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Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder

SMC. de Zwarte, RM. Brouwer, I. Agartz, M. Alda, S. Alonso-Lana, CE. Bearden, A. Bertolino, A. Bonvino, E. Bramon, EEL. Buimer, W. Cahn, EJ. Canales-Rodríguez, DM. Cannon, TD. Cannon, X. Caseras, J. Castro-Fornieles, Q. Chen, Y. Chung, E. De la...

. 2022 ; 43 (1) : 414-430. [pub] 20201007

Language English Country United States

Document type Journal Article, Meta-Analysis, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.

Persistent link   https://www.medvik.cz/link/bmc22011483

Grant support
I01 CX000227 CSRD VA - United States
32003B_156914 Swiss National Science Foundation - Switzerland
G0901310 Medical Research Council - United Kingdom
G0801418 Medical Research Council - United Kingdom
R01 MH116147 NIMH NIH HHS - United States
P30 NS076408 NINDS NIH HHS - United States
R01MH121246 NIH HHS - United States
U01 MH108150 NIMH NIH HHS - United States
I01CX000227 VA - United States
P41 EB015922 NIBIB NIH HHS - United States
091630 Wellcome Trust - United Kingdom
P41 EB027061 NIBIB NIH HHS - United States
064971 Wellcome Trust - United Kingdom
R01 MH118695 NIMH NIH HHS - United States
1S10OD017974-01 NIH HHS - United States
S10 OD017974 NIH HHS - United States
MR/L010305/1 Medical Research Council - United Kingdom
U54EB020403 NIH HHS - United States
R01 MH111671 NIMH NIH HHS - United States
NIHR200756 Department of Health - United Kingdom
R01 MH113619 NIMH NIH HHS - United States
P30 NS076408 NIH HHS - United States
T32 AG058507 NIA NIH HHS - United States
P41 EB015922 NIH HHS - United States
U54 EB020403 NIBIB NIH HHS - United States
R01 MH117601 NIMH NIH HHS - United States
T32AG058507 NIA NIH HHS - United States
R03 MH105808 NIH HHS - United States
085475/B/08/Z Wellcome Trust - United Kingdom
R01 MH121246 NIMH NIH HHS - United States
Wellcome Trust - United Kingdom
103703 Wellcome Trust - United Kingdom
106469, 142255 CIHR - Canada
R01 MH116147 NIH HHS - United States
085475/Z/08/Z Wellcome Trust - United Kingdom
R01 MH117601 NIH HHS - United States
R01 MH111671 NIH HHS - United States
R03 MH105808 NIMH NIH HHS - United States
R01 MH085667 NIMH NIH HHS - United States
R01 MH052857 NIMH NIH HHS - United States
R01 MH080912 NIMH NIH HHS - United States

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

APHP Mondor University Hospitals Créteil France

Bipolar and Depressive Disorders Unit Hospital Clinic University of Barcelona Barcelona Spain

Boys Town National Research Hospital Omaha NE USA

Cardiff University Brain Research Imaging Centre Cardiff University Cardiff UK

Center for Neurobehavioral Genetics University of California Los Angeles California USA

Center for the Neurobiology of Learning and Memory University of California Irvine Irvine California USA

Centre for Affective Disorders Department of Psychological Medicine Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Centre for Neuroimaging and Cognitive Genomics Clinical Neuroimaging Laboratory NCBES Galway Neuroscience Centre College of Medicine Nursing and Health Sciences National University of Ireland Galway Galway Ireland

Centre for Psychiatry Research Department of Clinical Neuroscience Karolinska Institutet and Stockholm Health Care Services Stockholm Region Stockholm Sweden

Child and Adolescent Psychiatry Department Hospital General Universitario Gregorio Marañón School of Medicine Universidad Complutense Madrid Spain

CIBERSAM Madrid Spain

Cigli State Hospital Department of Psychiatry Izmir Turkey

Clinical Translational Neuroscience Laboratory Department of Psychiatry and Human Behavior University of California Irvine Irvine California USA

Department of Basic and Clinical Neuroscience Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Department of Basic Medical Science Neuroscience and Sense Organs University of Bari 'Aldo Moro' Bari Italy

Department of Child and Adolescent Psychiatry and Psychology 2017SGR881 Institute of Neuroscience Hospital Clínic of Barcelona Barcelona Spain

Department of Child and Adolescent Psychiatry Psychology Erasmus University Medical Center Sophia Children's Hospital Rotterdam Netherlands

Department of Forensic and Neurodevelopmental Science Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden

Department of Neuroradiology Karolinska University Hospital Stockholm Sweden

Department of Neurosciences Health Sciences Institute Dokuz Eylül University Izmir Turkey

Department of Psychiatry 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Psychiatry and Behavioral Sciences Mercer University School of Medicine Macon Georgia USA

Department of Psychiatry and Behavioral Sciences The University of Texas Health Science Center at Houston Houston Texas USA

