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

• DOI: 10.1038/s41398-021-01622-1
• Publication Date: 2021-10-01T20:19:17Z
• Authors: Anita Harrewijn; Elise M. Cardinale; Nynke A. Groenewold; Janna Marie Bas-H...; Moji Aghajani; Kevin Hilbert; Narcis Cardoner; Daniel Porta-Cast...; Savannah Gosnell; Ramiro Salas; Andrea P. Jackowski; Pedro M. Pan; Giovanni A. Salum; Karina S. Blair; James R. 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. Thomopo...; Randy Buckner; Jared A. Nielsen; Jordan W. Smoller; Jair C. Soares; Benson Mwangi; Mon-Ju Wu; Giovana B. Zunta-...; Michal Assaf; Gretchen J. Diefe...; Paolo Brambilla; Eleonora Maggioni; David Hofmann; Thomas Straube; Carmen Andreescu; Rachel Berta; Erica Tamburo; Rebecca B. Price; Gisele G. Manfro; Federica Agosta; Elisa Canu; Camilla Cividini; Massimo Filippi; Milutin Kostić; Ana Munjiza Jovan...; Bianca A. V. Albe...; Brenda Benson; Gabrielle F. Freitag; Courtney A. Filippi; Andrea L. Gold; Ellen Leibenluft; Grace V. Ringlein; Kathryn E. Werwath; Hannah Zwiebel; André Zugman; Hans J. Grabe; Sandra Van der Au...; Katharina Wittfeld; Henry Völzke; Robin Bülow; Nicholas L. Balde...; Monique Ernst; Christian Grillon; Lilianne R. Mujic...; Helena van Nieuwe...; Hugo D. 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. Kaczku...; Bart Larsen; Theodore D. Satte...; Jennifer Harper; Michael 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...; Anderson M. Winkler; Daniel S. Pine
• Keywords: Adult; Male; Biological Psychology; Clinical Sciences; 150; 610; Clinical sciences; Neurosciences. Biological psychiatry. Neuropsychiatry; psychology; Anxiety; Article; neuroscience; 03 medical and health sciences; 0302 clinical medicine; Behavioral and Social Science; Psychology; Humans; ddc:610; generalized anxiety disorder; structural brain imaging; cortical thickness; Child; diagnostic imaging [Brain]; diagnostic imaging [Anxiety Disorders]; Biomedical and Clinical Sciences; Neurosciences; Brain; Anxiety Disorders; Magnetic Resonance Imaging; Brain Disorders; 3. Good health; multicentric network; Public Health and Health Services; Adult; Anxiety; Child; Female; Humans; Magnetic Resonance Imaging; Male; Anxiety Disorders; Brain; Women's Health; Biomedical Imaging; Biological psychology; Mental health; Female; 4.2 Evaluation of markers and technologies; Neuroscience; RC321-571

AbstractThe 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.