title: Patterns of Gray Matter Abnormalities in Schizophrenia Based on an International Mega-analysis.
abstract: Analyses of gray matter concentration (GMC) deficits in patients with schizophrenia (Sz) have identified robust changes throughout the cortex. We assessed the relationships between diagnosis, overall symptom severity, and patterns of gray matter in the largest aggregated structural imaging dataset to date. We performed both source-based morphometry (SBM) and voxel-based morphometry (VBM) analyses on GMC images from 784 Sz and 936 controls (Ct) across 23 scanning sites in Europe and the United States. After correcting for age, gender, site, and diagnosis by site interactions, SBM analyses showed 9 patterns of diagnostic differences. They comprised separate cortical, subcortical, and cerebellar regions. Seven patterns showed greater GMC in Ct than Sz, while 2 (brainstem and cerebellum) showed greater GMC for Sz. The greatest GMC deficit was in a single pattern comprising regions in the superior temporal gyrus, inferior frontal gyrus, and medial frontal cortex, which replicated over analyses of data subsets. VBM analyses identified overall cortical GMC loss and one small cluster of increased GMC in Sz, which overlapped with the SBM brainstem component. We found no significant association between the component loadings and symptom severity in either analysis. This mega-analysis confirms that the commonly found GMC loss in Sz in the anterior temporal lobe, insula, and medial frontal lobe form a single, consistent spatial pattern even in such a diverse dataset. The separation of GMC loss into robust, repeatable spatial patterns across multiple datasets paves the way for the application of these methods to identify subtle genetic and clinical cohort effects.
authors.affiliation: The Mind Research Network, Albuquerque, NM;
authors.forename: Cota Navin
authors.initials: CN
authors.lastname: Gupta
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: The Mind Research Network, Albuquerque, NM;
authors.forename: Srinivas
authors.initials: S
authors.lastname: Rachakonda
authors.affiliation: The Mind Research Network, Albuquerque, NM;
authors.forename: Jiayu
authors.initials: J
authors.lastname: Chen
authors.affiliation: The Mind Research Network, Albuquerque, NM;
authors.forename: Veena
authors.initials: V
authors.lastname: Patel
authors.affiliation: The Mind Research Network, Albuquerque, NM; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM;
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liu
authors.affiliation: The Mind Research Network, Albuquerque, NM;
authors.forename: Judith
authors.initials: J
authors.lastname: Segall
authors.affiliation: Department of Psychiatry and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Zwiers
authors.affiliation: Department of Psychiatry and Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands;
authors.forename: Alejandro
authors.initials: A
authors.lastname: Arias-Vasquez
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;
authors.forename: Jan
authors.initials: J
authors.lastname: Buitelaar
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; Department of Language and Genetics, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands;
authors.forename: Simon E
authors.initials: SE
authors.lastname: Fisher
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;
authors.forename: Guillen
authors.initials: G
authors.lastname: Fernandez
authors.affiliation: Department of Psychiatry & Human Behavior, School of Medicine, University of California, Irvine, CA;
authors.forename: Theo G M
authors.initials: TG
authors.lastname: van Erp
authors.affiliation: Department of Psychiatry & Human Behavior, School of Medicine, University of California, Irvine, CA;
authors.forename: Steven
authors.initials: S
authors.lastname: Potkin
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Francisco, CA;
authors.forename: Judith
authors.initials: J
authors.lastname: Ford
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Francisco, CA;
authors.forename: Daniel
authors.initials: D
authors.lastname: Mathalon
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, CA;
authors.forename: Sarah
authors.initials: S
authors.lastname: McEwen
authors.affiliation: Division of Electronics and Information Engineering, Chonbuk National University, Jeonju, Korea;
authors.forename: Hyo Jong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN;
authors.forename: Bryon A
authors.initials: BA
authors.lastname: Mueller
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA;
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Greve
authors.affiliation: NORMENT, KG Jebsen Center for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway;
authors.forename: Ole
authors.initials: O
authors.lastname: Andreassen
authors.affiliation: NORMENT, KG Jebsen Center for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Research, Diakonhjemmet Hospital, Oslo, Norway;
authors.forename: Ingrid
authors.initials: I
authors.lastname: Agartz
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA; Department of Psychiatry, Massachusetts General Hospital, HMS, Boston, MA;
authors.forename: Randy L
authors.initials: RL
authors.lastname: Gollub
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN; Minneapolis VA Healthcare System, Minneapolis, MN;
authors.forename: Scott R
authors.initials: SR
authors.lastname: Sponheim
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA; Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany;
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehrlich
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL; Department of Radiology, Northwestern University, Chicago, IL;
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University, New Haven, CT; Institute of Living, Hartford Healthcare Corporation, Hartford, CT; Department of Neurobiology, School of Medicine, Yale University, New Haven, CT;
authors.forename: Godfrey
authors.initials: G
authors.lastname: Pearlson
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University, New Haven, CT; Institute of Living, Hartford Healthcare Corporation, Hartford, CT;
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University, New Haven, CT; Institute of Living, Hartford Healthcare Corporation, Hartford, CT;
authors.forename: Emma
authors.initials: E
authors.lastname: Sprooten
authors.affiliation: The Mind Research Network, Albuquerque, NM;
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Mayer
authors.affiliation: The Mind Research Network, Albuquerque, NM;
authors.forename: Julia
authors.initials: J
authors.lastname: Stephen
authors.affiliation: Department of Neurosurgery, University of New Mexico Health Sciences Center, Albuquerque, NM;
authors.forename: Rex E
authors.initials: RE
authors.lastname: Jung
authors.affiliation: University of New Mexico Health Sciences Center, Albuquerque, NM; Department of Psychiatry, University of New Mexico, Albuquerque, NM; Raymond G. Murphy VA Medical Center, Albuquerque, NM;
authors.forename: Jose
authors.initials: J
authors.lastname: Canive
authors.affiliation: University of New Mexico Health Sciences Center, Albuquerque, NM; Department of Psychiatry, University of New Mexico, Albuquerque, NM;
authors.forename: Juan
authors.initials: J
authors.lastname: Bustillo
authors.affiliation: The Mind Research Network, Albuquerque, NM; Department of Psychology and Neuroscience Institute, Georgia State University, Atlanta, GA jturner@mrn.org.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Turner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000473:pathology*; D012720:Severity of Illness Index; D055815:Young Adult
keywords: independent component analysis; schizophrenia; source-based morphometry; symptoms; voxel-based morphometry