psychiatryПСИХИАТРИЯPsychiatry (Moscow) (Psikhiatriya)1683-83192618-6667FSBSI “The Mental Health Research Centre”; LLC «Publisher «MIA»10.30629/2618-6667-2023-21-7-14-23psychiatry-1080Research ArticleПСИХОПАТОЛОГИЯ, КЛИНИЧЕСКАЯ И БИОЛОГИЧЕСКАЯ ПСИХИАТРИЯPSYCHOPATHOLOGY, CLINICAL AND BIOLOGICAL PSYCHIATRYПоиск ассоциации полиморфизмов rs6280 гена DRD3, rs4680 гена COMT, rs6265 гена BDNF с шизофренией, резистентной к антипсихотической терапии, в российской популяцииSearch for Association of Polymorphisms rs6280 of the DRD3 Gene, rs4680 of the COMT Gene, rs6265 of the Gene BDNF with Schizophrenia Resistant to Antipsychotic Therapy in Russian Populationshttps://orcid.org/0000-0002-1516-082XКайданМ. А.KaydanM. A.

Мария Андреевна Кайдан, врач-психиатр, младший научный сотрудник, лаборатория фундаментальных методов исследования

РИНЦ:1038412

ScopusID: 57221300664

Москва

Maria A. Kaydan, Psychiatrist, Junior Researcher, Laboratory for Fundamental Research Methods of theScientific Research, Center of Neuropsychiatry

RSCI: 1038412

ScopusID: 57221300664

Moscow

kaydan.maria@yandex.ruhttps://orcid.org/0000-0001-7507-327XЗахароваН. В.ZakharovaN. V.

Наталья Вячеславовна Захарова, кандидат медицинских наук, руководитель лаборатории, лаборатория фундаментальных методов исследования

РИНЦ: 208381

ScopusID: 57204144307

Москва

Natalia V. Zakharova, Cand. of Sci. (Med.), Head of Laboratory, Laboratory for Fundamental Research Methods of the Scientific Research, Center of Neuropsychiatry

RSCI: 208381

ScopusID: 57204144307

Moscow

nataliza80@gmail.comhttps://orcid.org/0000-0003-0247-2717ЗоркинаЯ. А.ZorkinaYa. A.

Яна Александровна Зоркина, кандидат биологических наук, старший научный сотрудник, отдел шизофрении и других первично психотических расстройств

РИНЦ: 666540

ScopusID: 5721112308

Москва

Yana A. Zorkina, Cand. of Sci. (Biol.), Senior Researcher, Department of Schizophrenia and Other Primary Psychotic Disorders, Center of Neuropsychiatry

RSCI: 666540

ScopusID: 5721112308

Moscow

zorkina.ya@serbsky.ruhttps://orcid.org/0000-0002-3073-6305КостюкГ. П.KostyukG. P.

Георгий Петрович Костюк, доктор медицинских наук, профессор, главный врач; заведующий кафедрой, кафедра психического здоровья, факультет психологии

РИНЦ: 353668

ScopusID: 57200081884

Москва

George P. Kostyuk, Dr. of Sci. (Med.), Professor, Chief; Head of the Department, Department of Mental Health, Faculty of Psychology

RSCI: 353668

ScopusID: 57200081884

Moscow

kgr@yandex.ruГБУЗ г. Москвы «Психиатрическая клиническая больница № 1 им. Н.А. Алексеева Департамента здравоохранения города Москвы»РоссияAlekseev Psychiatric Hospital No. 1, Moscow Healthcare DepartmentRussian FederationГБУЗ г. Москвы «Психиатрическая клиническая больница № 1 им. Н.А. Алексеева Департамента здравоохранения города Москвы»; ФГБУ «Национальный медицинский исследовательский центр психиатрии и наркологии имени В.П. Сербского» Министерства здравоохранения Российской ФедерацииРоссияAlekseev Psychiatric Hospital No. 1, Moscow Healthcare Department; V. Serbsky National Medical Research Centre for Psychiatry and Narcology, Russian Ministry of HealthRussian FederationГБУЗ г. Москвы «Психиатрическая клиническая больница № 1 им. Н.А. Алексеева Департамента здравоохранения города Москвы»; ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова»; ФГБОУ ВО «Российский биотехнологический университет (РОСБИОТЕХ)»; ФГФОУ ВО Первый МГМУ имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияAlekseev Psychiatric Hospital No. 1, Moscow Healthcare Department; Federal State Budget Educational Institution of Higher Education M.V. Lomonosov Moscow State University; Federal State Budgetary Educational Institution of Higher Education Russian Biotechnological University; I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)Russian Federation2023300120242171423Copyright © Кайдан М.А., Захарова Н.В., Зоркина Я.А., Костюк Г.П., 20242024Кайдан М.А., Захарова Н.В., Зоркина Я.А., Костюк Г.П.Kaydan M.A., Zakharova N.V., Zorkina Y.A., Kostyuk G.P.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/1080

