psychiatryПСИХИАТРИЯPsychiatry (Moscow) (Psikhiatriya)1683-83192618-6667FSBSI “The Mental Health Research Centre”; LLC «Publisher «MIA»10.30629/2618-6667-2023-21-5-25-39psychiatry-1040Research ArticleМАТЕРИАЛЫ КОНФЕРЕНЦИИ «НЕЙРОВОСПАЛЕНИЕ ПРИ ЗАБОЛЕВАНИЯХ МОЗГА: ФУНДАМЕНТАЛЬНЫЕ И ПРАКТИЧЕСКИЕ АСПЕКТЫ» МОСКВА 31.01.2023Реактивность микроглии в префронтальной коре при шизофренииMicroglial Reactivity in the Prefrontal Cortex in Schizophreniahttps://orcid.org/0000-0001-9543-7421УрановаН. А.UranovaN. A.

Наталия Александровна Уранова, доктор медицинских наук, заведующая лабораторией, лаборатория клинической нейроморфологии

Москва

Natalya A. Uranova, Dr. of Sci. (Med.), Head of Laboratory, Laboratory of Clinical Neuropathology

Moscow

uranovan@mail.ruhttps://orcid.org/0000-0002-6920-316XВихреваО. В.VikhrevaO. V.

Ольга Васильевна Вихрева, кандидат биологичеcких наук, старший научный сотрудник, лаборатория клинической нейроморфологии

Москва

Olga V. Vikhreva, Сand. of Sci. (Biol.), Senior Researcher, Laboratory of Clinical Neuropathology

Moscow

volgavasil@yandex.ruФГБНУ «Научный центр психического здоровья»РоссияFSBSI “Mental Health Research Centre”Russian Federation2023231020232152539Copyright © Уранова Н.А., Вихрева О.В., 20232023Уранова Н.А., Вихрева О.В.Uranova N.A., Vikhreva O.V.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/1040

Обоснование: шизофрения связана с нейровоспалением и дисрегуляцией иммунной системы с участием микроглии. Исследования реактивности микроглии при шизофрении находятся на начальном этапе. Результаты нейровизуализационных и постмортальных оценок противоречивы.Цель исследования: анализ и обобщение результатов морфометрического изучения реактивности микроглии на ультраструктурном уровне в префронтальной коре аутопсийного мозга при шизофрении по сравнению с контролем без психической патологии. Материал и методы: исследован слой 5 префронтальной коры (поле 10 по Бродману) в 21 случае шизофрении и 20 контрольных случаях с помощью трансмиссионной электронной микроскопии и морфометрии. Результаты и заключение: установлено, что шизофрения характеризуется сочетанием признаков активации прогрессирующей дистрофии и ускоренного старения микроглии. Реактивность микроглии при шизофрении связана с возрастом, возрастом начала болезни, длительностью болезни и типом течения болезни, что свидетельствует об участии микроглии в патологическом процессе при шизофрении. Повреждение и дефицит митохондрий и нарушения энергетического метаболизма могут играть ведущую роль в дисфункции микроглии при шизофрении.

Background: schizophrenia is associated with neuroinflammation and dysregulation of the immune system involving microglia. The study of microglial reactivity in schizophrenia is at an early stage. The results of neuroimaging and postmortem studies are contradictory. Aim of the study: to analyze and summarize the results of morphometric studies of the microglial reactivity at the ultrastructural level in postmortem prefrontal cortex in schizophrenia compared to healthy controls. Material and methods: the study was performed in layer 5 of the prefrontal cortex in 21 cases of schizophrenia and 20 control cases using transmission electron microscopy and morphometry. Results and conclusion: we found that chronic schizophrenia is characterized by a combination of signs of activation, progressive dystrophy and accelerated aging of microglia. The reactivity of microglia in schizophrenia is associated with age, the age of onset of the disease, the duration of the disease and the type of course of the disease, which indicates the participation of microglia in the pathological process in schizophrenia. Damage and deficit mitochondria and the disturbance of energy metabolism can play a key role in microglial dysfunction in schizophrenia.

микроглияультраструктураморфометрияпрефронтальная корашизофренияmicrogliaultrastructuremorphometryprefrontal cortexschizophreniaReferencesMüller N. Inflammation in schizophrenia: Pathogenetic aspects and therapeutic considerations. Schizophr Bull. 2018;44(5):973–982. doi: 10.1093/schbul/sby024Müller N. Inflammation in schizophrenia: Pathogenetic aspects and therapeutic considerations. Schizophr Bull. 2018;44(5):973–982. doi: 10.1093/schbul/sby024Mongan D, Ramesar M, Föcking M, Cannon M, Cotter D. Role of inflammation in the pathogenesis of schizophrenia: A review of the evidence, proposed mechanisms and implications for treatment. Early Interv Psychiatry. 2020;14(4):385–397. doi: 10.1111/eip.12859Mongan D, Ramesar M, Föcking M, Cannon M, Cotter D. Role of inflammation in the pathogenesis of schizophrenia: A review of the evidence, proposed mechanisms and implications for treatment. Early Interv Psychiatry. 2020;14(4):385–397. doi: 10.1111/eip.12859Laskaris LE, Di Biase MA, Everall I, Chana G, Christopoulos A, Skafidas E, Cropley VL, Pantelis C. Microglial activation and progressive brain changes in schizophrenia. Br J Pharmacol. 2016;173(4):666–680. doi: 10.1111/bph.13364Laskaris LE, Di Biase MA, Everall I, Chana G, Christopoulos A, Skafidas E, Cropley VL, Pantelis C. Microglial activation and progressive brain changes in schizophrenia. Br J Pharmacol. 2016;173(4):666–680. doi: 10.1111/bph.13364Munn NA. Microglia dysfunction in schizophrenia: an integrative theory. Med Hypotheses. 2000 54(2):198– 202. doi: 10.1054/mehy.1999.0018Munn NA. Microglia dysfunction in schizophrenia: an integrative theory. Med Hypotheses. 