Brain Imaging of the Cortex in ADHD

A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples

Martine Hoogman, Ryan Muetzel, Joao P. Guimaraes, Elena Shumskaya, Maarten Mennes, Marcel P. Zwiers, Neda Jahanshad, Gustavo Sudre, Thomas Wolfers, Eric A. Earl, Juan Carlos Soliva Vila, Yolanda Vives-Gilabert, Sabin Khadka, Stephanie E. Novotny, Catharina A. Hartman, Dirk J. Heslenfeld, Lizanne J. S. Schweren, Sara Ambrosino, Bob Oranje, Patrick de Zeeuw & 95 others Tiffany M. Chaim-Avancini, Pedro G. P. Rosa, Marcus V. Zanetti, Charles B. Malpas, Gregor Kohls, Georg G. von Polier, Jochen Seitz, Joseph Biederman, Alysa E. Doyle, Anders M. Dale, Theo G. M. van Erp, Jeffery N. Epstein, Terry L. Jernigan, Ramona Baur-Streubel, Georg C. Ziegler, Kathrin C. Zierhut, Anouk Schrantee, Marie F. Høvik, Astri J. Lundervold, Clare Kelly, Hazel McCarthy, Norbert Skokauskas, Ruth L. O'Gorman Tuura, Anna Calvo, Sara Lera-Miguel, Rosa Nicolau, Kaylita C. Chantiluke, Anastasia Christakou, Alasdair Vance, Mara Cercignani, Matt C. Gabel, Philip Asherson, Sarah Baumeister, Daniel Brandeis, Sarah Hohmann, Ivanei E. Bramati, Fernanda Tovar-Moll, Andreas J. Fallgatter, Bernd Kardatzki, Lena Schwarz, Anatoly Anikin, Alexandr Baranov, Tinatin Gogberashvili, Dmitry Kapilushniy, Anastasia Solovieva, Hanan El Marroun, Tonya White, Georgii Karkashadze, Leyla Namazova-Baranova, Thomas Ethofer, Paulo Mattos, Tobias Banaschewski, David Coghill, Kerstin J Plessen, Jonna Kuntsi, Mitul A. Mehta, Yannis Paloyelis, Neil A. Harrison, Mark A. Bellgrove, Tim J. Silk, Ana I. Cubillo, Katya Rubia, Luisa Lazaro, Silvia Brem, Susanne Walitza, Thomas Frodl, Mariam Zentis, Francisco X. Castellanos, Yuliya N Yoncheva, Jan Haavik, Liesbeth Reneman, Annette Conzelmann, Klaus-Peter Lesch, Paul Pauli, Andreas Reif, Leanne Tamm, Kerstin Konrad, Eileen Oberwelland Weiss, Geraldo F Busatto, Mario R Louza, Sarah Durston, Pieter J Hoekstra, Jaap Oosterlaan, Michael C. Stevens, J Antoni Ramos-Quiroga, Oscar Vilarroya, Damien A Fair, Joel T Nigg, Paul M Thompson, Jan K Buitelaar, Stephen V Faraone, Philip Shaw, Henning Tiemeier, Janita Bralten, Barbara Franke

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies.

    Methods: Cortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707).

    Results: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample.

    Conclusions: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

    Original languageEnglish
    Pages (from-to)531-542
    Number of pages12
    JournalAmerican Journal of Psychiatry
    Volume176
    Issue number7
    Early online date24 Apr 2019
    DOIs
    Publication statusPublished - 1 Jul 2019

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    Attention Deficit Disorder with Hyperactivity
    Neuroimaging
    Population
    Temporal Lobe
    Endophenotypes
    Atlases
    Gyrus Cinguli
    Child Behavior
    Frontal Lobe
    Checklist
    Longitudinal Studies
    Siblings
    Pediatrics

