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

Sonja M C de Zwarte | Rachel M Brouwer | Ingrid Agartz | Martin Alda | Silvia Alonso-Lana | Carrie E Bearden | Alessandro Bertolino | Aurora Bonvino | Elvira Bramon | Elizabeth E L Buimer | Wiepke Cahn | Erick J Canales-Rodríguez | Dara M Cannon | Tyrone D Cannon | Xavier Caseras | Josefina Castro-Fornieles | Qiang Chen | Yoonho Chung | Elena De la Serna | Caterina Del Mar Bonnin | Caroline Demro | Annabella Di Giorgio | Gaelle E Doucet | Mehmet Cagdas Eker | Susanne Erk | Mar Fatjó-Vilas | Scott C Fears | Sonya F Foley | Sophia Frangou | Janice M Fullerton | David C Glahn | Vina M Goghari | Jose M Goikolea | Aaron L Goldman | Ali Saffet Gonul | Oliver Gruber | Tomas Hajek | Emma L Hawkins | Andreas Heinz | Ceren Hidiroglu Ongun | Manon H J Hillegers | Josselin Houenou | Hilleke E Hulshoff Pol | Christina M Hultman | Martin Ingvar | Viktoria Johansson | Erik G Jönsson | Fergus Kane | Matthew J Kempton | Marinka M G Koenis | Miloslav Kopecek | Bernd Krämer | Stephen M Lawrie | Rhoshel K Lenroot | Machteld Marcelis | Venkata S Mattay | Colm McDonald | Andreas Meyer-Lindenberg | Stijn Michielse | Philip B Mitchell | Dolores Moreno | Robin M Murray | Benson Mwangi | Leila Nabulsi | Jason Newport | Cheryl A Olman | Jim van Os | Bronwyn J Overs | Aysegul Ozerdem | Giulio Pergola | Marco M Picchioni | Camille Piguet | Edith Pomarol-Clotet | Joaquim Radua | Ian S Ramsay | Anja Richter | Gloria Roberts | Raymond Salvador | Aybala Saricicek Aydogan | Salvador Sarró | Peter R Schofield | Esma M Simsek | Fatma Simsek | Jair C Soares | Scott R Sponheim | Gisela Sugranyes | Timothea Toulopoulou | Giulia Tronchin | Eduard Vieta | Henrik Walter | Daniel R Weinberger | Heather C Whalley | Mon-Ju Wu | Nefize Yalin | Ole A Andreassen | Christopher R K Ching | Sophia I Thomopoulos | Theo G M van Erp | Neda Jahanshad | Paul M Thompson | René S Kahn | Neeltje E M van Haren
Human brain mapping | 2022

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.

Pubmed ID: 33027543 RIS Download

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Associated grants

  • Agency: CSRD VA, United States
    Id: I01 CX000227
  • Agency: Swiss National Science Foundation, Switzerland
    Id: 32003B_156914
  • Agency: Medical Research Council, United Kingdom
    Id: G0901310
  • Agency: Medical Research Council, United Kingdom
    Id: G0801418
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH116147
  • Agency: NIH HHS, United States
    Id: R01MH121246
  • Agency: NIMH NIH HHS, United States
    Id: U01 MH108150
  • Agency: VA, United States
    Id: I01CX000227
  • Agency: NIBIB NIH HHS, United States
    Id: P41 EB015922
  • Agency: Wellcome Trust, United Kingdom
    Id: 091630
  • Agency: NIBIB NIH HHS, United States
    Id: P41 EB027061
  • Agency: Wellcome Trust, United Kingdom
    Id: 064971
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH118695
  • Agency: NIH HHS, United States
    Id: 1S10OD017974-01
  • Agency: NIH HHS, United States
    Id: S10 OD017974
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L010305/1
  • Agency: NIH HHS, United States
    Id: U54EB020403
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH111671
  • Agency: Department of Health, United Kingdom
    Id: NIHR200756
  • Agency: NINDS NIH HHS, United States
    Id: P30 NS076408
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH129742
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH113619
  • Agency: NIH HHS, United States
    Id: P30 NS076408
  • Agency: NIA NIH HHS, United States
    Id: T32 AG058507
  • Agency: NIH HHS, United States
    Id: P41 EB015922
  • Agency: NIBIB NIH HHS, United States
    Id: U54 EB020403
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH117601
  • Agency: NIA NIH HHS, United States
    Id: T32AG058507
  • Agency: NIH HHS, United States
    Id: R03 MH105808
  • Agency: Wellcome Trust, United Kingdom
    Id: 085475/B/08/Z
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH121246
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Wellcome Trust, United Kingdom
    Id: 103703
  • Agency: CIHR, Canada
    Id: 106469, 142255
  • Agency: NIH HHS, United States
    Id: R01 MH116147
  • Agency: Wellcome Trust, United Kingdom
    Id: 085475/Z/08/Z
  • Agency: NIH HHS, United States
    Id: R01 MH117601
  • Agency: NIH HHS, United States
    Id: R01 MH111671
  • Agency: NIMH NIH HHS, United States
    Id: R03 MH105808
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH085667
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH052857
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH080912

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