2000 54(2):198– 202. doi: 10.1054/mehy.1999.0018Monji A, Kato T, Kanba S. Cytokines and schizophrenia: Microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci. 2009;63(3):257–265. doi: 10.1111/j.1440-1819.2009.01945.xMonji A, Kato T, Kanba S. Cytokines and schizophrenia: Microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci. 2009;63(3):257–265. doi: 10.1111/j.1440-1819.2009.01945.xBayer TA, Falkai P, Maier W. Genetic and non-genetic vulnerability factors in schizophrenia: the basis of the “two hit hypothesis”. J Psychiatr Res. 1999;33(6):543–548. doi: 10.1016/s0022-3956(99)00039-4Bayer TA, Falkai P, Maier W. Genetic and non-genetic vulnerability factors in schizophrenia: the basis of the “two hit hypothesis”. J Psychiatr Res. 1999;33(6):543–548. doi: 10.1016/s0022-3956(99)00039-4Feigenson KA, Kusnecov AW, Silverstein SM. Inflammation and the two-hit hypothesis of schizophrenia. Neurosci Biobehav Rev. 2014;38:72–93. doi: 10.1016/j. neubiorev.2013.11.006Feigenson KA, Kusnecov AW, Silverstein SM. Inflammation and the two-hit hypothesis of schizophrenia. Neurosci Biobehav Rev. 2014;38:72–93. doi: 10.1016/j. neubiorev.2013.11.006van Berckel BN, Bossong MG, Boellaard R, Kloet R, Schuitemaker A, Caspers E, Luurtsema G, Windhorst AD, Cahn W, Lammertsma AA, Kahn RS. Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol Psychiatry. 2008;64(9):820– 822. doi: 10.1016/j.biopsych.2008.04.025van Berckel BN, Bossong MG, Boellaard R, Kloet R, Schuitemaker A, Caspers E, Luurtsema G, Windhorst AD, Cahn W, Lammertsma AA, Kahn RS. Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol Psychiatry. 2008;64(9):820– 822. doi: 10.1016/j.biopsych.2008.04.025Doorduin J, de Vries EF, Willemsen AT, de Groot JC, Dierckx RA, Klein HC. Neuroinflammation in schizophrenia-related psychosis: a PET study. J Nucl Med. 2009;50(11):1801–1807. doi: 10.2967/jnumed.109.066647Doorduin J, de Vries EF, Willemsen AT, de Groot JC, Dierckx RA, Klein HC. Neuroinflammation in schizophrenia-related psychosis: a PET study. J Nucl Med. 2009;50(11):1801–1807. doi: 10.2967/jnumed.109.066647van der Doef TF, de Witte LD, Sutterland AL, Jobse E, Yaqub M, Boellaard R, de Haan L, Eriksson J, Lammertsma AA, Kahn RS, van Berckel BN. In vivo (R)-[(11)C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis. NPJ Schizophr. 2016;31(2):16031. doi: 10.1038/npjschz.2016.31van der Doef TF, de Witte LD, Sutterland AL, Jobse E, Yaqub M, Boellaard R, de Haan L, Eriksson J, Lammertsma AA, Kahn RS, van Berckel BN. In vivo (R)-[(11)C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis. NPJ Schizophr. 2016;31(2):16031. doi: 10.1038/npjschz.2016.31Di Biase MA, Zalesky A, O’keefe G, Laskaris L, Baune BT, Weickert CS, Olver J, McGorry PD, Amminger GP, Nelson B, Scott AM, Hickie I, Banati R, Turkheimer F, Yaqub M, Everall IP, Pantelis C, Cropley V. PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia. Transl Psychiatry. 2017;7(8):e1225. doi: 10.1038/tp.2017.193Di Biase MA, Zalesky A, O’keefe G, Laskaris L, Baune BT, Weickert CS, Olver J, McGorry PD, Amminger GP, Nelson B, Scott AM, Hickie I, Banati R, Turkheimer F, Yaqub M, Everall IP, Pantelis C, Cropley V. PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia. Transl Psychiatry. 2017;7(8):e1225. doi: 10.1038/tp.2017.193Uranova NA, Bonartsev PD, Androsova LV, Rakhmanova VI, Kaleda VG. Impaired monocyte activation in schizophrenia: ultrastructural abnormalities and increased IL-1β production. Eur Arch Psychiatry Clin Neurosci. 2017;267(5):417–426. doi: 10.1007/s00406-017-0782-1Uranova NA, Bonartsev PD, Androsova LV, Rakhmanova VI, Kaleda VG. Impaired monocyte activation in schizophrenia: ultrastructural abnormalities and increased IL-1β production. Eur Arch Psychiatry Clin Neurosci. 2017;267(5):417–426. doi: 10.1007/s00406-017-0782-1Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of Microglia. Physiol Rev. 2011;91(2):461– 553. doi: 10.1152/physrev.00011.2010Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of Microglia. Physiol Rev. 2011;91(2):461– 553. doi: 10.1152/physrev.00011.2010van Kesteren CF, Gremmels H, de Witte LD, Hol EM, Van Gool AR, Falkai P.G., Kahn RS, Sommer IE. Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies. Transl Psychiatry. 2017;7(3):e1075. doi: 10.1038/tp.2017.4van Kesteren CF, Gremmels H, de Witte LD, Hol EM, Van Gool AR, Falkai P.G., Kahn RS, Sommer IE. Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies. Transl Psychiatry. 2017;7(3):e1075. doi: 10.1038/tp.2017.4Gober R, Ardalan M, Shiadeh SMJ, Duque L, Garamszegi SP, Ascona M, Barreda A, Sun X, Mallard C, Vontell RT. Microglia activation in postmortem brains with schizophrenia demonstrates distinct morphological changes between brain regions. Brain Pathol. 2022;32(1):e13003. doi: 10.1111/bpa.13003Gober R, Ardalan M, Shiadeh SMJ, Duque L, Garamszegi SP, Ascona M, Barreda A, Sun X, Mallard C, Vontell RT. Microglia activation in postmortem brains with schizophrenia demonstrates distinct morphological changes between brain regions. Brain Pathol. 2022;32(1):e13003. doi: 10.1111/bpa.13003Fillman SG, Cloonan N, Catts VS, Miller LC, Wong J, McCrossin T, Cairns M, Weickert CS. Increased in-flammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry. 2013;18(2):206–214. doi: 10.1038/mp.2012.110Fillman SG, Cloonan N, Catts VS, Miller LC, Wong J, McCrossin T, Cairns M, Weickert CS. Increased in-flammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry. 2013;18(2):206–214. doi: 10.1038/mp.2012.110Глезер ИИ, Сухорукова ЛИ. Структурные особенности нейроглии при шизофрении с периодическим и непрерывным типами течения (гистологическое и электронно-микроскопическое исследование). Журнал неврологии и психиатрии имени С.С. Корсакова. 1966;66(10):1529–1537. PMID: 6000316. Glezer II, Sukhorukova LI. Structural features of neuroglia in schizophrenia of the periodic and uninterruped types (histological and electron microscopic study. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 1966;66(10):1529–1537 (In Russ.). PMID: 6000316.Глезер ИИ, Сухорукова ЛИ. Структурные особенности нейроглии при шизофрении с периодическим и непрерывным типами течения (гистологическое и электронно-микроскопическое исследование). Журнал неврологии и психиатрии имени С.С. Корсакова. 1966;66(10):1529–1537. PMID: 6000316. Glezer II, Sukhorukova LI. Structural features of neuroglia in schizophrenia of the periodic and uninterruped types (histological and electron microscopic study. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 1966;66(10):1529–1537 (In Russ.). PMID: 6000316.Limongi R, Mackinley M, Dempster K, Khan AR, Gati JS, Palaniyappan L. Frontal-striatal connectivity and positive symptoms of schizophrenia: implications for the mechanistic basis of prefrontal rTMS. Eur Arch Psychiatry Clin Neurosci. 2021;271(1):3–15. doi: 10.1007/s00406-020-01163-6Limongi R, Mackinley M, Dempster K, Khan AR, Gati JS, Palaniyappan L. Frontal-striatal connectivity and positive symptoms of schizophrenia: implications for the mechanistic basis of prefrontal rTMS. Eur Arch Psychiatry Clin Neurosci. 2021;271(1):3–15. doi: 10.1007/s00406-020-01163-6Fuentes-Claramonte P, Ramiro N, Torres L, Argila-Plaza I, Salgado-Pineda P, Soler-Vidal J, García-León MÁ, Albacete A, Bosque C, Panicalli F, Boix E, Munuera J, Tristany J, Sarró S, Bernardo M, Salvador R, McKenna PJ, Pomarol-Clotet E. Negative schizophrenic symptoms as prefrontal cortex dysfunction: Examination using a task measuring goal neglect. Neuroimage Clin. 2022;35:103119. doi: 10.1016/j. nicl.2022.103119Fuentes-Claramonte P, Ramiro N, Torres L, Argila-Plaza I, Salgado-Pineda P, Soler-Vidal J, García-León MÁ, Albacete A, Bosque C, Panicalli F, Boix E, Munuera J, Tristany J, Sarró S, Bernardo M, Salvador R, McKenna PJ, Pomarol-Clotet E. Negative schizophrenic symptoms as prefrontal cortex dysfunction: Examination using a task measuring goal neglect. Neuroimage Clin. 2022;35:103119. doi: 10.1016/j. nicl.2022.103119Uranova NA, Vikhreva OV, Rakhmanova VI. Abnormal microglial reactivity in gray matter of the prefrontal cortex in schizophrenia. Asian J Psychiatr. 2021;63:102752. doi: 10.1016/j.ajp.2021.102752Uranova NA, Vikhreva OV, Rakhmanova VI. Abnormal microglial reactivity in gray matter of the prefrontal cortex in schizophrenia. Asian J Psychiatr. 2021;63:102752. doi: 10.1016/j.ajp.2021.102752Вихрева ОВ, Уранова НА. Реактивность микроглии в префронтальной коре при разных типах течения шизофрении. Журнал неврологии и психиатрии имени С.С. Корсакова 2021;121(12):77–83. doi: 10.17116/jnevro202112112177 Vikhreva OV, Uranova NA. Microglial reactivity in the prefrontal cortex in different types of schizophrenia. S.S. Korsakov Journal of Neurology and Psychiatry/Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2021;121(12):77–83. (In Russ.). doi: 10.17116/jnevro202112112177Вихрева ОВ, Уранова НА. Реактивность микроглии в префронтальной коре при разных типах течения шизофрении. Журнал неврологии и психиатрии имени С.С. Корсакова 2021;121(12):77–83. doi: 10.17116/jnevro202112112177 Vikhreva OV, Uranova NA. Microglial reactivity in the prefrontal cortex in different types of schizophrenia. S.S. Korsakov Journal of Neurology and Psychiatry/Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2021;121(12):77–83. (In Russ.). doi: 10.17116/jnevro202112112177Giridharan VV, Scaini G, Colpo GD, Doifode T, Pinjari OF, Teixeira AL, Petronilho F, Macêdo D, Quevedo J, Barichello T. Clozapine Prevents Poly (I:C) Induced Inflammation by Modulating NLRP3 Pathway in Microglial Cells. Cells. 2020;9(3):577. doi: 10.3390/cells9030577Giridharan VV, Scaini G, Colpo GD, Doifode T, Pinjari OF, Teixeira AL, Petronilho F, Macêdo D, Quevedo J, Barichello T. Clozapine Prevents Poly (I:C) Induced Inflammation by Modulating NLRP3 Pathway in Microglial Cells. Cells. 2020;9(3):577. doi: 10.3390/cells9030577Zhang L, Zhao J. Profile of minocycline and its potential in the treatment of schizophrenia. Neuropsychiatr Dis Treat. 2014;10:1103–1111. doi: 10.2147/NDT. S64236Zhang L, Zhao J. Profile of minocycline and its potential in the treatment of schizophrenia. Neuropsychiatr Dis Treat. 2014;10:1103–1111. doi: 10.2147/NDT. S64236Lu Y, Zhou M, Li Y, Li Y, Hua Y, Fan Y. Minocycline promotes functional recovery in ischemic stroke by modulating microglia polarization through STAT1/STAT6 pathways. Biochem Pharmacol. 2021;186:114464. doi: 10.1016/j.bcp.2021.114464Lu Y, Zhou M, Li Y, Li Y, Hua Y, Fan Y. Minocycline promotes functional recovery in ischemic stroke by modulating microglia polarization through STAT1/STAT6 pathways. Biochem Pharmacol. 2021;186:114464. doi: 10.1016/j.bcp.2021.114464Zheng W, Zhu XM, Zhang QE, Cheng G, Cai DB, He J, Ng CH, Ungvari GS, Peng XJ, Ning YP, Xiang YT. Adjunctive minocycline for major mental disorders: A systematic review. J Psychopharmacol. 2019;33(10):1215–1226. doi: 10.1177/0269881119858286Zheng W, Zhu XM, Zhang QE, Cheng G, Cai DB, He J, Ng CH, Ungvari GS, Peng XJ, Ning YP, Xiang YT. Adjunctive minocycline for major mental disorders: A systematic review. J Psychopharmacol. 2019;33(10):1215–1226. doi: 10.1177/0269881119858286De Picker LJ, Victoriano GM, Richards R, Gorvett AJ, Lyons S, Buckland GR, Tofani T, Norman JL, Chatelet DS, Nicoll JAR, Boche D. Immune environment of the brain in schizophrenia and during the psychotic episode: A human post-mortem study. Brain Behav Immun. 2021;97:319–327. doi: 10.1016/j. bbi.2021.07.017De Picker LJ, Victoriano GM, Richards R, Gorvett AJ, Lyons S, Buckland GR, Tofani T, Norman JL, Chatelet DS, Nicoll JAR, Boche D. Immune environment of the brain in schizophrenia and during the psychotic episode: A human post-mortem study. Brain Behav Immun. 