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

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

*Corresponding author for this work
5 Citations (Scopus)


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.

Original languageEnglish
JournalHuman Brain Mapping
Issue number1
Pages (from-to)352-372
Number of pages21
Publication statusPublished - 01.2022


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