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@ARTICLE{Georgiadis:1030921,
author = {Georgiadis, Foivos and Larivière, Sara and Glahn, David
and Hong, L. Elliot and Kochunov, Peter and Mowry, Bryan and
Loughland, Carmel and Pantelis, Christos and Henskens, Frans
A. and Green, Melissa J. and Cairns, Murray J. and Michie,
Patricia T. and Rasser, Paul E. and Catts, Stanley and
Tooney, Paul and Scott, Rodney J. and Schall, Ulrich and
Carr, Vaughan and Quidé, Yann and Krug, Axel and Stein,
Frederike and Nenadić, Igor and Brosch, Katharina and
Kircher, Tilo and Gur, Raquel and Gur, Ruben and
Satterthwaite, Theodore D. and Karuk, Andriana and Pomarol-
Clotet, Edith and Radua, Joaquim and Fuentes-Claramonte,
Paola and Salvador, Raymond and Spalletta, Gianfranco and
Voineskos, Aristotle and Sim, Kang and Crespo-Facorro,
Benedicto and Tordesillas Gutiérrez, Diana and Ehrlich,
Stefan and Crossley, Nicolas and Grotegerd, Dominik and
Repple, Jonathan and Lencer, Rebekka and Dannlowski, Udo and
Calhoun, Vince and Rootes-Murdy, Kelly and Demro, Caroline
and Ramsay, Ian S. and Sponheim, Scott R. and Schmidt, Andre
and Borgwardt, Stefan and Tomyshev, Alexander and Lebedeva,
Irina and Höschl, Cyril and Spaniel, Filip and Preda,
Adrian and Nguyen, Dana and Uhlmann, Anne and Stein, Dan J.
and Howells, Fleur and Temmingh, Henk S. and Diaz Zuluaga,
Ana M. and López Jaramillo, Carlos and Iasevoli, Felice and
Ji, Ellen and Homan, Stephanie and Omlor, Wolfgang and
Homan, Philipp and Kaiser, Stefan and Seifritz, Erich and
Misic, Bratislav and Valk, Sofie L. and Thompson, Paul and
van Erp, Theo G. M. and Turner, Jessica A. and Bernhardt,
Boris and Kirschner, Matthias},
title = {{C}onnectome architecture shapes large-scale cortical
alterations in schizophrenia: a worldwide {ENIGMA} study},
journal = {Molecular psychiatry},
volume = {29},
number = {6},
issn = {1359-4184},
address = {London},
publisher = {Macmillan},
reportid = {FZJ-2024-05514},
pages = {1869 - 1881},
year = {2024},
abstract = {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.},
cin = {INM-7},
ddc = {610},
cid = {I:(DE-Juel1)INM-7-20090406},
pnm = {5253 - Neuroimaging (POF4-525) / 5251 - Multilevel Brain
Organization and Variability (POF4-525)},
pid = {G:(DE-HGF)POF4-5253 / G:(DE-HGF)POF4-5251},
typ = {PUB:(DE-HGF)16},
pubmed = {38336840},
UT = {WOS:001159797300001},
doi = {10.1038/s41380-024-02442-7},
url = {https://juser.fz-juelich.de/record/1030921},
}