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

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Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder
Human Brain Mapping ( IF 4.8 ) Pub Date : 2020-10-07 , DOI: 10.1002/hbm.25206
Sonja M C de Zwarte ₁ , Rachel M Brouwer ₁ , Ingrid Agartz _{2,

3,

4} , Martin Alda _{5,

6} , Silvia Alonso-Lana _{7,

8} , Carrie E Bearden _{9,

10} , Alessandro Bertolino ₁₁ , Aurora Bonvino ₁₁ , Elvira Bramon ₁₂ , Elizabeth E L Buimer ₁ , Wiepke Cahn ₁ , Erick J Canales-Rodríguez _{7,

8} , Dara M Cannon ₁₃ , Tyrone D Cannon _{14,

15} , Xavier Caseras ₁₆ , Josefina Castro-Fornieles _{8,

17,

18,

19} , Qiang Chen ₂₀ , Yoonho Chung ₁₄ , Elena De la Serna _{8,

17,

18,

19} , Caterina Del Mar Bonnin _{8,

18,

21} , Caroline Demro ₂₂ , Annabella Di Giorgio ₂₃ , Gaelle E Doucet _{24,

25} , Mehmet Cagdas Eker ₂₆ , Susanne Erk ₂₇ , Mar Fatjó-Vilas _{7,

8} , Scott C Fears _{28,

29} , Sonya F Foley ₃₀ , Sophia Frangou ₂₄ , Janice M Fullerton _{31,

32} , David C Glahn _{33,

34,

35} , Vina M Goghari ₃₆ , Jose M Goikolea _{8,

18,

21} , Aaron L Goldman ₂₀ , Ali Saffet Gonul _{26,

37} , Oliver Gruber ₃₈ , Tomas Hajek _{5,

6} , Emma L Hawkins ₃₉ , Andreas Heinz ₂₆ , Ceren Hidiroglu Ongun ₄₀ , Manon H J Hillegers _{1,

41} , Josselin Houenou _{42,

43,

44} , Hilleke E Hulshoff Pol ₁ , Christina M Hultman ₄₅ , Martin Ingvar _{46,

47} , Viktoria Johansson _{3,

45} , Erik G Jönsson _{2,

3} , Fergus Kane ₄₈ , Matthew J Kempton ₄₈ , Marinka M G Koenis _{15,

33} , Miloslav Kopecek _{6,

49} , Bernd Krämer ₃₈ , Stephen M Lawrie ₃₉ , Rhoshel K Lenroot _{31,

50,

51} , Machteld Marcelis ₅₂ , Venkata S Mattay _{20,

53} , Colm McDonald ₁₃ , Andreas Meyer-Lindenberg ₅₄ , Stijn Michielse ₅₂ , Philip B Mitchell ₅₀ , Dolores Moreno _{8,

55} , Robin M Murray ₄₈ , Benson Mwangi ₅₆ , Leila Nabulsi ₁₃ , Jason Newport ₅ , Cheryl A Olman ₅₇ , Jim van Os _{1,

52} , Bronwyn J Overs ₃₁ , Aysegul Ozerdem _{58,

59,

60} , Giulio Pergola ₁₁ , Marco M Picchioni ₆₁ , Camille Piguet _{43,

44,

62,

63} , Edith Pomarol-Clotet _{7,

8} , Joaquim Radua _{3,

8,

18,

64} , Ian S Ramsay ₂₂ , Anja Richter ₃₈ , Gloria Roberts ₅₀ , Raymond Salvador _{7,

8} , Aybala Saricicek Aydogan _{59,

65} , Salvador Sarró _{7,

8} , Peter R Schofield _{32,

33} , Esma M Simsek ₆₆ , Fatma Simsek _{26,

66,

67} , Jair C Soares ₅₆ , Scott R Sponheim _{22,

68} , Gisela Sugranyes _{8,

17,

18,

19} , Timothea Toulopoulou _{69,

70} , Giulia Tronchin ₁₃ , Eduard Vieta _{8,

18,

21} , Henrik Walter ₂₇ , Daniel R Weinberger ₂₁ , Heather C Whalley ₄₀ , Mon-Ju Wu ₅₇ , Nefize Yalin ₇₁ , Ole A Andreassen _{2,

72} , Christopher R K Ching ₇₃ , Sophia I Thomopoulos ₇₃ , Theo G M van Erp _{74,

