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

Schijven D; Postema MC; Fukunaga M; Matsumoto J; Miura K; de Zwarte SMC; van Haren NEM; Cahn W; Hulshoff Pol HE; Kahn RS; Ayesa-Arriola R; Ortiz-García de la Foz V; Tordesillas-Gutierrez D; Vázquez-Bourgon J; Crespo-Facorro B; Dahl A; Alnæs D; Agartz I; Westlye LT; Jönsson EG; Andreassen OA; Bruggemann JM; Kochunov P; Michie PT; Catts SV; Quidé Y; Mowry BJ; Schall U; Rasser PE; Carr VJ; Scott RJ; Loughland CM; Pantelis C; Green MJ; Henskens FA; de Haan L; Brosch K; Weickert CS; Weickert TW; Stein F; Jansen A; Pfarr JK; Ringwald KG; Krämer B; Gruber O; Kircher TTJ; Nenadić I; Preda A; Mathalon DH; Bustillo J; Satterthwaite TD; Chen J; Potkin SG; Ford JM; Calhoun VD; Fan F; Xiang H; Wang Z; Tan Y; Garcia-Leon MA; Fuentes-Claramonte P; Ehrlich S; Bernardoni F; Ciullo V; Piras F; Vecchio D; Banaj N; Guerrero-Pedraza A; Salvador R; Sarró S; Pomarol-Clotet E; Voineskos AN; Sim K; Ciufolini S; Dazzan P; Spalletta G; Michielse S; van Amelsvoort T; Dickie EW; Borgwardt S; Schmidt A; Whalley HC; McIntosh AM; Kim WS; Murray RM; Andreou C; Chung YC; Grotegerd D; Emsley R; Dannlowski U; Lencer R; du Plessis S; Lawrie SM; Scheffler F; Luckhoff HK; Pergola G; Bertolino A; Antonucci LA; Fazio L; Stephen JM; Mayer AR; Edmond JT; Rootes-Murdy K; Cervenka S; Sellgren CM; Tomyshev AS; Lebedeva I; Lois NG; Arango C; Díaz-Caneja CM; Janssen J; Kwak YB; Kim M; Spaniel F; Skoch A; Hajek T; Kaiser S; Kirschner M; Georgiadis F; Uhlmann A; Oertel V; Stäblein M; Knöchel C; Bakker G; James A; Kwon JS; Oh S; Homan P; Surbeck W; Franke B; Fisher SE; Gur RC; Glahn DC; Jahanshad N; Hashimoto R; Stein DJ; Howells FM; Diaz-Zuluaga AM; Temmingh HS; López-Jaramillo C; Pineda-Zapata JA; Ji E; Homan S; Luders E; Medland SE; Thompson PM; Turner JA; van Erp TGM; Francks C

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.