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Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combine...

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Autores principales: Harrewijn, Anita, Cardinale, Elise M., Groenewold, Nynke A., Bas-Hoogendam, Janna Marie, Aghajani, Moji, Hilbert, Kevin, Cardoner, Narcis, Porta-Casteràs, Daniel, Gosnell, Savannah, Salas, Ramiro, Jackowski, Andrea P., Pan, Pedro M., Salum, Giovanni A., Blair, Karina S., Blair, James R., Hammoud, Mira Z., Milad, Mohammed R., Burkhouse, Katie L., Phan, K. Luan, Schroeder, Heidi K., Strawn, Jeffrey R., Beesdo-Baum, Katja, Jahanshad, Neda, Thomopoulos, Sophia I., Buckner, Randy, Nielsen, Jared A., Smoller, Jordan W., Soares, Jair C., Mwangi, Benson, Wu, Mon-Ju, Zunta-Soares, Giovana B., Assaf, Michal, Diefenbach, Gretchen J., Brambilla, Paolo, Maggioni, Eleonora, Hofmann, David, Straube, Thomas, Andreescu, Carmen, Berta, Rachel, Tamburo, Erica, Price, Rebecca B., Manfro, Gisele G., Agosta, Federica, Canu, Elisa, Cividini, Camilla, Filippi, Massimo, Kostić, Milutin, Munjiza Jovanovic, Ana, Alberton, Bianca A. V., Benson, Brenda, Freitag, Gabrielle F., Filippi, Courtney A., Gold, Andrea L., Leibenluft, Ellen, Ringlein, Grace V., Werwath, Kathryn E., Zwiebel, Hannah, Zugman, André, Grabe, Hans J., Van der Auwera, Sandra, Wittfeld, Katharina, Völzke, Henry, Bülow, Robin, Balderston, Nicholas L., Ernst, Monique, Grillon, Christian, Mujica-Parodi, Lilianne R., van Nieuwenhuizen, Helena, Critchley, Hugo D., Makovac, Elena, Mancini, Matteo, Meeten, Frances, Ottaviani, Cristina, Ball, Tali M., Fonzo, Gregory A., Paulus, Martin P., Stein, Murray B., Gur, Raquel E., Gur, Ruben C., Kaczkurkin, Antonia N., Larsen, Bart, Satterthwaite, Theodore D., Harper, Jennifer, Myers, Michael, Perino, Michael T., Sylvester, Chad M., Yu, Qiongru, Lueken, Ulrike, Veltman, Dick J., Thompson, Paul M., Stein, Dan J., Van der Wee, Nic J. A., Winkler, Anderson M., Pine, Daniel S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486763/
https://www.ncbi.nlm.nih.gov/pubmed/34599145
http://dx.doi.org/10.1038/s41398-021-01622-1
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author Harrewijn, Anita
Cardinale, Elise M.
Groenewold, Nynke A.
Bas-Hoogendam, Janna Marie
Aghajani, Moji
Hilbert, Kevin
Cardoner, Narcis
Porta-Casteràs, Daniel
Gosnell, Savannah
Salas, Ramiro
Jackowski, Andrea P.
Pan, Pedro M.
Salum, Giovanni A.
Blair, Karina S.
Blair, James R.
Hammoud, Mira Z.
Milad, Mohammed R.
Burkhouse, Katie L.
Phan, K. Luan
Schroeder, Heidi K.
Strawn, Jeffrey R.
Beesdo-Baum, Katja
Jahanshad, Neda
Thomopoulos, Sophia I.
Buckner, Randy
Nielsen, Jared A.
Smoller, Jordan W.
Soares, Jair C.
Mwangi, Benson
Wu, Mon-Ju
Zunta-Soares, Giovana B.
Assaf, Michal
Diefenbach, Gretchen J.
Brambilla, Paolo
Maggioni, Eleonora
Hofmann, David
Straube, Thomas
Andreescu, Carmen
Berta, Rachel
Tamburo, Erica
Price, Rebecca B.
Manfro, Gisele G.
Agosta, Federica
Canu, Elisa
Cividini, Camilla
Filippi, Massimo
Kostić, Milutin
Munjiza Jovanovic, Ana
Alberton, Bianca A. V.
Benson, Brenda
Freitag, Gabrielle F.
Filippi, Courtney A.
Gold, Andrea L.
Leibenluft, Ellen
Ringlein, Grace V.
Werwath, Kathryn E.
Zwiebel, Hannah
Zugman, André
Grabe, Hans J.
Van der Auwera, Sandra
Wittfeld, Katharina
Völzke, Henry
Bülow, Robin
Balderston, Nicholas L.
