Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study

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dc.contributor.authorGeorgiadis, Foivos
dc.contributor.authorLariviere, Sara
dc.contributor.authorGlahn, David
dc.contributor.authorHong, L. Elliot
dc.contributor.authorKochunov, Peter
dc.contributor.authorMowry, Bryan
dc.contributor.authorLoughland, Carmel
dc.contributor.authorPantelis, Christos
dc.contributor.authorHenskens, Frans A.
dc.contributor.authorGreen, Melissa J.
dc.contributor.authorCairns, Murray J.
dc.contributor.authorMichie, Patricia T.
dc.contributor.authorRasser, Paul E.
dc.contributor.authorCatts, Stanley
dc.contributor.authorTooney, Paul
dc.contributor.authorScott, Rodney J.
dc.contributor.authorSchall, Ulrich
dc.contributor.authorCarr, Vaughan
dc.contributor.authorQuide, Yann
dc.contributor.authorKrug, Axel
dc.contributor.authorStein, Frederike
dc.contributor.authorNenadic, Igor
dc.contributor.authorBrosch, Katharina
dc.contributor.authorKircher, Tilo
dc.contributor.authorGur, Raquel
dc.contributor.authorGur, Ruben
dc.contributor.authorSatterthwaite, Theodore D.
dc.contributor.authorKaruk, Andriana
dc.contributor.authorPomarol-Clotet, Edith
dc.contributor.authorRadua, Joaquim
dc.contributor.authorFuentes-Claramonte, Paola
dc.contributor.authorSalvador, Raymond
dc.contributor.authorSpalletta, Gianfranco
dc.contributor.authorVoineskos, Aristotle
dc.contributor.authorSim, Kang
dc.contributor.authorCrespo-Facorro, Benedicto
dc.contributor.authorGutierrez, Diana Tordesillas
dc.contributor.authorEhrlich, Stefan
dc.contributor.authorCrossley, Nicolas
dc.contributor.authorGrotegerd, Dominik
dc.contributor.authorRepple, Jonathan
dc.contributor.authorLencer, Rebekka
dc.contributor.authorDannlowski, Udo
dc.contributor.authorCalhoun, Vince
dc.contributor.authorRootes-Murdy, Kelly
dc.contributor.authorDemro, Caroline
dc.contributor.authorRamsay, Ian S.
dc.contributor.authorSponheim, Scott R.
dc.contributor.authorSchmidt, Andre
dc.contributor.authorBorgwardt, Stefan
dc.contributor.authorTomyshev, Alexander
dc.contributor.authorLebedeva, Irina
dc.contributor.authorHoeschl, Cyril
dc.contributor.authorSpaniel, Filip
dc.contributor.authorPreda, Adrian
dc.contributor.authorNguyen, Dana
dc.contributor.authorUhlmann, Anne
dc.contributor.authorStein, Dan J.
dc.contributor.authorHowells, Fleur
dc.contributor.authorTemmingh, Henk S.
dc.contributor.authorZuluaga, Ana M. Diaz
dc.contributor.authorJaramillo, Carlos Lopez
dc.contributor.authorIasevoli, Felice
dc.contributor.authorJi, Ellen
dc.contributor.authorHoman, Stephanie
dc.contributor.authorOmlor, Wolfgang
dc.contributor.authorHoman, Philipp
dc.contributor.authorKaiser, Stefan
dc.contributor.authorSeifritz, Erich
dc.contributor.authorMisic, Bratislav
dc.contributor.authorValk, Sofie L.
dc.contributor.authorThompson, Paul
dc.contributor.authorvan Erp, Theo G. M.
dc.contributor.authorTurner, Jessica A.
dc.contributor.authorBernhardt, Boris
dc.contributor.authorKirschner, Matthias
dc.date.accessioned2025-01-20T17:09:08Z
dc.date.available2025-01-20T17:09:08Z
dc.date.issued2024
dc.description.abstractSchizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia's alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.
dc.description.funderThe Australian Schizophrenia Research Bank (ASRB) was supported by NHMRC (Enabling Grant, ID 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief Investigators for ASRB were Ca
dc.fuente.origenWOS
dc.identifier.doi10.1038/s41380-024-02442-7
dc.identifier.eissn1476-5578
dc.identifier.issn1359-4184
dc.identifier.urihttps://doi.org/10.1038/s41380-024-02442-7
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/91015
dc.identifier.wosidWOS:001159797300001
dc.issue.numero6
dc.language.isoen
dc.pagina.final1868
dc.pagina.inicio1857
dc.revistaMolecular psychiatry
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleConnectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study
dc.typeartículo
dc.volumen29
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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