safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2025-499safetyrisk-499Research ArticleГЛАВНАЯ ТЕМА: ТОНКОЕ ИСКУССТВО ВРАЧЕВАНИЯ ДУШИ: КАМО ГРЯДЕШИ?MAIN TOPIC: THE SUBTLE ART OF SOUL HEALING: QUO VADIS?Циркулирующие микроРНК — перспективные биомаркеры для оценки риска развития антипсихотик-индуцированного метаболического синдрома (обзор): часть 2Circulating MicroRNAs Are Promising Biomarkers for Assessing the Risk of Antipsychotic-Induced Metabolic Syndrome (Review): Part 2https://orcid.org/0000-0002-2840-837XШнайдерН. А.ShnayderN. A.

Шнайдер Наталья Алексеевна, д-р мед. наук, ­профессор

ул. Бехтерева, д. 3, Санкт-Петербург, 192019; ул. Партизана Железняка, д. 1, Красноярск, 660022

Natalia А. Shnayder - Dr. Sci. (Med.), Professor.

3 Bekhterev St., St Petersburg 192019; 1 Partisan Zheleznyak St., Krasnoyarsk 660022

NASchnaider@yandex.ruhttps://orcid.org/0000-0003-1874-9434НасыроваР. Ф.NasyrovaR. F.

Насырова Регина Фаритовна, д-р мед. наук

ул. Бехтерева, д. 3, Санкт-Петербург, 192019; пр. Ленина, д. 92, г. Тула, 300012

Regina F. Nasyrova - Dr. Sci. (Med.)

3 Bekhterev St., St Petersburg 192019; 92 Lenin Ave, Tula 300012

regina_nmrcpn@mail.ruhttps://orcid.org/0009-0005-5895-1778ПекарецН. А.PekaretsN. A.

Пекарец Николай Александрович

ул. Бехтерева, д. 3, Санкт-Петербург, 192019

Nikolai A. Pekarets

3 Bekhterev St., St Petersburg 192019

pekaretsnick@mail.ruhttps://orcid.org/0000-0001-8279-4198ГречкинаВ. В.GrechkinaV. V.

Гречкина Виолетта Владимировна

ул. Бехтерева, д. 3, Санкт-Петербург, 192019

Violetta V. Grechkina

3 Bekhterev St., St Petersburg 192019

grechkina.vv@mail.ruhttps://orcid.org/0000-0002-8493-0058ПетроваМ. М.PetrovaM. M.

Петрова Марина Михайловна, д-р мед. наук, ­профессор

ул. Партизана Железняка, д. 1, Красноярск, 660022

Marina M. Petrova - Dr. Sci. (Med.), Professor.

1 Partisan Zheleznyak St., Krasnoyarsk 660022

stk99@yandex.ruИнститут персонализированной психиатрии и неврологии, Национальный медицинский исследовательский центр психиатрии и неврологии имени В.М. Бехтерева; Центр коллективного пользования «Молекулярные и клеточные технологии», Красноярский государственный медицинский университет имени профессора В.Ф. Войно-ЯсенецкогоРоссияInstitute of Personalized Psychiatry and Neurology, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology; Shared Core Facilities “Molecular and Cell Technologies”, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical UniversityRussian FederationИнститут персонализированной психиатрии и неврологии, Национальный медицинский исследовательский центр психиатрии и неврологии имени В.М. Бехтерева; Федеральное государственное бюджетное образовательное учреждение высшего образования «Тульский государственный университет»РоссияInstitute of Personalized Psychiatry and Neurology, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology; Tula State UniversityRussian FederationИнститут персонализированной психиатрии и неврологии, Национальный медицинский исследовательский центр психиатрии и неврологии имени В.М. БехтереваРоссияInstitute of Personalized Psychiatry and Neurology, V.M. Bekhterev National Medical Research Center for Psychiatry and NeurologyRussian FederationЦентр коллективного пользования «Молекулярные и клеточные технологии», Красноярский государственный медицинский университет имени профессора В.Ф. Войно-ЯсенецкогоРоссияShared Core Facilities “Molecular and Cell Technologies”, Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical UniversityRussian Federation202518122025134394410Copyright © Шнайдер Н.А., Насырова Р.Ф., Пекарец Н.А., Гречкина В.В., Петрова М.М., 20252025Шнайдер Н.А., Насырова Р.Ф., Пекарец Н.А., Гречкина В.В., Петрова М.М.Shnayder N.A., Nasyrova R.F., Pekarets N.A., Grechkina V.V., Petrova M.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/499ВВЕДЕНИЕ

ВВЕДЕНИЕ. В первой части статьи был рассмотрен антипсихотик-индуцированный метаболический синдром (АИМетС) как распространенная нежелательная реакция при фармакотерапии психических расстройств и болезней зависимости. Показаны подходы к спектру и оценке основных и дополнительных клинических и лабораторных маркеров метаболического синдрома (МетС) у пациентов с расстройствами шизофренического спектра в целом и АИМетС в частности. Изменение уровня экспрессии циркулирующих микроРНК в крови может рассматриваться как одна из перспективных методологий прогнозирования и диагностики АИМетС.

