TY - JOUR
T1 - Connectome architecture shapes large-scale cortical alterations in schizophrenia
T2 - a worldwide ENIGMA study
AU - ENIGMA Schizophrenia Consortium
AU - Georgiadis, Foivos
AU - Larivière, Sara
AU - Glahn, David
AU - Hong, L. Elliot
AU - Kochunov, Peter
AU - Mowry, Bryan
AU - Loughland, Carmel
AU - Pantelis, Christos
AU - Henskens, Frans A.
AU - Green, Melissa J.
AU - Cairns, Murray J.
AU - Michie, Patricia T.
AU - Rasser, Paul E.
AU - Catts, Stanley
AU - Tooney, Paul
AU - Scott, Rodney J.
AU - Schall, Ulrich
AU - Carr, Vaughan
AU - Quidé, Yann
AU - Krug, Axel
AU - Stein, Frederike
AU - Nenadić, Igor
AU - Brosch, Katharina
AU - Kircher, Tilo
AU - Gur, Raquel
AU - Gur, Ruben
AU - Satterthwaite, Theodore D.
AU - Karuk, Andriana
AU - Pomarol- Clotet, Edith
AU - Radua, Joaquim
AU - Fuentes-Claramonte, Paola
AU - Salvador, Raymond
AU - Spalletta, Gianfranco
AU - Voineskos, Aristotle
AU - Sim, Kang
AU - Crespo-Facorro, Benedicto
AU - Tordesillas Gutiérrez, Diana
AU - Ehrlich, Stefan
AU - Crossley, Nicolas
AU - Grotegerd, Dominik
AU - Repple, Jonathan
AU - Lencer, Rebekka
AU - Dannlowski, Udo
AU - Calhoun, Vince
AU - Rootes-Murdy, Kelly
AU - Demro, Caroline
AU - Ramsay, Ian S.
AU - Sponheim, Scott R.
AU - Schmidt, Andre
AU - Borgwardt, Stefan
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/6
Y1 - 2024/6
N2 - 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 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.
AB - 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 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.
UR - http://www.scopus.com/inward/record.url?scp=85184502158&partnerID=8YFLogxK
U2 - 10.1038/s41380-024-02442-7
DO - 10.1038/s41380-024-02442-7
M3 - Journal articles
C2 - 38336840
AN - SCOPUS:85184502158
SN - 1359-4184
VL - 29
SP - 1869
EP - 1881
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 6
ER -