    Cite this

    Hoogman, M., Muetzel, R., Guimaraes, J. P., Shumskaya, E., Mennes, M., Zwiers, M. P., ... Franke, B. (2019). Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples. American Journal of Psychiatry, 176(7), 531-542. https://doi.org/10.1176/appi.ajp.2019.18091033
    Hoogman, Martine ; Muetzel, Ryan ; Guimaraes, Joao P. ; Shumskaya, Elena ; Mennes, Maarten ; Zwiers, Marcel P. ; Jahanshad, Neda ; Sudre, Gustavo ; Wolfers, Thomas ; Earl, Eric A. ; Soliva Vila, Juan Carlos ; Vives-Gilabert, Yolanda ; Khadka, Sabin ; Novotny, Stephanie E. ; Hartman, Catharina A. ; Heslenfeld, Dirk J. ; Schweren, Lizanne J. S. ; Ambrosino, Sara ; Oranje, Bob ; de Zeeuw, Patrick ; Chaim-Avancini, Tiffany M. ; Rosa, Pedro G. P. ; Zanetti, Marcus V. ; Malpas, Charles B. ; Kohls, Gregor ; von Polier, Georg G. ; Seitz, Jochen ; Biederman, Joseph ; Doyle, Alysa E. ; Dale, Anders M. ; van Erp, Theo G. M. ; Epstein, Jeffery N. ; Jernigan, Terry L. ; Baur-Streubel, Ramona ; Ziegler, Georg C. ; Zierhut, Kathrin C. ; Schrantee, Anouk ; Høvik, Marie F. ; Lundervold, Astri J. ; Kelly, Clare ; McCarthy, Hazel ; Skokauskas, Norbert ; O'Gorman Tuura, Ruth L. ; Calvo, Anna ; Lera-Miguel, Sara ; Nicolau, Rosa ; Chantiluke, Kaylita C. ; Christakou, Anastasia ; Vance, Alasdair ; Cercignani, Mara ; Gabel, Matt C. ; Asherson, Philip ; Baumeister, Sarah ; Brandeis, Daniel ; Hohmann, Sarah ; Bramati, Ivanei E. ; Tovar-Moll, Fernanda ; Fallgatter, Andreas J. ; Kardatzki, Bernd ; Schwarz, Lena ; Anikin, Anatoly ; Baranov, Alexandr ; Gogberashvili, Tinatin ; Kapilushniy, Dmitry ; Solovieva, Anastasia ; El Marroun, Hanan ; White, Tonya ; Karkashadze, Georgii ; Namazova-Baranova, Leyla ; Ethofer, Thomas ; Mattos, Paulo ; Banaschewski, Tobias ; Coghill, David ; Plessen, Kerstin J ; Kuntsi, Jonna ; Mehta, Mitul A. ; Paloyelis, Yannis ; Harrison, Neil A. ; Bellgrove, Mark A. ; Silk, Tim J. ; Cubillo, Ana I. ; Rubia, Katya ; Lazaro, Luisa ; Brem, Silvia ; Walitza, Susanne ; Frodl, Thomas ; Zentis, Mariam ; Castellanos, Francisco X. ; Yoncheva, Yuliya N ; Haavik, Jan ; Reneman, Liesbeth ; Conzelmann, Annette ; Lesch, Klaus-Peter ; Pauli, Paul ; Reif, Andreas ; Tamm, Leanne ; Konrad, Kerstin ; Oberwelland Weiss, Eileen ; Busatto, Geraldo F ; Louza, Mario R ; Durston, Sarah ; Hoekstra, Pieter J ; Oosterlaan, Jaap ; Stevens, Michael C. ; Ramos-Quiroga, J Antoni ; Vilarroya, Oscar ; Fair, Damien A ; Nigg, Joel T ; Thompson, Paul M ; Buitelaar, Jan K ; Faraone, Stephen V ; Shaw, Philip ; Tiemeier, Henning ; Bralten, Janita ; Franke, Barbara. / Brain Imaging of the Cortex in ADHD : A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples. In: American Journal of Psychiatry. 2019 ; Vol. 176, No. 7. pp. 531-542.
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    title = "Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples",
    abstract = "Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies.Methods: Cortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707).Results: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample.Conclusions: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.",
    author = "Martine Hoogman and Ryan Muetzel and Guimaraes, {Joao P.} and Elena Shumskaya and Maarten Mennes and Zwiers, {Marcel P.} and Neda Jahanshad and Gustavo Sudre and Thomas Wolfers and Earl, {Eric A.} and {Soliva Vila}, {Juan Carlos} and Yolanda Vives-Gilabert and Sabin Khadka and Novotny, {Stephanie E.} and Hartman, {Catharina A.} and Heslenfeld, {Dirk J.} and Schweren, {Lizanne J. S.} and Sara Ambrosino and Bob Oranje and {de Zeeuw}, Patrick and Chaim-Avancini, {Tiffany M.} and Rosa, {Pedro G. P.} and Zanetti, {Marcus V.} and Malpas, {Charles B.} and Gregor Kohls and {von Polier}, {Georg G.} and Jochen Seitz and Joseph Biederman and Doyle, {Alysa E.