title: Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium.
abstract: The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
authors.forename: T G M
authors.initials: TG
authors.lastname: van Erp
authors.affiliation: Imaging Genetics Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Hibar
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Rasmussen
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.|Olin Neuropsychiatric Research Center, Institute of Living, Hartford, CT, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Glahn
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.|Olin Neuropsychiatric Research Center, Institute of Living, Hartford, CT, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Pearlson
authors.affiliation: Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: O A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.|Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Agartz
authors.affiliation: Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: L T
authors.initials: LT
authors.lastname: Westlye
authors.affiliation: Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: U K
authors.initials: UK
authors.lastname: Haukvik
authors.affiliation: MMIL, Department of Radiology, University of California, San Diego, CA, USA.|Department of Cognitive Science, Neurosciences and Psychiatry, University of California, San Diego, CA, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: I
authors.initials: I
authors.lastname: Melle
authors.affiliation: Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: C B
authors.initials: CB
authors.lastname: Hartberg
authors.affiliation: Department of Psychiatry, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Gruber
authors.affiliation: Department of Psychiatry, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kraemer
authors.affiliation: Department of Psychiatry, University Medical Center Göttingen, Göttingen, Germany.|Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg August University, Göttingen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Zilles
authors.affiliation: Cognitive Genetics and Therapy Group, School of Psychology, National University of Ireland, Galway, Ireland.|Neuropsychiatric Genetics research group, Department of Psychiatry and Trinity College Institute of Psychiatry, Trinity College, Dublin, Ireland.
authors.forename: G
authors.initials: G
authors.lastname: Donohoe
authors.affiliation: Imaging Genetics Center, University of Southern California, Los Angeles, CA, USA.|Neuropsychiatric Genetics research group, Department of Psychiatry and Trinity College Institute of Psychiatry, Trinity College, Dublin, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Kelly
authors.affiliation: Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Ireland.
authors.forename: C
authors.initials: C
authors.lastname: McDonald
authors.affiliation: Cognitive Genetics and Therapy Group, School of Psychology, National University of Ireland, Galway, Ireland.|Neuropsychiatric Genetics research group, Department of Psychiatry and Trinity College Institute of Psychiatry, Trinity College, Dublin, Ireland.
authors.forename: D W
authors.initials: DW
authors.lastname: Morris
authors.affiliation: Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Ireland.
authors.forename: D M
authors.initials: DM
authors.lastname: Cannon
authors.affiliation: Neuropsychiatric Genetics research group, Department of Psychiatry and Trinity College Institute of Psychiatry, Trinity College, Dublin, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Corvin
authors.affiliation: Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M W J
authors.initials: MW
authors.lastname: Machielsen
authors.affiliation: Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Koenders
authors.affiliation: Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: de Haan
authors.affiliation: University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Satterthwaite
authors.affiliation: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Wolf
authors.affiliation: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Gur
authors.affiliation: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Gur
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Potkin
authors.affiliation: Department of Psychiatry, University of California, San Francisco, CA, USA.|San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Mathalon
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Mueller
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
authors.forename: A
authors.identifier: http://orcid.org/0000-0003-3373-2438
authors.initials: A
authors.lastname: Preda
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Macciardi
authors.affiliation: Translational Developmental Neuroscience Section, Department of Child and Adolescent Psychiatry, Technische Universität, Dresden, Germany.|Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.|MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ehrlich
authors.affiliation: Translational Developmental Neuroscience Section, Department of Child and Adolescent Psychiatry, Technische Universität, Dresden, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Walton
authors.affiliation: Translational Developmental Neuroscience Section, Department of Child and Adolescent Psychiatry, Technische Universität, Dresden, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hass
authors.affiliation: Mind Research Network, Albuquerque, NM, USA.|Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA.
authors.forename: V D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: Mind Research Network, Albuquerque, NM, USA.|Advanced Biomedical Informatics Group, LLC, Iowa City, IA, USA.|The University of Iowa, Iowa City, IA, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Bockholt
authors.affiliation: Minneapolis VA Healthcare System & Department of Psychiatry, University of Minnesota, Twin Cities, MN, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Sponheim
authors.affiliation: Mind Research Network, Albuquerque, NM, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Shoemaker
authors.affiliation: Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: N E M
authors.initials: NE
authors.lastname: van Haren
authors.affiliation: Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H E
authors.initials: HE
authors.lastname: Hulshoff Pol
authors.affiliation: Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H E H
authors.initials: HE
authors.lastname: Pol
authors.affiliation: Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.|Center for Neurobehavioral Genetics, University of California, Los Angeles, CA, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Ophoff
authors.affiliation: Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: R S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander, Spain.|CIBERSAM, Centro Investigación Biomédica en Red de Salud Mental, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Roiz-Santiañez
authors.affiliation: Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander, Spain.|CIBERSAM, Centro Investigación Biomédica en Red de Salud Mental, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Crespo-Facorro
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Northwestern University, Evanston, IL, USA.|Department of Radiology, Northwestern University Feinberg School of Medicine, Northwestern University, Evanston, IL, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Northwestern University, Evanston, IL, USA.
authors.forename: K I
authors.initials: KI
authors.lastname: Alpert
authors.affiliation: Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: E G
authors.initials: EG
authors.lastname: Jönsson
authors.affiliation: Division of Psychiatry, University of Edinburgh Medical School, Edinburgh, UK.
authors.forename: R
authors.initials: R
authors.lastname: Dimitrova
authors.affiliation: Division of Psychiatry, University of Edinburgh Medical School, Edinburgh, UK.
authors.forename: C
authors.initials: C
authors.lastname: Bois
authors.affiliation: Division of Psychiatry, University of Edinburgh Medical School, Edinburgh, UK.
authors.forename: H C
authors.initials: HC
authors.lastname: Whalley
authors.affiliation: Division of Psychiatry, University of Edinburgh Medical School, Edinburgh, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: McIntosh
authors.affiliation: Division of Psychiatry, University of Edinburgh Medical School, Edinburgh, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Lawrie
authors.affiliation: Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan.
authors.forename: R
authors.identifier: http://orcid.org/0000-0002-5941-4238
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Imaging Genetics Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Mind Research Network, Albuquerque, NM, USA.|Departments of Psychology and Neuroscience, Georgia State University, Atlanta, GA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Turner
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D011446:Prospective Studies; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology*