Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets

Merel C Postema; Martine Hoogman; Sara Ambrosino; Philip Asherson; Tobias Banaschewski; Cibele E Bandeira; Alexandr Baranov; Claiton H D Bau; Sarah Baumeister; Ramona Baur-Streubel; Mark A Bellgrove; Joseph Biederman; Janita Bralten; Daniel Brandeis; Silvia Brem; Jan K Buitelaar; Geraldo F Busatto; Francisco X Castellanos; Mara Cercignani; Tiffany M Chaim-Avancini; Kaylita C Chantiluke; Anastasia Christakou; David Coghill; Annette Conzelmann; Ana I Cubillo; Renata B Cupertino; Patrick de Zeeuw; Alysa E Doyle; Sarah Durston; Eric A Earl; Jeffery N Epstein; Thomas Ethofer; Damien A Fair; Andreas J Fallgatter; Stephen V Faraone; Thomas Frodl; Matt C Gabel; Tinatin Gogberashvili; Eugenio H Grevet; Jan Haavik; Neil A. Harrison; Catharina A Hartman; Dirk J Heslenfeld; Pieter J Hoekstra; Sarah Hohmann; Marie F Høvik; Terry L Jernigan; Bernd Kardatzki; Georgii Karkashadze; Clare Kelly; Gregor Kohls; Kerstin Konrad; Jonna Kuntsi; Luisa Lazaro; Sara Lera-Miguel; Klaus-Peter Lesch; Mario R Louza; Astri J Lundervold; Charles B Malpas; Paulo Mattos; Hazel McCarthy; Leyla  Namazova-Baranova; Rosa Nicolau; Joel T Nigg; Stephanie E Novotny; Eileen Oberwelland Weiss; Ruth L O'Gorman Tuura; Jaap Oosterlaan; Bob Oranje; Yannis Paloyelis; Paul Pauli; Felipe A.  Picon; Kerstin J Plessen; J Antoni Ramos-Quiroga; Andreas Reif; Liesbeth Reneman; Pedro G P Rosa; Katya Rubia; Anouk Schrantee; Lizanne J S Schweren; Jochen Seitz; Philip Shaw; Tim J Silk; Norbert Skokauskas; Juan Carlos Soliva Vila; Michael C Stevens; Gustavo Sudre; Leanne Tamm; Fernanda Tovar-Moll; Theo G M van Erp; Alasdair Vance; Oscar Vilarroya; Yolanda Vives-Gilabert; Georg G von Polier; Susanne Walitza; Yuliya N Yoncheva; Marcus V Zanetti; Georg C Ziegler; David C. Glahn; Neda Jahanshad; Sarah E. Medland; Paul M Thompson; Simon E.  Fisher; Barbara Franke; Clyde Francks

doi:10.1111/jcpp.13396

Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets

, Merel C Postema, Martine Hoogman, Sara Ambrosino, Philip Asherson, Tobias Banaschewski, Cibele E Bandeira, Alexandr Baranov, Claiton H D Bau, Sarah Baumeister, Ramona Baur-Streubel, Mark A Bellgrove, Joseph Biederman, Janita Bralten, Daniel Brandeis, Silvia Brem, Jan K Buitelaar, Geraldo F Busatto, Francisco X Castellanos, Mara CercignaniTiffany M Chaim-Avancini, Kaylita C Chantiluke, Anastasia Christakou, David Coghill, Annette Conzelmann, Ana I Cubillo, Renata B Cupertino, Patrick de Zeeuw, Alysa E Doyle, Sarah Durston, Eric A Earl, Jeffery N Epstein, Thomas Ethofer, Damien A Fair, Andreas J Fallgatter, Stephen V Faraone, Thomas Frodl, Matt C Gabel, Tinatin Gogberashvili, Eugenio H Grevet, Jan Haavik, Neil A. Harrison, Catharina A Hartman, Dirk J Heslenfeld, Pieter J Hoekstra, Sarah Hohmann, Marie F Høvik, Terry L Jernigan, Bernd Kardatzki, Georgii Karkashadze, Clare Kelly, Gregor Kohls, Kerstin Konrad, Jonna Kuntsi, Luisa Lazaro, Sara Lera-Miguel, Klaus-Peter Lesch, Mario R Louza, Astri J Lundervold, Charles B Malpas, Paulo Mattos, Hazel McCarthy, Leyla Namazova-Baranova, Rosa Nicolau, Joel T Nigg, Stephanie E Novotny, Eileen Oberwelland Weiss, Ruth L O'Gorman Tuura, Jaap Oosterlaan, Bob Oranje, Yannis Paloyelis, Paul Pauli, Felipe A. Picon, Kerstin J Plessen, J Antoni Ramos-Quiroga, Andreas Reif, Liesbeth Reneman, Pedro G P Rosa, Katya Rubia, Anouk Schrantee, Lizanne J S Schweren, Jochen Seitz, Philip Shaw, Tim J Silk, Norbert Skokauskas, Juan Carlos Soliva Vila, Michael C Stevens, Gustavo Sudre, Leanne Tamm, Fernanda Tovar-Moll, Theo G M van Erp, Alasdair Vance, Oscar Vilarroya, Yolanda Vives-Gilabert, Georg G von Polier, Susanne Walitza, Yuliya N Yoncheva, Marcus V Zanetti, Georg C Ziegler, David C. Glahn, Neda Jahanshad, Sarah E. Medland, Paul M Thompson, Simon E. Fisher, Barbara Franke, Clyde Francks (Lead / Corresponding author)