2021;97:319–327. doi: 10.1016/j. bbi.2021.07.017Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature. 2008;454(7203):455–462. doi: 10.1038/nature07203Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature. 2008;454(7203):455–462. doi: 10.1038/nature07203Patel S, Sharma D, Kalia K, Tiwari V. Crosstalk between endoplasmic reticulum stress and oxidative stress in schizophrenia: The dawn of new therapeutic approaches. Neurosci Biobehav Rev. 2017;83:589–603. doi: 10.1016/j.neubiorev.2017.08.025Patel S, Sharma D, Kalia K, Tiwari V. Crosstalk between endoplasmic reticulum stress and oxidative stress in schizophrenia: The dawn of new therapeutic approaches. Neurosci Biobehav Rev. 2017;83:589–603. doi: 10.1016/j.neubiorev.2017.08.025Monji A, Kato TA, Mizoguchi Y, Horikawa H, Seki Y, Kasai M, Yamauchi Y, Yamada S, Kanba S. Neuroin-flammation in schizophrenia especially focused on the role of microglia. Prog Neuropsychopharmacol Biol Psychiatry. 2013;42:115–121. doi: 10.1016/j. pnpbp.2011.12.002Monji A, Kato TA, Mizoguchi Y, Horikawa H, Seki Y, Kasai M, Yamauchi Y, Yamada S, Kanba S. Neuroin-flammation in schizophrenia especially focused on the role of microglia. Prog Neuropsychopharmacol Biol Psychiatry. 2013;42:115–121. doi: 10.1016/j. pnpbp.2011.12.002Takano A, Arakawa R, Ito H, Tateno A, Takahashi H, Matsumoto R, Okubo Y, Suhara T. Peripheral benzodiazepine receptors in patients with chronic schizophrenia: a PET study with [11C]DAA1106. Int J Neuropsychopharmacol. 2010;13(7):943–950. doi: 10.1017/S1461145710000313Takano A, Arakawa R, Ito H, Tateno A, Takahashi H, Matsumoto R, Okubo Y, Suhara T. Peripheral benzodiazepine receptors in patients with chronic schizophrenia: a PET study with [11C]DAA1106. Int J Neuropsychopharmacol. 2010;13(7):943–950. doi: 10.1017/S1461145710000313Kirkpatrick B, Kennedy BK. Accelerated aging in schizophrenia and related disorders: future research. Schizophr. Res. 2018;196:4–8. doi: 10.1016/j. schres.2017.06.034Kirkpatrick B, Kennedy BK. Accelerated aging in schizophrenia and related disorders: future research. Schizophr. Res. 2018;196:4–8. doi: 10.1016/j. schres.2017.06.034Kochunov P, Glahn DC, Rowland LM, Olvera RL, Winkler A, Yang YH, Sampath H, Carpenter WT, Duggirala R, Curran J, Blangero J, Hong LE. Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression. Biol Psychiatry. 2013;73(5):482–491. doi: 10.1016/j.biopsych. 2012.10.002Kochunov P, Glahn DC, Rowland LM, Olvera RL, Winkler A, Yang YH, Sampath H, Carpenter WT, Duggirala R, Curran J, Blangero J, Hong LE. Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression. Biol Psychiatry. 2013;73(5):482–491. doi: 10.1016/j.biopsych. 2012.10.002Клюшник ТП, Зозуля СА, Андросова ЛВ, Отман ИН, Дупин АМ, Пантелеева ГП, Олейчик ИВ, Абрамова ЛИ, Столяров СА, Шипилова ЕС, Борисова ОА. Иммунологический мониторинг эндогенных приступообразных психозов. Журнал неврологии и психиатрии имени С.С. Корсакова. 2014;114(2):37–41. Klyushnik TP, Zozulya SA, Androsova LV, Sarmanova ZV, Otman IN, Dupin AM, Panteleeva GP, Abramova LI, Stoliarov SA, Shipilova ES, Borisova OA. Immunological monitoring of endogenous attack-like psychoses. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2014;114(2):37–41. (In Russ.).Клюшник ТП, Зозуля СА, Андросова ЛВ, Отман ИН, Дупин АМ, Пантелеева ГП, Олейчик ИВ, Абрамова ЛИ, Столяров СА, Шипилова ЕС, Борисова ОА. Иммунологический мониторинг эндогенных приступообразных психозов. Журнал неврологии и психиатрии имени С.С. Корсакова. 2014;114(2):37–41. Klyushnik TP, Zozulya SA, Androsova LV, Sarmanova ZV, Otman IN, Dupin AM, Panteleeva GP, Abramova LI, Stoliarov SA, Shipilova ES, Borisova OA. Immunological monitoring of endogenous attack-like psychoses. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2014;114(2):37–41. (In Russ.).Андросова ЛВ, Михайлова НМ, Зозуля СА, Дупин АМ, Клюшник ТП. Маркеры воспаления при шизофрении позднего возраста. Журнал неврологии и психиатрии имени С.С. Корсакова. 2014;114(12):60–64. doi: 10.1016/j.schres.2015.07.018 Androsova LV, Mikhaylova NM, Zozulia SA, Dupin AM, Kliushnik TP. Inflammatory markers in schizophrenia in aged. S.S. Korsakov Journal of Neurology and Psychiatry/Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2014;114(12):60–64. (In Russ.). doi: 10.17116/jnevro201411412160-64Андросова ЛВ, Михайлова НМ, Зозуля СА, Дупин АМ, Клюшник ТП. Маркеры воспаления при шизофрении позднего возраста. Журнал неврологии и психиатрии имени С.С. Корсакова. 2014;114(12):60–64. doi: 10.1016/j.schres.2015.07.018 Androsova LV, Mikhaylova NM, Zozulia SA, Dupin AM, Kliushnik TP. Inflammatory markers in schizophrenia in aged. S.S. Korsakov Journal of Neurology and Psychiatry/Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2014;114(12):60–64. (In Russ.). doi: 10.17116/jnevro201411412160-64Watkins CC, Andrews SR. Clinical studies of neuroinflammatory mechanisms in schizophrenia. Schizophr Res. 2016;176(1):14–22. doi: 10.1016/j. schres.2015.07.018Watkins CC, Andrews SR. Clinical studies of neuroinflammatory mechanisms in schizophrenia. Schizophr Res. 2016;176(1):14–22. doi: 10.1016/j. schres.2015.07.018Xu H, Yang F. The interplay of dopamine metabolism abnormalities and mitochondrial defects in the pathogenesis of schizophrenia. Transl Psychiatry. 2022;12(1):464. doi: 10.1038/s41398-022-02233-0Xu H, Yang F. The interplay of dopamine metabolism abnormalities and mitochondrial defects in the pathogenesis of schizophrenia. Transl Psychiatry. 