Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.

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TitleWidespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.
Publication TypeJournal Article
Year of Publication2018
AuthorsKelly, 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, J-X, 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, F-M, Faskowitz, J, Fatouros-Bergman, H, Flyckt, L, Ford, JM, Fouche, J-P, 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, Pol, HEHulshoff, 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, J Zapata, P, 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, C Weickert, S, 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
JournalMol Psychiatry
Date Published2018 05
KeywordsAdult, Aged, Aged, 80 and over, Brain, Cohort Studies, Corpus Callosum, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Schizophrenia, White Matter, Young Adult

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.

Alternate JournalMol. Psychiatry
PubMed ID29038599
PubMed Central IDPMC5984078
Grant ListP41 EB015922 / EB / NIBIB NIH HHS / United States
R01 EB015611 / EB / NIBIB NIH HHS / United States
U24 RR021992 / RR / NCRR NIH HHS / United States
U54 EB020403 / EB / NIBIB NIH HHS / United States
U01 MH108148 / MH / NIMH NIH HHS / United States
104036/Z/14/Z / / Wellcome Trust / United Kingdom
U24 RR025736 / RR / NCRR NIH HHS / United States
R01 MH112180 / MH / NIMH NIH HHS / United States
P50 MH080272 / MH / NIMH NIH HHS / United States
R21 MH106793 / MH / NIMH NIH HHS / United States