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Abstract

Objective: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.

Methods: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.

Results: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.

Conclusion: Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

Original language	English
Pages (from-to)	1202-1219
Number of pages	18
Journal	Journal of Child Psychology and Psychiatry
Volume	62
Issue number	10
Early online date	22 Mar 2021
DOIs	https://doi.org/10.1111/jcpp.13396
Publication status	Published - Oct 2021

Keywords

Attention-deficit
brain asymmetry
brain laterality
hyperactivity disorder
large-scale data
structural MRI

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Developmental and Educational Psychology
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/jcpp.13396Licence: CC BY-NC

Final Published VersionFinal published version, 893 KBLicence: CC BY-NC

Cite this

, Postema, M. C., Hoogman, M., Ambrosino, S., Asherson, P., Banaschewski, T., Bandeira, C. E., Baranov, A., Bau, C. H. D., Baumeister, S., Baur-Streubel, R., Bellgrove, M. A., Biederman, J., Bralten, J., Brandeis, D., Brem, S., Buitelaar, J. K., Busatto, G. F., Castellanos, F. X., ... Francks, C. (2021). Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets. Journal of Child Psychology and Psychiatry, 62(10), 1202-1219. https://doi.org/10.1111/jcpp.13396

@article{4279589e27f84a0e95c466a2df8ef9da,

title = "Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets",

abstract = "Objective: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.Methods: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.Results: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.Conclusion: Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.",

keywords = "Attention-deficit, brain asymmetry, brain laterality, hyperactivity disorder, large-scale data, structural MRI",

author = "Postema, {Merel C} and Martine Hoogman and Sara Ambrosino and Philip Asherson and Tobias Banaschewski and Bandeira, {Cibele E} and Alexandr Baranov and Bau, {Claiton H D} and Sarah Baumeister and Ramona Baur-Streubel and Bellgrove, {Mark A} and Joseph Biederman and Janita Bralten and Daniel Brandeis and Silvia Brem and Buitelaar, {Jan K} and Busatto, {Geraldo F} and Castellanos, {Francisco X} and Mara Cercignani and Chaim-Avancini, {Tiffany M} and Chantiluke, {Kaylita C} and Anastasia Christakou and David Coghill and Annette Conzelmann and Cubillo, {Ana I} and Cupertino, {Renata B} and {de Zeeuw}, Patrick and Doyle, {Alysa E} and Sarah Durston and Earl, {Eric A} and Epstein, {Jeffery N} and Thomas Ethofer and Fair, {Damien A} and Fallgatter, {Andreas J} and Faraone, {Stephen V} and Thomas Frodl and Gabel, {Matt C} and Tinatin Gogberashvili and Grevet, {Eugenio H} and Jan Haavik and Harrison, {Neil A.} and Hartman, {Catharina A} and Heslenfeld, {Dirk J} and Hoekstra, {Pieter J} and Sarah Hohmann and H{\o}vik, {Marie F} and Jernigan, {Terry L} and Bernd Kardatzki and Georgii Karkashadze and Clare Kelly and Gregor Kohls and Kerstin Konrad and Jonna Kuntsi and Luisa Lazaro and Sara Lera-Miguel and Klaus-Peter Lesch and Louza, {Mario R} and Lundervold, {Astri J} and Malpas, {Charles B} and Paulo Mattos and Hazel McCarthy and Leyla Namazova-Baranova and Rosa Nicolau and Nigg, {Joel T} and Novotny, {Stephanie E} and {Oberwelland Weiss}, Eileen and {O'Gorman Tuura}, {Ruth L} and Jaap Oosterlaan and Bob Oranje and Yannis Paloyelis and Paul Pauli and Picon, {Felipe A.} and Plessen, {Kerstin J} and Ramos-Quiroga, {J Antoni} and Andreas Reif and Liesbeth Reneman and Rosa, {Pedro G P} and Katya Rubia and Anouk Schrantee and Schweren, {Lizanne J S} and Jochen Seitz and Philip Shaw and Silk, {Tim J} and Norbert Skokauskas and {Soliva Vila}, {Juan Carlos} and Stevens, {Michael C} and Gustavo Sudre and Leanne Tamm and Fernanda Tovar-Moll and {van Erp}, {Theo G M} and Alasdair Vance and Oscar Vilarroya and Yolanda Vives-Gilabert and {von Polier}, {Georg G} and Susanne Walitza and Yoncheva, {Yuliya N} and Zanetti, {Marcus V} and Ziegler, {Georg C} and Glahn, {David C.} and Neda Jahanshad and Medland, {Sarah E.} and Thompson, {Paul M} and Fisher, {Simon E.} and Barbara Franke and Clyde Francks",

