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 Oranje; 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

doi:10.1176/appi.ajp.2019.18091033

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 OranjeTiffany 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

Psychology

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

123 Citations (Scopus)

Abstract

Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonrepli-cations 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=20.21). 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 language	English
Pages (from-to)	531-542
Number of pages	12
Journal	American Journal of Psychiatry
Volume	176
Issue number	7
DOIs	https://doi.org/10.1176/appi.ajp.2019.18091033
Publication status	Published - Jul 2019

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10.1176/appi.ajp.2019.18091033

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Hoogman, M., Muetzel, R., Guimaraes, J. P., Shumskaya, E., Mennes, M., Zwiers, M. P., Jahanshad, N., Sudre, G., Wolfers, T., Earl, E. A., Soliva Vila, J. C., Vives-Gilabert, Y., Khadka, S., Novotny, S. E., Hartman, C. A., Heslenfeld, D. J., Schweren, L. J. S., Ambrosino, S., Oranje, B., ... 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 Oranje, 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.

@article{a027a073661e4ebd9217da9ec09d1a04,

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 nonrepli-cations 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{\textquoteright}s d=20.21). 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 Oranje}, 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 Lesch, {Klaus Peter} 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",

year = "2019",

month = jul,

doi = "10.1176/appi.ajp.2019.18091033",

language = "English",

volume = "176",

pages = "531--542",

journal = "American Journal of Psychiatry",

issn = "0002-953X",

publisher = "American Psychiatric Publishing",

number = "7",

}

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 Oranje, 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, KP, 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 Oranje, 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, 07.2019, p. 531-542.

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

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 Oranje, 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

Y1 - 2019/7

N2 - Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonrepli-cations 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=20.21). 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 nonrepli-cations 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=20.21). 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

C2 - 31014101

AN - SCOPUS:85069237582

VL - 176

SP - 531

EP - 542

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

SN - 0002-953X

IS - 7

ER -

Brain imaging of the cortex in ADHD: A coordinated analysis of large-scale clinical and population-based samples

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