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

Sonja M C de Zwarte¹, Rachel M Brouwer¹, Ingrid Agartz^{2

3

4}, Martin Alda^{5

6}, Silvia Alonso-Lana^{7

8}, Carrie E Bearden^{9

10}, Alessandro Bertolino¹¹, Aurora Bonvino¹¹, Elvira Bramon¹², Elizabeth E L Buimer¹, Wiepke Cahn¹, Erick J Canales-Rodríguez^{7

8}, Dara M Cannon¹³, Tyrone D Cannon^{14

15}, Xavier Caseras¹⁶, Josefina Castro-Fornieles^{8

17

18

19}, Qiang Chen²⁰, Yoonho Chung¹⁴, Elena De la Serna^{8

17

18

19}, Caterina Del Mar Bonnin^{8

18

21}, Caroline Demro²², Annabella Di Giorgio²³, Gaelle E Doucet^{24

25}, Mehmet Cagdas Eker²⁶, Susanne Erk²⁷, Mar Fatjó-Vilas^{7

8}, Scott C Fears^{28

29}, Sonya F Foley³⁰, Sophia Frangou²⁴, Janice M Fullerton^{31

32}, David C Glahn^{33

34

35}, Vina M Goghari³⁶, Jose M Goikolea^{8

18

21}, Aaron L Goldman²⁰, Ali Saffet Gonul^{26

37}, Oliver Gruber³⁸, Tomas Hajek^{5

6}, Emma L Hawkins³⁹, Andreas Heinz²⁶, Ceren Hidiroglu Ongun⁴⁰, Manon H J Hillegers^{1

41}, Josselin Houenou^{42

43

44}, Hilleke E Hulshoff Pol¹, Christina M Hultman⁴⁵, Martin Ingvar^{46

47}, Viktoria Johansson^{3

45}, Erik G Jönsson^{2

3}, Fergus Kane⁴⁸, Matthew J Kempton⁴⁸, Marinka M G Koenis^{15

33}, Miloslav Kopecek^{6

49}, Bernd Krämer³⁸, Stephen M Lawrie³⁹, Rhoshel K Lenroot^{31

50

51}, Machteld Marcelis⁵², Venkata S Mattay^{20

53}, Colm McDonald¹³, Andreas Meyer-Lindenberg⁵⁴, Stijn Michielse⁵², Philip B Mitchell⁵⁰, Dolores Moreno^{8

55}, Robin M Murray⁴⁸, Benson Mwangi⁵⁶, Leila Nabulsi¹³, Jason Newport⁵, Cheryl A Olman⁵⁷, Jim van Os^{1

52}, Bronwyn J Overs³¹, Aysegul Ozerdem^{58

59

60}, Giulio Pergola¹¹, Marco M Picchioni⁶¹, Camille Piguet^{43

44

62

63}, Edith Pomarol-Clotet^{7

8}, Joaquim Radua^{3

8

18

64}, Ian S Ramsay²², Anja Richter³⁸, Gloria Roberts⁵⁰, Raymond Salvador^{7

8}, Aybala Saricicek Aydogan^{59

65}, Salvador Sarró^{7

8}, Peter R Schofield^{32

33}, Esma M Simsek⁶⁶, Fatma Simsek^{26

67

66}, Jair C Soares⁵⁶, Scott R Sponheim^{22

68}, Gisela Sugranyes^{8

17

18

19}, Timothea Toulopoulou^{69

70}, Giulia Tronchin¹³, Eduard Vieta^{8

18

21}, Henrik Walter²⁷, Daniel R Weinberger²¹, Heather C Whalley⁴⁰, Mon-Ju Wu⁵⁷, Nefize Yalin⁷¹, Ole A Andreassen^{2