note = "Copyright: {\textcopyright} 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.",

year = "2021",

month = oct,

doi = "10.1111/jcpp.13396",

language = "English",

volume = "62",

pages = "1202--1219",

journal = "Journal of Child Psychology and Psychiatry",

issn = "0021-9630",

publisher = "Wiley",

number = "10",

}

Postema, MC, Hoogman, M, Ambrosino, S, Asherson, P, Banaschewski, T, Bandeira, CE, Baranov, A, Bau, CHD, Baumeister, S, Baur-Streubel, R, Bellgrove, MA, Biederman, J, Bralten, J, Brandeis, D, Brem, S, Buitelaar, JK, Busatto, GF, Castellanos, FX, Cercignani, M, Chaim-Avancini, TM, Chantiluke, KC, Christakou, A, Coghill, D, Conzelmann, A, Cubillo, AI, Cupertino, RB, de Zeeuw, P, Doyle, AE, Durston, S, Earl, EA, Epstein, JN, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Frodl, T, Gabel, MC, Gogberashvili, T, Grevet, EH, Haavik, J, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hoekstra, PJ, Hohmann, S, Høvik, MF, Jernigan, TL, Kardatzki, B, Karkashadze, G, Kelly, C, Kohls, G, Konrad, K, Kuntsi, J, Lazaro, L, Lera-Miguel, S, Lesch, K-P, Louza, MR, Lundervold, AJ, Malpas, CB, Mattos, P, McCarthy, H, Namazova-Baranova, L, Nicolau, R, Nigg, JT, Novotny, SE, Oberwelland Weiss, E, O'Gorman Tuura, RL, Oosterlaan, J, Oranje, B, Paloyelis, Y, Pauli, P, Picon, FA, Plessen, KJ, Ramos-Quiroga, JA, Reif, A, Reneman, L, Rosa, PGP, Rubia, K, Schrantee, A, Schweren, LJS, Seitz, J, Shaw, P, Silk, TJ, Skokauskas, N, Soliva Vila, JC, Stevens, MC, Sudre, G, Tamm, L, Tovar-Moll, F, van Erp, TGM, Vance, A, Vilarroya, O, Vives-Gilabert, Y, von Polier, GG, Walitza, S, Yoncheva, YN, Zanetti, MV, Ziegler, GC, Glahn, DC, Jahanshad, N, Medland, SE, Thompson, PM, Fisher, SE & Franke, B & Francks, C 2021, 'Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets', Journal of Child Psychology and Psychiatry, vol. 62, no. 10, pp. 1202-1219. https://doi.org/10.1111/jcpp.13396

