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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">psychiatry</journal-id><journal-title-group><journal-title xml:lang="ru">ПСИХИАТРИЯ</journal-title><trans-title-group xml:lang="en"><trans-title>Psychiatry (Moscow) (Psikhiatriya)</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1683-8319</issn><issn pub-type="epub">2618-6667</issn><publisher><publisher-name>FSBSI “The Mental Health Research Centre”;   LLC «Publisher «MIA»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.30629/2618-6667-2025-23-6-28-45</article-id><article-id custom-type="elpub" pub-id-type="custom">psychiatry-1475</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ПСИХОПАТОЛОГИЯ, КЛИНИЧЕСКАЯ И БИОЛОГИЧЕСКАЯ ПСИХИАТРИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>PSYCHOPATHOLOGY, CLINICAL AND BIOLOGICAL PSYCHIATRY</subject></subj-group></article-categories><title-group><article-title>Различный ответ на клозапин при терапевтически резистентной шизофрении в контексте структурной МРТ и ЭЭГ покоя</article-title><trans-title-group xml:lang="en"><trans-title>Different Clozapine Response in Treatment-resistant Schizophrenia in the Context of Structural MRI and Resting State EEG</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3997-1782</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Дудина</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Dudina</surname><given-names>A. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Анастасия Николаевна Дудина, младший научный сотрудник, лаборатория нейровизуализации и мультимодального анализа</p><p>Москва</p></bio><bio xml:lang="en"><p>Anastasia N. Dudina, Junior Researcher, Laboratory of Neuroimaging and Multimodal Analysis</p><p>Moscow</p></bio><email xlink:type="simple">andudina95@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3001-7842</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тихонов</surname><given-names>Д. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Tikhonov</surname><given-names>D. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Денис Витальевич Тихонов, кандидат медицинских наук, старший научный сотрудник, отдел юношеской психиатрии</p><p>Москва</p></bio><bio xml:lang="en"><p>Denis V. Tikhonov, Cand. Sci. (Med.), Senior Researcher, Department of Youth Psychiatry</p><p>Moscow</p></bio><email xlink:type="simple">denvt@list.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6034-4698</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Вершинина</surname><given-names>О. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Vershinina</surname><given-names>O. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ольга Юрьевна Вершинина, врач-рентгенолог, лаборатория нейровизуализации и мультимодального анализа</p><p>Москва</p></bio><bio xml:lang="en"><p>Olga Y. Vershinina, Radiologist, Laboratory of Neuroimaging and Multimodal Analysis</p><p>Moscow</p></bio><email xlink:type="simple">o.y.vershinina@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1209-1443</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Каледа</surname><given-names>В. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Kaleda</surname><given-names>V. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Василий Глебович Каледа, доктор медицинских наук, профессор, руководитель отдела юношеской психиатрии</p><p>Москва</p></bio><bio xml:lang="en"><p>Vasiliy G. Kaleda, Dr. of Sci. (Med.), Professor, Head of Youth Psychiatry Department</p><p>Moscow</p></bio><email xlink:type="simple">kaleda-vg@ncpz.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0649-6663</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лебедева</surname><given-names>И. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Lebedeva</surname><given-names>I. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ирина Сергеевна Лебедева, доктор биологических наук, профессор, руководитель лаборатории, лаборатория нейровизуализации и мультимодального анализа</p><p>Москва</p></bio><bio xml:lang="en"><p>Irina S. Lebedeva, Dr. of Sci. (Biol.), Professor, Head of Laboratory, Laboratory of Neuroimaging and Multimodal Analysis</p><p>Moscow</p></bio><email xlink:type="simple">irina.lebedeva@ncpz.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБНУ «Научный центр психического здоровья»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>FSBSI Mental Health Research Centre</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>13</day><month>02</month><year>2026</year></pub-date><volume>23</volume><issue>6</issue><fpage>28</fpage><lpage>45</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Дудина А.Н., Тихонов Д.В., Вершинина О.Ю., Каледа В.Г., Лебедева И.С., 2026</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="ru">Дудина А.Н., Тихонов Д.В., Вершинина О.Ю., Каледа В.Г., Лебедева И.С.</copyright-holder><copyright-holder xml:lang="en">Dudina A.N., Tikhonov D.V., Vershinina O.Y., Kaleda V.G., Lebedeva I.S.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.journalpsychiatry.com/jour/article/view/1475">https://www.journalpsychiatry.com/jour/article/view/1475</self-uri><abstract><sec><title>Обоснование</title><p>Обоснование: выделение отдельных подтипов шизофрении на основании различного терапевтического ответа и поиск биомаркеров ответа на клозапин находятся в самом начале пути.</p></sec><sec><title>Цель исследования</title><p>Цель исследования: определение профиля структурно-функциональных аномалий головного мозга в группах пациентов с ультрарезистентной шизофренией (УТРШ) и клозапин-респондеров (КРШ), а также поиск ассоциаций выявленных аномалий с клиническими характеристиками.</p></sec><sec><title>Пациенты и методы</title><p>Пациенты и методы: проведено клиническое, МРТ и ЭЭГ-обследование двух групп праворуких пациентов мужского пола с диагнозом параноидной шизофрении (F20.0 по МКБ-10) и групп здорового контроля. Выборку для анализа МРТ составили 15 пациентов группы КРШ, 18 пациентов группы УТРШ и 21 психически здоровый испытуемый. Анализ ЭЭГ-данных производили в выборке из 12 и 15 пациентов с диагнозом шизофрении (КРШ и УТРШ соответственно). Контрольная группа была подобрана отдельно и включала 26 человек. Для анализа МРТ-данных Т1-взвешенные изображения были обработаны в пакете FreeSurfer 7.1.1, в результате чего для каждого испытуемого были получены показатели корковых, подкорковых и стволовых структур. Для анализа ЭЭГ были получены показатели спектральной мощности (СМ) тета-, альфа- и гамма-ритмов. Были проведены межгрупповые сравнения и рассчитаны корреляции с психометрическими показателями Шкалы позитивных и негативных симптомов (PANSS), Шкалы Калгари для оценки депрессии при шизофрении (CDSS) и дозировкой антипсихотиков в хлорпромазиновом эквиваленте.</p></sec><sec><title>Результаты</title><p>Результаты: в группе УТРШ были обнаружены сходные с КРШ изменения подкорковых структур и уменьшение толщины коры (при КРШ по сравнению с нормой — правой височной коры; при УТРШ — лобной, височной, затылочной, теменной, островковой и поясной коры билатерально), также в обеих группах была выше СМ тета-ритма. СМ тета-ритма коррелировала со средней дневной дозой нейролептиков в группе УТРШ.</p></sec><sec><title>Выводы</title><p>Выводы: полученные результаты указывают на более распространенное и выраженное кортикальное истончение при ультрарезистентности. Эффекты проводимой терапии были отмечены, в первую очередь, для функциональных характеристик (СМ тета-ритма), хотя нельзя исключить и опосредованные эффекты изменения состояния головного мозга.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Background</title><p>Background: the identification of distinct schizophrenia subtypes based on therapeutic response, as well as the search for biomarkers of clozapine response, is still in its early stages.</p></sec><sec><title>Objective</title><p>Objective: to establish the profile of structural and functional abnormalities of the brain in groups of ultra-treatment-resistant schizophrenia patients (UTRS) and clozapine responders (CRS), as well as the associations of the identied abnormalities with clinical characteristics.</p></sec><sec><title>Patients and Methods</title><p>Patients and Methods: two groups of right-handed male patients diagnosed with paranoid schizophrenia (F20.0) and healthy controls underwent MRI, EEG and clinical examination. The MRI data analysis included 15 patients of the CRS group, 18 patients of the UTRS group, and 21 healthy controls. In the EEG data analysis, the samples consisted of 12 and 15 patients, respectively, while the control group was selected separately and included 26 subjects. For the analysis of MRI data, T1-weighted images were processed using FreeSurfer 7.1.1. For each subject, values for the cortical, subcortical, and brain stem structures were obtained. For EEG analysis, spectral power (SP) values of theta, alpha and gamma rhythms were obtained. Intergroup comparisons and correlations with clinical scales (PANSS, CDSS) and antipsychotic dosage in chlorpromazine equivalent were performed.</p></sec><sec><title>Results</title><p>Results: in the UTRS group, changes in subcortical structures similar to those in the CR group were observed, along with a decrease in the cortical thickness (in CRS compared to control — right temporal cortex; in UTRS — frontal, temporal, occipital, insular, and cingulate cortices bilaterally). Additionally, the theta rhythm SP was higher in both groups. The theta rhythm SP correlated with the average daily dose of antipsychotics in the UTRS group.</p></sec><sec><title>Conclusion</title><p>Conclusion: the results indicate that ultra-treatment-resistance is associated with more widespread and pronounced cortical thinning. The effects of the therapy were primarily noted in functional characteristics (theta rhythm SP), although indirect effects from changes in the state of the brain cannot be excluded.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>терапевтически резистентная шизофрения</kwd><kwd>клозапин</kwd><kwd>МРТ</kwd><kwd>ЭЭГ</kwd><kwd>толщина коры</kwd><kwd>гиппокамп</kwd><kwd>тета-ритм</kwd><kwd>миндалевидное тело</kwd><kwd>бледный шар</kwd></kwd-group><kwd-group xml:lang="en"><kwd>treatment-resistant schizophrenia</kwd><kwd>clozapine</kwd><kwd>MRI</kwd><kwd>EEG</kwd><kwd>cortical thickness</kwd><kwd>hippocampus</kwd><kwd>theta rhythm</kwd><kwd>amygdala</kwd><kwd>globus pallidus</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена при поддержке гранта РНФ № 24-15-00220.</funding-statement><funding-statement xml:lang="en">This research was funded by the Russian Science Foundation grant № 24-15-00220.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Elkis H, Buckley PF. 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