I.P. Pavlov Journal of Higher Nervous ActivityI.P. Pavlov Journal of Higher Nervous ActivityЖурнал высшей нервной деятельности им. И.П. Павлова0044-46773034-5316The Russian Academy of Sciences65203510.31857/S0044467723030097TTGUVKФИЗИОЛОГИЯ ВЫСШЕЙ НЕРВНОЙ (КОГНИТИВНОЙ) ДЕЯТЕЛЬНОСТИ ЧЕЛОВЕКАФИЗИОЛОГИЯ ВЫСШЕЙ НЕРВНОЙ (КОГНИТИВНОЙ) ДЕЯТЕЛЬНОСТИ ЧЕЛОВЕКАNEUROIMAGING (RESTING-STATE fMRI) AND NEUROPSYCHOLOGICAL CHARACTERISTICS OF NON-CONVERTERS WITH CLINICAL HIGH RISK FOR PSYCHOSISНейровизуализационные (фМРТ покоя) и нейропсихологические особенности “неманифестировавших” пациентов из группы клинически высокого риска шизофренииLebedevaI. S.ЛебедеваИ. С.lebedeva-i@yandex.ruPanikratovaY. R.ПаникратоваЯ. Р.lebedeva-i@yandex.ruAbdullinaE. G.АбдуллинаЕ. Г.lebedeva-i@yandex.ruMigalinaV. V.МигалинаВ. В.lebedeva-i@yandex.ruTikhonovD. V.ТихоновД. В.lebedeva-i@yandex.ruOmelchenkoM. A.ОмельченкоМ. А.lebedeva-i@yandex.ruKaledaV. G.КаледаВ. Г.lebedeva-i@yandex.ruMental Health Research CenterФГБНУ Научный центр психического здоровья0105202373336938302022025Copyright ©; 2023, И.С. Лебедева, Я.Р. Паникратова, Е.Г. Абдуллина, В.В. Мигалина, Д.В. Тихонов, М.А. Омельченко, В.Г. КаледаCopyright ©; 2023, И.С. Лебедева, Я.Р. Паникратова, Е.Г. Абдуллина, В.В. Мигалина, Д.В. Тихонов, М.А. Омельченко, В.Г. Каледа2023И.С. Лебедева, Я.Р. Паникратова, Е.Г. Абдуллина, В.В. Мигалина, Д.В. Тихонов, М.А. Омельченко, В.Г. КаледаИ.С. Лебедева, Я.Р. Паникратова, Е.Г. Абдуллина, В.В. Мигалина, Д.В. Тихонов, М.А. Омельченко, В.Г. Каледаhttps://innoscience.ru/0044-4677/article/view/652035

Based on the concept of clinical high risk for psychosis, we aimed to reveal characteristics of brain functioning (resting-state fMRI) and neurocognition in 27 patients with non-psychotic mental disorders with attenuated schizophrenia symptoms who did not transit to psychosis for a long period of observation, in contrast to 24 patients with first-episode schizophrenia and 27 mentally healthy subjects. The main group was characterized by higher local coherence of BOLD signal in the right visual cortex and higher functional connectivity between the occipital component of the visual network and the right prefrontal component of the salience network (as compared to patients with schizophrenia). In both patient groups, a decreased productivity in verbal fluency tests was found. The neuroimaging and neuropsychological findings in the main group can be considered via the dichotomy of protective and pathological mechanisms in patients with high risk for psychosis.

В рамках концепции “клинически высокого риска манифестации психоза” была поставлена цель выявления функциональных особенностей головного мозга (по данным фМРТ покоя) и нейропсихологических характеристик у 27 больных с непсихотическими психическими заболеваниями с аттенуированными симптомами шизофрении, психоз у которых не манифестировал в течение длительного периода наблюдения, по сравнению с 24 пациентами с первым эпизодом шизофрении и 27 психически здоровыми испытуемыми. Основная группа характеризовалась более высокой согласованностью BOLD-сигнала в зрительной коре правого полушария и большей функциональной связанностью между затылочным компонентом зрительной сети и компонентом сети определения значимости в правой префронтальной коре (по сравнению с больными шизофренией). В обеих группах пациентов было обнаружено снижение показателей продуктивности вербальных ассоциаций. Выявленные нейровизуализационные и нейропсихологические особенности пациентов основной группы можно рассматривать как отражение действия “защитных” и “патологических” механизмов при высоком риске манифестации шизофрении.

