Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.
Journal: Molecular psychiatry
Volume: 23
Issue: 5
Year of Publication: 2019
Affiliated Institutions: Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA. Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Carlton South, VIC, Australia. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. University of Edinburgh, Edinburgh, UK. University of Oslo, Oslo, Norway. Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain. Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy. Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. Neuroscience Research Australia and School of Psychiatry, University of New South Wales, Sydney, NSW, Australia. University of New Mexico, Albuquerque, NM, USA. The Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA. Centre for Neuroimaging and Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, National University of Ireland Galway, Galway, Ireland. Discipline of Psychiatry, School of Medicine, University of Queensland, Herston, QLD, Australia. Department of Computer Science and Engineering, The Ohio State University, Columbus, OH, USA. Beijing Huilongguan Hospital, Beijing, China. Worldwide Research and Development, Pfizer, Cambridge, MA, USA. Santa Lucia Foundation, Rome, Italy. Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea. Department of Psychiatry and Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland. University Hospital Marqués de Valdecilla, IDIVAL, Department of Medicine and Psychiatry, School of Medicine, University of Cantabria, Santander, Spain. Center for Addiction and Mental Health, Toronto, ON, Canada. Division of Psychological and Social Medicine and Developmental Neurosciences, Technische Universität Dresden, Faculty of Medicine, University Hospital C.G. Carus, Dresden, Germany. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden. University of New South Wales, School of Psychiatry, Sydney, NSW, Australia. University of California, VAMC, San Francisco, CA, USA. Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa. Division of Cerebral Integration, National Institute for Physiological Sciences, Aichi, Japan. Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital and Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. Harvard Medical School, Boston, MA, USA. Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA. Zhumadian Psychiatry Hospital, Henan Province, China. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA. Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan. Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia. School of Electrical Engineering and Computer Science, University of Newcastle, Callaghan, NSW, Australia. National Institute of Mental Health, Klecany, Czech Republic. University of Western Australia, Perth, WA, Australia. Erasmus University Medical Center, Rotterdam, The Netherlands. Laboratory for Neuroimaging, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt/Main, Germany. Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Sunshine Coast Mind and Neuroscience Institute, University of the Sunshine Coast QLD, Australia, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia. Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA. Research Group in Psychiatry (GIPSI), Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Mood Disorder Program, Hospital Universitario San Vicente Fundación, Medellín, Colombia. University of Iowa, Iowa City, IA, USA. VABHS, Harvard Medical School, Boston, MA, USA. Department of Psychiatry, Trinity College Dublin, Dublin, Ireland. Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA. The University of Texas Health Science Center at Houston, Houston, TX, USA. Harvard Medical School and Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess, Medical Center, Boston, MA, USA. The University of Newcastle, Newcastle, NSW, Australia. Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia and Queensland Centre for Mental Health Research, Brisbane and Queensland Centre for Mental Health Research, Brisbane, QLD, Australia. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia. Instituto de Alta Tecnología Médica, Medellín, Colombia. Hunter Medical Research Institute, Newcastle, NSW, Australia. SU/UCT MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa. Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, VIC, Australia. Schizophrenia Research Institute, Sydney, NSW, Australia. Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia. Chongqing Three Gorges Central Hospital, Chongqing, China. CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Santander, Spain. Department of Psychiatry, University of Iowa, Iowa City, IA, USA. Research Group in Psychiatry (GIPSI), Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellín, Colombia. Neuropsychiatry Unit, Royal Melbourne Hospital, Parkville, VIC, Australia. Kimel Family Translational Imaging-Genetics Research Laboratory, Campbell Family Mental Health Research Institute, CAMH Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Luoyang Fifth People's Hospital, Henan Province, China. Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. Department of Computer Science and Electrical Engineering, University of Maryland, Baltimore, MD, USA. Psychology Department & Neuroscience Institute, Georgia State University, Atlanta, GA, USA.
Abstract summary
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.Authors & Co-authors: Kelly Jahanshad Zalesky Kochunov Agartz Alloza Andreassen Arango Banaj Bouix Bousman Brouwer Bruggemann Bustillo Cahn Calhoun Cannon Carr Catts Chen Chen Chen Chiapponi Cho Ciullo Corvin Crespo-Facorro Cropley De Rossi Diaz-Caneja Dickie Ehrlich Fan Faskowitz Fatouros-Bergman Flyckt Ford Fouche Fukunaga Gill Glahn Gollub Goudzwaard Guo Gur Gur Gurholt Hashimoto Hatton Henskens Hibar Hickie Hong Horacek Howells Hulshoff Pol Hyde Isaev Jablensky Jansen Janssen Jönsson Jung Kahn Kikinis Liu Klauser Knöchel Kubicki Lagopoulos Langen Lawrie Lenroot Lim Lopez-Jaramillo Lyall Magnotta Mandl Mathalon McCarley McCarthy-Jones McDonald McEwen McIntosh Melicher Mesholam-Gately Michie Mowry Mueller Newell O'Donnell Oertel-Knöchel Oestreich Paciga Pantelis Pasternak Pearlson Pellicano Pereira Pineda Zapata Piras Potkin Preda Rasser Roalf Roiz Roos Rotenberg Satterthwaite Savadjiev Schall Scott Seal Seidman Shannon Weickert Whelan Shenton Kwon Spalletta Spaniel Sprooten Stäblein Stein Sundram Tan Tan Tang Temmingh Westlye Tønnesen Tordesillas-Gutierrez Doan Vaidya van Haren Vargas Vecchio Velakoulis Voineskos Voyvodic Wang Wan Wei Weickert Whalley White Whitford Wojcik Xiang Xie Yamamori Yang Yao Zhang Zhao van Erp Turner Thompson Donohoe
Study Outcome
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Statistics
Citations : Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jönsson B et al. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 2011; 21: 655–679.Authors : 158
Identifiers
Doi : 10.1038/mp.2017.170SSN : 1476-5578