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

• Type of Material: Article
• Authors: Boris A Gutman, Illinois Institute of Technology; Theo GM van Erp, University of California Irvine; Kathryn Alpert, Northwestern University; Christopher RK Ching, University of Southern California; Dmitry Isaev, Duke University; Anjani Ragothaman, Oregon Health and Science university; Neda Jahanshad, University of Southern California; Arvin Saremi, University of Southern California; Artemis Zavaliangos-Petropulu, University of Southern California; David C Glahn, Boston Childrens Hospital; Li Shen, University of Pennsylvania; Shan Cong, University of Pennsylvania; Dag Alnæs, University of Oslo; Ole A Andreassen, University of Oslo; Trung D Nhat, University of Oslo; Lars T Westlye, University of Oslo; Peter Kochunov, Univ Maryland; Theodore D Satterthwaite, University of Pennsylvania; Daniel H Wolf, University of Pennsylvania; Alexander J Huang, University of California Irvine; Charles Kessler, University of California Irvine; Andrea Weideman, University of California Irvine; Dana Nguyen, University of California Irvine; Bryon A Mueller, University of Minnesota, Minneapolis; Lawrence Faziola, University of California Irvine; Steven G Potkin, University of California Irvine; Adrian Preda, University of California Irvine; Dana H Mathalon, University of California San Francisco; Juan Bustillo, University of New Mexico; Vince Calhoun, Emory University; Judith M Ford, VA San Francisco Healthcare Syst; Esther Walton, University of Bath; Stefan Ehrlich, Technische Universitat Dresden; Giuseppe Ducci, ASL Roma1 DSM; Nerisa Banaj, IRCCS Santa Lucia Foundation; Fabrizio Piras, IRCCS Santa Lucia Foundation; Federica Piras, IRCCS Santa Lucia Foundation; Gianfranco Spalletta, IRCCS Santa Lucia Foundation; Erick J Canales‐Rodríguez, University Hospital Marqués de Valdecilla, IDIVAL, CIBERSAM; Paola Fuentes-Claramonte, University Hospital Marqués de Valdecilla, IDIVAL, CIBERSAM; Edith Pomarol-Clotet, University Hospital Marqués de Valdecilla, IDIVAL, CIBERSAM; Joaquim Radua, University Hospital Marqués de Valdecilla, IDIVAL, CIBERSAM; Raymond Salvador, University Hospital Marqués de Valdecilla, IDIVAL, CIBERSAM; Salvador Sarro, University Hospital Marqués de Valdecilla, IDIVAL, CIBERSAM; Erin W Dickie, Centre for Addiction and Mental Health (CAMH); Aristotle Voineskos, Centre for Addiction and Mental Health (CAMH); Diana Tordesillas-Gutierrez, Marqués de Valdecilla University Hospital; Benedicto Crespo-Facorro, University of Sevilla; Esther Setién‐Suero, University Hospital Marqués de Valdecilla, IDIVAL, CIBERSAM; Jacqueline M van Son, University of Sevilla; Stefan Borgwardt, University of Basel; Fabienne Schoenborn-Harrisberger, University of Basel; Derek Morris, National University of Ireland Galway; Gary Donohoe, National University of Ireland Galway; Laurena Holleran, National University of Ireland Galway; Dara Cannon, National University of Ireland Galway; Colm McDonald, National University of Ireland Galway; Aiden Corvin, Trinity College Dublin; Michael Gill, Trinity College Dublin; Geraldo Busatto Filho, Universidade de Sao Paulo; Pedro GP Rosa, Universidade de Sao Paulo; Mauricio H Serpa, Universidade de Sao Paulo; Marcus Zanetti, Universidade de Sao Paulo; Irina Lebedeva, Mental Health Research Center; Vasily Kaleda, Mental Health Research Center; Alexander Tomyshev, Mental Health Research