Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Dick Schijven, Merel C. Postema, Masaki Fukunaga, Junya Matsumoto, Kenichiro Miura, Sonja M.C. de Zwarte, Neeltje E.M. van Haren, Wiepke Cahn, Hilleke E. Hulshoff Pol, René S. Kahn, Rosa Ayesa-Arriola, Víctor Ortiz García de la Foz, Diana Tordesillas-Gutierrez, Javier Vázquez-Bourgon, Benedicto Crespo-Facorro, Dag Alnæs, Andreas Dahl, Lars T. Westlye, Ingrid Agartz, Ole A. AndreassenErik G. Jönsson, Peter Kochunov, Jason M. Bruggemann, Stanley V. Catts, Patricia T. Michie, Bryan J. Mowry, Yann Quidé, Paul E. Rasser, Ulrich Schall, Rodney J. Scott, Vaughan J. Carr, Melissa J. Green, Frans A. Henskens, Carmel M. Loughland, Christos Pantelis, Cynthia Shannon Weickert, Thomas W. Weickert, Lieuwe de Haan, Katharina Brosch, Julia Katharina Pfarr, Kai G. Ringwald, Frederike Stein, Andreas Jansen, Tilo T.J. Kircher, Igor Nenadić, Bernd Krämer, Oliver Gruber, Theodore D. Satterthwaite, Juan Bustillo, Daniel H. Mathalon, Adrian Preda, Vince D. Calhoun, Judith M. Ford, Steven G. Potkin, Jingxu Chen, Yunlong Tan, Zhiren Wang, Hong Xiang, Fengmei Fan, Fabio Bernardoni, Stefan Ehrlich, Paola Fuentes-Claramonte, Maria Angeles Garcia-Leon, Amalia Guerrero-Pedraza, Raymond Salvador, Salvador Sarró, Edith Pomarol-Clotet, Valentina Ciullo, Fabrizio Piras, Daniela Vecchio, Nerisa Banaj, Gianfranco Spalletta, Stijn Michielse, Therese van Amelsvoort, Erin W. Dickie, Aristotle N. Voineskos, Kang Sim, Simone Ciufolini, Paola Dazzan, Robin M. Murray, Woo Sung Kim, Young Chul Chung, Christina Andreou, André Schmidt, Stefan Borgwardt, Andrew M. McIntosh, Heather C. Whalley, Stephen M. Lawrie, Stefan du Plessis, Hilmar K. Luckhoff, Freda Scheffler, Robin Emsley, Dominik Grotegerd, Rebekka Lencer, Udo Dannlowski, Jesse T. Edmond, Kelly Rootes-Murdy, Julia M. Stephen, Andrew R. Mayer, Linda A. Antonucci, Leonardo Fazio, Giulio Pergola, Alessandro Bertolino, Covadonga M. Díaz-Caneja, Joost Janssen, Noemi G. Lois, Celso Arango, Alexander S. Tomyshev, Irina Lebedeva, Simon Cervenka, Carl M. Sellgren, Foivos Georgiadis, Matthias Kirschner, Stefan Kaiser, Tomas Hajek, Antonin Skoch, Filip Spaniel, Minah Kim, Yoo Bin Kwak, Sanghoon Oh, Jun Soo Kwon, Anthony James, Geor Bakker, Christian Knöchel, Michael Stäblein, Viola Oertel, Anne Uhlmann, Fleur M. Howells, Dan J. Stein, Henk S. Temmingh, Ana M. Diaz-Zuluaga, Julian A. Pineda-Zapata, Carlos López-Jaramillo, Stephanie Homan, Ellen Ji, Werner Surbeck, Philipp Homan, Simon E. Fisher, Barbara Franke, Ruben C. Gur, David C. Glahn, Ryota Hashimoto, Neda Jahanshad, Eileen Luders, Paul M. Thompson, Sarah E. Medland, Jessica A. Turner, Theo G.M. van Erp, Clyde Francks*

*Corresponding author for this work
6 Citations (Scopus)

Abstract

Left–right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case–control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case–control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case–control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case–control status. Subtle case–control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

Original languageEnglish
Article numbere2213880120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number14
ISSN0027-8424
DOIs
Publication statusPublished - 04.04.2023

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

DFG Research Classification Scheme

  • 206-03 Experimental and Theoretical Neurosciences of Networks
  • 206-04 Cognitive, Systemic and Behavioural Neurobiology
  • 206-08 Cognitive and Systemic Human Neuroscience

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