TY - JOUR
T1 - 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
AU - Gutman, Boris A.
AU - van Erp, Theo G.M.
AU - Alpert, Kathryn
AU - Ching, Christopher R.K.
AU - Isaev, Dmitry
AU - Ragothaman, Anjani
AU - Jahanshad, Neda
AU - Saremi, Arvin
AU - Zavaliangos-Petropulu, Artemis
AU - Glahn, David C.
AU - Shen, Li
AU - Cong, Shan
AU - Alnæs, Dag
AU - Andreassen, Ole Andreas
AU - Doan, Nhat Trung
AU - Westlye, Lars T.
AU - Kochunov, Peter
AU - Satterthwaite, Theodore D.
AU - Wolf, Daniel H.
AU - Huang, Alexander J.
AU - Kessler, Charles
AU - Weideman, Andrea
AU - Nguyen, Dana
AU - Mueller, Bryon A.
AU - Faziola, Lawrence
AU - Potkin, Steven G.
AU - Preda, Adrian
AU - Mathalon, Daniel H.
AU - Bustillo, Juan
AU - Calhoun, Vince
AU - Ford, Judith M.
AU - Walton, Esther
AU - Ehrlich, Stefan
AU - Ducci, Giuseppe
AU - Banaj, Nerisa
AU - Piras, Fabrizio
AU - Piras, Federica
AU - Spalletta, Gianfranco
AU - Canales-Rodríguez, Erick J.
AU - Fuentes-Claramonte, Paola
AU - Pomarol-Clotet, Edith
AU - Radua, Joaquim
AU - Salvador, Raymond
AU - Sarró, Salvador
AU - Dickie, Erin W.
AU - Voineskos, Aristotle
AU - Tordesillas-Gutiérrez, Diana
AU - Crespo-Facorro, Benedicto
AU - Setién-Suero, Esther
AU - van Son, Jacqueline Mayoral
AU - Borgwardt, Stefan
AU - Schönborn-Harrisberger, Fabienne
AU - Morris, Derek
AU - Donohoe, Gary
AU - Holleran, Laurena
AU - Cannon, Dara
AU - McDonald, Colm
AU - Corvin, Aiden
AU - Gill, Michael
AU - Filho, Geraldo Busatto
AU - Rosa, Pedro G.P.
AU - Serpa, Mauricio H.
AU - Zanetti, Marcus V.
AU - Lebedeva, Irina
AU - Kaleda, Vasily
AU - Tomyshev, Alexander
AU - Crow, Tim
AU - James, Anthony
AU - Cervenka, Simon
AU - Sellgren, Carl M.
AU - Fatouros-Bergman, Helena
AU - Agartz, Ingrid
AU - Howells, Fleur
AU - Stein, Dan J.
AU - Temmingh, Henk
AU - Uhlmann, Anne
AU - de Zubicaray, Greig I.
AU - McMahon, Katie L.
AU - Wright, Margie
AU - Cobia, Derin
AU - Csernansky, John G.
AU - Thompson, Paul M.
AU - Turner, Jessica A.
AU - Wang, Lei
N1 - Funding Information:
One of the authors (TGMvE) has had a research contract with Otsuka Pharmaceutical. One of the authors (AP) has served as a consultant for Boehringer Ingelheim. One of the authors (DJS) has received research grants and/or honoraria from Lundbeck and Sun. One of the authors (DHM) has served as a consultant for Boehringer Ingelheim, Aptinyx, and Greenwich Biosciences. One of the authors (SC) has received grant support from AstraZeneca as co‐investigator, and has served as a speaker for Otsuka Pharmaceuticals. Authors PMT, CRKC, and NJ received a research grant from Biogen, Inc. (Boston) for research unrelated to this manuscript. The remaining authors declare no potential conflict of interest.
Funding Information:
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 Funding information
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.
Publisher Copyright:
© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - schizophrenia
KW - structure
KW - subcortical shape
UR - http://www.scopus.com/inward/record.url?scp=85114302135&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114302135&partnerID=8YFLogxK
U2 - 10.1002/hbm.25625
DO - 10.1002/hbm.25625
M3 - Article
C2 - 34498337
AN - SCOPUS:85114302135
VL - 43
SP - 352
EP - 372
JO - Human Brain Mapping
JF - Human Brain Mapping
SN - 1065-9471
IS - 1
ER -