Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group
Kelly S, Jahanshad N, Zalesky A, Kochunov P, Agartz I, Alloza C, Andreassen OA, Arango C, Banaj N, Bouix S, Bousman CA, Brouwer RM, Bruggemann J, Bustillo J, Cahn W, Calhoun V, Cannon D, Carr V, Catts S, Chen J, Chen JX, Chen X, Chiapponi C, Cho KK, Ciullo V, Corvin AS, Crespo-Facorro B, Cropley V, De Rossi P, Diaz-Caneja CM, Dickie EW, Ehrlich S, Fan FM, Faskowitz J, Fatouros-Bergman H, Flyckt L, Ford JM, Fouche JP, Fukunaga M, Gill M, Glahn DC, Gollub R, Goudzwaard ED, Guo H, Gur RE, Gur RC, Gurholt TP, Hashimoto R, Hatton SN, Henskens FA, Hibar DP, Hickie IB, Hong LE, Horacek J, Howells FM, Hulshoff Pol HE, Hyde CL, Isaev D, Jablensky A, Jansen PR, Janssen J, Jönsson EG, Jung LA, Kahn RS, Kikinis Z, Liu K, Klauser P, Knöchel C, Kubicki M, Lagopoulos J, Langen C, Lawrie S, Lenroot RK, Lim KO, Lopez-Jaramillo C, Lyall A, Magnotta V, Mandl RCW, Mathalon DH, McCarley RW, McCarthy-Jones S, McDonald C, McEwen S, McIntosh A, Melicher T, Mesholam-Gately RI, Michie PT, Mowry B, Mueller BA, Newell DT, O’Donnell P, Oertel-Knöchel V, Oestreich L, Paciga SA, Pantelis C, Pasternak O, Pearlson G, Pellicano GR, Pereira A, Pineda Zapata J, Piras F, Potkin SG, Preda A, Rasser PE, Roalf DR, Roiz R, Roos A, Rotenberg D, Satterthwaite TD, Savadjiev P, Schall U, Scott RJ, Seal ML, Seidman LJ, Shannon Weickert C, Whelan CD, Shenton ME, Kwon JS, Spalletta G, Spaniel F, Sprooten E, Stäblein M, Stein DJ, Sundram S, Tan Y, Tan S, Tang S, Temmingh HS, Westlye LT, Tønnesen S, Tordesillas-Gutierrez D, Doan NT, Vaidya J, van Haren NEM, Vargas CD, Vecchio D, Velakoulis D, Voineskos A, Voyvodic JQ, Wang Z, Wan P, Wei D, Weickert TW, Whalley H, White T, Whitford TJ, Wojcik JD, Xiang H, Xie Z, Yamamori H, Yang F, Yao N, Zhang G, Zhao J, van Erp TGM, Turner J, Thompson PM, Donohoe G
Mol. Psychiatry 2018 05;23(5):1261-1269
The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
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