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

S Kelly^{1

2}, N Jahanshad¹, A Zalesky³, P Kochunov⁴, I Agartz^{5

6

7}, C Alloza⁸, O A Andreassen⁹, C Arango¹⁰, N Banaj¹¹, S Bouix¹², C A Bousman^{3

13

14

15}, R M Brouwer¹⁶, J Bruggemann¹⁷, J Bustillo¹⁸, W Cahn¹⁶, V Calhoun^{19

20}, D Cannon²¹, V Carr¹⁷, S Catts²², J Chen²³, J-X Chen²⁴, X Chen²⁵, C Chiapponi²⁶, Kl K Cho²⁷, V Ciullo¹¹, A S Corvin²⁸, B Crespo-Facorro^{29

30}, V Cropley³, P De Rossi^{11

31

32}, C M Diaz-Caneja¹⁰, E W Dickie³³, S Ehrlich³⁴, F-M Fan²⁴, J Faskowitz¹, H Fatouros-Bergman⁶, L Flyckt^{35

36}, J M Ford³⁷, J-P Fouche³⁸, M Fukunaga³⁹, M Gill²⁸, D C Glahn⁴⁰, R Gollub^{2

41}, E D Goudzwaard⁴², H Guo⁴³, R E Gur⁴⁴, R C Gur⁴⁴, T P Gurholt⁵, R Hashimoto^{45

46}, S N Hatton⁴⁷, F A Henskens^{48

49

50}, D P Hibar¹, I B Hickie⁴⁷, L E Hong⁴, J Horacek^{51

52}, F M Howells³⁸, H E Hulshoff Pol¹⁶, C L Hyde²⁵, D Isaev¹, A Jablensky⁵³, P R Jansen⁵⁴, J Janssen^{16

10}, E G Jönsson^{5

6}, L A Jung⁵⁵, R S Kahn¹⁶, Z Kikinis¹², K Liu³, P Klauser^{3

56

57}, C Knöchel⁵⁵, M Kubicki⁵⁸, J Lagopoulos⁵⁹, C Langen⁵⁴, S Lawrie⁸, R K Lenroot¹⁷, K O Lim⁶⁰, C Lopez-Jaramillo⁶¹, A Lyall^{12

62}, V Magnotta⁶³, R C W Mandl¹⁶, D H Mathalon³⁷, R W McCarley⁶⁴, S McCarthy-Jones⁶⁵, C McDonald²¹, S McEwen⁶⁶, A McIntosh⁸, T Melicher^{67

52}, R I Mesholam-Gately⁶⁸, P T Michie^{69

70

50}, B Mowry⁷¹, B A Mueller⁶⁰, D T Newell¹², P O'Donnell²⁵, V Oertel-Knöchel⁵⁵, L Oestreich⁷¹, S A Paciga²⁵, C Pantelis^{3

13

72

70}, O Pasternak⁵⁸, G Pearlson⁴⁰, G R Pellicano¹¹, A Pereira⁷³, J Pineda Zapata⁷⁴, F Piras^{11

75}, S G Potkin⁴², A Preda⁴², P E Rasser^{50

76}, D R Roalf⁴⁴, R Roiz^{29

30}, A Roos⁷⁷, D Rotenberg³³, T D Satterthwaite⁴⁴, P Savadjiev⁵⁸, U Schall^{50

76}, R J Scott^{50

75}, M L Seal⁷⁸, L J Seidman^{2

62

68}, C Shannon Weickert^{70

79

80}, C D Whelan¹, M E Shenton^{58

81}, J S Kwon²⁷, G Spalletta^{11

82}, F Spaniel^{51

52}, E Sprooten⁴⁰, M Stäblein⁵⁵, D J Stein^{38

83}, S Sundram^{13

84}, Y Tan²⁴, S Tan²⁴, S Tang⁸⁵, H S Temmingh³⁸, L T Westlye^{5

86}, S Tønnesen⁵, D Tordesillas-Gutierrez^{30

87}, N T Doan⁵, J Vaidya⁸⁸, N E M van Haren¹⁶, C D Vargas⁸⁹, D Vecchio¹¹, D Velakoulis⁹⁰, A Voineskos⁹¹, J Q Voyvodic¹⁶, Z Wang²⁴, P Wan⁴³, D Wei⁹², T W Weickert^{70