Department of Psychiatry and Behavioral Sciences University of Minnesota Minneapolis Minnesota USA

Department of Psychiatry and Behavioral Sciences University of New Mexico Albuquerque New Mexico USA

Department of Psychiatry and Biobehavioral Science University of California Los Angeles California USA

Department of Psychiatry and Neuropsychology School for Mental Health and Neuroscience Maastricht University Medical Centre Maastricht University Maastricht Netherlands

Department of Psychiatry and Psychology Mayo Clinic Rochester Minnesota USA

Department of Psychiatry and Psychotherapy Central Institute of Mental Health Medical Faculty Mannheim University of Heidelberg Mannheim Germany

Department of Psychiatry Dalhousie University Halifax Nova Scotia Canada

Department of Psychiatry Diakonhjemmet Hospital Oslo Norway

Department of Psychiatry Faculty of Medicine Dokuz Eylül University Izmir Turkey

Department of Psychiatry Faculty of Medicine Izmir Katip Çelebi University Izmir Turkey

Department of Psychiatry Faculty of Medicine University of Geneva Geneva Switzerland

Department of Psychiatry Icahn School of Medicine at Mount Sinai New York New York USA

Department of Psychiatry University Medical Center Utrecht Brain Center University Medical Center Utrecht Utrecht University Utrecht Netherlands

Department of Psychiatry Yale University School of Medicine New Haven Connecticut USA

Department of Psychology and Center for Magnetic Resonance Research University of Minnesota Minneapolis Minnesota USA

Department of Psychology and Graduate Department of Psychological Clinical Science University of Toronto Toronto Ontario Canada

Department of Psychology Bilkent University Ankara Turkey

Department of Psychology Faculty of Arts Dokuz Eylül University İzmir Turkey

Department of Psychology University of California California Los Angeles USA

Department of Psychology Yale University New Haven Connecticut USA

Departments of Neurology and Radiology Johns Hopkins University School of Medicine Baltimore Maryland USA

Division of Mental Health and Addiction Oslo University Hospital Oslo Norway

Division of Psychiatry Neuroscience in Mental Health Research Department University College London London UK

Division of Psychiatry Royal Edinburgh Hospital University of Edinburgh Edinburgh UK

Early Psychosis Interventions and Clinical detection lab Department of Psychosis Studies Institute of Psychiatry Psychology and Neuroscience King's College London London UK

FIDMAG Germanes Hospitalàries Research Foundation Barcelona Spain

Harvard Medical School Boston Massachusetts USA

Imaging Genetics Center Mark and Mary Stevens Neuroimaging and Informatics Institute Keck School of Medicine University of Southern California Marina del Rey California USA

INSERM U955 Team 15 Translational Psychiatry Créteil France

Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona Spain

Institute of Psychiatry Psychology and Neuroscience King's College London London UK

IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo Italy

Lieber Institute for Brain Development Johns Hopkins Medical Campus Baltimore Maryland USA

Minneapolis VA Health Care System Minneapolis Minnesota USA

MRC Centre for Neuropsychiatric Genetics and Genomics Cardiff University Cardiff UK

National Institute of Mental Health Klecany Czech Republic

Neuroscience Research Australia Sydney Australia

NeuroSpin neuroimaging platform Psychiatry Team UNIACT Lab CEA Saclay Gif Sur Yvette France

Norwegian Centre for Mental Disorders Research Institute of Clinical Medicine University of Oslo Oslo Norway

Olin Neuropsychiatry Research Center Institute of Living Hartford Hospital Hartford Connecticut USA

Psychosis Studies Institute of Psychiatry Psychology and Neuroscience King's College London London UK

Research Division of Mind and Brain Department of Psychiatry and Psychotherapy Charité Universitätsmedizin Berlin Freie Universität Berlin Humboldt Universität zu Berlin and Berlin Institute of Health Berlin Germany

School of Medical Sciences University of New South Wales Sydney Australia

School of Medicine Universitat Internacional de Catalunya Barcelona Spain

School of Psychiatry University of New South Wales Sydney Australia

Section for Experimental Psychopathology and Neuroimaging Department of General Psychiatry University of Heidelberg Heidelberg Germany

Section for Neuroscience Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden

Semel Institute for Neuroscience and Human Behavior University of California California Los Angeles USA

SoCAT LAB Department of Psychiatry School of Medicine Ege University Izmir Turkey

Tommy Fuss Center for Neuropsychiatric Disease Research Boston Children's Hospital Boston Massachusetts USA