2022;12(1):464. doi: 10.1038/s41398-022-02233-0Roberts RC. Mitochondrial dysfunction in schizophrenia: with a focus on postmortem studies. Mitochondrion. 2021;56:91–101. doi: 10.1016/j. mito.2020.11.009Roberts RC. Mitochondrial dysfunction in schizophrenia: with a focus on postmortem studies. Mitochondrion. 2021;56:91–101. doi: 10.1016/j. mito.2020.11.009Савушкина ОК, Терешкина ЕБ, Прохорова ТА, Воробьеа ЕА, Бокша ИС, Бурбаева ГШ. Распределение изоформы креатинкиназы Б в мозге при шизофрении. Журнал неврологии и психиатрии имени С.С. Корсакова. 2016;116(9):62–68. doi: 10.17116/jnevro20161169162-68 Savushkina OK, Tereshkina EB, Prokhorova TA, Vorobeva EA, Boksha IS, Burbaeva GSh. Creatine kinase isoform B distribution in the brain in schizophrenia. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2016;116(9):62-68. (In Russ.). doi: 10.17116/jnevro20161169162-68Савушкина ОК, Терешкина ЕБ, Прохорова ТА, Воробьеа ЕА, Бокша ИС, Бурбаева ГШ. Распределение изоформы креатинкиназы Б в мозге при шизофрении. Журнал неврологии и психиатрии имени С.С. Корсакова. 2016;116(9):62–68. doi: 10.17116/jnevro20161169162-68 Savushkina OK, Tereshkina EB, Prokhorova TA, Vorobeva EA, Boksha IS, Burbaeva GSh. Creatine kinase isoform B distribution in the brain in schizophrenia. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2016;116(9):62-68. (In Russ.). doi: 10.17116/jnevro20161169162-68Whitehurst T, Howes O. The role of mitochondria in the pathophysiology of schizophrenia: A critical review of the evidence focusing on mitochondrial complex one. Neurosci Biobehav Rev. 2022;132:449–464. doi: 10.1016/j.neubiorev.2021.11.047Whitehurst T, Howes O. The role of mitochondria in the pathophysiology of schizophrenia: A critical review of the evidence focusing on mitochondrial complex one. Neurosci Biobehav Rev. 2022;132:449–464. doi: 10.1016/j.neubiorev.2021.11.047Da Silva T, Wu A, Laksono I, Prce I, Maheandiran M, Kiang M, Andreazza AC, Mizrahi R. Mitochondrial function in individuals at clinical high risk for psychosis. Sci Rep. 2018;18;8(1):6216. doi: 10.1038/s41598-018-24355-6Da Silva T, Wu A, Laksono I, Prce I, Maheandiran M, Kiang M, Andreazza AC, Mizrahi R. Mitochondrial function in individuals at clinical high risk for psychosis. Sci Rep. 2018;18;8(1):6216. doi: 10.1038/s41598-018-24355-6Maurer I, Zierz S, Moller H. Evidence for a mitochondrial oxidative phosphorylation defect in brains from patients with schizophrenia. Schizophr Res. 2001;48(1):125–136. doi: 10.1016/s0920-9964(00)00075-xMaurer I, Zierz S, Moller H. Evidence for a mitochondrial oxidative phosphorylation defect in brains from patients with schizophrenia. Schizophr Res. 2001;48(1):125–136. doi: 10.1016/s0920-9964(00)00075-xIwamoto K, Bundo M, Kato T. Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Hum Mol Genet. 2005;14(2):241–253. doi: 10.1093/hmg/ddi022Iwamoto K, Bundo M, Kato T. Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Hum Mol Genet. 2005;14(2):241–253. doi: 10.1093/hmg/ddi022Smesny S, Gussew A, Biesel NJ, Schack S, Walther M, Rzanny R, Milleit B, Gaser C, Sobanski T, Schultz CC, Amminger P, Hipler UC, Sauer H, Reichenbach JR. Glutamatergic dysfunction linked to energy and membrane lipid metabolism in frontal and anterior cingulate cortices of never treated first-episode schizophrenia patients. Schizophr Res. 2015;168(1– 2):322–329. doi: 10.1016/j.schres.2015.07.013Smesny S, Gussew A, Biesel NJ, Schack S, Walther M, Rzanny R, Milleit B, Gaser C, Sobanski T, Schultz CC, Amminger P, Hipler UC, Sauer H, Reichenbach JR. Glutamatergic dysfunction linked to energy and membrane lipid metabolism in frontal and anterior cingulate cortices of never treated first-episode schizophrenia patients. Schizophr Res. 2015;168(1– 2):322–329. doi: 10.1016/j.schres.2015.07.013Kung L, Roberts RC. Mitochondrial pathology in human schizophrenic str iatum: a postmortem ultrastructural study. Synapse. 1999;31:67–75. doi: 10.1002/(SICI)1098-2396(199901)31:1<67:: AID-SYN9>3.0.CO;2-#Kung L, Roberts RC. Mitochondrial pathology in human schizophrenic str iatum: a postmortem ultrastructural study. Synapse. 1999;31:67–75. doi: 10.1002/(SICI)1098-2396(199901)31:1<67:: AID-SYN9>3.0.CO;2-#Chan ST, McCarthy MJ, Vawter MP. Psychiatric drugs impact mitochondrial function in brain and other tissues. Schizophr Res. 2020;217:136–147. doi: 10.1016/j.schres.2019.09.007Chan ST, McCarthy MJ, Vawter MP. Psychiatric drugs impact mitochondrial function in brain and other tissues. Schizophr Res. 2020;217:136–147. doi: 10.1016/j.schres.2019.09.007Fan Y, Simmen T. Mechanistic Connections between Endoplasmic Reticulum (ER) Redox Control and Mitochondrial Metabolism. Cells. 2019;8(9):1071. doi: 10.3390/cells8091071Fan Y, Simmen T. Mechanistic Connections between Endoplasmic Reticulum (ER) Redox Control and Mitochondrial Metabolism. Cells. 2019;8(9):1071. doi: 10.3390/cells8091071He B. Viruses, endoplasmic reticulum stress, and interferon responses. Cell Death Differ. 2006;13(3):393– 403. doi: 10.1038/sj.cdd.4401833He B. Viruses, endoplasmic reticulum stress, and interferon responses. Cell Death Differ. 2006;13(3):393– 403. doi: 10.1038/sj.cdd.4401833Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, Shiosaka S, Hammarback JA, Urano F, Imaizumi K. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 2006;26(24):9220–9231. doi: 10.1128/MCB.01453-06 Epub 2006 Oct 9. PMID: 17030611; PMCID: PMC1698520.Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, Shiosaka S, Hammarback JA, Urano F, Imaizumi K. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 2006;26(24):9220–9231. doi: 10.1128/MCB.01453-06 Epub 2006 Oct 9. PMID: 17030611; PMCID: PMC1698520.Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL, Wayland M, Freeman T, Dudbridge F, Lilley KS, Karp NA, Hester S, Tkachev D, Mimmack ML, Yolken RH, Webster MJ, Torrey EF, Bahn S. Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry. 2004;9(7):684–697,643. doi: 10.1038/sj.mp.4001511Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL, Wayland M, Freeman T, Dudbridge F, Lilley KS, Karp NA, Hester S, Tkachev D, Mimmack ML, Yolken RH, Webster MJ, Torrey EF, Bahn S. Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry. 2004;9(7):684–697,643. doi: 10.1038/sj.mp.4001511Schulmann A, Ryu E, Goncalves V, Rollins B, Christiansen M, Frye MA, Biernacka J, Vawter MP. Novel Complex Interactions between Mitochondrial and Nuclear DNA in Schizophrenia and Bipolar Disorder. Mol Neuropsychiatry. 2019;5(1):13–27. doi: 10.1159/000495658Schulmann A, Ryu E, Goncalves V, Rollins B, Christiansen M, Frye MA, Biernacka J, Vawter MP. Novel Complex Interactions between Mitochondrial and Nuclear DNA in Schizophrenia and Bipolar Disorder. Mol Neuropsychiatry. 2019;5(1):13–27. doi: 10.1159/000495658Ross T, Szczepanek K, Bowler E, Hu Y, Larner A, Lesnefsky EJ, Chen Q. Reverse electron flow-mediated ROS generation in ischemia-damaged mitochondria: role of complex I inhibition vs. depolarization of inner mitochondrial membrane. Biochim Biophys Acta. 2013;1830(10):4537–4542. doi: 10.1016/j. bbagen.2013.05.035Ross T, Szczepanek K, Bowler E, Hu Y, Larner A, Lesnefsky EJ, Chen Q. Reverse electron flow-mediated ROS generation in ischemia-damaged mitochondria: role of complex I inhibition vs. depolarization of inner mitochondrial membrane. Biochim Biophys Acta. 2013;1830(10):4537–4542. doi: 10.1016/j. bbagen.2013.05.035Suárez-Méndez S, García-de la Cruz DD, Tovilla-Zárate CA, Genis-Mendoza AD, Ramón-Torres RA, González-Castro TB, Juárez-Rojop IE. Diverse roles of mtDNA in schizophrenia: Implications in its pathophysiology and as biomarker for cognitive impairment. Prog Biophys Mol Biol. 2020;155:36–41. doi: 10.1016/j.pbiomolbio.2020.04.004Suárez-Méndez S, García-de la Cruz DD, Tovilla-Zárate CA, Genis-Mendoza AD, Ramón-Torres RA, González-Castro TB, Juárez-Rojop IE. Diverse roles of mtDNA in schizophrenia: Implications in its pathophysiology and as biomarker for cognitive impairment. Prog Biophys Mol Biol. 2020;155:36–41. doi: 10.1016/j.pbiomolbio.2020.04.004Ben-Shachar D. Mitochondrial dysfunction in schizophrenia: a possible linkage to dopamine. J Neurochem. 2002;83(6):1241–1251. doi: 10.1046/j.1471-4159.2002.01263.xBen-Shachar D. Mitochondrial dysfunction in schizophrenia: a possible linkage to dopamine. J Neurochem. 2002;83(6):1241–1251. doi: 10.1046/j.1471-4159.2002.01263.xKarry R, Klein E, Ben Shachar D. Mitochondrial complex I subunits expression is altered in schizophrenia: a postmortem study. Biol Psychiatry. 2004;55(7):676– 684. doi: 10.1016/j.biopsych.2003.12.012Karry R, Klein E, Ben Shachar D. Mitochondrial complex I subunits expression is altered in schizophrenia: a postmortem study. Biol Psychiatry. 2004;55(7):676– 684. doi: 10.1016/j.biopsych.2003.12.012Lemasters JJ. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction and aging. Rejuvenation Res. 2005;8(1):3–5. doi: 10.1089/rej.2005.8.3Lemasters JJ. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction and aging. Rejuvenation Res. 2005;8(1):3–5. doi: 10.1089/rej.2005.8.3Bernstein HG, Keilhoff G, Dobrowolny H, Steiner J. Enhanced mitochondrial autophagy (mitophagy) in oligodendrocytes might play a role in white matter pathology in schizophrenia. Med Hypotheses. 2020;134:109443. doi: 10.1016/j.mehy.2019.109443Bernstein HG, Keilhoff G, Dobrowolny H, Steiner J. Enhanced mitochondrial autophagy (mitophagy) in oligodendrocytes might play a role in white matter pathology in schizophrenia. Med Hypotheses. 2020;134:109443. doi: 10.1016/j.mehy.2019.109443Comer AL, Carrier M, Tremblay M-È, Cruz-Martín A. The inflamed brain in schizophrenia: the convergence of genetic and environmental risk factors that lead to uncontrolled neuroinflammation. Front Cell Neurosci. 2020;14:274. doi: 10.3389/fncel.2020.00274Comer AL, Carrier M, Tremblay M-È, Cruz-Martín A. The inflamed brain in schizophrenia: the convergence of genetic and environmental risk factors that lead to uncontrolled neuroinflammation. Front Cell Neurosci. 2020;14:274. doi: 10.3389/fncel.2020.00274Bergink V, Gibney SM, Drexhage HA. Autoimmunity, inflammation, and psychosis: a search for peripheral markers. Biol Psychiatry. 2014;75:324–331. doi: 10.1016/j.biopsych.2013.09.037Bergink V, Gibney SM, Drexhage HA. Autoimmunity, inflammation, and psychosis: a search for peripheral markers. Biol Psychiatry. 2014;75:324–331. doi: 10.1016/j.biopsych.2013.09.037Rey R, Suaud-Chagny MF, Bohec AL, Dorey JM, d’Amato T, Tamouza R, Leboyer M. Overexpression of complement component C4 in the dorsolateral prefrontal cortex, parietal cortex, superior temporal gyrus and associative striatum of patients with schizophrenia. Brain Behav Immun. 2020;90:216–225. doi: 10.1016/j. bbi.2020.08.019Rey R, Suaud-Chagny MF, Bohec AL, Dorey JM, d’Amato T, Tamouza R, Leboyer M. Overexpression of complement component C4 in the dorsolateral prefrontal cortex, parietal cortex, superior temporal gyrus and associative striatum of patients with schizophrenia. Brain Behav Immun. 2020;90:216–225. doi: 10.1016/j. bbi.2020.08.019Arion D, Unger T, Lewis DA, Levitt P, Mirnics K. Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia. Biol Psychiatry. 2007;62(7):711–721. doi: 10.1016/j.biopsych. 2006.12.021Arion D, Unger T, Lewis DA, Levitt P, Mirnics K. Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia. Biol Psychiatry. 2007;62(7):711–721. doi: 10.1016/j.biopsych. 