Обоснование: резистентная шизофрения, несмотря на применение новых антипсихотиков и методов диагностики, все еще достигает 50% среди всех случаев шизофрении. Поиск новых методов ранней диагностики с помощью персонализированных инструментов генетического анализа представляется актуальным и перспективным в настоящее время. Цель исследования — провести анализ ассоциации полиморфизмов COMT rs4680, DRD3 rs6280, BDNF rs6265 с развитием резистентности у пациентов с шизофренией. Пациенты и методы: генетический анализ методом ПЦР в реальном времени проведен у 264 больных шизофренией, обследованных клиническим и психометрическим методами. По итогам проспективного наблюдения больных в течение 6 нед. и анализа эффективности психофармакотерапии все обследованные были разделены на две группы: тех, у кого терапия была эффективна, и пациентов с резистентностью к антипсихотической терапии. Результаты: обнаружена значимая ассоциация с неэффективностью психофармакотерапии у больных шизофренией гомозигот в рецессивной модели и гетерозигот в кодоминантной модели полиморфизма rs6265 гена BDNF. Выводы: полиморфизм rs6265 гена BDNF может рассматриваться как диагностический маркер развития резистентной шизофрении, однако необходимо дальнейшее изучение этой ассоциации для подтверждения чувствительности и специфичности.

Background: resistant schizophrenia, despite the introduction of new antipsychotics and diagnostic methods, still reaches 50%of cases among all patients with schizophrenia. The search for new methods of early diagnosis using personalized genetic analysis tools seems relevant and promising at the present time. The aim of the study was to analyze the associations of polymorphisms COMT rs4680, DRD3 rs6280, BDNF rs6265 with the development of a therapeutic resistance in patients with schizophrenia. Patients and methods: а real-time genetic analysis of 264 patients with schizophrenia examined by clinical and psychometric methods. A prospective follow-up for 6 weeks was carried out with further division of the sample into 2 groups: respondents and patients with resistance based on the evaluation of the effectiveness of psychopharmacotherapy. Results: a significant association with the ineffectiveness of psychopharmacotherapy found in patients with schizophrenia being homozygotes in the recessive model and being heterozygotes in the codominant model of the rs6265 polymorphism of the BDNF gene. Conclusions: the rs6265 polymorphism of the BDNF gene can be considered as a diagnostic marker for the development of treatment resistant schizophrenia, but requires further study to confirm sensitivity and specificity.

резистентная шизофренияантипсихотикиэффективность терапиигенетическое тестированиеresistant schizophreniaantipsychoticsgenetic testefficacy of therapyИсследование проведено за счет средств, выделенных для выполнения работ по госзаданию Департамента здравоохранения г. Москвы по теме «Совершенствование методов диагностики, профилактики и лечения психиатрических расстройств на основе стратегий персонализированной медицины».The study was carried out at the expense of funds allocated for the implementation of work on state assignment No. 123031600072–3 of the Moscow Department of Health “Molecular genetics and neurophysiological predictors of primary psychotic disorders” dated March 16, 2023.ReferencesSiskind D, Orr S, Sinha S, Yu O, Brijball B, Warren N, MacCabe JH, Smart SE, Kisely S. Rates of treatment-resistant schizophrenia from first-episode cohorts: systematic review and meta-analysis. 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The authors declare that there are no conflicts of interest present.