Ernst, Monique
Grillon, Christian
Mujica-Parodi, Lilianne R.
van Nieuwenhuizen, Helena
Critchley, Hugo D.
Makovac, Elena
Mancini, Matteo
Meeten, Frances
Ottaviani, Cristina
Ball, Tali M.
Fonzo, Gregory A.
Paulus, Martin P.
Stein, Murray B.
Gur, Raquel E.
Gur, Ruben C.
Kaczkurkin, Antonia N.
Larsen, Bart
Satterthwaite, Theodore D.
Harper, Jennifer
Myers, Michael
Perino, Michael T.
Sylvester, Chad M.
Yu, Qiongru
Lueken, Ulrike
Veltman, Dick J.
Thompson, Paul M.
Stein, Dan J.
Van der Wee, Nic J. A.
Winkler, Anderson M.
Pine, Daniel S.
author_facet Harrewijn, Anita
Cardinale, Elise M.
Groenewold, Nynke A.
Bas-Hoogendam, Janna Marie
Aghajani, Moji
Hilbert, Kevin
Cardoner, Narcis
Porta-Casteràs, Daniel
Gosnell, Savannah
Salas, Ramiro
Jackowski, Andrea P.
Pan, Pedro M.
Salum, Giovanni A.
Blair, Karina S.
Blair, James R.
Hammoud, Mira Z.
Milad, Mohammed R.
Burkhouse, Katie L.
Phan, K. Luan
Schroeder, Heidi K.
Strawn, Jeffrey R.
Beesdo-Baum, Katja
Jahanshad, Neda
Thomopoulos, Sophia I.
Buckner, Randy
Nielsen, Jared A.
Smoller, Jordan W.
Soares, Jair C.
Mwangi, Benson
Wu, Mon-Ju
Zunta-Soares, Giovana B.
Assaf, Michal
Diefenbach, Gretchen J.
Brambilla, Paolo
Maggioni, Eleonora
Hofmann, David
Straube, Thomas
Andreescu, Carmen
Berta, Rachel
Tamburo, Erica
Price, Rebecca B.
Manfro, Gisele G.
Agosta, Federica
Canu, Elisa
Cividini, Camilla
Filippi, Massimo
Kostić, Milutin
Munjiza Jovanovic, Ana
Alberton, Bianca A. V.
Benson, Brenda
Freitag, Gabrielle F.
Filippi, Courtney A.
Gold, Andrea L.
Leibenluft, Ellen
Ringlein, Grace V.
Werwath, Kathryn E.
Zwiebel, Hannah
Zugman, André
Grabe, Hans J.
Van der Auwera, Sandra
Wittfeld, Katharina
Völzke, Henry
Bülow, Robin
Balderston, Nicholas L.
Ernst, Monique
Grillon, Christian
Mujica-Parodi, Lilianne R.
van Nieuwenhuizen, Helena
Critchley, Hugo D.
Makovac, Elena
Mancini, Matteo
Meeten, Frances
Ottaviani, Cristina
Ball, Tali M.
Fonzo, Gregory A.
Paulus, Martin P.
Stein, Murray B.
Gur, Raquel E.
Gur, Ruben C.
Kaczkurkin, Antonia N.
Larsen, Bart
Satterthwaite, Theodore D.
Harper, Jennifer
Myers, Michael
Perino, Michael T.
Sylvester, Chad M.
Yu, Qiongru
Lueken, Ulrike
Veltman, Dick J.
Thompson, Paul M.
Stein, Dan J.
Van der Wee, Nic J. A.
Winkler, Anderson M.
Pine, Daniel S.
author_sort Harrewijn, Anita
collection PubMed
description The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.