2006.12.021Голимбет ВЕ, Клюшник ТП. Молекулярно-генетический и иммунологический аспекты формирования психопатологических симптомов при шизофрении. Журнал неврологии и психиатрии имени С.С. Корсакова. 2022;122(10):66–71. doi: 10.17116/jnevro202212210166 Golimbet VE, Kliushnik TP. Molecular-genetic and immunological aspects of the formation of psychopathological symptoms in schizophrenia. S.S. Korsakov Journal of Neurology and Psychiatry/Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2022;122(10):66–71. (In Russ.). doi: 10.17116/jnevro202212210166Голимбет ВЕ, Клюшник ТП. Молекулярно-генетический и иммунологический аспекты формирования психопатологических симптомов при шизофрении. Журнал неврологии и психиатрии имени С.С. Корсакова. 2022;122(10):66–71. doi: 10.17116/jnevro202212210166 Golimbet VE, Kliushnik TP. Molecular-genetic and immunological aspects of the formation of psychopathological symptoms in schizophrenia. S.S. Korsakov Journal of Neurology and Psychiatry/Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2022;122(10):66–71. (In Russ.). doi: 10.17116/jnevro202212210166Okusaga OO. Accelerated aging in schizophrenia patients: the potential role of oxidative stress. Aging Dis. 2013;5(4):256–262. doi: 10.14336/AD.2014.0500256Okusaga OO. Accelerated aging in schizophrenia patients: the potential role of oxidative stress. Aging Dis. 2013;5(4):256–262. doi: 10.14336/AD.2014.0500256Miller BJ, Goldsmith DR. Towards an Immunophenotype of Schizophrenia: Progress, Potential Mechanisms, and Future Directions. Neuropsychopharmacology. 2017;42(1):299–317. doi: 10.1038/npp.2016.211Miller BJ, Goldsmith DR. Towards an Immunophenotype of Schizophrenia: Progress, Potential Mechanisms, and Future Directions. Neuropsychopharmacology. 2017;42(1):299–317. doi: 10.1038/npp.2016.211Anderson G, Maes M. Schizophrenia: linking prenatal infection to cytokines, the tryptophan catabolite (TRYCAT) pathway, NMDA receptor hypofunction, neurodevelopment and neuroprogression. Prog Neuropsychopharmacol Biol Psychiatry. 2013;42:5–19. doi: 10.1016/j.pnpbp.2012.06.014Anderson G, Maes M. Schizophrenia: linking prenatal infection to cytokines, the tryptophan catabolite (TRYCAT) pathway, NMDA receptor hypofunction, neurodevelopment and neuroprogression. Prog Neuropsychopharmacol Biol Psychiatry. 2013;42:5–19. doi: 10.1016/j.pnpbp.2012.06.014Do KQ, Trabesinger AH, Kirsten-Krüger M, Lauer CJ, Dydak U, Hell D, Holsboer F, Boesiger P, Cuénod M. Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci. 2000;12(10):3721–3728. doi: 10.1046/j.1460-9568.2000.00229.xDo KQ, Trabesinger AH, Kirsten-Krüger M, Lauer CJ, Dydak U, Hell D, Holsboer F, Boesiger P, Cuénod M. Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci. 2000;12(10):3721–3728. doi: 10.1046/j.1460-9568.2000.00229.xGawryluk JW, Wang JF, Andreazza AC, Shao L, Young LT. Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol. 2011;14(1):123–130. doi: 10.1017/S1461145710000805Gawryluk JW, Wang JF, Andreazza AC, Shao L, Young LT. Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol. 2011;14(1):123–130. doi: 10.1017/S1461145710000805Xin L, Mekle R, Fournier M, Baumann PS, Ferrari C, Alameda L, Jenni R, Lu H, Schaller B, Cuenod M, Conus P, Gruetter R, Do KQ. Genetic Polymorphism Associated Prefrontal Glutathione and Its Coupling with Brain Glutamate and Peripheral Redox Status in Early Psychosis. Schizophr Bull. 2016;42(5):1185–1196. doi: 10.1093/schbul/sbw038Xin L, Mekle R, Fournier M, Baumann PS, Ferrari C, Alameda L, Jenni R, Lu H, Schaller B, Cuenod M, Conus P, Gruetter R, Do KQ. Genetic Polymorphism Associated Prefrontal Glutathione and Its Coupling with Brain Glutamate and Peripheral Redox Status in Early Psychosis. Schizophr Bull. 2016;42(5):1185–1196. doi: 10.1093/schbul/sbw038Nakanishi H, Wu Z. Microglia-aging: roles of microglial lysosome- and mitochondria-derived reactive oxygen species in brain aging. Behav Brain Res. 2009;201(1):1–7. doi: 10.1016/j.bbr.2009.02.001Nakanishi H, Wu Z. Microglia-aging: roles of microglial lysosome- and mitochondria-derived reactive oxygen species in brain aging. Behav Brain Res. 2009;201(1):1–7. doi: 10.1016/j.bbr.2009.02.001Peferoen L, Kipp M, van der Valk P, van Noort JM, Amor S. Oligodendrocyte-microglia cross-talk in the central nervous system. Immunology. 2014;141(3):302–313. doi: 10.1111/imm.12163Peferoen L, Kipp M, van der Valk P, van Noort JM, Amor S. Oligodendrocyte-microglia cross-talk in the central nervous system. Immunology. 2014;141(3):302–313. doi: 10.1111/imm.12163Catale C, Gironda S, Lo Iacono L, Carola V. Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development. J Clin Med. 2020;9(2):468. doi: 10.3390/jcm9020468Catale C, Gironda S, Lo Iacono L, Carola V. Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development. J Clin Med. 2020;9(2):468. doi: 10.3390/jcm9020468Ferle V, Repouskou A, Aspiotis G, Raftogianni A, Chrousos G, Stylianopoulou F, Stamatakis A. Synergistic effects of early life mild adversity and chronic social defeat on rat brain microglia and cytokines. Physiol Behav. 2020;215:112791. doi: 10.1016/j.physbeh. 2019.112791Ferle V, Repouskou A, Aspiotis G, Raftogianni A, Chrousos G, Stylianopoulou F, Stamatakis A. Synergistic effects of early life mild adversity and chronic social defeat on rat brain microglia and cytokines. Physiol Behav. 2020;215:112791. doi: 10.1016/j.physbeh. 