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


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; de la Foz, Víctor Ortiz-García; 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; Nenadić, 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 (2023). Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium. Proceedings of the National Academy of Sciences of the United States of America, 120(14):e2213880120.

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, 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.

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, 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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
06 Faculty of Arts > Institute of Psychology
Special Collections > Centers of Competence > Healthy Longevity Center
Dewey Decimal Classification:610 Medicine & health
150 Psychology
Scopus Subject Areas:Health Sciences > Multidisciplinary
Uncontrolled Keywords:Schizophrenia, brain imaging, asymmetry, cortical, subcortical
Language:English
Date:28 March 2023
Deposited On:20 Nov 2023 11:05
Last Modified:31 Mar 2024 03:35
Publisher:National Academy of Sciences
ISSN:0027-8424
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1101/2022.03.01.22271652
PubMed ID:36976765
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)