} and Dale, {Anders M.} and {van Erp}, {Theo G. M.} and Epstein, {Jeffery N.} and Jernigan, {Terry L.} and Ramona Baur-Streubel and Ziegler, {Georg C.} and Zierhut, {Kathrin C.} and Anouk Schrantee and H{\o}vik, {Marie F.} and Lundervold, {Astri J.} and Clare Kelly and Hazel McCarthy and Norbert Skokauskas and {O'Gorman Tuura}, {Ruth L.} and Anna Calvo and Sara Lera-Miguel and Rosa Nicolau and Chantiluke, {Kaylita C.} and Anastasia Christakou and Alasdair Vance and Mara Cercignani and Gabel, {Matt C.} and Philip Asherson and Sarah Baumeister and Daniel Brandeis and Sarah Hohmann and Bramati, {Ivanei E.} and Fernanda Tovar-Moll and Fallgatter, {Andreas J.} and Bernd Kardatzki and Lena Schwarz and Anatoly Anikin and Alexandr Baranov and Tinatin Gogberashvili and Dmitry Kapilushniy and Anastasia Solovieva and {El Marroun}, Hanan and Tonya White and Georgii Karkashadze and Leyla Namazova-Baranova and Thomas Ethofer and Paulo Mattos and Tobias Banaschewski and David Coghill and Plessen, {Kerstin J} and Jonna Kuntsi and Mehta, {Mitul A.} and Yannis Paloyelis and Harrison, {Neil A.} and Bellgrove, {Mark A.} and Silk, {Tim J.} and Cubillo, {Ana I.} and Katya Rubia and Luisa Lazaro and Silvia Brem and Susanne Walitza and Thomas Frodl and Mariam Zentis and Castellanos, {Francisco X.} and Yoncheva, {Yuliya N} and Jan Haavik and Liesbeth Reneman and Annette Conzelmann and Klaus-Peter Lesch and Paul Pauli and Andreas Reif and Leanne Tamm and Kerstin Konrad and {Oberwelland Weiss}, Eileen and Busatto, {Geraldo F} and Louza, {Mario R} and Sarah Durston and Hoekstra, {Pieter J} and Jaap Oosterlaan and Stevens, {Michael C.} and Ramos-Quiroga, {J Antoni} and Oscar Vilarroya and Fair, {Damien A} and Nigg, {Joel T} and Thompson, {Paul M} and Buitelaar, {Jan K} and Faraone, {Stephen V} and Philip Shaw and Henning Tiemeier and Janita Bralten and Barbara Franke",
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    pages = "531--542",
    journal = "American Journal of Psychiatry",
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    Hoogman, M, Muetzel, R, Guimaraes, JP, Shumskaya, E, Mennes, M, Zwiers, MP, Jahanshad, N, Sudre, G, Wolfers, T, Earl, EA, Soliva Vila, JC, Vives-Gilabert, Y, Khadka, S, Novotny, SE, Hartman, CA, Heslenfeld, DJ, Schweren, LJS, Ambrosino, S, Oranje, B, de Zeeuw, P, Chaim-Avancini, TM, Rosa, PGP, Zanetti, MV, Malpas, CB, Kohls, G, von Polier, GG, Seitz, J, Biederman, J, Doyle, AE, Dale, AM, van Erp, TGM, Epstein, JN, Jernigan, TL, Baur-Streubel, R, Ziegler, GC, Zierhut, KC, Schrantee, A, Høvik, MF, Lundervold, AJ, Kelly, C, McCarthy, H, Skokauskas, N, O'Gorman Tuura, RL, Calvo, A, Lera-Miguel, S, Nicolau, R, Chantiluke, KC, Christakou, A, Vance, A, Cercignani, M, Gabel, MC, Asherson, P, Baumeister, S, Brandeis, D, Hohmann, S, Bramati, IE, Tovar-Moll, F, Fallgatter, AJ, Kardatzki, B, Schwarz, L, Anikin, A, Baranov, A, Gogberashvili, T, Kapilushniy, D, Solovieva, A, El Marroun, H, White, T, Karkashadze, G, Namazova-Baranova, L, Ethofer, T, Mattos, P, Banaschewski, T, Coghill, D, Plessen, KJ, Kuntsi, J, Mehta, MA, Paloyelis, Y, Harrison, NA, Bellgrove, MA, Silk, TJ, Cubillo, AI, Rubia, K, Lazaro, L, Brem, S, Walitza, S, Frodl, T, Zentis, M, Castellanos, FX, Yoncheva, YN, Haavik, J, Reneman, L, Conzelmann, A, Lesch, K-P, Pauli, P, Reif, A, Tamm, L, Konrad, K, Oberwelland Weiss, E, Busatto, GF, Louza, MR, Durston, S, Hoekstra, PJ, Oosterlaan, J, Stevens, MC, Ramos-Quiroga, JA, Vilarroya, O, Fair, DA, Nigg, JT, Thompson, PM, Buitelaar, JK, Faraone, SV, Shaw, P, Tiemeier, H, Bralten, J & Franke, B 2019, 'Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples', American Journal of Psychiatry, vol. 176, no. 7, pp. 531-542. https://doi.org/10.1176/appi.ajp.2019.18091033