75} , Neda Jahanshad ₇₃ , Paul M Thompson ₇₃ , René S Kahn _{1,

24} , Neeltje E M van Haren _{1,

41}

Affiliation

Department of Psychiatry, University Medical Center Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden.
Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway.
Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
National Institute of Mental Health, Klecany, Czech Republic.
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental), Madrid, Spain.
Semel Institute for Neuroscience and Human Behavior, University of California, California, Los Angeles, USA.
Department of Psychology, University of California, California, Los Angeles, USA.
Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.
Division of Psychiatry, Neuroscience in Mental Health Research Department, University College London, London, UK.
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.
Department of Psychology, Yale University, New Haven, Connecticut, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Department of Child and Adolescent Psychiatry and Psychology, 2017SGR881, Institute of Neuroscience, Hospital Clínic of Barcelona, Barcelona, Spain.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
University of Barcelona, Barcelona, Spain.
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
Bipolar and Depressive Disorders Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, Minnesota, USA.
IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Boys Town National Research Hospital, Omaha, NE, USA.
SoCAT LAB, Department of Psychiatry, School of Medicine, Ege University, Izmir, Turkey.
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.
Department of Psychiatry and Biobehavioral Science, University of California, Los Angeles, California, USA.
Center for Neurobehavioral Genetics, University of California, Los Angeles, California, USA.
Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, UK.
Neuroscience Research Australia, Sydney, Australia.
School of Medical Sciences, University of New South Wales, Sydney, Australia.
Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut, USA.
Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, Massachusetts, USA.
Harvard Medical School, Boston, Massachusetts, USA.
Department of Psychology and Graduate Department of Psychological Clinical Science, University of Toronto, Toronto, Ontario, Canada.
Department of Psychiatry and Behavioral Sciences, Mercer University School of Medicine, Macon, Georgia, USA.
Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany.
Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK.
Department of Psychology, Faculty of Arts, Dokuz Eylül University, İzmir, Turkey.
Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, Netherlands.
APHP, Mondor University Hospitals, Créteil, France.
INSERM U955 Team 15 "Translational Psychiatry", Créteil, France.
NeuroSpin neuroimaging platform, Psychiatry Team, UNIACT Lab, CEA Saclay, Gif-Sur-Yvette, France.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Section for Neuroscience, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.
Department of Psychiatry, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
School of Psychiatry, University of New South Wales, Sydney, Australia.
Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, New Mexico, USA.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht University, Maastricht, Netherlands.
Departments of Neurology and Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón (IiSGM), School of Medicine, Universidad Complutense, Madrid, Spain.
Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Department of Psychology and Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, USA.
Department of Psychiatry, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.
Department of Neurosciences, Health Sciences Institute, Dokuz Eylül University, Izmir, Turkey.
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
School of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain.
Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Department of Psychiatry, Faculty of Medicine, Izmir Katip Çelebi University, Izmir, Turkey.
Cigli State Hospital, Department of Psychiatry, Izmir, Turkey.
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Minneapolis VA Health Care System, Minneapolis, Minnesota, USA.
Department of Psychology, Bilkent University, Ankara, Turkey.
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA.
Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California, USA.
Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, California, USA.

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.

中文翻译：

精神分裂症或双相情感障碍家族性高危人群的智力、受教育程度和大脑结构

被诊断患有精神分裂症 (SZ-FDR) 的患者的一级亲属对患者表现出相似的大脑异常和认知改变模式，尽管效应量较小。双相情感障碍 (BD-FDR) 患者的一级亲属表现出不同的模式；平均而言，与对照组相比，颅内体积更大，并且 BD-FDR 认知改变的发现不一致。在这里，我们对 5,795 名个体（1,103 名 SZ-FDR、867 名 BD-FDR、2,190 名对照组、942 名精神分裂症患者、693 名双相情感障碍患者）的全球和区域大脑测量（皮质和皮质下）、当前智商和教育程度进行了荟萃分析) 来自 36 个精神分裂症和/或双相情感障碍家族队列，采用标准化方法。与对照组相比，SZ-FDR 表现出广泛分布的更薄皮层模式，而 BD-FDR 具有广泛的较大皮质表面积。SZ-FDR 的智商较低（d = −0.42, p = 3 × 10 ⁻⁵ ), BD-FDR 智商降低的证据不足 ( d = −0.23, p =.045）。与对照组相比，两个相关组的教育程度相似。在调整智商或受教育程度时，对大脑测量的群体效应发生了变化，尽管变化不大。变化朝着预期的方向发展，SZ-FDR 的大脑异常不太明显，而 BD-FDR 的影响更明显。总之，SZ-FDR 和 BD-FDR 显示出不同的脑结构异常模式。相比之下，与对照组相比，两者的智商得分较低，学习成绩相似。鉴于在调整 IQ 或教育程度后 SZ-FDR 和 BD-FDR 之间的大脑差异仍然存在，我们认为精神分裂症或双相情感障碍易感性背后的差异大脑发育过程可能与一般认知障碍无关。

更新日期：2020-10-07

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