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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • S. Kelly - , Keck School of Medicine at University of Southern California, Harvard University (Author)
  • N. Jahanshad - , Keck School of Medicine at University of Southern California (Author)
  • A. Zalesky - , University of Melbourne (Author)
  • P. Kochunov - , University of Maryland, Baltimore (Author)
  • I. Agartz - , University of Oslo, Karolinska Institutet, Diakonhjemmet Hospital (Author)
  • C. Alloza - , University of Edinburgh (Author)
  • O. A. Andreassen - , University of Oslo (Author)
  • C. Arango - , Complutense University (Author)
  • N. Banaj - , IRCCS Fondazione Santa Lucia - Roma (Author)
  • S. Bouix - , Harvard University (Author)
  • C. A. Bousman - , University of Melbourne, Florey Institute of Neuroscience and Mental Health, Swinburne University of Technology (Author)
  • R. M. Brouwer - , Utrecht University (Author)
  • J. Bruggemann - , University of New South Wales (Author)
  • J. Bustillo - , University of New Mexico (Author)
  • W. Cahn - , Utrecht University (Author)
  • V. Calhoun - , University of New Mexico, The Mind Research Network (Author)
  • D. Cannon - , University of Galway (Author)
  • V. Carr - , University of New South Wales (Author)
  • S. Catts - , University of Queensland (Author)
  • J. Chen - , Ohio State University (Author)
  • J. X. Chen - , Huilongguan Hospital (Author)
  • X. Chen - , Pfizer (Author)
  • C. Chiapponi - , IRCCS Fondazione Santa Lucia - Roma (Author)
  • Kl K. Cho - , Seoul National University (Author)
  • V. Ciullo - , IRCCS Fondazione Santa Lucia - Roma (Author)
  • A. S. Corvin - , Trinity College Dublin (Author)
  • B. Crespo-Facorro - , Hospital Universitario Marques de Valdecilla, CIBER - Center for Biomedical Research Network (Author)
  • V. Cropley - , University of Melbourne (Author)
  • P. De Rossi - , IRCCS Fondazione Santa Lucia - Roma, University of Rome La Sapienza (Author)
  • C. M. Diaz-Caneja - , Complutense University (Author)
  • E. W. Dickie - , University of Toronto (Author)
  • S. Ehrlich - , Division of Psychological and Social Medicine and Developmental Neurosciences, University Hospital Carl Gustav Carus Dresden (Author)
  • F. M. Fan - , Huilongguan Hospital (Author)
  • J. Faskowitz - , Keck School of Medicine at University of Southern California (Author)
  • H. Fatouros-Bergman - , Karolinska Institutet (Author)
  • L. Flyckt - , University of Melbourne, University of Queensland (Author)
  • J. M. Ford - , University of California at San Francisco (Author)
  • J. P. Fouche - , University of Cape Town (Author)
  • M. Fukunaga - , National Institutes of Natural Sciences - National Institute for Physiological Sciences (Author)
  • M. Gill - , Trinity College Dublin (Author)
  • D. C. Glahn - , Yale University (Author)
  • R. Gollub - , Harvard University, Massachusetts General Hospital (Author)
  • E. D. Goudzwaard - , University of California at Irvine (Author)
  • H. Guo - , Zhumadian Psychiatry Hospital (Author)
  • R. E. Gur - , University of Pennsylvania (Author)
  • R. C. Gur - , Osaka University (Author)
  • T. P. Gurholt - , University of Oslo (Author)
  • R. Hashimoto - , Osaka University, University of Sydney (Author)
  • S. N. Hatton - , University of Newcastle (Author)
  • F. A. Henskens - , University of Newcastle, Hunter Medical Research Institute (HMRI), National Institute of Mental Health (Author)
  • D. P. Hibar - , Keck School of Medicine at University of Southern California (Author)
  • I. B. Hickie - , University of Newcastle (Author)
  • L. E. Hong - , University of Maryland, Baltimore (Author)
