psychiatryПСИХИАТРИЯPsychiatry (Moscow) (Psikhiatriya)1683-83192618-6667FSBSI “The Mental Health Research Centre”; LLC «Publisher «MIA»10.30629/2618-6667-2024-22-6-16-26psychiatry-1273Research ArticleПСИХОПАТОЛОГИЯ, КЛИНИЧЕСКАЯ И БИОЛОГИЧЕСКАЯ ПСИХИАТРИЯPSYCHOPATHOLOGY, CLINICAL AND BIOLOGICAL PSYCHIATRYВариация содержания трех тандемных повторов в ДНК лейкоцитов крови детей с психическими нарушениями как потенциальный маркер дифференциальной диагностики шизофрении и расстройств аутистического спектраVariation in the Content of Three Tandem Repeats (Ribosomal, Satellite III and Telomeric) in the DNA of Blood Leukocytes of Children with Mental Disorders, as a Potential Marker for the Differential Diagnosis of Childhood Schizophrenia and Autism Spectrum Disordershttps://orcid.org/0000-0003-1206-5832ЕршоваЕ. С.ErshovaE. S.

Елизавета Сергеевна Ершова, кандидат биологических наук, ведущий научный сотрудник, лаборатория молекулярной биологии

Москва,

Россия, https://orcid.org/0000-0003-1206-5832

Elizaveta S. Ershova, Cand. Sci. (Biol.), Leading researcher, Molecular biology laboratory

Moscow

https://orcid.org/0000-0002-0299-426XЧудаковаЮ. М.ChudakovaYu. M.

Юлия Михайловна Чудакова, кандидат биологических наук, научный сотрудник, лаборатория молекулярной биологии

Москва

Yulia M. Chudakova, Cand. Sci. (Biol.), Researcher, Molecular biology laboratory

Moscow

https://orcid.org/0000-0003-1847-0548ВейкоН. Н.VeikoN. N.

Наталья Николаевна Вейко, доктор биологических наук, доцент, главный научный сотрудник, лаборатория молекулярной биологии

Москва

Natalya N. Veiko, Dr. Sci. (Biol.), Docent, Chief researcher, Molecular biology laboratory

Moscow

https://orcid.org/0000-0002-6697-8306МартыновА. В.MartynovA. V.

Андрей Владимирович Мартынов, кандидат биологических наук, старший научный сотрудник, лаборатория молекулярной биологии

Москва

Andrey V. Martynov, Cand. Sci. (Biol.), Senior researcher, Molecular biology laboratory

Moscow

https://orcid.org/0000-0002-3659-3608КостюкС. Э.KostyukS. E.

Светлана Эдмундовна Костюк, лаборант-исследователь, лаборатория молекулярной биологии

Москва

Svetlana E. Kostyuk, Laboratory researcher, Molecular biology laboratory

Moscow

https://orcid.org/0000-0002-6336-9900КостюкС. В.KostyukS. V.

Светлана Викторовна Костюк, доктор биологических наук, доцент, заведующая лабораторией, лаборатория молекулярной биологии

Москва

Svetlana V. Kostyuk, Dr. Sci. (Biol.), Docent, Head of laboratory, Molecular biology laboratory

Moscow

https://orcid.org/0000-0002-7775-1692НикитинаС. Г.NikitinaS. G.

Светлана Геннадьевна Никитина, кандидат медицинских наук, старший научный сотрудник, отдел детской психиатрии

Москва

Svetlana G. Nikitina, Cand. Sci. (Med.), Senior researcher, Department of Child Psychiatry

Moscow

https://orcid.org/0000-0002-3919-7045БалакиреваЕ. Е.BalakirevaE. E.

Елена Евгеньевна Балакирева, кандидат медицинских наук, заведующая отделом, ведущий научный сотрудник, отдел детской психиатрии

Москва

Elena E. Balakireva, Cand. Sci. (Med.), Leading researcher, Head of department, Department of Child Psychiatry

Moscow

ФГБНУ «Медико-генетический научный центр им. академика Н.П. Бочкова»РоссияFSBSI Research Centre for Medical GeneticsRussian FederationФГБНУ «Научный центр психического здоровья»РоссияFSBSI Mental Health Research CentreRussian Federation2024230220252261626Copyright © Ершова Е.С., Чудакова Ю.М., Вейко Н.Н., Мартынов А.В., Костюк С.Э., Костюк С.В., Никитина С.Г., Балакирева Е.Е., 20252025Ершова Е.С., Чудакова Ю.М., Вейко Н.Н., Мартынов А.В., Костюк С.Э., Костюк С.В., Никитина С.Г., Балакирева Е.Е.Ershova E.S., Chudakova Y.M., Veiko N.N., Martynov A.V., Kostyuk S.E., Kostyuk S.V., Nikitina S.G., Balakireva E.E.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/1273