72}, Christopher R K Ching⁷³, Sophia I Thomopoulos⁷³, Theo G M van Erp^{74

75}, Neda Jahanshad⁷³, Paul M Thompson⁷³, René S Kahn^{1

24}, Neeltje E M van Haren^{1

41}

Affiliations

¹ Department of Psychiatry, University Medical Center Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
² Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden.
⁴ Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway.
⁵ Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
⁶ National Institute of Mental Health, Klecany, Czech Republic.
⁷ FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
⁸ CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Madrid, Spain.
⁹ Semel Institute for Neuroscience and Human Behavior, University of California, California, Los Angeles, USA.
¹⁰ Department of Psychology, University of California, California, Los Angeles, USA.
¹¹ Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.
¹² Division of Psychiatry, Neuroscience in Mental Health Research Department, University College London, London, UK.
¹³ 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.
¹⁴ Department of Psychology, Yale University, New Haven, Connecticut, USA.
¹⁵ Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
¹⁶ MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
¹⁷ Department of Child and Adolescent Psychiatry and Psychology, 2017SGR881, Institute of Neuroscience, Hospital Clínic of Barcelona, Barcelona, Spain.
¹⁸ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
¹⁹ University of Barcelona, Barcelona, Spain.
²⁰ Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
²¹ Bipolar and Depressive Disorders Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain.
²² Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, Minnesota, USA.
²³ IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
²⁴ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
²⁵ Boys Town National Research Hospital, Omaha, NE, USA.
²⁶ SoCAT LAB, Department of Psychiatry, School of Medicine, Ege University, Izmir, Turkey.
²⁷ 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.
²⁸ Department of Psychiatry and Biobehavioral Science, University of California, Los Angeles, California, USA.
²⁹ Center for Neurobehavioral Genetics, University of California, Los Angeles, California, USA.
³⁰ Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, UK.
³¹ Neuroscience Research Australia, Sydney, Australia.
³² School of Medical Sciences, University of New South Wales, Sydney, Australia.
³³ Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut, USA.
³⁴ Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, Massachusetts, USA.
³⁵ Harvard Medical School, Boston, Massachusetts, USA.
³⁶ Department of Psychology and Graduate Department of Psychological Clinical Science, University of Toronto, Toronto, Ontario, Canada.
³⁷ Department of Psychiatry and Behavioral Sciences, Mercer University School of Medicine, Macon, Georgia, USA.
³⁸ Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany.
³⁹ Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK.
⁴⁰ Department of Psychology, Faculty of Arts, Dokuz Eylül University, İzmir, Turkey.
⁴¹ Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, Netherlands.
⁴² APHP, Mondor University Hospitals, Créteil, France.
⁴³ INSERM U955 Team 15 "Translational Psychiatry", Créteil, France.
⁴⁴ NeuroSpin neuroimaging platform, Psychiatry Team, UNIACT Lab, CEA Saclay, Gif-Sur-Yvette, France.
⁴⁵ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁴⁶ Section for Neuroscience, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁴⁷ Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
⁴⁸ Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.
⁴⁹ Department of Psychiatry, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
⁵⁰ School of Psychiatry, University of New South Wales, Sydney, Australia.
⁵¹ Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, New Mexico, USA.
⁵² Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht University, Maastricht, Netherlands.
⁵³ Departments of Neurology and Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁵⁴ Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
⁵⁵ Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón (IiSGM), School of Medicine, Universidad Complutense, Madrid, Spain.
⁵⁶ Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
⁵⁷ Department of Psychology and Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, USA.
⁵⁸ Department of Psychiatry, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.
⁵⁹ Department of Neurosciences, Health Sciences Institute, Dokuz Eylül University, Izmir, Turkey.
⁶⁰ Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.
⁶¹ Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁶² Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
⁶³ School of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain.
⁶⁴ Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁶⁵ Department of Psychiatry, Faculty of Medicine, Izmir Katip Çelebi University, Izmir, Turkey.
⁶⁶ Cigli State Hospital, Department of Psychiatry, Izmir, Turkey.
⁶⁷ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁶⁸ Minneapolis VA Health Care System, Minneapolis, Minnesota, USA.
⁶⁹ Department of Psychology, Bilkent University, Ankara, Turkey.
⁷⁰ Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁷¹ Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁷² Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁷³ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA.
⁷⁴ Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California, USA.
⁷⁵ Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, California, USA.

PMID: 33027543
PMCID: PMC8675411
DOI: 10.1002/hbm.25206

Meta-Analysis

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

Sonja M C de Zwarte et al. Hum Brain Mapp. 2022 Jan.

. 2022 Jan;43(1):414-430.

doi: 10.1002/hbm.25206. Epub 2020 Oct 7.