  • J. Horacek - , Charles University Prague, University of Western Australia (Author)
  • F. M. Howells - , National Institutes of Natural Sciences - National Institute for Physiological Sciences (Author)
  • H. E. Hulshoff Pol - , Utrecht University (Author)
  • C. L. Hyde - , Pfizer (Author)
  • D. Isaev - , Keck School of Medicine at University of Southern California (Author)
  • A. Jablensky - , Erasmus University Rotterdam (Author)
  • P. R. Jansen - , Goethe University Frankfurt a.M. (Author)
  • J. Janssen - , Complutense University, Utrecht University (Author)
  • E. G. Jönsson - , University of Oslo, Karolinska Institutet (Author)
  • L. A. Jung - , Monash University (Author)
  • R. S. Kahn - , Utrecht University (Author)
  • Z. Kikinis - , Harvard University (Author)
  • K. Liu - , University of Melbourne (Author)
  • P. Klauser - , University of Melbourne, University of Lausanne, Harvard University (Author)
  • C. Knöchel - , Monash University (Author)
  • M. Kubicki - , University of the Sunshine Coast (Author)
  • J. Lagopoulos - , University of Minnesota System (Author)
  • C. Langen - , Goethe University Frankfurt a.M. (Author)
  • S. Lawrie - , University of Edinburgh (Author)
  • R. K. Lenroot - , University of New South Wales (Author)
  • K. O. Lim - , Universidad de Antioquia (Author)
  • C. Lopez-Jaramillo - , Massachusetts General Hospital (Author)
  • A. Lyall - , Harvard University, University of Iowa (Author)
  • V. Magnotta - , Harvard University (Author)
  • R. C.W. Mandl - , Utrecht University (Author)
  • D. H. Mathalon - , University of Cape Town (Author)
  • R. W. McCarley - , Trinity College Dublin (Author)
  • S. McCarthy-Jones - , University of California at Los Angeles (Author)
  • C. McDonald - , University of Galway (Author)
  • S. McEwen - , University of Texas Health Science Center at Houston (Author)
  • A. McIntosh - , University of Edinburgh (Author)
  • T. Melicher - , University of Western Australia, Harvard University (Author)
  • R. I. Mesholam-Gately - , University of Newcastle (Author)
  • P. T. Michie - , National Institute of Mental Health, Schizophrenia Research Institute, University of Queensland (Author)
  • B. Mowry - , University of Melbourne (Author)
  • B. A. Mueller - , Universidad de Antioquia (Author)
  • D. T. Newell - , Harvard University (Author)
  • P. O'Donnell - , Pfizer (Author)
  • V. Oertel-Knöchel - , Monash University (Author)
  • L. Oestreich - , University of Melbourne (Author)
  • S. A. Paciga - , Pfizer (Author)
  • C. Pantelis - , University of Melbourne, Florey Institute of Neuroscience and Mental Health, University of Queensland (Author)
  • O. Pasternak - , University of the Sunshine Coast (Author)
  • G. Pearlson - , Massachusetts General Hospital (Author)
  • G. R. Pellicano - , IRCCS Fondazione Santa Lucia - Roma (Author)
  • A. Pereira - , Instituto de Alta Tecnología Médica (Author)
  • J. Pineda Zapata - , University of Newcastle (Author)
  • F. Piras - , IRCCS Fondazione Santa Lucia - Roma, University of Newcastle (Author)
  • S. G. Potkin - , Zhumadian Psychiatry Hospital (Author)
  • A. Preda - , Zhumadian Psychiatry Hospital (Author)
  • P. E. Rasser - , National Institute of Mental Health, University of Stellenbosch (Author)
  • D. R. Roalf - , Osaka University (Author)
  • R. Roiz - , Hospital Universitario Marques de Valdecilla, CIBER - Center for Biomedical Research Network (Author)
  • A. Roos - , Royal Children's Hospital Melbourne (Author)
  • D. Rotenberg - , University of Toronto (Author)
  • T. D. Satterthwaite - , Osaka University (Author)
  • P. Savadjiev - , University of the Sunshine Coast (Author)