Актуальность: проблемным вопросом детской психиатрии является дифференциальная диагностика шизофрении, начавшейся в детском возрасте, и расстройств аутистического спектра (РАС). Ранее авторами было показано, что геномы детей с шизофренией, как и геномы взрослых пациентов с шизофренией, содержат больше копий рибосомных генов, чем геномы детей с РАС. У взрослых пациентов с шизофренией также снижено содержание сателлита III (1q12) и короче средняя длина теломер в лейкоцитах крови. Цель работы: анализ содержания трех повторов генома (рибосомного, сателлита III и теломерного) в образцах ДНК лейкоцитов крови детей с эндогенными психическими нарушениями с целью поиска генетического маркера, позволяющего проводить дифференциальную диагностику между шизофренией и РАС. Пациенты, группы контроля, методы исследования: изучены две выборки пациентов общим количеством 136 человек с диагнозами F84.х и F20.8 по МКБ-10. Группу контроля составили 93 ребенка и 78 взрослых без признаков психических расстройств. Выделение ДНК проводили методом экстракции органическими растворителями. Содержание трех повторов в ДНК определяли методом нерадиоактивной количественной гибридизации. Данные анализировали с использованием пакета «StatPlus2007 Professional software», «MedCalc», Excel Microsoft Office, «StatGraph». Результаты: образцы ДНК детей с шизофренией содержат больше рибосомных генов и меньше сателлита III, чем ДНК детей с РАС и здоровых детей (p < 0,001, U-тест). Кровь пациентов с РАС и шизофренией содержит меньше теломерного повтора, чем кровь здоровых доноров (p < 10−10). Показатель Kш, равный отношению R2/(S·T), который учитывает повышенное содержание рибосомного повтора и сниженное содержание сателлита и теломерного повтора в ДНК детей с шизофренией, обнаружил максимальные различия между группами пациентов детского возраста с шизофренией и РАС (p < 10−11, U-тест; RОС-анализ: AUC = 0,88, p < 0,001). Выводы: показатель Kш потенциально может быть применен в практике для подтверждения диагноза шизофрении у детей с психической патологией. 

Background: a problematic issue in child psychiatry is the differential diagnosis of early childhood schizophrenia and autism spectrum disorders (ASD). Previously, the authors showed that the genomes of children with schizophrenia, like the genomes of adult patients, contain more copies of ribosomal genes than the genomes of children with ASD. For adult patients with schizophrenia, a decrease in the content of satellite III repeat (1q12) in blood leukocytes and a decrease in the average telomere length were also shown. The aim of study was an analysis of the content of three genome repeats (ribosomal, satellite III and telomeric) in DNA samples of blood leukocytes of children with endogenous mental disorders in order to search for a genetic marker that allows for differential diagnosis of early childhood schizophrenia and ASD. Patients, Control groups and Methods: blood samples from 136 patients with ASD (F84.0 and F84.1 according to ICD-10) and childhood-onset schizophrenia (F20.8xx3 according to ICD-10) were obtained from the Department of Child Psychiatry of the Mental Health Research Centre. DNA samples from the healthy control group (93 children and 78 adults) were taken from the collection of samples of Research Centre for Medical Genetics. The selection of patients was carried out using the clinical-psychopathological method. DNA was isolated by extraction with organic solvents. The content of three repeats in DNA was carried out using non-radioactive quantitative hybridization. Data were analyzed using the package “StatPlus2007 Professional software”, “MedCalc”, Excel Microsoft Office, “StatGraph”. Results: patients DNA samples from children with schizophrenia contain more ribosomal genes and less satellite III than DNA from children with ASD and DNA from healthy children (p < 0.001, U test). DNA samples of patients with ASD and schizophrenia contain fewer telomeric repeats than healthy child controls (p < 10−10). The Ksz indicator, equal to the ratio R2/(S·T), which takes into account the increased content of the ribosomal repeat and the reduced content of the satellite and telomeric repeat in the DNA of children diagnosed with childhood schizophrenia, showed the maximum differences between the group of children with schizophrenia and the group of children with ASD (p < 10−11, U test; ROC analysis: AUC = 0.88, p < 0.001). Conclusion: the Ksz indicator can potentially be used in practice to confirm the diagnosis of schizophrenia in children with mental pathology.

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