A meta‐analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium
Authors: Gutman Boris A. , van Erp Theo G.M. , Alpert Kathryn , Ching Christopher R. K. , Isaev Dmitry , Ragothaman Anjani , Jahanshad Neda , Saremi Arvin , Zavaliangos‐Petropulu Artemis , Glahn David C. , Shen Li , Cong Shan , Alnæs Dag , Andreassen Ole Andreas , Doan Nhat Trung , Westlye Lars T. , Kochunov Peter , Satterthwaite Theodore D. , Wolf Daniel H. , Huang Alexander J. , Kessler Charles , Weideman Andrea , Nguyen Dana , Mueller Bryon A. , Faziola Lawrence , Potkin Steven G. , Preda Adrian , Mathalon Daniel H. , Bustillo Juan , Calhoun Vince , Ford Judith M. , Walton Esther , Ehrlich Stefan , Ducci Giuseppe , Banaj Nerisa , Piras Fabrizio , Piras Federica , Spalletta Gianfranco , Canales‐Rodríguez Erick J. , Fuentes‐Claramonte Paola , Pomarol‐Clotet Edith , Radua Joaquim , Salvador Raymond , Sarró Salvador , Dickie Erin W. , Voineskos Aristotle , Tordesillas‐Gutiérrez Diana , Crespo‐Facorro Benedicto , Setién‐Suero Esther , van Son Jacqueline Mayoral , Borgwardt Stefan , Schönborn‐Harrisberger Fabienne , Morris Derek , Donohoe Gary , Holleran Laurena , Cannon Dara , McDonald Colm , Corvin Aiden , Gill Michael , Filho Geraldo Busatto , Rosa Pedro G. P. , Serpa Mauricio H. , Zanetti Marcus V. , Lebedeva Irina , Kaleda Vasily , Tomyshev Alexander , Crow Tim , James Anthony , Cervenka Simon , Sellgren Carl M , Fatouros‐Bergman Helena , Agartz Ingrid , Howells Fleur , Stein Dan J. , Temmingh Henk , Uhlmann Anne , de Zubicaray Greig I. , McMahon Katie L. , Wright Margie , Cobia Derin , Csernansky John G. , Thompson Paul M. , Turner Jessica A. , Wang Lei 
Published: September 2021

Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta‐analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1‐weighted structural MRI scans. Mass univariate meta‐analyses revealed more‐concave‐than‐convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more‐convex‐than‐concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta‐analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.