Academic Journal
Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study
| Title: | Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study |
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| Authors: | Georgiadis, Foivos, Larivière, Sara, Glahn, David, Hong, L. Elliot, Kochunov, Peter, Mowry, Bryan, Loughland, Carmel, Pantelis, Christos, Henskens, Frans Alexander, Green, Melissa, Cairns, Murray, Michie, Patricia, Rasser, Paul E., Catts, Stanley, Tooney, Paul, Scott, Rodney, Schall, Ulrich, Carr, Vaughan, Quidé, Yann, Krug, Axel, Stein, Frederike, Nenadić, Igor, Brosch, Katharina, Kircher, Tilo, Gur, Raquel, Satterthwaite, Theodore, Karuk, Andriana, Pomarol- Clotet, Edith, Radua, Joaquim, Fuentes-Claramonte, Paola, Salvador, Raymond, Spalletta, Gianfranco, Voineskos, Aristotle, Sim, Kang, Crespo-Facorro, Benedicto, Tordesillas Gutiérrez, Diana, Ehrlich, Stefan, Crossley, Nicolas, Grotegerd, Dominik, Repple, Jonathan, Lencer, Rebekka, Dannlowski, Udo, Calhoun, Vince, Rootes-Murdy, Kelly, Demro, Caroline, Ramsay, Ian, Sponheim, Scott, Schmidt, André, Borgwardt, Stefan, Tomyshev, Alexander, Lebedeva, Irina, Höschl, Cyril, Spaniel, Filip, Preda, Adrian, Nguyen, Dana, Uhlmann, Anne, Stein, Dan, Howells, Fleur, Temmingh, Henk S., Diaz Zuluaga, Ana M., López Jaramillo, Carlos, Iasevoli, Felice, Ji, Ellen, Homan, Stephanie, Omlor, Wolfgang, Homan, Philipp, Kaiser, Stefan, Seifritz, Erich, Misic, Bratislav, Valk, Sofie Louise, Thompson, Paul, van Erp, Theo, Turner, Jessica, ENIGMA Schizophrenia Consortium, Bernhardt, Boris, Kirschner, Matthias |
| Contributors: | ENIGMA Schizophrenia Consortium, The University of Newcastle. College of Health, Medicine & Wellbeing, School of Medicine and Public Health |
| Source: | Mol Psychiatry Molecular Psychiatry Molecular psychiatry 29(6), 1869-1881 (2024). doi:10.1038/s41380-024-02442-7 Molecular Psychiatry, vol 29, iss 6 |
| Publisher Information: | Cold Spring Harbor Laboratory, 2023. |
| Publication Year: | 2023 |
| Subject Terms: | Male, 0301 basic medicine, Radiology, Nuclear Medicine and Imaging, Neuroimaging Data Analysis, Developmental psychology, 5202 Biological Psychology, Social Sciences, 32 Biomedical and Clinical Sciences, Analysis of Brain Functional Connectivity Networks, Gene, Functional connectivity, 0302 clinical medicine, 03 Salud y bienestar, Neural Pathways, Pathology, 2.1 Biological and endogenous factors, Psychology, Disease, anzsrc-for: 5203 Clinical and health psychology, 10. No inequality, Cerebral Cortex, Psychiatry, 0303 health sciences, ENIGMA, Brain, Life Sciences, 3 Good Health and Well Being, Schizophrenia (object-oriented programming), Middle Aged, Serious Mental Illness, Mental Illness, Magnetic Resonance Imaging, 3. Good health, FOS: Psychology, Mental Health, anzsrc-for: 3202 Clinical sciences, 52 Psychology, Biomedical Imaging, Medicine, Female, anzsrc-for: 5202 Biological Psychology, Human Connectome Project, Adult, ENIGMA Schizophrenia Consortium, Cognitive Neuroscience, Generalizability theory, Experimental and Cognitive Psychology, 59/57, Nerve Net/physiopathology [MeSH], Neural Pathways/physiopathology [MeSH], 59/36, Male [MeSH], Nerve Net/diagnostic imaging [MeSH], Schizophrenia/pathology [MeSH], Cerebral Cortex/physiopathology [MeSH], Female [MeSH], Brain/pathology [MeSH], Adult [MeSH], Cerebral Cortex/pathology [MeSH], Humans [MeSH], Connectome/methods [MeSH], Middle Aged [MeSH], 692/699/476/1799, Article, Brain/physiopathology [MeSH], Neural Pathways/pathology [MeSH], Nerve Net/pathology [MeSH], Young Adult [MeSH], Magnetic Resonance Imaging/methods [MeSH], Schizophrenia/physiopathology [MeSH], 631/378, article, anzsrc-for: 52 Psychology, Young Adult, 03 medical and health sciences, anzsrc-for: 32 Biomedical and Clinical Sciences, Clinical Research, Health Sciences, Connectome, Genetics, Humans, Network Analysis of Psychopathology and Mental Disorders, anzsrc-for: 17 Psychology and Cognitive Sciences, morphological alterations, DISC1, Biology, Neurosciences, Psychosis, bipolar, Brain Disorders, schizophrenia, Brain Connectivity, Diffusion Magnetic Resonance Imaging, anzsrc-for: 11 Medical and Health Sciences, FOS: Biological sciences, anzsrc-for: 06 Biological Sciences, Schizophrenia, 03 Good Health and Well-being, Nerve Net, Neuroscience |
| Description: | While schizophrenia is considered a prototypical network disorder characterized by widespread brain-morphological alterations, it still remains unclear whether distributed structural alterations robustly reflect underlying network layout. Here, 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 2,439 adults with schizophrenia and 2,867 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 identify 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. Schizophrenia-related structural alterations co-localized with interconnected functional and structural hubs and harbored temporo-paralimbic and frontal epicenters. Findings were robust across sites and related to individual symptom profiles. We observed localized unique epicenters for first-episode psychosis and early stages, and transmodal epicenters that were shared across first-episode to chronic stages. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, yielding insights in 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 contributes to recognizing potentially common pathways to better understand macroscale structural alterations, and inter-individual variability in schizophrenia. |
| Document Type: | Article Other literature type |
| File Description: | application/pdf |
| ISSN: | 1476-5578 1359-4184 |
| DOI: | 10.1101/2023.02.12.527904 |
| DOI: | 10.1038/s41380-024-02442-7 |
| DOI: | 10.60692/9ag5b-y2482 |
| DOI: | 10.60692/0xg6r-zr982 |
| DOI: | 10.34734/fzj-2024-05514 |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/38336840 https://hdl.handle.net/11588/979847 http://hdl.handle.net/21.11116/0000-000E-73EE-5 http://hdl.handle.net/21.11116/0000-000F-0D27-8 http://hdl.handle.net/21.11116/0000-000E-73F0-1 https://juser.fz-juelich.de/record/1030921 https://repository.publisso.de/resource/frl:6504001 https://escholarship.org/uc/item/6vf2025w https://escholarship.org/content/qt6vf2025w/qt6vf2025w.pdf |
| Rights: | CC BY |
| Accession Number: | edsair.doi.dedup.....ef29e469949643c00cd0b9ef4c2397b0 |
| Database: | OpenAIRE |
| ISSN: | 14765578 13594184 |
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| DOI: | 10.1101/2023.02.12.527904 |