Estimating Multimodal Structural Brain Variability in Schizophrenia Spectrum Disorders: A Worldwide ENIGMA Study
Wolfgang Omlor, Finn Rabe, Simon Fuchs, Werner Surbeck, Giacomo Cecere, Gao-Yang Huang, Stephanie Homan, Nils Kallen, Foivos Georgiadis, Tobias R. Spiller, Erich Seifritz, Thomas W. Weickert, Jason Bruggemann, Cynthia Shannon Weickert, Steven Potkin, Ryota Hashimoto, Kang Sim, Kelly Rootes-Murdy, Yann Quidé, Josselin Houenou, Nerisa Banaj, Daniela Vecchio, Fabrizio Piras, Federica Piras, Gianfranco Spalletta, Raymond Salvador, Andriana Karuk, Edith Pomarol‐Clotet, Amanda Rodrigue, Godfrey D. Pearlson, David C. Glahn, David Tomeček, Filip Španiel, Antonín Škoch, Matthias Kirschner, Stefan Kaiser, Peter Kochunov, Fengmei Fan, Ole A. Andreassen, Lars T. Westlye, Pierre Berthet, Vince D. Calhoun, Fleur M. Howells, Anne Uhlmann, Freda Scheffler, Dan J. Stein, Felice Iasevoli, Murray J. Cairns, Vaughan J. Carr, Stanley V. Catts, Maria A. Di Biase, Assen Jablensky, Melissa J. Green, Frans Henskens, Paul Klauser, Carmel M. Loughland, Patricia T. Michie, Bryan Mowry, Christos Pantelis, Paul E. Rasser, Ulrich Schall, Rodney J. Scott, Andrew Zalesky, Andrea de Bartolomeis, Annarita Barone, Mariateresa Ciccarelli, Arturo Brunetti, Sirio Cocozza, Giuseppe Pontillo, Mario Tranfa, Annabella Di Giorgio, Sophia I. Thomopoulos, Neda Jahanshad, Paul M. Thompson, Theo G.M. van Erp, Jessica A. Turner, Philipp Homan
Abstract
OBJECTIVE: The clinical diversity of schizophrenia is reflected by structural brain variability. It remains unclear how this variability manifests across different gray and white matter features. In this meta- and mega-analysis, the authors investigated how brain heterogeneity in schizophrenia is distributed across multimodal structural indicators. METHODS: The authors used the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6,037 individuals for a given brain measure. Variability and mean values of cortical thickness, cortical surface area, cortical folding index, subcortical volume, and fractional anisotropy were examined in individuals with schizophrenia and healthy control subjects. RESULTS: Individuals with schizophrenia showed greater variability in cortical thickness, cortical surface area, subcortical volume, and fractional anisotropy within the frontotemporal and subcortical network. This increased structural variability was mainly associated with psychopathological symptom domains, and the schizophrenia group frequently displayed lower mean values in the respective structural measures. Unexpectedly, folding patterns were more uniform in individuals with schizophrenia, particularly in the right caudal anterior cingulate region. The mean folding values of the right caudal anterior cingulate region did not differ between the schizophrenia and healthy control groups, and folding patterns in this region were not associated with disease-related parameters. CONCLUSIONS: In patients with schizophrenia, uniform folding patterns in the right caudal anterior cingulate region contrasted with the multimodal variability in the frontotemporal and subcortical network. While variability in the frontotemporal and subcortical network was associated with disease-related diversity, uniform folding may indicate a less flexible interplay between genetic and environmental factors during neurodevelopment.