Center; Tim Crow, University of Oxford; Anthony James, University of Oxford; Simon Cervenka, Karolinska Institutet; Carl M Sellgren, Karolinska Institutet; Helena Fatouros-Bergman, Karolinska Institutet; Ingrid Agartz, University of Oslo; Fleur Howells, University of Cape Town; Dan J Stein, University of Cape Town; Henk Temmingh, University of Cape Town; Anne Uhlmann, University of Cape Town; Greig de Zubicaray, Queensland University of Technology (QUT); Katie L McMahon, Queensland University of Technology (QUT); Margie Wright, University of Queensland; Derin Cobia, Northwestern University; John G Csernansky, Northwestern University; Paul M Thompson, University of Southern California; Jessica A Turner, Georgia State University; Lei Wang, Northwestern University
• Language: English
• Date: 2021-09-08
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/hbm.25625
• Title of Journal or Parent Work: HUMAN BRAIN MAPPING
• Volume: 43
• Issue: 1
• Start Page: 352
• End Page: 372
• Grant/Funding Information: Research reported in this publication was supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) of the National Institutes of Health under Award Number U54EB020403 and R01MH116147. For additional grant support and acknowledgments, see Supplementary Materials.; Center for Integrated Healthcare, U.S. Department of Veterans Affairs, Grant/Award Number: I01 CX000497; Commonwealth Health Research Board, Grant/Award Number: HRA_POR/2011/100; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grant/Award Numbers: 478466/2009, 480370/2009; Department of Energy, Labor and Economic Growth, Grant/Award Number: DE‐FG02‐99ER62764; Forskningsrådet om Hälsa, Arbetsliv och Välfärd, Grant/Award Numbers: K2009‐62X‐15077‐06‐3, K2012‐61X‐15077‐09‐3, 523‐2014‐3467, 2009‐7053, 2013‐2838; Fundação Amazônia Paraense de Amparo à Pesquisa, Grant/Award Numbers: 2009/14891‐9, 2010/18672‐7, 2012/23796‐2, 2013/039; Instituto de Salud Carlos III, Grant/Award Numbers: FIS 00/3095, 01/3129, PI020499, PI060507, PI10/001; National Health and Medical Research Council, Grant/Award Numbers: 1009064, 496682; National Institutes of Health, Grant/Award Numbers: 1RC1MH089257, MH 60722, MH019112, MH064045, MH085096, MH098130, MO1 RR025758, P41RR14075, P50 MH071616, R01 DA053028, R01 EB020062, R01 HD050735, R01 MH056584, R01 MH084803, R01 MH116147, R01 MH117601, R01EB005846, R01EB015611, R01MH074797, R21 MH097196, R21MH097196, R37MH43375, S10 OD023696, T32 AG058507, T32 MH073526, TR000153, U01 MH097435, U24 RR021382A, U24 RR021992, U24 RR025736, U24 RR21992, U24RR021992, U54 EB020403, U54EB020403, UL1 TR000153; National Science Foundation, Grant/Award Numbers: 1636893, 1734853; Norges Forskningsråd, Grant/Award Numbers: 213837, 217776, 223273; Science Foundation Ireland, Grant/Award Numbers: 08/IN.1/B1916, 12/IP/1359; Wellcome Trust, Grant/Award Number: 072894/2/03/Z
• Keywords: subcortical shape; schizophrenia; TEMPORAL-LOBE; NEURONS; Neuroimaging; ANTIPSYCHOTIC TREATMENT; structure; Life Sciences & Biomedicine; GENETIC INFLUENCES; Neurosciences; CORTICAL THICKNESS; BASAL GANGLIA; NETWORK; Radiology, Nuclear Medicine & Medical Imaging; Neurosciences & Neurology; THALAMIC VOLUME; Science & Technology; HIPPOCAMPAL SHAPE; 1ST-EPISODE SCHIZOPHRENIA
• Research Categories: Engineering, Biomedical; Health Sciences, Mental Health; Psychology, Behavioral

Abstract

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.