТЬИPROBLEM-S0LVING ARTICLESВыявление биологических основ психических заболеваний: эпигенетические исследования как новое направление в диагностике и леченииRevealing the biological basis of mental illness: epigenetic research as a new direction in diagnosis and treatmenthttps://orcid.org/0000-0003-1467-8739ХальчицкийС. Е.KhalchitskyS. E.

Хальчицкий Сергей Егорович

Санкт-Петербург

Sergei E. Khalchitsky

Saint-Petersburg

s_khalchitski@mail.ruhttps://orcid.org/0000-0001-7829-2486ИвановМ. В.IvanovM. V.

Иванов Михаил Владимирович

Санкт-Петербург

Mikhail V. Ivanov

Saint-Petersburg

profmikhailivanov@gmail.comhttps://orcid.org/0000-0001-5723-8851СогоянМ. В.SogoyanM. V.

Согоян Марина Ваниковна

Санкт-Петербург

Marina V. Sogoyan

Saint-Petersburg

sogoyanmarina@mail.ruhttps://orcid.org/0000-0001-7977-2094ЯнушкоМ. Г.YanushkoM. G.

Янушко Мария Григорьевна

Санкт-Петербург

Maria G. Yanushko

Saint-Petersburg

yanushko@list.ruhttps://orcid.org/0000-0002-3418-8596ТумоваМ. А.TumovaM. A.

Тумова Марианна Анатольевна

Санкт-Петербург

Marianna A. Tumova

Saint-Petersburg

marianna_tumova@mail.ruhttps://orcid.org/0000-0003-4082-2319МуслимоваЛ. М.MuslimovaL. M.

Муслимова Лилия Мухаметшевна

Санкт-Петербург

Lilia M. Muslimova

Saint-Petersburg

muslimova.lil@yandex.ruhttps://orcid.org/0000-0001-5851-0626СтановаяВ. В.StanovayaV. V.

Становая Виктория Владимировна

Санкт-Петербург

Viktoria V. Stanovaya

Saint-Petersburg

vika06.95@mail.ruhttps://orcid.org/0000-0002-2601-5484ХуторянскаяЮ. В.KhutoryanskayaJ. V.

Хуторянская Юлия Валерьевна

Санкт-Петербург

Julia V. Khutoryanskaya

Saint-Petersburg

julia.khutoryanskaya@gmail.comhttps://orcid.org/0000-0003-4235-5048ВиссарионовС. В.VissarionovS. V.

Виссарионов Сергей Валентинович

Санкт-Петербург

Sergei V. Vissarionov

Saint-Petersburg

vissarionovs@gmail.comНациональный медицинский исследовательский центр детской травматологии и ортопедии им. Г.И.ТурнераРоссияH. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma SurgeryRussian FederationНациональный медицинский исследовательский центр психиатрии и неврологии им. В.М. БехтереваРоссияV.M. Bekhterev national research medical center for psychiatry and neurologyRussian FederationНациональный медицинский исследовательский центр детской травматологии и ортопедии им. Г.И.ТурнераРоссия1H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma SurgeryRussian FederationСанкт-Петербургский государственный педиатрический медицинский университетРоссияSt.-Petersburg State Pediatric Medical UniversityRussian Federation2021011020215531931Copyright © 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., 20212021Хальчицкий 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.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.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.bekhterevreview.com/jour/article/view/582

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.

Summary. Mental disorders are clinically heterogeneous chronic diseases resulting from complex interactions between genotype variants and environmental factors. Epigenetic processes, such as DNA methylation and post-translational histone modification, determine the interpretation by the body at the cellular and tissue levels of various environmental factors. Given that epigenetic modifications are environmentally sensitive, stable and reversible, epigenetic research in psychiatry may be a promising approach to better understanding and treating mental illness. This review discusses the clinical opportunities and challenges posed by epigenetic research in psychiatry. Using individual examples, the main conclusions are drawn that confirm the role of adverse life events, alone or in combination with genetic risk, in the epigenetic programming of neuropsychiatric systems. Further epigenetic studies show encouraging results in the use of methylation changes as diagnostic markers of disease manifestations and provide predictive tools for assessing progression and response to treatment. The potential for the use of targeted epigenetic pharmacotherapy, combined with psychosocial methods, in the context of the personalized medicine of the future in psychiatry is discussed next. It concludes with a discussion of methodological limitations that can make it difficult to interpret epigenetic data in psychiatry. They mainly arise due to the heterogeneity of individuals, both at the level of the whole organism and at the level of tissues, and require new strategies to better assess the biological significance of epigenetic data and their translational use in psychiatry. Overall, we believe that epigenetics can provide new insights and a more comprehensive understanding of the etiology and pathogenesis of mental illness, and should ultimately improve the nosology, treatment and prevention of mental disorders.

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The authors declare that there are no conflicts of interest present.