TY - JOUR

T1 - Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets

AU - Postema, Merel C

AU - Hoogman, Martine

AU - Ambrosino, Sara

AU - Asherson, Philip

AU - Banaschewski, Tobias

AU - Bandeira, Cibele E

AU - Baranov, Alexandr

AU - Bau, Claiton H D

AU - Baumeister, Sarah

AU - Baur-Streubel, Ramona

AU - Bellgrove, Mark A

AU - Biederman, Joseph

AU - Bralten, Janita

AU - Brandeis, Daniel

AU - Brem, Silvia

AU - Buitelaar, Jan K

AU - Busatto, Geraldo F

AU - Castellanos, Francisco X

AU - Cercignani, Mara

AU - Chaim-Avancini, Tiffany M

AU - Chantiluke, Kaylita C

AU - Christakou, Anastasia

AU - Coghill, David

AU - Conzelmann, Annette

AU - Cubillo, Ana I

AU - Cupertino, Renata B

AU - de Zeeuw, Patrick

AU - Doyle, Alysa E

AU - Durston, Sarah

AU - Earl, Eric A

AU - Epstein, Jeffery N

AU - Ethofer, Thomas

AU - Fair, Damien A

AU - Fallgatter, Andreas J

AU - Faraone, Stephen V

AU - Frodl, Thomas

AU - Gabel, Matt C

AU - Gogberashvili, Tinatin

AU - Grevet, Eugenio H

AU - Haavik, Jan

AU - Harrison, Neil A.

AU - Hartman, Catharina A

AU - Heslenfeld, Dirk J

AU - Hoekstra, Pieter J

AU - Hohmann, Sarah

AU - Høvik, Marie F

AU - Jernigan, Terry L

AU - Kardatzki, Bernd

AU - Karkashadze, Georgii

AU - Kelly, Clare

AU - Kohls, Gregor

AU - Konrad, Kerstin

AU - Kuntsi, Jonna

AU - Lazaro, Luisa

AU - Lera-Miguel, Sara

AU - Lesch, Klaus-Peter

AU - Louza, Mario R

AU - Lundervold, Astri J

AU - Malpas, Charles B

AU - Mattos, Paulo

AU - McCarthy, Hazel

AU - Namazova-Baranova, Leyla

AU - Nicolau, Rosa

AU - Nigg, Joel T

AU - Novotny, Stephanie E

AU - Oberwelland Weiss, Eileen

AU - O'Gorman Tuura, Ruth L

AU - Oosterlaan, Jaap

AU - Oranje, Bob

AU - Paloyelis, Yannis

AU - Pauli, Paul

AU - Picon, Felipe A.

AU - Plessen, Kerstin J

AU - Ramos-Quiroga, J Antoni

AU - Reif, Andreas

AU - Reneman, Liesbeth

AU - Rosa, Pedro G P

AU - Rubia, Katya

AU - Schrantee, Anouk

AU - Schweren, Lizanne J S

AU - Seitz, Jochen

AU - Shaw, Philip

AU - Silk, Tim J

AU - Skokauskas, Norbert

AU - Soliva Vila, Juan Carlos

AU - Stevens, Michael C

AU - Sudre, Gustavo

AU - Tamm, Leanne

AU - Tovar-Moll, Fernanda

AU - van Erp, Theo G M

AU - Vance, Alasdair

AU - Vilarroya, Oscar

AU - Vives-Gilabert, Yolanda

AU - von Polier, Georg G

AU - Walitza, Susanne

AU - Yoncheva, Yuliya N

AU - Zanetti, Marcus V

AU - Ziegler, Georg C

AU - Glahn, David C.

AU - Jahanshad, Neda

AU - Medland, Sarah E.

AU - Thompson, Paul M

AU - Fisher, Simon E.

AU - Franke, Barbara

AU - Francks, Clyde

PY - 2021/10

Y1 - 2021/10

N2 - Objective: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.Methods: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.Results: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.Conclusion: Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

AB - Objective: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.Methods: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.Results: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.Conclusion: Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

KW - Attention-deficit

KW - brain asymmetry

KW - brain laterality

KW - hyperactivity disorder

KW - large-scale data

KW - structural MRI

UR - http://www.scopus.com/inward/record.url?scp=85102832651&partnerID=8YFLogxK

U2 - 10.1111/jcpp.13396

DO - 10.1111/jcpp.13396

M3 - Article

C2 - 33748971

SN - 0021-9630

VL - 62

SP - 1202

EP - 1219

JO - Journal of Child Psychology and Psychiatry

JF - Journal of Child Psychology and Psychiatry

IS - 10

ER -

Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets

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Keywords

ASJC Scopus subject areas

UN SDGs

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