    Brain Imaging of the Cortex in ADHD : A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples. / Hoogman, Martine; Muetzel, Ryan; Guimaraes, Joao P.; Shumskaya, Elena; Mennes, Maarten; Zwiers, Marcel P.; Jahanshad, Neda; Sudre, Gustavo; Wolfers, Thomas; Earl, Eric A.; Soliva Vila, Juan Carlos; Vives-Gilabert, Yolanda; Khadka, Sabin; Novotny, Stephanie E.; Hartman, Catharina A.; Heslenfeld, Dirk J.; Schweren, Lizanne J. S.; Ambrosino, Sara; Oranje, Bob; de Zeeuw, Patrick; Chaim-Avancini, Tiffany M.; Rosa, Pedro G. P.; Zanetti, Marcus V.; Malpas, Charles B.; Kohls, Gregor; von Polier, Georg G.; Seitz, Jochen; Biederman, Joseph; Doyle, Alysa E.; Dale, Anders M.; van Erp, Theo G. M.; Epstein, Jeffery N.; Jernigan, Terry L.; Baur-Streubel, Ramona; Ziegler, Georg C.; Zierhut, Kathrin C.; Schrantee, Anouk; Høvik, Marie F.; Lundervold, Astri J.; Kelly, Clare; McCarthy, Hazel; Skokauskas, Norbert; O'Gorman Tuura, Ruth L.; Calvo, Anna; Lera-Miguel, Sara; Nicolau, Rosa; Chantiluke, Kaylita C.; Christakou, Anastasia; Vance, Alasdair; Cercignani, Mara; Gabel, Matt C.; Asherson, Philip; Baumeister, Sarah; Brandeis, Daniel; Hohmann, Sarah; Bramati, Ivanei E.; Tovar-Moll, Fernanda; Fallgatter, Andreas J.; Kardatzki, Bernd; Schwarz, Lena; Anikin, Anatoly; Baranov, Alexandr; Gogberashvili, Tinatin; Kapilushniy, Dmitry; Solovieva, Anastasia; El Marroun, Hanan; White, Tonya; Karkashadze, Georgii; Namazova-Baranova, Leyla; Ethofer, Thomas; Mattos, Paulo; Banaschewski, Tobias; Coghill, David; Plessen, Kerstin J; Kuntsi, Jonna; Mehta, Mitul A.; Paloyelis, Yannis; Harrison, Neil A.; Bellgrove, Mark A.; Silk, Tim J.; Cubillo, Ana I.; Rubia, Katya; Lazaro, Luisa; Brem, Silvia; Walitza, Susanne; Frodl, Thomas; Zentis, Mariam; Castellanos, Francisco X.; Yoncheva, Yuliya N; Haavik, Jan; Reneman, Liesbeth; Conzelmann, Annette; Lesch, Klaus-Peter; Pauli, Paul; Reif, Andreas; Tamm, Leanne; Konrad, Kerstin; Oberwelland Weiss, Eileen; Busatto, Geraldo F; Louza, Mario R; Durston, Sarah; Hoekstra, Pieter J; Oosterlaan, Jaap; Stevens, Michael C.; Ramos-Quiroga, J Antoni; Vilarroya, Oscar; Fair, Damien A; Nigg, Joel T; Thompson, Paul M; Buitelaar, Jan K; Faraone, Stephen V; Shaw, Philip; Tiemeier, Henning; Bralten, Janita; Franke, Barbara.