resting-state fMRIverbal fluencyclinical high risk for psychosisschizophreniaфМРТ покоявербальные ассоциацииклинически высокий риск манифестации психозашизофренияАхутина Т.В. (ред.) Методы нейропсихологического обследования детей 6–9 лет. М.: В. Секачев, 2016. С. 280.Омельченко М.А. Клинические предпосылки высокого риска развития эндогенного психоза: вопросы диагностики и терапии. Психиатрия. 2020. 18 (2): 82–91. https://doi.org/10.30629/2618-6667-2020-18-2-82-91Филимоненко Ю.И., Тимофеев В.И. Руководство к методике исследования интеллекта для взрослых Д. Векслера (WAIS). СПб.: ИМАТОН, 1995. С. 57.Adamek P., Langova V., Horacek J. Early-stage visual perception impairment in schizophrenia, bottom-up and back again. Schizophrenia (Heidelb). 2022. 8 (1): 27. https://doi.org/10.1038/s41537-022-00237-9Addington J., Farris M., Stowkowy J., Santesteban-Echarri O., Metzak P., Kalathil M.S. Predictors of Transition to Psychosis in Individuals at Clinical High Risk. Curr. Psychiatry Rep. 2019. 21 (6): 39. https://doi.org/10.1007/s11920-019-1027-yAddington J., Piskulic D., Liu L., Lockwood J., Cadenhead K.S., Cannon T.D., Cornblatt B.A., McGlashan T.H., Perkins D.O., Seidman L.J., Tsuang M.T., Walker E.F., Bearden C.E., Mathalon D.H., Woods S.W. Comorbid diagnoses for youth at clinical high risk of psychosis. Schizophr. Res. 2017. 190: 90–95. https://doi.org/10.1016/j.schres.2017.03.043Aita S.L., Beach J.D., Taylor S.E., Borgogna N.C., Harrell M.N., Hill B.D. Executive, language, or both? An examination of the construct validity of verbal fluency measures. Appl. Neuropsychol. Adult. 2019. 26 (5): 441–451. https://doi.org/10.1080/23279095.2018.1439830Andreou C., Borgwardt S. Structural and functional imaging markers for susceptibility to psychosis. Mol. Psychiatry. 2020. 25 (11): 2773–2785. https://doi.org/10.1038/s41380-020-0679-7Anticevic A., Haut K., Murray J.D., Repovs G., Yang G.J., Diehl C., McEwen S.C., Bearden C.E., Addington J., Goodyear B., Cadenhead K.S., Mirzakhanian H., Cornblatt B.A., Olvet D., Mathalon D.H., McGlashan T.H., Perkins D.O., Belger A., Seidman L.J., Tsuang M.T., van Erp T.G., Walker E.F., Hamann S., Woods S.W., Qiu M., Cannon T.D. Association of Thalamic Dysconnectivity and Conversion to Psychosis in Youth and Young Adults at Elevated Clinical Risk. JAMA Psychiatry. 2015. 72 (9): 882–891. https://doi.org/10.1001/jamapsychiatry.2015.0566Bolt L.K., Amminger G.P., Farhall J., McGorry P.D., Nelson B., Markulev C., Yuen H.P., Schafer M.R., Mossaheb N., Schlogelhofer M., Smesny S., Hickie I.B., Berger G.E., Chen E.Y.H., de Haan L., Nieman D.H., Nordentoft M., Riecher-Rossler A., Verma S., Thompson A., Yung A.R., Allott K.A. Neurocognition as a predictor of transition to psychotic disorder and functional outcomes in ultra-high risk participants: Findings from the NEURAPRO randomized clinical trial. Schizophr. Res. 2019. 206: 67–74. https://doi.org/10.1016/j.schres.2018.12.013Bosanac P., Castle D.J. Schizophrenia and depression. Med J Aust. 2013. 199 (S6): S36–39. https://doi.org/10.5694/mja12.10516Cao H., Chen O.Y., Chung Y., Forsyth J.K., McEwen S.C., Gee D.G., Bearden C.E., Addington J., Goodyear B., Cadenhead K.S., Mirzakhanian H., Cornblatt B.A., Carrion R.E., Mathalon D.H., McGlashan T.H., Perkins D.O., Belger A., Seidman L.J., Thermenos H., Tsuang M.T., van Erp T.G.M., Walker E.F., Hamann S., Anticevic A., Woods S.W., Cannon T.D. Cerebello-thalamo-cortical hyperconnectivity as a state-independent functional neural signature for psychosis prediction and characterization. Nat Commun. 2018. 9 (1): 3836. https://doi.org/10.1038/s41467-018-06350-7Catalan A., Salazar de Pablo G., Aymerich C., Damiani S., Sordi V., Radua J., Oliver D., McGuire P., Giuliano A.J., Stone W.S., Fusar-Poli P. Neurocognitive Functioning in Individuals at Clinical High Risk for Psychosis: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2021. https://doi.org/10.1001/jamapsychiatry.2021.1290Chai X.J., Castanon A.N., Ongur D., Whitfield-Gabrieli S. Anticorrelations in resting state networks without global signal regression. Neuroimage. 2012. 59 (2): 1420–1428. https://doi.org/10.1016/j.neuroimage.2011.08.048Chechko N., Cieslik E.C., Muller V.I., Nickl-Jockschat T., Derntl B., Kogler L., Aleman A., Jardri R., Sommer I.E., Gruber O., Eickhoff S.B. Differential Resting-State Connectivity Patterns of the Right Anterior and Posterior Dorsolateral Prefrontal Cortices (DLPFC) in Schizophrenia. Front. Psychiatry. 2018. 9: 211. https://doi.org/10.3389/fpsyt.2018.00211Collin G., Seidman L.J., Keshavan M.S., Stone W.S., Qi Z., Zhang T., Tang Y., Li H., Anteraper S.A., Niznikiewicz M.A., McCarley R.W., Shenton M.E., Wang J., Whitfield-Gabrieli S. Functional connectome organization predicts conversion to psychosis in clinical high-risk youth from the SHARP program. Mol. Psychiatry. 2020. 25 (10): 2431–2440. https://doi.org/10.1038/s41380-018-0288-xDelis D.C., Kaplan E., Kramer J.H. Delis-Kaplan Executive Function System: Examiner’s Manual. San Antonio, TX: The Psychological Corporation, 2001. P. 388.Ellis J.K., Walker E.F., Goldsmith D.R. Selective Review of Neuroimaging Findings in Youth at Clinical High Risk for Psychosis: On the Path to Biomarkers for Conversion. Front. Psychiatry. 2020. 11: 567534. https://doi.org/10.3389/fpsyt.2020.567534Gottesman I.I., Gould T.D. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. 2003. 160 (4): 636–645. https://doi.org/10.1176/appi.ajp.160.4.636Grill-Spector K., Malach R. The human visual cortex. Annu Rev Neurosci. 2004. 27: 649–677. https://doi.org/10.1146/annurev.neuro.27.0702-03.144220Gustavson D.E., Panizzon M.S., Franz C.E., Reynolds C.A., Corley R.P., Hewitt J.K., Lyons M.J., Kremen W.S., Friedman N.P. Integrating verbal fluency with executive functions: Evidence from twin studies in adolescence and middle age. J. Exp. Psychol Gen. 2019. 148 (12): 2104–2119. https://doi.org/10.1037/xge0000589Hafner H. From Onset and Prodromal Stage to a Life-Long Course of Schizophrenia and Its Symptom Dimensions: How Sex, Age, and Other Risk Factors Influence Incidence and Course of Illness. Psychiatry J. 2019. 2019: 9804836. https://doi.org/10.1155/2019/9804836Hamilton M. A rating scale for depression. J. Neurol. Neurosurg. 1960. 23: 56–62. https://doi.org/10.1136/jnnp.23.1.56Hedges E.P., Dickson H., Tognin S., Modinos G., Antoniades M., van der Gaag M., de Haan L., McGorry P., Pantelis C., Riecher-Rossler A., Bressan R., Barrantes-Vidal N., Krebs M.O., Nordentoft M., Ruhrmann S., Sachs G., Rutten B.P., van Os J., Study E.-G.H.R., Valmaggia L.R., McGuire P., Kempton M.J. Verbal memory performance predicts remission and functional outcome in people at clinical high-risk for psychosis. Schizophr. Res. Cogn. 2022. 28: 100222. https://doi.org/10.1016/j.scog.2021.100222Kapur S. Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am. J. Psychiatry. 2003. 160 (1): 13–23. https://doi.org/10.1176/appi.ajp.160.1.13Kay S.R., Fiszbein A., Opler L.A. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 1987. 13 (2): 261–276. https://doi.org/10.1093/schbul/13.2.261Keri S., Benedek G. Visual contrast sensitivity alterations in inferred magnocellular pathways and anomalous perceptual experiences in people at high-risk for psychosis. Vis. Neurosci. 2007. 24 (2): 183–189. https://doi.org/10.1017/S0952523807070253Kim D., Kim J.W., Koo T.H., Yun H.R., Won S.H. Shared and distinct neurocognitive endophenotypes of schizophrenia and psychotic bipolar disorder. Clin. Psychopharmacol. Neurosci. 2015. 13 (1): 94–102. https://doi.org/10.9758/cpn.2015.13.1.94Kronke K.M., Wolff M., Shi Y., Kraplin A., Smolka M.N., Buhringer G., Goschke T. Functional connectivity in a triple-network saliency model is associated with real-life self-control. Neuropsychologia. 2020. 149: 107667. https://doi.org/10.1016/j.neuropsychologia.2020.