Роль гипоталамо-гипофизарно-надпочечниковой оси в развитии депрессивного расстройства и формировании терапевтической резистентности

Обоснование: в патогенезе депрессивного расстройства важную роль играет изменение работы гипоталамо-гипофизарно-надпочечниковой (ГГН) оси. Особенности функционирования ГГН-оси определяются как биологическими факторами, так и психологическими обстоятельствами, что в совокупности может увеличивать риск развития депрессии в дальнейшем.

Цель: проанализировать современные научные публикации о патофизиологических механизмах депрессивного расстройства, связанных с нарушением работы ГГН-оси, причинно-следственной связи гиперкортицизма и депрессии, роли гиперкортицизма в формировании клинической симптоматики и его влиянии на течение депрессивного состояния.

Материал и методы: по ключевым словам «гиперкортицизм», «депрессивное расстройство», «кортизол», «терапевтически резистентная депрессия», «синдром Кушинга», «болезнь Кушинга» проведен поиск публикаций в базах Medline/PubMed, Scopus, Web of Science, РИНЦ и других источниках.

Заключение: исследователями отмечается высокая коморбидность патологии ГГН-оси и депрессии, причем это касается как эндокринных заболеваний с повышением секреции кортизола, так и с ее снижением. Гиперкортицизм вследствие синдрома или болезни Кушинга часто сопровождается стойкими, необратимыми психическими нарушениями, в особенности тревожными и депрессивными расстройствами, которые сохраняются даже после нормализации уровня кортизола. Для пациентов с депрессией характерно стойкое повышение секреции кортизола и отсутствие его подавления в ходе малой пробы с дексаметазоном (МПД), однако в ряде случаев имеет место, наоборот, снижение секреции кортизола. В литературе описаны возможные механизмы развития гиперкортицизма. Наряду с гиперкортицизмом у пациентов с депрессией продемонстрировано повышение уровня адренокортикотропного гормона (АКТГ) и ослабление секреции АКТГ в ответ на введение экзогенного кортикотропин-рилизинг-гормона (КРГ), что косвенно указывает на гиперсекрецию КРГ. Гиперкортицизм способствует утяжелению и трансформации депрессивных симптомов. Дисфункция ГГН-оси играет важную роль в формировании терапевтической резистентности у пациентов, страдающих депрессивным расстройством. Дальнейшее изучение особенностей функционирования ГГН-оси при депрессии необходимо для уточнения патогенетических механизмов заболевания и разработки новых методов терапии.

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