Эпигенетические и геномные механизмы в патогенезе посттравматического стрессового расстройства (обзор)
Актуальность: Посттравматическое стрессовое расстройство является одним из наиболее показательных примеров взаимодействий между генетической и средовой компонентами заболевания. Психологическая травматизация является доминирующим, но не единственным этиологическим фактором. За последние 20 лет накоплено достаточное количество данных, подтверждающих роль наследственной компоненты в формировании, так называемого, «уязвимого фенотипа». Эпигенетические процессы рассматриваются в качестве механизма средового (психотравмирующего) воздействия, которое провоцирует изменения в экспрессии генов и стабильности генома, что может приводить к проявлению конкретных симптомов. Цель исследования: Обобщить и сопоставить основные результаты исследований эпигенетических механизмов регуляции генома при посттравматическом стрессовом расстройстве. Материалы и методы: Проведён теоретический анализ опубликованных результатов исследований эпигенетических маркеров посттравматического стрессового расстройства. Поиск осуществлялся в базе данных PubMed. Результаты: Выполненные к настоящему моменту исследования обладают рядом общих признаков (опора на ретроспективные данные о психотравмирующем событии, полученные методом самоотчёта; использование для анализа доступных тканей; применение ретроспективного поперечно-срезового дизайна). Систематика исследований основывается как на доминирующей методологии (поиск и изучение генов-кандидатов; методы полногеномных или эпигеномных ассоциаций), так и на анализе метилирования ДНК, посттрансляционных модификаций гистонов, структурной организации хроматина. Предлагается объяснение патогенеза посттравматического стрессового расстройства и с помощью цитогеномной гипотезы (изменения уровней геномной нестабильности, переделяющие психическое состояние индивида). Обозначены ограничения и перспективы изучения эпигенетических механизмов в патогенезе посттравматического стрессового расстройства. Заключение: Эпигенетический и геномный анализ молекулярных основ ПТСР наиболее целостно раскрывает характер взаимодействия генотипа и средовых воздействий в виде психотравмирующего события. Изучение эпигенетических модификаций и уровней геномной нестабильности, которые являются потенциально обратимыми, может внести существенный вклад в усовершенствование системы профилактики и оказания клинико-психологической помощи индивидам, пережившим психотравмирующее воздействие.
Фаустова АГ, Юров ИЮ. Эпигенетические и геномные механизмы в патогенезе посттравматического стрессового расстройства (обзор). Научные результаты биомедицинских исследований. 2022;8(1):15-35.[Faustova AG, Iourov IY. Epigenetic and genomic mechanisms in the pathogenesis of posttraumatic stress disorder (review). Research Results in Biomedicine. 2022;8(1):15-35. Russian]. DOI: 10.18413/2658-6533-2022-8-1-0-2
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