University of Barcelona Barcelona Spain

References provided by Crossref.org

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$a Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder / $c SMC. de Zwarte, RM. Brouwer, I. Agartz, M. Alda, S. Alonso-Lana, CE. Bearden, A. Bertolino, A. Bonvino, E. Bramon, EEL. Buimer, W. Cahn, EJ. Canales-Rodríguez, DM. Cannon, TD. Cannon, X. Caseras, J. Castro-Fornieles, Q. Chen, Y. Chung, E. De la Serna, C. Del Mar Bonnin, C. Demro, A. Di Giorgio, GE. Doucet, MC. Eker, S. Erk, M. Fatjó-Vilas, SC. Fears, SF. Foley, S. Frangou, JM. Fullerton, DC. Glahn, VM. Goghari, JM. Goikolea, AL. Goldman, AS. Gonul, O. Gruber, T. Hajek, EL. Hawkins, A. Heinz, C. Hidiroglu Ongun, MHJ. Hillegers, J. Houenou, HE. Hulshoff Pol, CM. Hultman, M. Ingvar, V. Johansson, EG. Jönsson, F. Kane, MJ. Kempton, MMG. Koenis, M. Kopecek, B. Krämer, SM. Lawrie, RK. Lenroot, M. Marcelis, VS. Mattay, C. McDonald, A. Meyer-Lindenberg, S. Michielse, PB. Mitchell, D. Moreno, RM. Murray, B. Mwangi, L. Nabulsi, J. Newport, CA. Olman, J. van Os, BJ. Overs, A. Ozerdem, G. Pergola, MM. Picchioni, C. Piguet, E. Pomarol-Clotet, J. Radua, IS. Ramsay, A. Richter, G. Roberts, R. Salvador, A. Saricicek Aydogan, S. Sarró, PR. Schofield, EM. Simsek, F. Simsek, JC. Soares, SR. Sponheim, G. Sugranyes, T. Toulopoulou, G. Tronchin, E. Vieta, H. Walter, DR. Weinberger, HC. Whalley, MJ. Wu, N. Yalin, OA. Andreassen, CRK. Ching, SI. Thomopoulos, TGM. van Erp, N. Jahanshad, PM. Thompson, RS. Kahn, NEM. van Haren
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$a First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.
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$a Mwangi, Benson $u Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, Texas, USA
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$a Nabulsi, Leila $u Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland
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$a Newport, Jason $u Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada
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$a Olman, Cheryl A $u Department of Psychology and Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, USA
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$a van Os, Jim $u Department of Psychiatry, University Medical Center Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands $u Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht University, Maastricht, Netherlands
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$a Overs, Bronwyn J $u Neuroscience Research Australia, Sydney, Australia
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$a Ozerdem, Aysegul $u Department of Psychiatry, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey $u Department of Neurosciences, Health Sciences Institute, Dokuz Eylül University, Izmir, Turkey $u Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA
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$a Pergola, Giulio $u Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy $1 https://orcid.org/0000000291931841
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$a Picchioni, Marco M $u Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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$a Piguet, Camille $u INSERM U955 Team 15 "Translational Psychiatry", Créteil, France $u NeuroSpin neuroimaging platform, Psychiatry Team, UNIACT Lab, CEA Saclay, Gif-Sur-Yvette, France $u Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland $u School of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain
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$a Pomarol-Clotet, Edith $u FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain $u CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Madrid, Spain $1 https://orcid.org/0000000281598563
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$a Radua, Joaquim $u Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden $u CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Madrid, Spain $u Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain $u Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK $1 https://orcid.org/0000000312405438
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$a Richter, Anja $u Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany
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$a Roberts, Gloria $u School of Psychiatry, University of New South Wales, Sydney, Australia
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$a Salvador, Raymond $u FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain $u CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Madrid, Spain $1 https://orcid.org/0000000155571562
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$a Saricicek Aydogan, Aybala $u Department of Neurosciences, Health Sciences Institute, Dokuz Eylül University, Izmir, Turkey $u Department of Psychiatry, Faculty of Medicine, Izmir Katip Çelebi University, Izmir, Turkey $1 https://orcid.org/0000000289627269
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$a Schofield, Peter R $u School of Medical Sciences, University of New South Wales, Sydney, Australia $u Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut, USA $1 https://orcid.org/0000000329679662
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$a Sugranyes, Gisela $u CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Madrid, Spain $u Department of Child and Adolescent Psychiatry and Psychology, 2017SGR881, Institute of Neuroscience, Hospital Clínic of Barcelona, Barcelona, Spain $u Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain $u University of Barcelona, Barcelona, Spain $1 https://orcid.org/0000000225457862
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$a Toulopoulou, Timothea $u Department of Psychology, Bilkent University, Ankara, Turkey $u Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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$a Tronchin, Giulia $u Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland
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$a Walter, Henrik $u Research Division of Mind and Brain, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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$a Weinberger, Daniel R $u Bipolar and Depressive Disorders Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
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$a Whalley, Heather C $u Department of Psychology, Faculty of Arts, Dokuz Eylül University, İzmir, Turkey
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$a Wu, Mon-Ju $u Department of Psychology and Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, USA
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$a Yalin, Nefize $u Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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$a Andreassen, Ole A $u Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway $u Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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