Consortium PSYCHIATRICUMConsortium PSYCHIATRICUMConsortium PSYCHIATRICUM2712-76722713-2919Eco-Vector1549410.17816/CP15494RESEARCHИССЛЕДОВАНИЕResearch ArticleGenetic Associations of Anhedonia: Insights into Overlap of Mental and Somatic DisordersГенетические ассоциации ангедонии: новые аспекты взаимосвязи психических и соматических расстройствhttps://orcid.org/0000-0002-4658-2195KasyanovEvgenyКасьяновЕвгений Дмитриевич
Russian Federation

MD, Cand. Sci (Med.), Senior Researcher, Department of social neuropsychiatry

к.м.н., с.н.с. отделения социальной нейропсихиатрии

i@kasyan.ruhttps://orcid.org/0000-0001-9896-6556PinakhinaDaryaПинахинаДарья Владимировна
Russian Federation

Researcher, Department of social neuropsychiatry; Researcher

н.с. отделения социальной нейропсихиатрии

i@kasyan.ruhttps://orcid.org/0000-0003-0567-7734RakitkoAleksandrРакитькоАлександр Сергеевич
Russian Federation

Cand. Sci (Phys Math), Head of Science; Researcher

к.ф.-м.н., директор по науке

i@kasyan.ruhttps://orcid.org/0000-0003-0823-0540VergasovaEkaterinaВергасоваЕкатерина Олеговна
Russian Federation

Bioinformatician

биоинформатик

i@kasyan.ruhttps://orcid.org/0000-0002-0712-6939YermakovichDanatЕрмаковичДанат Павлович
Russian Federation

Researcher

н.с.

i@kasyan.ruhttps://orcid.org/0000-0002-5282-2036RukavishnikovGrigoriyРукавишниковГригорий Викторович
Russian Federation

MD, Cand. Sci (Med.), Leading Researcher, Head of the Social Neuropsychiatry Department

к.м.н., вед.н.с., руководитель отделения социальной нейропсихиатрии

i@kasyan.ruhttps://orcid.org/0000-0002-5470-4359572501556005156-9223MalyshkoLarisaМалышкоЛариса Владимировна
Russian Federation

Junior Researcher, Scientific and Organizational Department

м.н.с. научно организационного отделения

i@kasyan.ruhttps://orcid.org/0000-0001-7538-123XPopovYaroslavПоповЯрослав Вячеславович
Russian Federation

Researcher

н.с.

i@kasyan.ruhttps://orcid.org/0000-0001-5678-6557KovalenkoElenaКоваленкоЕлена Владимировна
Russian Federation

Researcher

н.с.

i@kasyan.ruhttps://orcid.org/0000-0001-7524-5617IlinskayaAnnaИльинскаяАнна Юрьевна
Latvia

Laboratory manager

руководитель лаборатории

i@kasyan.ruhttps://orcid.org/0000-0003-4077-4740KimAnnaКимАнна Александровна
Russian Federation

Researcher

н.с.

i@kasyan.ruhttps://orcid.org/0000-0001-5585-0035PlotnikovNikolayПлотниковНиколай Анатольевич
Russian Federation

Researcher

с.н.с.

i@kasyan.ruhttps://orcid.org/0000-0001-5618-42069772-0024NeznanovNikolayНезнановНиколай Григорьевич
Russian Federation

MD, Dr. Sci (Med.), Professor, Director; Head of the Department of Psychiatry and Narcology

д.м.н., проф., директор; зав. каф. психиатрии и наркологии

i@kasyan.ruhttps://orcid.org/0000-0003-4377-2759IlinskyValeriyИльинскийВалерий Владимирович
Russian Federation

CEO

генеральный директор

i@kasyan.ruhttps://orcid.org/0000-0002-8771-625X3718-6729KibitovAleksandrКибитовАлександр Олегович
Russian Federation

MD, Dr. Sci (Med.), Chief Researcher, Head of the Department of Genomics of Mental Disorders

д.м.н., гл.н.с., руководитель отделения геномики психических расстройств

i@kasyan.ruhttps://orcid.org/0000-0001-7036-5927MazoGalinaМазоГалина Элевна
Russian Federation

