Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
Authors: Schijven Dick , Postema Merel C. , Fukunaga Masaki , Matsumoto Junya , Miura Kenichiro , de Zwarte Sonja M.C. , van Haren Neeltje E.M. , Cahn Wiepke , Hulshoff Pol Hilleke E. , Kahn René S. , Ayesa-Arriola Rosa , Ortiz-García de la Foz Víctor , Tordesillas-Gutierrez Diana , Vázquez-Bourgon Javier , Crespo-Facorro Benedicto , Alnæs Dag , Dahl Andreas , Westlye Lars T. , Agartz Ingrid , Andreassen Ole A. , Jönsson Erik G. , Kochunov Peter , Bruggemann Jason M. , Catts Stanley V. , Michie Patricia T. , Mowry Bryan J. , Quidé Yann , Rasser Paul E. , Schall Ulrich , Scott Rodney J. , Carr Vaughan J. , Green Melissa J. , Henskens Frans A. , Loughland Carmel M. , Pantelis Christos , Weickert Cynthia Shannon , Weickert Thomas W. , de Haan Lieuwe , Brosch Katharina , Pfarr Julia-Katharina , Ringwald Kai G. , Stein Frederike , Jansen Andreas , Kircher Tilo T.J. , Nenadic Igor , Krämer Bernd , Gruber Oliver , Satterthwaite Theodore D. , Bustillo Juan , Mathalon Daniel H. , Preda Adrian , Calhoun Vince D. , Ford Judith M. , Potkin Steven G. , Chen Jingxu , Tan Yunlong , Wang Zhiren , Xiang Hong , Fan Fengmei , Bernardoni Fabio , Ehrlich Stefan , Fuentes-Claramonte Paola , Garcia-Leon Maria Angeles , Guerrero-Pedraza Amalia , Salvador Raymond , Sarró Salvador , Pomarol-Clotet Edith , Ciullo Valentina , Piras Fabrizio , Vecchio Daniela , Banaj Nerisa , Spalletta Gianfranco , Michielse Stijn , van Amelsvoort Therese , Dickie Erin W. , Voineskos Aristotle N. , Sim Kang , Ciufolini Simone , Dazzan Paola , Murray Robin M. , Kim Woo-Sung , Chung Young-Chul , Andreou Christina , Schmidt André , Borgwardt Stefan , McIntosh Andrew M. , Whalley Heather C. , Lawrie Stephen M. , du Plessis Stefan , Luckhoff Hilmar K. , Scheffler Freda , Emsley Robin , Grotegerd Dominik , Lencer Rebekka , Dannlowski Udo , Edmond Jesse T. , Rootes-Murdy Kelly , Stephen Julia M. , Mayer Andrew R. , Antonucci Linda A. , Fazio Leonardo , Pergola Giulio , Bertolino Alessandro , Díaz-Caneja Covadonga M. , Janssen Joost , Lois Noemi G. , Arango Celso , Tomyshev Alexander S. , Lebedeva Irina , Cervenka Simon , Sellgren Carl M. , Georgiadis Foivos , Kirschner Matthias , Kaiser Stefan , Hajek Tomas , Skoch Antonin , Spaniel Filip , Kim Minah , Kwak Yoo Bin , Oh Sanghoon , Kwon Jun Soo , James Anthony , Bakker Geor , Knöchel Christian , Stäblein Michael , Oertel Viola , Uhlmann Anne , Howells Fleur M. , Stein Dan J. , Temmingh Henk S. , Diaz-Zuluaga Ana M. , Pineda-Zapata Julian A. , López-Jaramillo Carlos , Homan Stephanie , Ji Ellen , Surbeck Werner , Homan Philipp , Fisher Simon E. , Franke Barbara , Glahn David C. , Gur Ruben C. , Hashimoto Ryota , Jahanshad Neda , Luders Eileen , Medland Sarah E. , Thompson Paul M. , Turner Jessica A. , van Erp Theo G.M. , Francks Clyde 
Published: March 2022

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, using MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets in the ENIGMA consortium, 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 macro-structural 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.