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