| Title: |
Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study |
| Authors: |
Georgiadis, F; Larivière, S; Glahn, D; Hong, LE; Kochunov, P; Mowry, B; Loughland, C; Pantelis, C; Henskens, FA; Green, MJ; Cairns, MJ; Michie, PT; Rasser, PE; Catts, S; Tooney, P; Scott, RJ; Schall, U; Carr, V; Quidé, Y; Krug, A; Stein, F; Nenadić, I; Brosch, K; Kircher, T; Gur, R; Satterthwaite, TD; Karuk, A; Pomarol- Clotet, E; Radua, J; Fuentes-Claramonte, P; Salvador, R; Spalletta, G; Voineskos, A; Sim, K; Crespo-Facorro, B; Tordesillas Gutiérrez, D; Ehrlich, S; Crossley, N; Grotegerd, D; Repple, J; Lencer, R; Dannlowski, U; Calhoun, V; Rootes-Murdy, K; Demro, C; Ramsay, IS; Sponheim, SR; Schmidt, A; Borgwardt, S; Tomyshev, A; Lebedeva, I; Höschl, C; Spaniel, F; Preda, A; Nguyen, D; Uhlmann, A; Stein, DJ; Howells, F; Temmingh, HS; Diaz Zuluaga, AM; López Jaramillo, C; Iasevoli, F; Ji, E; Homan, S; Omlor, W; Homan, P; Kaiser, S; Seifritz, E; Misic, B; Valk, SL; Thompson, P; van Erp, TGM; Turner, JA; Bernhardt, B; Kirschner, M; Quide, Yann |
| Source: |
urn:ISSN:1359-4184 ; urn:ISSN:1476-5578 ; Molecular Psychiatry, 29, 6, 1869-1881 |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2024 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
5202 Biological Psychology; 32 Biomedical and Clinical Sciences; 52 Psychology; Serious Mental Illness; Neurosciences; Brain Disorders; Biomedical Imaging; Mental Health; Mental Illness; Schizophrenia; Clinical Research; 2.1 Biological and endogenous factors; Humans; Connectome; Adult; Female; Male; Magnetic Resonance Imaging; Cerebral Cortex; Nerve Net; Brain; Middle Aged; Neural Pathways; Young Adult; ENIGMA Schizophrenia Consortium; anzsrc-for: 5202 Biological Psychology; anzsrc-for: 32 Biomedical and Clinical Sciences; anzsrc-for: 52 Psychology; anzsrc-for: 06 Biological Sciences; anzsrc-for: 11 Medical and Health Sciences |
| Description: |
Schizophrenia 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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://hdl.handle.net/1959.4/102131 |
| DOI: |
10.1038/s41380-024-02442-7 |
| Availability: |
https://hdl.handle.net/1959.4/102131; https://unsworks.unsw.edu.au/bitstreams/d177ab7b-23cc-45f4-8410-ad551919c0f1/download; https://doi.org/10.1038/s41380-024-02442-7 |
| Rights: |
open access ; https://purl.org/coar/access_right/c_abf2 ; CC-BY ; https://creativecommons.org/licenses/by/4.0/ ; CC BY ; free_to_read |
| Accession Number: |
edsbas.75D2814A |
| Database: |
BASE |