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spelling pubmed-84867632021-10-19 Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group Harrewijn, Anita Cardinale, Elise M. Groenewold, Nynke A. Bas-Hoogendam, Janna Marie Aghajani, Moji Hilbert, Kevin Cardoner, Narcis Porta-Casteràs, Daniel Gosnell, Savannah Salas, Ramiro Jackowski, Andrea P. Pan, Pedro M. Salum, Giovanni A. Blair, Karina S. Blair, James R. Hammoud, Mira Z. Milad, Mohammed R. Burkhouse, Katie L. Phan, K. Luan Schroeder, Heidi K. Strawn, Jeffrey R. Beesdo-Baum, Katja Jahanshad, Neda Thomopoulos, Sophia I. Buckner, Randy Nielsen, Jared A. Smoller, Jordan W. Soares, Jair C. Mwangi, Benson Wu, Mon-Ju Zunta-Soares, Giovana B. Assaf, Michal Diefenbach, Gretchen J. Brambilla, Paolo Maggioni, Eleonora Hofmann, David Straube, Thomas Andreescu, Carmen Berta, Rachel Tamburo, Erica Price, Rebecca B. Manfro, Gisele G. Agosta, Federica Canu, Elisa Cividini, Camilla Filippi, Massimo Kostić, Milutin Munjiza Jovanovic, Ana Alberton, Bianca A. V. Benson, Brenda Freitag, Gabrielle F. Filippi, Courtney A. Gold, Andrea L. Leibenluft, Ellen Ringlein, Grace V. Werwath, Kathryn E. Zwiebel, Hannah Zugman, André Grabe, Hans J. Van der Auwera, Sandra Wittfeld, Katharina Völzke, Henry Bülow, Robin Balderston, Nicholas L. Ernst, Monique Grillon, Christian Mujica-Parodi, Lilianne R. van Nieuwenhuizen, Helena Critchley, Hugo D. Makovac, Elena Mancini, Matteo Meeten, Frances Ottaviani, Cristina Ball, Tali M. Fonzo, Gregory A. Paulus, Martin P. Stein, Murray B. Gur, Raquel E. Gur, Ruben C. Kaczkurkin, Antonia N. Larsen, Bart Satterthwaite, Theodore D. Harper, Jennifer Myers, Michael Perino, Michael T. Sylvester, Chad M. Yu, Qiongru Lueken, Ulrike Veltman, Dick J. Thompson, Paul M. Stein, Dan J. Van der Wee, Nic J. A. Winkler, Anderson M. Pine, Daniel S. Transl Psychiatry Article The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology. Nature Publishing Group UK 2021-10-01 /pmc/articles/PMC8486763/ /pubmed/34599145 http://dx.doi.org/10.1038/s41398-021-01622-1 Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Harrewijn, Anita
Cardinale, Elise M.
Groenewold, Nynke A.
Bas-Hoogendam, Janna Marie
Aghajani, Moji
Hilbert, Kevin
Cardoner, Narcis
Porta-Casteràs, Daniel
Gosnell, Savannah
Salas, Ramiro
Jackowski, Andrea P.
Pan, Pedro M.
Salum, Giovanni A.
Blair, Karina S.
Blair, James R.
Hammoud, Mira Z.
Milad, Mohammed R.
Burkhouse, Katie L.
Phan, K. Luan
Schroeder, Heidi K.
Strawn, Jeffrey R.
Beesdo-Baum, Katja
Jahanshad, Neda
Thomopoulos, Sophia I.
Buckner, Randy
Nielsen, Jared A.
Smoller, Jordan W.
Soares, Jair C.
Mwangi, Benson
Wu, Mon-Ju
Zunta-Soares, Giovana B.
Assaf, Michal
Diefenbach, Gretchen J.
Brambilla, Paolo
Maggioni, Eleonora
Hofmann, David
Straube, Thomas
Andreescu, Carmen
Berta, Rachel
Tamburo, Erica
Price, Rebecca B.
Manfro, Gisele G.
Agosta, Federica
Canu, Elisa
Cividini, Camilla
Filippi, Massimo
Kostić, Milutin
Munjiza Jovanovic, Ana
Alberton, Bianca A. V.
Benson, Brenda
Freitag, Gabrielle F.
Filippi, Courtney A.
Gold, Andrea L.
Leibenluft, Ellen
Ringlein, Grace V.
Werwath, Kathryn E.
Zwiebel, Hannah
Zugman, André
Grabe, Hans J.
Van der Auwera, Sandra
Wittfeld, Katharina
Völzke, Henry
Bülow, Robin
Balderston, Nicholas L.
Ernst, Monique
Grillon, Christian
Mujica-Parodi, Lilianne R.
van Nieuwenhuizen, Helena
Critchley, Hugo D.
Makovac, Elena
Mancini, Matteo
Meeten, Frances
Ottaviani, Cristina
Ball, Tali M.
Fonzo, Gregory A.
Paulus, Martin P.
Stein, Murray B.
Gur, Raquel E.
Gur, Ruben C.
Kaczkurkin, Antonia N.
Larsen, Bart
Satterthwaite, Theodore D.
Harper, Jennifer
Myers, Michael
Perino, Michael T.
Sylvester, Chad M.
Yu, Qiongru
Lueken, Ulrike
Veltman, Dick J.
Thompson, Paul M.
Stein, Dan J.
Van der Wee, Nic J. A.
Winkler, Anderson M.
Pine, Daniel S.
Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group
title Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group
title_full Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group
title_fullStr Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group
title_full_unstemmed Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group
title_short Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group
title_sort cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the enigma-anxiety working group
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486763/
https://www.ncbi.nlm.nih.gov/pubmed/34599145
http://dx.doi.org/10.1038/s41398-021-01622-1
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