79

80}, H Whalley⁸, T White⁵⁴, T J Whitford³⁵, J D Wojcik⁶⁸, H Xiang⁸⁵, Z Xie²⁵, H Yamamori⁴⁶, F Yang²⁴, N Yao⁹³, G Zhang⁹⁴, J Zhao^{21

95}, T G M van Erp⁴², J Turner⁹⁶, P M Thompson¹, G Donohoe²¹

Affiliations

¹ Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
² Harvard Medical School, Boston, MA, USA.
³ Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.
⁴ Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
⁵ 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.
⁶ Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
⁷ Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
⁸ University of Edinburgh, Edinburgh, UK.
⁹ University of Oslo, Oslo, Norway.
¹⁰ Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.
¹¹ Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
¹² Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹³ Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
¹⁴ Department of General Practice, The University of Melbourne, Parkville, VIC, Australia.
¹⁵ Swinburne University of Technology, Melbourne, VIC, Australia.
¹⁶ Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁷ Neuroscience Research Australia and School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
¹⁸ University of New Mexico, Albuquerque, NM, USA.
¹⁹ The Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA.
²⁰ The Mind Research Network, Albuquerque, NM, USA.
²¹ Centre for Neuroimaging and Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, National University of Ireland Galway, Galway, Ireland.
²² Discipline of Psychiatry, School of Medicine, University of Queensland, Herston, QLD, Australia.
²³ Department of Computer Science and Engineering, The Ohio State University, Columbus, OH, USA.
²⁴ Beijing Huilongguan Hospital, Beijing, China.
²⁵ Worldwide Research and Development, Pfizer, Cambridge, MA, USA.
²⁶ Santa Lucia Foundation, Rome, Italy.
²⁷ Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
²⁸ Department of Psychiatry and Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
²⁹ University Hospital Marqués de Valdecilla, IDIVAL, Department of Medicine and Psychiatry, School of Medicine, University of Cantabria, Santander, Spain.
³⁰ CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Santander, Spain.
³¹ Department NESMOS, Faculty of Medicine and Psychology, University 'Sapienza' of Rome, Rome, Italy.
³² Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
³³ Center for Addiction and Mental Health, Toronto, ON, Canada.
³⁴ Division of Psychological and Social Medicine and Developmental Neurosciences, Technische Universität Dresden, Faculty of Medicine, University Hospital C.G. Carus, Dresden, Germany.
³⁵ University of New South Wales, School of Psychiatry, Sydney, NSW, Australia.
³⁶ The University of Queensland, Queensland Brain Institute and Centre for Advanced Imaging, Brisbane, QLD, Australia.
³⁷ University of California, VAMC, San Francisco, CA, USA.
³⁸ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
³⁹ Division of Cerebral Integration, National Institute for Physiological Sciences, Aichi, Japan.
⁴⁰ Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital and Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁴¹ Departments of Psychiatry and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁴² Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
⁴³ Zhumadian Psychiatry Hospital, Henan Province, China.
⁴⁴ Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
⁴⁵ Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan.
⁴⁶ Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
⁴⁷ Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
⁴⁸ School of Electrical Engineering and Computer Science, University of Newcastle, Callaghan, NSW, Australia.
⁴⁹ Health Behaviour Research Group, University of Newcastle, Callaghan, NSW, Australia.
⁵⁰ Hunter Medical Research Institute, Newcastle, NSW, Australia.