    In: American Journal of Psychiatry, Vol. 176, No. 7, 01.07.2019, p. 531-542.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Brain Imaging of the Cortex in ADHD

    T2 - A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples

    AU - Hoogman, Martine

    AU - Muetzel, Ryan

    AU - Guimaraes, Joao P.

    AU - Shumskaya, Elena

    AU - Mennes, Maarten

    AU - Zwiers, Marcel P.

    AU - Jahanshad, Neda

    AU - Sudre, Gustavo

    AU - Wolfers, Thomas

    AU - Earl, Eric A.

    AU - Soliva Vila, Juan Carlos

    AU - Vives-Gilabert, Yolanda

    AU - Khadka, Sabin

    AU - Novotny, Stephanie E.

    AU - Hartman, Catharina A.

    AU - Heslenfeld, Dirk J.

    AU - Schweren, Lizanne J. S.

    AU - Ambrosino, Sara

    AU - Oranje, Bob

    AU - de Zeeuw, Patrick

    AU - Chaim-Avancini, Tiffany M.

    AU - Rosa, Pedro G. P.

    AU - Zanetti, Marcus V.

    AU - Malpas, Charles B.

    AU - Kohls, Gregor

    AU - von Polier, Georg G.

    AU - Seitz, Jochen

    AU - Biederman, Joseph

    AU - Doyle, Alysa E.

    AU - Dale, Anders M.

    AU - van Erp, Theo G. M.

    AU - Epstein, Jeffery N.

    AU - Jernigan, Terry L.

    AU - Baur-Streubel, Ramona

    AU - Ziegler, Georg C.

    AU - Zierhut, Kathrin C.

    AU - Schrantee, Anouk

    AU - Høvik, Marie F.

    AU - Lundervold, Astri J.

    AU - Kelly, Clare

    AU - McCarthy, Hazel

    AU - Skokauskas, Norbert

    AU - O'Gorman Tuura, Ruth L.

    AU - Calvo, Anna

    AU - Lera-Miguel, Sara

    AU - Nicolau, Rosa

    AU - Chantiluke, Kaylita C.

    AU - Christakou, Anastasia

    AU - Vance, Alasdair

    AU - Cercignani, Mara

    AU - Gabel, Matt C.

    AU - Asherson, Philip

    AU - Baumeister, Sarah

    AU - Brandeis, Daniel

    AU - Hohmann, Sarah

    AU - Bramati, Ivanei E.

    AU - Tovar-Moll, Fernanda

    AU - Fallgatter, Andreas J.

    AU - Kardatzki, Bernd

    AU - Schwarz, Lena

    AU - Anikin, Anatoly

    AU - Baranov, Alexandr

    AU - Gogberashvili, Tinatin

    AU - Kapilushniy, Dmitry

    AU - Solovieva, Anastasia

    AU - El Marroun, Hanan

    AU - White, Tonya

    AU - Karkashadze, Georgii

    AU - Namazova-Baranova, Leyla

    AU - Ethofer, Thomas

    AU - Mattos, Paulo

    AU - Banaschewski, Tobias

    AU - Coghill, David

    AU - Plessen, Kerstin J

    AU - Kuntsi, Jonna

    AU - Mehta, Mitul A.

    AU - Paloyelis, Yannis

    AU - Harrison, Neil A.

    AU - Bellgrove, Mark A.

    AU - Silk, Tim J.

    AU - Cubillo, Ana I.

    AU - Rubia, Katya

    AU - Lazaro, Luisa

    AU - Brem, Silvia

    AU - Walitza, Susanne

    AU - Frodl, Thomas

    AU - Zentis, Mariam

    AU - Castellanos, Francisco X.

    AU - Yoncheva, Yuliya N

    AU - Haavik, Jan

    AU - Reneman, Liesbeth

    AU - Conzelmann, Annette

    AU - Lesch, Klaus-Peter

    AU - Pauli, Paul

    AU - Reif, Andreas

    AU - Tamm, Leanne

    AU - Konrad, Kerstin

    AU - Oberwelland Weiss, Eileen

    AU - Busatto, Geraldo F

    AU - Louza, Mario R

    AU - Durston, Sarah

    AU - Hoekstra, Pieter J

    AU - Oosterlaan, Jaap

    AU - Stevens, Michael C.

    AU - Ramos-Quiroga, J Antoni

    AU - Vilarroya, Oscar

    AU - Fair, Damien A

    AU - Nigg, Joel T

    AU - Thompson, Paul M

    AU - Buitelaar, Jan K

    AU - Faraone, Stephen V

    AU - Shaw, Philip

    AU - Tiemeier, Henning

    AU - Bralten, Janita

    AU - Franke, Barbara

    PY - 2019/7/1

    Y1 - 2019/7/1

    N2 - Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies.Methods: Cortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707).Results: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample.Conclusions: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

    AB - Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies.Methods: Cortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707).Results: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample.Conclusions: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

    UR - http://www.scopus.com/inward/record.url?scp=85069237582&partnerID=8YFLogxK

    U2 - 10.1176/appi.ajp.2019.18091033

    DO - 10.1176/appi.ajp.2019.18091033

    M3 - Article

    VL - 176

    SP - 531

    EP - 542

    JO - American Journal of Psychiatry

    JF - American Journal of Psychiatry

    SN - 0002-953X

    IS - 7

    ER -