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

doi:10.1002/hbm.25206

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 BonninCaroline 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

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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.

Original language	English (US)
Pages (from-to)	414-430
Number of pages	17
Journal	Human Brain Mapping
Volume	43
Issue number	1
DOIs	https://doi.org/10.1002/hbm.25206
State	Published - Jan 2022

Keywords

bipolar disorder
education
intelligence
neuroimaging
relatives
schizophrenia

ASJC Scopus subject areas

Anatomy
Radiological and Ultrasound Technology
Radiology Nuclear Medicine and imaging
Neurology
Clinical Neurology

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de Zwarte, S. M. C., Brouwer, R. M., Agartz, I., Alda, M., Alonso-Lana, S., Bearden, C. E., Bertolino, A., Bonvino, A., Bramon, E., Buimer, E. E. L., Cahn, W., Canales-Rodríguez, E. J., Cannon, D. M., Cannon, T. D., Caseras, X., Castro-Fornieles, J., Chen, Q., Chung, Y., De la Serna, E., ... van Haren, N. E. M. (2022). Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder. Human Brain Mapping, 43(1), 414-430. https://doi.org/10.1002/hbm.25206

de Zwarte, SMC, Brouwer, RM, Agartz, I, Alda, M, Alonso-Lana, S, Bearden, CE, Bertolino, A, Bonvino, A, Bramon, E, Buimer, EEL, Cahn, W, Canales-Rodríguez, EJ, Cannon, DM, Cannon, TD, Caseras, X, Castro-Fornieles, J, Chen, Q, Chung, Y, De la Serna, E, del Mar Bonnin, C, Demro, C, Di Giorgio, A, Doucet, GE, Eker, MC, Erk, S, Fatjó-Vilas, M, Fears, SC, Foley, SF, Frangou, S, Fullerton, JM, Glahn, DC, Goghari, VM, Goikolea, JM, Goldman, AL, Gonul, AS, Gruber, O, Hajek, T, Hawkins, EL, Heinz, A, Hidiroglu Ongun, C, Hillegers, MHJ, Houenou, J, Hulshoff Pol, HE, Hultman, CM, Ingvar, M, Johansson, V, Jönsson, EG, Kane, F, Kempton, MJ, Koenis, MMG, Kopecek, M, Krämer, B, Lawrie, SM, Lenroot, RK, Marcelis, M, Mattay, VS, McDonald, C, Meyer-Lindenberg, A, Michielse, S, Mitchell, PB, Moreno, D, Murray, RM, Mwangi, B, Nabulsi, L, Newport, J, Olman, CA, van Os, J, Overs, BJ, Ozerdem, A, Pergola, G, Picchioni, MM, Piguet, C, Pomarol-Clotet, E, Radua, J, Ramsay, IS, Richter, A, Roberts, G, Salvador, R, Saricicek Aydogan, A, Sarró, S, Schofield, PR, Simsek, EM, Simsek, F, Soares, JC, Sponheim, SR, Sugranyes, G, Toulopoulou, T, Tronchin, G, Vieta, E, Walter, H, Weinberger, DR, Whalley, HC, Wu, MJ, Yalin, N, Andreassen, OA, Ching, CRK, Thomopoulos, SI, van Erp, TGM, Jahanshad, N, Thompson, PM, Kahn, RS & van Haren, NEM 2022, 'Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder', Human Brain Mapping, vol. 43, no. 1, pp. 414-430. https://doi.org/10.1002/hbm.25206

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

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",

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

note = "Publisher Copyright: {\textcopyright} 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.",

year = "2022",

month = jan,

doi = "10.1002/hbm.25206",

language = "English (US)",

volume = "43",

pages = "414--430",

journal = "Human Brain Mapping",

issn = "1065-9471",

publisher = "Wiley-Liss Inc.",

number = "1",

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TY - JOUR

T1 - Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder

AU - de Zwarte, Sonja M.C.

AU - Brouwer, Rachel M.

AU - Agartz, Ingrid

AU - Alda, Martin

AU - Alonso-Lana, Silvia

AU - Bearden, Carrie E.