⁵¹ National Institute of Mental Health, Klecany, Czech Republic.
⁵² Third Faculty of Medicine, Charles University, Prague, Czech Republic.
⁵³ University of Western Australia, Perth, WA, Australia.
⁵⁴ Erasmus University Medical Center, Rotterdam, The Netherlands.
⁵⁵ Laboratory for Neuroimaging, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt/Main, Germany.
⁵⁶ Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Clayton, VIC, Australia.
⁵⁷ Department of Psychiatry, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
⁵⁸ Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁵⁹ Sunshine Coast Mind and Neuroscience Institute, University of the Sunshine Coast QLD, Australia, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
⁶⁰ Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
⁶¹ Research Group in Psychiatry (GIPSI), Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Mood Disorder Program, Hospital Universitario San Vicente Fundación, Medellín, Colombia.
⁶² Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁶³ University of Iowa, Iowa City, IA, USA.
⁶⁴ VABHS, Harvard Medical School, Boston, MA, USA.
⁶⁵ Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
⁶⁶ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
⁶⁷ The University of Texas Health Science Center at Houston, Houston, TX, USA.
⁶⁸ Harvard Medical School and Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess, Medical Center, Boston, MA, USA.
⁶⁹ The University of Newcastle, Newcastle, NSW, Australia.
⁷⁰ Schizophrenia Research Institute, Sydney, NSW, Australia.
⁷¹ 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.
⁷² Centre for Neural Engineering (CfNE), Department of Electrical and Electronic Engineering, University of Melbourne, Parkville, VIC, Australia.
⁷³ The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
⁷⁴ Instituto de Alta Tecnología Médica, Medellín, Colombia.
⁷⁵ School of Biomedical Sciences, Faculty of Health, the University of Newcastle, Callaghan, NSW, Australia.
⁷⁶ Priority Centre for Brain and Mental Health Research, The University of Newcastle, Newcastle, NSW, Australia.
⁷⁷ SU/UCT MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa.
⁷⁸ Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, VIC, Australia.
⁷⁹ Neuroscience Research Australia, Sydney, NSW, Australia.
⁸⁰ School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
⁸¹ VA Boston Healthcare System, Boston, MA, USA.
⁸² Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
⁸³ Department of Psychiatry and MRC Unit on Anxiety and Stress Disorders, University of Cape Town, Cape Town, South Africa.
⁸⁴ Department of Psychiatry, School of Clinical Sciences, Monash University and Monash Health, Clayton, VIC, Australia.
⁸⁵ Chongqing Three Gorges Central Hospital, Chongqing, China.
⁸⁶ Department of Psychology, University of Oslo, Oslo, Norway.
⁸⁷ Neuroimaging Unit, Technological Facilities, Valdecilla Biomedical Research Institute IDIVAL, Santander, Spain.
⁸⁸ Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
⁸⁹ Research Group in Psychiatry (GIPSI), Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellín, Colombia.
⁹⁰ Neuropsychiatry Unit, Royal Melbourne Hospital, Parkville, VIC, Australia.
⁹¹ Kimel Family Translational Imaging-Genetics Research Laboratory, Campbell Family Mental Health Research Institute, CAMH Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁹² Luoyang Fifth People's Hospital, Henan Province, China.
⁹³ Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁹⁴ Department of Computer Science and Electrical Engineering, University of Maryland, Baltimore, MD, USA.
⁹⁵ School of Psychology, Shaanxi Normal University and Key Laboratory for Behavior and Cognitive Neuroscience of Shaanxi Province, Xi'an, Shaanxi, China.
⁹⁶ Psychology Department & Neuroscience Institute, Georgia State University, Atlanta, GA, USA.