Authors

Affiliations

¹ Department of Psychiatry, University Medical Center Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
² Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden.
⁴ Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway.
⁵ Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
⁶ National Institute of Mental Health, Klecany, Czech Republic.
⁷ FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
⁸ CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Madrid, Spain.
⁹ Semel Institute for Neuroscience and Human Behavior, University of California, California, Los Angeles, USA.
¹⁰ Department of Psychology, University of California, California, Los Angeles, USA.
¹¹ Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.
¹² Division of Psychiatry, Neuroscience in Mental Health Research Department, University College London, London, UK.
¹³ 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.
¹⁴ Department of Psychology, Yale University, New Haven, Connecticut, USA.
¹⁵ Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
¹⁶ MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
¹⁷ Department of Child and Adolescent Psychiatry and Psychology, 2017SGR881, Institute of Neuroscience, Hospital Clínic of Barcelona, Barcelona, Spain.
¹⁸ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
¹⁹ University of Barcelona, Barcelona, Spain.
²⁰ Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
²¹ Bipolar and Depressive Disorders Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain.
²² Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, Minnesota, USA.
²³ IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
²⁴ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
²⁵ Boys Town National Research Hospital, Omaha, NE, USA.
²⁶ SoCAT LAB, Department of Psychiatry, School of Medicine, Ege University, Izmir, Turkey.
²⁷ 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.
²⁸ Department of Psychiatry and Biobehavioral Science, University of California, Los Angeles, California, USA.
²⁹ Center for Neurobehavioral Genetics, University of California, Los Angeles, California, USA.
³⁰ Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, UK.
³¹ Neuroscience Research Australia, Sydney, Australia.
³² School of Medical Sciences, University of New South Wales, Sydney, Australia.
³³ Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut, USA.
³⁴ Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, Massachusetts, USA.
³⁵ Harvard Medical School, Boston, Massachusetts, USA.
³⁶ Department of Psychology and Graduate Department of Psychological Clinical Science, University of Toronto, Toronto, Ontario, Canada.
³⁷ Department of Psychiatry and Behavioral Sciences, Mercer University School of Medicine, Macon, Georgia, USA.
³⁸ Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany.
³⁹ Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK.
⁴⁰ Department of Psychology, Faculty of Arts, Dokuz Eylül University, İzmir, Turkey.
⁴¹ Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, Netherlands.
⁴² APHP, Mondor University Hospitals, Créteil, France.
⁴³ INSERM U955 Team 15 "Translational Psychiatry", Créteil, France.
⁴⁴ NeuroSpin neuroimaging platform, Psychiatry Team, UNIACT Lab, CEA Saclay, Gif-Sur-Yvette, France.
⁴⁵ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁴⁶ Section for Neuroscience, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁴⁷ Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
⁴⁸ Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.
⁴⁹ Department of Psychiatry, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
⁵⁰ School of Psychiatry, University of New South Wales, Sydney, Australia.
⁵¹ Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, New Mexico, USA.
⁵² Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht University, Maastricht, Netherlands.
⁵³ Departments of Neurology and Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁵⁴ Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
⁵⁵ Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón (IiSGM), School of Medicine, Universidad Complutense, Madrid, Spain.
⁵⁶ Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
⁵⁷ Department of Psychology and Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, USA.
⁵⁸ Department of Psychiatry, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.
⁵⁹ Department of Neurosciences, Health Sciences Institute, Dokuz Eylül University, Izmir, Turkey.
⁶⁰ Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.
⁶¹ Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁶² Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
⁶³ School of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain.
⁶⁴ Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁶⁵ Department of Psychiatry, Faculty of Medicine, Izmir Katip Çelebi University, Izmir, Turkey.
⁶⁶ Cigli State Hospital, Department of Psychiatry, Izmir, Turkey.
⁶⁷ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁶⁸ Minneapolis VA Health Care System, Minneapolis, Minnesota, USA.
⁶⁹ Department of Psychology, Bilkent University, Ankara, Turkey.
⁷⁰ Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁷¹ Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁷² Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁷³ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA.
⁷⁴ Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California, USA.
⁷⁵ Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, California, USA.

PMID: 33027543
PMCID: PMC8675411
DOI: 10.1002/hbm.25206

Abstract

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.

Keywords: bipolar disorder; education; intelligence; neuroimaging; relatives; schizophrenia.

PubMed Disclaimer

Conflict of interest statement

Dr Yalin has been an investigator in clinical studies conducted together with Janssen‐Cilag, Corcept Therapeutics, and COMPASS Pathways in the last 3 years. Dr Cannon reports that he is a consultant to Boerhinger Ingelheim Pharmaceuticals and Lundbeck A/S. Dr Meyer‐Lindenberg has received consultant fees from Boehringer Ingelheim, BrainsWay, Elsevier, Lundbeck International Neuroscience Foundation, and Science Advances. Drs Ching, Jahanshad, and Thompson received partial research support from Biogen, Inc. (Boston, MA) for work unrelated to the topic of this manuscript. Dr Vieta has received grants and served as consultant, advisor or CME speaker for the following entities (work unrelated to the topic of this manuscript): AB‐Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Galenica, Janssen, Lundbeck, Novartis, Otsuka, Sage, Sanofi‐Aventis, and Takeda. The remaining authors report no biomedical financial interests or potential conflicts of interest.

Figures

**FIGURE 1**
Cohen's d effect sizes comparing bipolar relatives and schizophrenia relatives to controls on (a) regional cortical thickness (left) and cortical surface area (right), (b) corrected for mean cortical thickness (left) and total surface area (right). Red lined regions survive false discovery rate correction for multiple testing (q < 0.05)

**FIGURE 2**
Cohen's d effect sizes comparing bipolar disorder patients (light blue), bipolar disorder relatives (blue), schizophrenia patients (pink), and schizophrenia relatives (red) to controls for intelligence quotient scores (IQ; top) and educational attainment (EduYears; bottom). The error bars depict the lower and upper 95% confidence intervals (CIs). *p < .001

**FIGURE 3**
Cohen's d effect sizes comparing schizophrenia relatives (red), and bipolar disorder relatives (blue) to controls on (a) global brain measures, corrected for (b) intracranial volume (ICV), (c) intelligent quotient (IQ), (d) educational attainment. Analyses displayed in (a) and (b) have been presented in our previous study, but are repeated here, for completeness, albeit with slightly different cohorts (de Zwarte, Brouwer, Agartz, et al., 2019). Error bars depict the lower and upper 95% confidence intervals (CIs). *q < 0.05, corrected. GM, gray matter; NA, not corrected for ICV; WM, white matter

See this image and copyright information in PMC

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

Affiliations

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

Authors

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Abstract

Conflict of interest statement

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