2019.112791Ribeiro BM, do Carmo MR, Freire RS, Rocha NF, Borella VC, de Menezes AT, Monte AS, Gomes PX, de Sousa FC, Vale ML, de Lucena DF, Gama CS, Macêdo D. Evidences for a progressive microglial activation and increase in iNOS expression in rats submitted to a neurodevelopmental model of schizophrenia: reversal by clozapine. Schizophr Res. 2013;151(1–3):12–19. doi: 10.1016/j.schres.2013.10.040Ribeiro BM, do Carmo MR, Freire RS, Rocha NF, Borella VC, de Menezes AT, Monte AS, Gomes PX, de Sousa FC, Vale ML, de Lucena DF, Gama CS, Macêdo D. Evidences for a progressive microglial activation and increase in iNOS expression in rats submitted to a neurodevelopmental model of schizophrenia: reversal by clozapine. Schizophr Res. 2013;151(1–3):12–19. doi: 10.1016/j.schres.2013.10.040Kindler J, Lim CK, Weickert CS, Boerrigter D, Galletly C, Liu D, Jacobs KR, Balzan R, Bruggemann J, O’Donnell M, Lenroot R, Guillemin GJ, Weickert TW. Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia. Mol Psychiatry. 2020;25(11):2860–2872. doi: 10.1038/s41380-019-0401-9Kindler J, Lim CK, Weickert CS, Boerrigter D, Galletly C, Liu D, Jacobs KR, Balzan R, Bruggemann J, O’Donnell M, Lenroot R, Guillemin GJ, Weickert TW. Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia. Mol Psychiatry. 2020;25(11):2860–2872. doi: 10.1038/s41380-019-0401-9Fillman SG, Weickert TW, Lenroot RK, Catts SV, Bruggemann JM, Catts VS, Weickert CS. Elevated peripheral cytokines characterize a subgroup of people with schizophrenia displaying poor verbal fluency and reduced Broca’s area volume. Mol Psychiatry. 2016;21(8):1090–1098. doi: 10.1038/mp.2015.90Fillman SG, Weickert TW, Lenroot RK, Catts SV, Bruggemann JM, Catts VS, Weickert CS. Elevated peripheral cytokines characterize a subgroup of people with schizophrenia displaying poor verbal fluency and reduced Broca’s area volume. Mol Psychiatry. 2016;21(8):1090–1098. doi: 10.1038/mp.2015.90McNamara NB, Munro DAD, Bestard-Cuche N, Uyeda A, Bogie JFJ, Hoffmann A, Holloway RK, Molina-Gonzalez I, Askew KE, Mitchell S, Mungall W, Dodds M, Dittmayer C, Moss J, Rose J, Szymkowiak S, Amann L, McColl BW, Prinz M, Spires-Jones TL, Stenzel W, Horsburgh K, Hendriks JJA, Pridans C, Muramatsu R, Williams A, Priller J, Miron VE. Microglia regulate central nervous system myelin growth and integrity. Nature. 2023;613(7942):120–129. doi: 10.1038/s41586-022-05534-yMcNamara NB, Munro DAD, Bestard-Cuche N, Uyeda A, Bogie JFJ, Hoffmann A, Holloway RK, Molina-Gonzalez I, Askew KE, Mitchell S, Mungall W, Dodds M, Dittmayer C, Moss J, Rose J, Szymkowiak S, Amann L, McColl BW, Prinz M, Spires-Jones TL, Stenzel W, Horsburgh K, Hendriks JJA, Pridans C, Muramatsu R, Williams A, Priller J, Miron VE. Microglia regulate central nervous system myelin growth and integrity. Nature. 2023;613(7942):120–129. doi: 10.1038/s41586-022-05534-yUranova N. The Neuropathology of white matter in schizophrenia. In: The Neuropathology of schizophrenia. Springer Nature. 2021:179–219. doi: 10.1007/978-3-030-68308-5Uranova N. The Neuropathology of white matter in schizophrenia. In: The Neuropathology of schizophrenia. Springer Nature. 2021:179–219. doi: 10.1007/978-3-030-68308-5Garver DL, Holcomb JA, Christensen JD. Compromised myelin integrity during psychosis with repair during remission in drug-responding schizophrenia. Int J Neuropsychopharmacol. 2008;11(1):49–61. doi: 10.1017/S1461145707007730Garver DL, Holcomb JA, Christensen JD. Compromised myelin integrity during psychosis with repair during remission in drug-responding schizophrenia. Int J Neuropsychopharmacol. 2008;11(1):49–61. doi: 10.1017/S1461145707007730Uranova NA, Vikhreva OV, Rakhmanova VI, Orlovskaya DD. Ultrastructural pathology of oligodendrocytes adjacent to microglia in prefrontal white matter in schizophrenia. NPJ Schizophr. 2018;4(1):26. doi: 10.1038/s41537-018-0068-2Uranova NA, Vikhreva OV, Rakhmanova VI, Orlovskaya DD. Ultrastructural pathology of oligodendrocytes adjacent to microglia in prefrontal white matter in schizophrenia. NPJ Schizophr. 2018;4(1):26. doi: 10.1038/s41537-018-0068-2Уранова НА, Вихрева ОВ, Романова ВИ. Особенности взаимодействия микроглии и олигодендроцитов в белом веществе при непрерывнотекущей шизофрении. Журнал неврологии и психиатрии имени С.С. Корсакова. 2022;122(12):128–137. doi: 10.17116/jnevro2022122121128 Uranova NA, Vikhreva OV, Rakhmanova VI. Specific interactions between microglia and oligodendrocytes in white matter in continuous schizophrenia. S.S. Korsakov Journal of Neurology and Psychiatry/Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2022;122(12):128–137. (In Russ.). doi: 10.17116/jnevro2022122121128Уранова НА, Вихрева ОВ, Романова ВИ. Особенности взаимодействия микроглии и олигодендроцитов в белом веществе при непрерывнотекущей шизофрении. Журнал неврологии и психиатрии имени С.С. Корсакова. 2022;122(12):128–137. doi: 10.17116/jnevro2022122121128 Uranova NA, Vikhreva OV, Rakhmanova VI. Specific interactions between microglia and oligodendrocytes in white matter in continuous schizophrenia. S.S. Korsakov Journal of Neurology and Psychiatry/Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2022;122(12):128–137. (In Russ.). doi: 10.17116/jnevro2022122121128Robicsek O, Ene HM, Karry R, Ytzhaki O, Asor E, McPhie D, Cohen BM, Ben-Yehuda R, Weiner I, Ben-Shachar D. Isolated Mitochondria Transfer Improves Neuronal Differentiation of Schizophrenia-Derived Induced Pluripotent Stem Cells and Rescues Deficits in a Rat Model of the Disorder. Schizophr Bull. 2018;44(2):432–442. doi: 10.1093/schbul/sbx077Robicsek O, Ene HM, Karry R, Ytzhaki O, Asor E, McPhie D, Cohen BM, Ben-Yehuda R, Weiner I, Ben-Shachar D. Isolated Mitochondria Transfer Improves Neuronal Differentiation of Schizophrenia-Derived Induced Pluripotent Stem Cells and Rescues Deficits in a Rat Model of the Disorder. Schizophr Bull. 2018;44(2):432–442. doi: 10.1093/schbul/sbx077

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