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

2021; Springer Nature; Volume: 11; Issue: 1 Linguagem: Inglês

10.1038/s41398-021-01622-1

2158-3188

Anita Harrewijn, Elise M. Cardinale, Nynke A. Groenewold, Janna Marie Bas‐Hoogendam, Moji Aghajani, Kevin Hilbert, Narcı́s Cardoner, Daniel Porta‐Casteràs, Savannah N. Gosnell, Ramiro Salas, Andrea Parolin Jackowski, Pedro Mário Pan, Giovanni Abrahão Salum, Karina S. Blair, James Blair, Mira Z. Hammoud, Mohammed R. Milad, Katie L. Burkhouse, K. Luan Phan, Heidi K. Schroeder, Jeffrey R. Strawn, Katja Beesdo‐Baum, Neda Jahanshad, Sophia I. Thomopoulos, Randy L. Buckner, Jared A. Nielsen, Jordan W. Smoller, Jair C. Soares, Benson Mwangi, Mon‐Ju Wu, Giovana Zunta‐Soares, Michal Assaf, Gretchen J. Diefenbach, Paolo Brambilla, Eleonora Maggioni, David Hofmann, Thomas Straube, Carmen Andreescu, Rachel Berta, Erica Tamburo, Rebecca B. Price, Gisele Gus Manfro, Federica Agosta, Elisa Canu, Camilla Cividini, Massimo Filippi, Milutin Kostić, Ana Munjiza, Bianca A. V. Alberton, Brenda E. Benson, Gabrielle F. Freitag, Courtney A. Filippi, Andrea L. Gold, Ellen Leibenluft, Grace Ringlein, Kathryn E. Werwath, Hannah Zwiebel, André Zugman, Hans J. Grabe, Sandra Van der Auwera, Katharina Wittfeld, Henry Völzke, Robin Bülow, Nicholas L. Balderston, Monique Ernst, Christian Grillon, Lilianne R. Mujica‐Parodi, Helena van Nieuwenhuizen, Hugo Critchley, Elena Makovac, Matteo Mancini, Frances Meeten, Cristina Ottaviani, Tali M. Ball, Gregory A. Fonzo, Martin P. Paulus, Murray B. Stein, Raquel E. Gur, Ruben C. Gur, Antonia N. Kaczkurkin, Bart Larsen, Theodore D. Satterthwaite, Jennifer C. Harper, Michael J. Myers, Michael T. Perino, Chad M. Sylvester, Qiongru Yu, Ulrike Lueken, Dick J. Veltman, Paul M. Thompson, Dan J. Stein, Nic J.A. van der Wee, Anderson M. Winkler, Daniel S. Pine,

Neuroscience and Music Perception

Abstract 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.