PMID: 29038599
PMCID: PMC5984078
DOI: 10.1038/mp.2017.170

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

S Kelly et al. Mol Psychiatry. 2018 May.

. 2018 May;23(5):1261-1269.

doi: 10.1038/mp.2017.170. Epub 2017 Oct 17.

Authors

Affiliations

¹ Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
² Harvard Medical School, Boston, MA, USA.
³ Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.
⁴ Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
⁵ 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.
⁶ Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
⁷ Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
⁸ University of Edinburgh, Edinburgh, UK.
⁹ University of Oslo, Oslo, Norway.
¹⁰ Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.
¹¹ Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
¹² Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹³ Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
¹⁴ Department of General Practice, The University of Melbourne, Parkville, VIC, Australia.
¹⁵ Swinburne University of Technology, Melbourne, VIC, Australia.
¹⁶ Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁷ Neuroscience Research Australia and School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
¹⁸ University of New Mexico, Albuquerque, NM, USA.
¹⁹ The Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA.
²⁰ The Mind Research Network, Albuquerque, NM, USA.
²¹ Centre for Neuroimaging and Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, National University of Ireland Galway, Galway, Ireland.
²² Discipline of Psychiatry, School of Medicine, University of Queensland, Herston, QLD, Australia.
²³ Department of Computer Science and Engineering, The Ohio State University, Columbus, OH, USA.
²⁴ Beijing Huilongguan Hospital, Beijing, China.
²⁵ Worldwide Research and Development, Pfizer, Cambridge, MA, USA.
²⁶ Santa Lucia Foundation, Rome, Italy.
²⁷ Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
²⁸ Department of Psychiatry and Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
²⁹ University Hospital Marqués de Valdecilla, IDIVAL, Department of Medicine and Psychiatry, School of Medicine, University of Cantabria, Santander, Spain.
³⁰ CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Santander, Spain.
³¹ Department NESMOS, Faculty of Medicine and Psychology, University 'Sapienza' of Rome, Rome, Italy.
³² Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
³³ Center for Addiction and Mental Health, Toronto, ON, Canada.
³⁴ Division of Psychological and Social Medicine and Developmental Neurosciences, Technische Universität Dresden, Faculty of Medicine, University Hospital C.G. Carus, Dresden, Germany.
³⁵ University of New South Wales, School of Psychiatry, Sydney, NSW, Australia.
³⁶ The University of Queensland, Queensland Brain Institute and Centre for Advanced Imaging, Brisbane, QLD, Australia.
³⁷ University of California, VAMC, San Francisco, CA, USA.
³⁸ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
³⁹ Division of Cerebral Integration, National Institute for Physiological Sciences, Aichi, Japan.
⁴⁰ Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital and Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁴¹ Departments of Psychiatry and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁴² Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
⁴³ Zhumadian Psychiatry Hospital, Henan Province, China.
⁴⁴ Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
⁴⁵ Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan.
⁴⁶ Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
⁴⁷ Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
⁴⁸ School of Electrical Engineering and Computer Science, University of Newcastle, Callaghan, NSW, Australia.
⁴⁹ Health Behaviour Research Group, University of Newcastle, Callaghan, NSW, Australia.
⁵⁰ Hunter Medical Research Institute, Newcastle, NSW, Australia.
⁵¹ National Institute of Mental Health, Klecany, Czech Republic.
⁵² Third Faculty of Medicine, Charles University, Prague, Czech Republic.
⁵³ University of Western Australia, Perth, WA, Australia.
⁵⁴ Erasmus University Medical Center, Rotterdam, The Netherlands.
⁵⁵ Laboratory for Neuroimaging, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt/Main, Germany.
⁵⁶ Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Clayton, VIC, Australia.
⁵⁷ Department of Psychiatry, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
⁵⁸ Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁵⁹ Sunshine Coast Mind and Neuroscience Institute, University of the Sunshine Coast QLD, Australia, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
⁶⁰ Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
⁶¹ Research Group in Psychiatry (GIPSI), Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Mood Disorder Program, Hospital Universitario San Vicente Fundación, Medellín, Colombia.
⁶² Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁶³ University of Iowa, Iowa City, IA, USA.
⁶⁴ VABHS, Harvard Medical School, Boston, MA, USA.
⁶⁵ Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
⁶⁶ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
⁶⁷ The University of Texas Health Science Center at Houston, Houston, TX, USA.
⁶⁸ Harvard Medical School and Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess, Medical Center, Boston, MA, USA.
⁶⁹ The University of Newcastle, Newcastle, NSW, Australia.
⁷⁰ Schizophrenia Research Institute, Sydney, NSW, Australia.
⁷¹ 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.
⁷² Centre for Neural Engineering (CfNE), Department of Electrical and Electronic Engineering, University of Melbourne, Parkville, VIC, Australia.
⁷³ The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
⁷⁴ Instituto de Alta Tecnología Médica, Medellín, Colombia.
⁷⁵ School of Biomedical Sciences, Faculty of Health, the University of Newcastle, Callaghan, NSW, Australia.
⁷⁶ Priority Centre for Brain and Mental Health Research, The University of Newcastle, Newcastle, NSW, Australia.
⁷⁷ SU/UCT MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa.
⁷⁸ Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, VIC, Australia.
⁷⁹ Neuroscience Research Australia, Sydney, NSW, Australia.
⁸⁰ School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
⁸¹ VA Boston Healthcare System, Boston, MA, USA.
⁸² Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
⁸³ Department of Psychiatry and MRC Unit on Anxiety and Stress Disorders, University of Cape Town, Cape Town, South Africa.
⁸⁴ Department of Psychiatry, School of Clinical Sciences, Monash University and Monash Health, Clayton, VIC, Australia.
⁸⁵ Chongqing Three Gorges Central Hospital, Chongqing, China.
⁸⁶ Department of Psychology, University of Oslo, Oslo, Norway.
⁸⁷ Neuroimaging Unit, Technological Facilities, Valdecilla Biomedical Research Institute IDIVAL, Santander, Spain.
⁸⁸ Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
⁸⁹ Research Group in Psychiatry (GIPSI), Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellín, Colombia.
⁹⁰ Neuropsychiatry Unit, Royal Melbourne Hospital, Parkville, VIC, Australia.
⁹¹ Kimel Family Translational Imaging-Genetics Research Laboratory, Campbell Family Mental Health Research Institute, CAMH Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁹² Luoyang Fifth People's Hospital, Henan Province, China.
⁹³ Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁹⁴ Department of Computer Science and Electrical Engineering, University of Maryland, Baltimore, MD, USA.
⁹⁵ School of Psychology, Shaanxi Normal University and Key Laboratory for Behavior and Cognitive Neuroscience of Shaanxi Province, Xi'an, Shaanxi, China.
⁹⁶ Psychology Department & Neuroscience Institute, Georgia State University, Atlanta, GA, USA.