MD, Dr. Sci (Med.), Head of the Institute of Translational Psychiatry

д.м.н., заместитель директора по инновационному научному развитию, руководитель Института трансляционной психиатрии

i@kasyan.ruV.M. Bekhterev National Medical Research Centre for Psychiatry and NeurologyФГБУ «Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева» Минздрава РоссииITMO UniversityФГАОУ ВО «Национальный исследовательский университет ИТМО»Genotek Ltd.ООО «Генотек»Eligens SIAPavlov First State Medical University of Saint PetersburgФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Минздрава России2706202406072024525-845151001202408052024Copyright ©; 2024, Kasyanov E., Pinakhina D., Rakitko A., Vergasova E., Yermakovich D., Rukavishnikov G., Malyshko L., Popov Y., Kovalenko E., Ilinskaya A., Kim A., Plotnikov N., Neznanov N., Ilinsky V., Kibitov A., Mazo G.Copyright ©; 2024, Касьянов Е., Пинахина Д., Ракитько А., Вергасова Е., Ермакович Д., Рукавишников Г., Малышко Л., Попов Я., Коваленко Е., Ильинская А., Ким А., Плотников Н., Незнанов Н., Ильинский В., Кибитов А., Мазо Г.2024Kasyanov E., Pinakhina D., Rakitko A., Vergasova E., Yermakovich D., Rukavishnikov G., Malyshko L., Popov Y., Kovalenko E., Ilinskaya A., Kim A., Plotnikov N., Neznanov N., Ilinsky V., Kibitov A., Mazo G.Касьянов Е., Пинахина Д., Ракитько А., Вергасова Е., Ермакович Д., Рукавишников Г., Малышко Л., Попов Я., Коваленко Е., Ильинская А., Ким А., Плотников Н., Незнанов Н., Ильинский В., Кибитов А., Мазо Г.https://creativecommons.org/licenses/by-nc-nd/4.0https://consortium-psy.com/jour/article/view/15494

BACKGROUND: Anhedonia is characterized by a reduced ability to anticipate, experience, and/or learn about pleasure. This phenomenon has a transdiagnostic nature and is one of the key symptoms of mood disorders, schizophrenia, addictions, and somatic conditions.

AIM: To evaluate the genetic architecture of anhedonia and its overlap with other mental disorders and somatic conditions.

METHODS: We performed a genome-wide association study of anhedonia on a sample of 4,520 individuals from a Russian non-clinical population. Using the available summary statistics, we calculated polygenic risk scores (PRS) to investigate the genetic relationship between anhedonia and other psychiatric or somatic phenotypes.

RESULTS: No variants with a genome-wide significant association were identified. PRS for major depression, bipolar disorder, and schizophrenia were significantly associated with anhedonia. Conversely, no significant associations were found between PRS for anxiety and anhedonia, which aligns well with existing clinical evidence. None of the PRS for somatic phenotypes attained a significance level after correction for multiple comparisons. A nominal significance for the anhedonia association was determined for omega-3 fatty acids, type 2 diabetes mellitus, and Crohn’s disease.

CONCLUSION: Anhedonia has a complex polygenic architecture, and its presence in somatic diseases or normal conditions may be due to a genetic predisposition to mood disorders or schizophrenia.

ВВЕДЕНИЕ: Ангедония характеризуется снижением способности предвосхищать, испытывать и/или усваивать удовольствие. Этот феномен имеет трансдиагностическую природу и является одним из ключевых симптомов расстройств настроения, шизофрении, аддикций и соматических состояний.

ЦЕЛЬ: Оценить генетическую архитектуру ангедонии и её перекрытие с другими психическими расстройствами и соматическими состояниями.

МЕТОДЫ: Проведено исследование полногеномного поиска ассоциаций ангедонии на выборке из 4 520 человек из российской неклинической популяции. Используя доступную сводную статистику, мы рассчитали шкалы полигенного риска (polygenic risk scores, PRS), чтобы исследовать генетическую связь между ангедонией и другими психиатрическими или соматическими фенотипами.

РЕЗУЛЬТАТЫ: Не было идентифицировано ни одного варианта, достигшего полногеномного уровня значимости. PRS для депрессии, биполярного расстройства и шизофрении были значимо ассоциированы с ангедонией. И наоборот, не обнаружено значимых ассоциаций между PRS для тревожных расстройств и ангедонии, что хорошо согласуется с существующими клиническими данными. Ни один из PRS для соматических фенотипов не достиг уровня значимости после коррекции на множественные сравнения. При номинальном уровне значимости ассоциация с ангедонией выявлена для PRS ω-3 жирных кислот, сахарного диабета 2-го типа и болезни Крона.

ЗАКЛЮЧЕНИЕ: Ангедония имеет сложную полигенную архитектуру, в связи с чем её присутствие при соматических заболеваниях или нормальных состояниях может быть обусловлено генетической предрасположенностью к расстройствам настроения или шизофрении.

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