  • U. Schall - , National Institute of Mental Health, University of Stellenbosch (Author)
  • R. J. Scott - , National Institute of Mental Health, University of Newcastle (Author)
  • M. L. Seal - , Neuroscience Research Australia (Author)
  • L. J. Seidman - , Harvard University, University of Iowa, University of Newcastle (Author)
  • C. Shannon Weickert - , University of Queensland, Department of Veterans Affairs, Baylor College of Medicine (Author)
  • C. D. Whelan - , Keck School of Medicine at University of Southern California (Author)
  • M. E. Shenton - , University of the Sunshine Coast, University of Cape Town (Author)
  • J. S. Kwon - , Seoul National University (Author)
  • G. Spalletta - , IRCCS Fondazione Santa Lucia - Roma, Monash University (Author)
  • F. Spaniel - , Charles University Prague, University of Western Australia (Author)
  • E. Sprooten - , Massachusetts General Hospital (Author)
  • M. Stäblein - , Monash University (Author)
  • D. J. Stein - , National Institutes of Natural Sciences - National Institute for Physiological Sciences, Chongqing Three Gorges University (Author)
  • S. Sundram - , Florey Institute of Neuroscience and Mental Health, University of Oslo (Author)
  • Y. Tan - , Huilongguan Hospital (Author)
  • S. Tan - , Huilongguan Hospital (Author)
  • S. Tang - , Marqués de Valdecilla Research Institute (IDIVAL) (Author)
  • H. S. Temmingh - , National Institutes of Natural Sciences - National Institute for Physiological Sciences (Author)
  • L. T. Westlye - , University of Oslo (Author)
  • S. Tønnesen - , University of Oslo (Author)
  • D. Tordesillas-Gutierrez - , CIBER - Center for Biomedical Research Network (Author)
  • N. T. Doan - , University of Oslo (Author)
  • J. Vaidya - , University of Toronto (Author)
  • N. E.M. Van Haren - , Utrecht University (Author)
  • C. D. Vargas - , Baylor College of Medicine (Author)
  • D. Vecchio - , IRCCS Fondazione Santa Lucia - Roma (Author)
  • D. Velakoulis - , Luoyang Fifth People's Hospital, Yale University (Author)
  • A. Voineskos - , University of Maryland, Baltimore (Author)
  • J. Q. Voyvodic - , Utrecht University (Author)
  • Z. Wang - , Huilongguan Hospital (Author)
  • P. Wan - , University of Pennsylvania (Author)
  • D. Wei - , Shaanxi Normal University (Author)
  • T. W. Weickert - , University of Queensland, Department of Veterans Affairs, Baylor College of Medicine (Author)
  • H. Whalley - , University of Edinburgh (Author)
  • T. White - , Goethe University Frankfurt a.M. (Author)
  • T. J. Whitford - , University of Queensland (Author)
  • J. D. Wojcik - , University of Newcastle (Author)
  • H. Xiang - , Marqués de Valdecilla Research Institute (IDIVAL), University of Iowa, Royal Melbourne Hospital (Author)
  • Z. Xie - , Pfizer (Author)
  • H. Yamamori - , University of Sydney (Author)
  • F. Yang - , Huilongguan Hospital (Author)
  • N. Yao - , Georgia State University (Author)
  • G. Zhang - , Georgia State University (Author)
  • J. Zhao - , University of Galway, Georgia State University (Author)
  • T. G.M. Van Erp - , Zhumadian Psychiatry Hospital (Author)
  • J. Turner - , University of Maryland, Baltimore (Author)
  • P. M. Thompson - , Keck School of Medicine at University of Southern California, Georgia State University (Author)
  • G. Donohoe - , University of Galway (Author)

Abstract

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.

Details

Original languageEnglish
Pages (from-to)1261-1269
Number of pages9
JournalMolecular psychiatry
Volume23
Issue number5
Publication statusPublished - 1 May 2018
Peer-reviewedYes

External IDs

PubMed 29038599
ORCID /0000-0003-2132-4445/work/160950881