PMID: 29038599
PMCID: PMC5984078
DOI: 10.1038/mp.2017.170

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.

PubMed Disclaimer

Conflict of interest statement

CSW is on an advisory board for Lundbeck, Australia Pty Ltd and in collaboration with Astellas Pharma Inc., Japan (no conflict of interest). The remaining authors declare no conflict of interest.

Figures

**Figure 1**
(a) Fractional anisotropy (FA) differences between schizophrenia patients and healthy controls for 25 white matter (WM) regions representing major fasciculi. Gradient bar indicates Cohen’s d effect sizes after meta-analysis. (b) Cohen’s d effect sizes after meta-analysis, sorted in increasing magnitude of Cohen’s d effect sizes across 29 cohorts for FA differences in schizophrenia patients (N=1963) versus healthy controls (N=2359), after including age, sex, age × sex, age² and age² × sex as covariates. Error bars represent 95% confidence intervals. Significant regions after adjusting for multiple regions tested (P<0.05/25=0.002) are highlighted in orange. (c) Forest plot of effect sizes for 29 cohorts. Interactive three-dimensional (3D) visualization of the results is available at www.enigma-viewer.org.

**Figure 2**
(a) Cohen’s d effect sizes, after meta-analysis, for fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) differences in schizophrenia patients versus healthy controls, after including age, sex, age × sex, age² and age² × sex as covariates for the top four regions of interest (ROIs) showing the largest FA effects (average FA, body of corpus callosum (BCC), corpus callosum (CC), anterior corona radiata (ACR) and genu of corpus callosum (GCC)). Error bars represent the 95% confidence intervals. The corpus callosum, ACR and FA across the whole brain are among the measures that show most robust effects in cohorts worldwide. (b) Relationship between FA and diffusivity (mean, axial and radial) Cohen’s d effect sizes after meta-analysis for differences between schizophrenia patients and healthy controls. The effect of RD is highly correlated, whereas axial diffusivity (AD) shows no correlation and low effect sizes.

See this image and copyright information in PMC

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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LinkOut - more resources

Full Text Sources

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