AU - Bertolino, Alessandro

AU - Bonvino, Aurora

AU - Bramon, Elvira

AU - Buimer, Elizabeth E.L.

AU - Cahn, Wiepke

AU - Canales-Rodríguez, Erick J.

AU - Cannon, Dara M.

AU - Cannon, Tyrone D.

AU - Caseras, Xavier

AU - Castro-Fornieles, Josefina

AU - Chen, Qiang

AU - Chung, Yoonho

AU - De la Serna, Elena

AU - del Mar Bonnin, Caterina

AU - Demro, Caroline

AU - Di Giorgio, Annabella

AU - Doucet, Gaelle E.

AU - Eker, Mehmet Cagdas

AU - Erk, Susanne

AU - Fatjó-Vilas, Mar

AU - Fears, Scott C.

AU - Foley, Sonya F.

AU - Frangou, Sophia

AU - Fullerton, Janice M.

AU - Glahn, David C.

AU - Goghari, Vina M.

AU - Goikolea, Jose M.

AU - Goldman, Aaron L.

AU - Gonul, Ali Saffet

AU - Gruber, Oliver

AU - Hajek, Tomas

AU - Hawkins, Emma L.

AU - Heinz, Andreas

AU - Hidiroglu Ongun, Ceren

AU - Hillegers, Manon H.J.

AU - Houenou, Josselin

AU - Hulshoff Pol, Hilleke E.

AU - Hultman, Christina M.

AU - Ingvar, Martin

AU - Johansson, Viktoria

AU - Jönsson, Erik G.

AU - Kane, Fergus

AU - Kempton, Matthew J.

AU - Koenis, Marinka M.G.

AU - Kopecek, Miloslav

AU - Krämer, Bernd

AU - Lawrie, Stephen M.

AU - Lenroot, Rhoshel K.

AU - Marcelis, Machteld

AU - Mattay, Venkata S.

AU - McDonald, Colm

AU - Meyer-Lindenberg, Andreas

AU - Michielse, Stijn

AU - Mitchell, Philip B.

AU - Moreno, Dolores

AU - Murray, Robin M.

AU - Mwangi, Benson

AU - Nabulsi, Leila

AU - Newport, Jason

AU - Olman, Cheryl A.

AU - van Os, Jim

AU - Overs, Bronwyn J.

AU - Ozerdem, Aysegul

AU - Pergola, Giulio

AU - Picchioni, Marco M.

AU - Piguet, Camille

AU - Pomarol-Clotet, Edith

AU - Radua, Joaquim

AU - Ramsay, Ian S.

AU - Richter, Anja

AU - Roberts, Gloria

AU - Salvador, Raymond

AU - Saricicek Aydogan, Aybala

AU - Sarró, Salvador

AU - Schofield, Peter R.

AU - Simsek, Esma M.

AU - Simsek, Fatma

AU - Soares, Jair C.

AU - Sponheim, Scott R.

AU - Sugranyes, Gisela

AU - Toulopoulou, Timothea

AU - Tronchin, Giulia

AU - Vieta, Eduard

AU - Walter, Henrik

AU - Weinberger, Daniel R.

AU - Whalley, Heather C.

AU - Wu, Mon Ju

AU - Yalin, Nefize

AU - Andreassen, Ole A.

AU - Ching, Christopher R.K.

AU - Thomopoulos, Sophia I.

AU - van Erp, Theo G.M.

AU - Jahanshad, Neda

AU - Thompson, Paul M.

AU - Kahn, René S.

AU - van Haren, Neeltje E.M.

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

KW - bipolar disorder

KW - education

KW - intelligence

KW - neuroimaging

KW - relatives

KW - schizophrenia

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U2 - 10.1002/hbm.25206

DO - 10.1002/hbm.25206

M3 - Article

C2 - 33027543

AN - SCOPUS:85092137687

SN - 1065-9471

VL - 43

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EP - 430

JO - Human Brain Mapping

JF - Human Brain Mapping

IS - 1

ER -

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

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