Journal Article

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

Hammoud, Mira Z, Stein, Dan J, Tamburo Erica, Diefenbach, Gretchen J, Blair, Karina S, Critchley, Hugo D, Gur, Raquel E, Porta-Casteràs, Daniel, Cardoner Narcis, Perino, Michael T, Straube, Thomas, Canu Elisa, Fonzo, Gregory A, Milad, Mohammed R, Paulus, Martin P, Lueken Ulrike, Soares, Jair C, Groenewold, Nynke A, Wittfeld Katharina, Mon-Ju, Wu, Kostić Milutin, Bülow, Robin, Salum, Giovanni A, Veltman, Dick J, Völzke Henry, Benson, Mwangi, Ball, Tali M, Ringlein Grace V, Filippi, Courtney A, Balderston, Nicholas L, Hilbert, Kevin, Kaczkurkin, Antonia N, Thompson, Paul M, Gold, Andrea L, Grabe, Hans J, Van der Auwera Sandra, Stein, Murray B, Filippi Massimo, Gur, Ruben C, Satterthwaite, Theodore D, Myers, Michael, Blair, James R, Van der Wee Nic J A, Cividini Camilla, Pine, Daniel S, Andreescu, Carmen, Makovac Elena, Sylvester, Chad M, Beesdo-Baum Katja, Smoller, Jordan W, Zugman André, Harrewijn Anita, Gosnell Savannah, Assaf Michal, Agosta Federica, Winkler, Anderson M, Maggioni Eleonora, Munjiza Jovanovic Ana, Strawn, Jeffrey R, Leibenluft Ellen, Zunta-Soares, Giovana B, Ernst, Monique, Ottaviani, Cristi

2021

Overview

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.

• Publisher: Nature Publishing Group
• Subject: Brain research / Generalized anxiety disorder / Working groups