psychiatryПСИХИАТРИЯPsychiatry (Moscow) (Psikhiatriya)1683-83192618-6667FSBSI “The Mental Health Research Centre”; LLC «Publisher «MIA»10.30629/2618-6667-2023-21-1-73-90psychiatry-921Research ArticleНАУЧНЫЕ ОБЗОРЫSCIENTIFIC REVIEWSРоль гипоталамо-гипофизарно-надпочечниковой оси в развитии депрессивного расстройства и формировании терапевтической резистентностиHypothalamo-Pituitary-Adrenal Axis in Depressive Disorders and Treatment Resistancehttps://orcid.org/0000-0002-4063-7183ЮнилайненО. А.YunilayneO. A.

Ольга Александровна Юнилайнен, кандидат медицинских наук

Москва

Olga A. Yunilaynen, Candidate of Medical Sciences

Moscow

olga84J@yandex.ruhttps://orcid.org/0000-0002-3328-2812СтаростинаЕ. Г.StarostinaE. G.

Елена Георгиевна Старостина, доктор медицинских наук, профессор, кафедра эндокринологии 

Москва

Elena G. Starostina, Dr. of Sci. (Med.), Department of endocrinology

Moscow

elena.starostina59@yandex.ruhttps://orcid.org/0000-0002-8344-0620ОлейчикИ. В.OleichikI. V.

Игорь Валентинович Олейчик, доктор медицинских наук

Москва

Igor V. Oleichik, Dr. of Sci. (Med.)

Moscow

i.oleichik@mail.ruФГБНУ «Научный центр психического здоровья»РоссияFSBSI “Mental Health Research Centre”Russian FederationГБУЗ Московской области «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского»РоссияM.F. Vladimirsky Moscow Regional Research Clinical InstituteRussian Federation2023030320232117390Copyright © Юнилайнен О.А., Старостина Е.Г., Олейчик И.В., 20232023Юнилайнен О.А., Старостина Е.Г., Олейчик И.В.Yunilayne O.A., Starostina E.G., Oleichik I.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.journalpsychiatry.com/jour/article/view/921Обоснование

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

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

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

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.

Background

Background: hypothalamo-pituitary-adrenal (HPA) axis plays an important role in the pathogenesis of depression. Patterns of HPA functioning depend on both biologic factors and psychological background, which, taken together, may increase the risk of depression later on. Objective: to analyze scientific publications on pathophysiology of depression, linked to HPA disruption, assess causal relationship between hypercorticism and depression, role of hypercorticism in clinical symptoms and course of depressive disorder.

Material and methods

Material and methods: according to the key words “hypercortiсism”, “depression disorder”, “cortisol”, “treatment resistant depression”, “Cushing’s syndrome”, “Сushing’s disease”, a search was conducted for publications in databases Medline/ PubMed, Scopus, Web of Science, RSCI and other resources.

Conclusion

Conclusion: there is a high comorbidity between depressive disorders and HPA axis abnormalities, including endocrine disorders with both increased and decreased cortisol secretion. Hypercorticism related to Сushing’s disease or Cushing’s syndrome is often associated with irreversible mental disorders, especially anxiety and depressive disorders, which persist after normalization of cortisol levels. Depressive patients are characterized by persistently elevated cortisol levels and their non-supression in the 1 mg dexamethasone suppression test (DST); however, sometimes they have reduced cortisol secretion. The possible pathophysiology mechanisms of hypercorticism are discussed. Beside hypercorticism, increased level of adrenocorticotropic hormone (ACTH) and decreased secretion of ACTH after CRH stimulation are demonstrated. It has been demonstrated that elevation of cortisol levels may precede the development of depression and as such can be used as marker of increased depression risk. Hypercorticism in patients with depression may promote its increased severity and transform ation of depressive symptoms. Persistent hypercorticism and non-supression of cortisol in DST are predictors of poor outcomes. HPA dysfunction seems to play an essential role in evolvement of treatment resistant depression. There is data on the efficacy of drugs modifying HPA activity for amelioration of affective disorders and psychotic symptoms in patients with depression. Further research into HPA functioning in patients with depression are needed to clarify pathogenetic mechanisms and development of newer treatment approaches to depression.

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