ЦЕЛЬ

ЦЕЛЬ. Рассмотреть роль циркулирующих микроРНК как эпигенетических биомаркеров развития основных звеньев патогенеза АИМетС.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Проведен анализ и систематизация результатов фундаментальных и клинических исследований роли циркулирующих микроРНК, влияющих на основные звенья патогенеза и прогрессирования АИМетС, опубликованных в период 2012–2024 гг. Проанализированы результаты исследований, отражающих роль микроРНК в ключевых звеньях патогенеза МетС и АИМетС: окислительном стрессе, системном воспалении, регуляции адипогенеза и развитии центрального ожирения, липидного метаболизма, гомеостаза холестерина липопротеинов высокой/низкой плотности, атерогенеза, жировом гепатозе, а также регуляции чувствительности к инсулину, его экспрессии, метаболизма глюкозы, аппетита, экспрессии нейропептида Y, орексина тиреоидных гормонов, паратиреоидного гормона, чувствительности к лептину. Показано, что персонализированная оценка безопасности фармакотерапии может зависеть от паттерна циркулирующих микроРНК, которые индуцируют или ингибируют основные звенья патогенеза АИМетС. Различия в результатах проанализированных исследований микроРНК могут быть обусловлены тем, что фундаментальные (преимущественно) и клинические исследования имели вариабельный дизайн, а также тем, что в них не учитывались другие модифицируемые и немодифицируемые факторы риска АИМетС. Предложена градация микроРНК по степени риска развития АИМетС.

ВЫВОДЫ

ВЫВОДЫ. Этот обзор демонстрирует, что чувствительность и специфичность эпигенетических биомаркеров АИМетС могут варьировать в широком диапазоне в зависимости от характера их влияния (предиктивного или протективного) на один или несколько основных звеньев патогенеза рассматриваемой распространенной нежелательной реакции психофармакотерапии. Наиболее изученными являются микроРНК — предиктивные биомаркеры окислительного стресса (miR-1, miR-21, miR-23b, miR-27a) и системного воспаления (miR-21, miR-23a, miR-27a) у пациентов с высоким риском развития МетС и АИМетС. Перспективными эпигенетическими биомаркерами АИМетС являются микроРНК, влияющие на уровень экспрессии нейропептидов и чувствительность к ним, включая нейропептид Y (miR-let7b, miR-29b, miR-33 и др.), лептин (miR-let7a, miR-9, miR-30e и др.) и орексин (miR-137, miR-637, miR-654 и др.).

INTRODUCTION

INTRODUCTION. The first part of this article discussed antipsychotic-induced metabolic syndrome (AIMetS) as a common adverse reaction to the pharmacotherapy of psychiatric and addiction disorders. The authors presented a review of basic and additional clinical and biochemical biomarkers of metabolic syndrome (MetS) in general and AIMetS in particular in patients with schizophrenia spectrum disorders and outlined approaches to measuring these biomarkers. Detecting changes in the expression of circulating microRNAs in the blood can be considered a promising method for predicting and diagnosing AIMetS.

AIM

AIM. This study aimed to evaluate the role of circulating microRNAs as epigenetic biomarkers of the key components of AIMetS pathogenesis.

DISCUSSION

DISCUSSION. The authors reviewed and collated the results of academic and clinical research (2012–2024) with a focus on the role of circulating microRNAs involved in the key AIMetS pathogenesis and progression pathways. The authors analysed the results of studies on the role of circulating microRNAs in the blood as regulators of the key components of MetS and AIMetS pathogenesis. The studied components of pathogenesis included oxidative stress, systemic inflammation, adipogenesis regulation (and abdominal adiposity development), lipid metabolism, high- and low-density lipoprotein cholesterol homeostasis, atherogenesis, and hepatic steatosis, as well as the regulation of insulin and leptin sensitivity, glucose metabolism and appetite, and insulin, neuropeptide Y, orexin, thyroid and parathyroid hormone expression. A personalised assessment of the safety of pharmacotherapy may depend on the pattern of circulating microRNAs that induce or inhibit the main components of AIMetS pathogenesis. The differences in the results of the reviewed microRNA studies may be due to the differences in the design of these academic (mainly) and clinical studies and their lack of consideration for modifiable and unmodifiable risk factors for developing AIMetS. The authors proposed a microRNA classification according to the risk level of developing AIMetS.

CONCLUSIONS

CONCLUSIONS. The findings demonstrate that the sensitivity and specificity of epigenetic biomarkers of AIMetS can vary widely, depending on the nature of their influence (predictive or protective) on one or several pathogenetic components of this widespread adverse reaction to psychopharmacotherapy. The most studied microRNAs are predictive biomarkers of oxidative stress (miR-1, miR-21, miR-23b, miR-27a, etc.) and systemic inflammation (miR-21, miR-23a, miR-27a, etc.) in patients at high risk of developing MetS and AIMetS. Promising epigenetic AIMetS biomarkers include microRNAs that affect the expression of and sensitivity to neuropeptides, including neuropeptide Y (miR-let7b, miR-29b, miR-33, etc.), leptin (miR-let7a, miR-9, miR-30e, etc.), and orexin (miR-137, miR-637, miR-654, etc.).

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