-107667Liang S., Deng W., Wang Q., Ma X., Li M., Brown M.R., Hu X., Li X., Greenshaw A.J., Li T. Performance of Verbal Fluency as an Endophenotype in Patients with Familial versus Sporadic Schizophrenia and Their Parents. Sci. Rep. 2016. 6: 32597. https://doi.org/10.1038/srep32597Lombardo M.V., Pramparo T., Gazestani V., Warrier V., Bethlehem R.A.I., Carter Barnes C., Lopez L., Lewis N.E., Eyler L., Pierce K., Courchesne E. Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes. Nat. Neurosci. 2018. 21 (12): 1680–1688. https://doi.org/10.1038/s41593-018-0281-3Miller T.J., McGlashan T.H., Woods S.W., Stein K., Driesen N., Corcoran C.M., Hoffman R., Davidson L. Symptom assessment in schizophrenic prodromal states. Psychiatr Q. 1999. 70 (4): 273–287. https://doi.org/10.1023/a:1022034115078Montchal M.E., Reagh Z.M., Yassa M.A. Precise temporal memories are supported by the lateral entorhinal cortex in humans. Nat. Neurosci. 2019. 22 (2): 284–288. https://doi.org/10.1038/s41593-018-0303-1Morosini P.L., Magliano L., Brambilla L., Ugolini S., Pioli R. Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to assess routine social funtioning. Acta Psychiatrica Scandinavica. 2000. 101 (4): 323–329. https://doi.org/10.1034/j.1600-0447.2000.10100-4323.xMurphy K., Birn R.M., Handwerker D.A., Jones T.B., Bandettini P.A. The impact of global signal regression on resting state correlations: are anti-correlated networks introduced? Neuroimage. 2009. 44 (3): 893–905. https://doi.org/10.1016/j.neuroimage.2008.09.036Newton R., Rouleau A., Nylander A.G., Loze J.Y., Resemann H.K., Steeves S., Crespo-Facorro B. Diverse definitions of the early course of schizophrenia-a targeted literature review. NPJ Schizophr. 2018. 4 (1): 21. https://doi.org/10.1038/s41537-018-0063-7Panikratova Y.R., Vlasova R.M., Akhutina T.V., Korneev A.A., Sinitsyn V.E., Pechenkova E.V. Functional connectivity of the dorsolateral prefrontal cortex contributes to different components of executive functions. Int. J. Psychophysiol. 2020. 151: 70–79. https://doi.org/10.1016/j.ijpsycho.2020.02.013Patel K.R., Cherian J., Gohil K., Atkinson D. Schizophrenia: Overview and Treatment Options. Pharmacy & Therapeutics. 2014. 39 (9): 638–645.Riecher-Rossler A., Pflueger M.O., Aston J., Borgwardt S.J., Brewer W.J., Gschwandtner U., Stieglitz R.D. Efficacy of using cognitive status in predicting psychosis: a 7-year follow-up. Biol Psychiatry. 2009. 66 (11): 1023–1030. https://doi.org/10.1016/j.biopsych.2009.07.020Shao Z., Janse E., Visser K., Meyer A.S. What do verbal fluency tasks measure? Predictors of verbal fluency performance in older adults. Front. Psychol. 2014. 5: 772. https://doi.org/10.3389/fpsyg.2014.00772Smieskova R., Fusar-Poli P., Riecher-Rossler A., Borgwardt S. Neuroimaging and resilience factors–staging of the at-risk mental state? Curr. Pharm. Des. 2012. 18 (4): 416–421. https://doi.org/10.2174/138161212799316046van der Werf M., Hanssen M., Kohler S., Verkaaik M., Verhey F.R., Investigators R., van Winkel R., van Os J., Allardyce J. Systematic review and collaborative recalculation of 133,693 incident cases of schizophrenia. Psychol. Med. 2014. 44 (1): 9–16. https://doi.org/10.1017/S0033291712002796van Os J., Guloksuz S. A critique of the “ultra-high risk” and “transition” paradigm. World Psychiatry. 2017. 16 (2): 200–206. https://doi.org/10.1002/wps.20423Wang C., Lee J., Ho N.F., Lim J.K.W., Poh J.S., Rekhi G., Krishnan R., Keefe R.S.E., Adcock R.A., Wood S.J., Fornito A., Chee M.W.L., Zhou J. Large-Scale Network Topology Reveals Heterogeneity in Individuals With at Risk Mental State for Psychosis: Findings From the Longitudinal Youth-at-Risk Study. Cereb. Cortex. 2018. 28 (12): 4234–4243. https://doi.org/10.1093/cercor/bhx278Wang L., Mruczek R.E., Arcaro M.J., Kastner S. Probabilistic Maps of Visual Topography in Human Cortex. Cereb. Cortex. 2015. 25 (10): 3911–3931. https://doi.org/10.1093/cercor/bhu277Williams D. Hierarchical Bayesian models of delusion. Conscious Cogn. 2018. 61: 129–147. https://doi.org/10.1016/j.concog.2018.03.003