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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Anita Harrewijn - , National Institute of Mental Health (NIMH) (Author)
  • Elise M. Cardinale - , National Institute of Mental Health (NIMH) (Author)
  • Nynke A. Groenewold - , University of Cape Town (Author)
  • Janna Marie Bas-Hoogendam - , Leiden University, Leiden University Medical Centre (LUMC) (Author)
  • Moji Aghajani - , GGZ InGeest, Amsterdam University Medical Centers (UMC) (Author)
  • Kevin Hilbert - , Humboldt University of Berlin (Author)
  • Narcis Cardoner - , Parc Taulí Research and Innovation Institute, Autonomous University of Barcelona, CIBER - Center for Biomedical Research Network (Author)
  • Daniel Porta-Casteràs - , Parc Taulí Research and Innovation Institute, Autonomous University of Barcelona, CIBER - Center for Biomedical Research Network (Author)
  • Savannah Gosnell - , Baylor College of Medicine (Author)
  • Ramiro Salas - , Baylor College of Medicine (Author)
  • Andrea P. Jackowski - , Federal University of São Paulo (Author)
  • Pedro M. Pan - , Federal University of São Paulo (Author)
  • Giovanni A. Salum - , Universidade Federal do Rio Grande do Sul (Author)
  • Karina S. Blair - , Boys Town National Research Hospital (Author)
  • James R. Blair - , Boys Town National Research Hospital (Author)
  • Mira Z. Hammoud - , New York University (Author)
  • Mohammed R. Milad - , New York University (Author)
  • Katie L. Burkhouse - , University of Illinois at Chicago (Author)
  • K. Luan Phan - , Ohio State University (Author)
  • Heidi K. Schroeder - , University of Cincinnati (Author)
  • Jeffrey R. Strawn - , University of Cincinnati (Author)
  • Katja Beesdo-Baum - , Chair of Behavioral Epidemiology (Author)
  • Neda Jahanshad - , University of Southern California (Author)
  • Sophia I. Thomopoulos - , University of Southern California (Author)
  • Randy Buckner - , Harvard University (Author)
  • Jared A. Nielsen - , Harvard University, Brigham Young University (Author)
  • Jordan W. Smoller - , Harvard University (Author)
  • Jair C. Soares - , University of Texas Health Science Center at Houston (Author)
  • Benson Mwangi - , University of Texas Health Science Center at Houston (Author)
  • Mon Ju Wu - , University of Texas Health Science Center at Houston (Author)
  • Giovana B. Zunta-Soares - , University of Texas Health Science Center at Houston (Author)
  • Michal Assaf - , Institute of Living, Yale University (Author)
  • Gretchen J. Diefenbach - , Yale University, Institute of Living (Author)
  • Paolo Brambilla - , IRCCS Fondazione Ca'Granda – Ospedale Maggiore Policlinico - Milano, University of Milan (Author)
  • Eleonora Maggioni - , IRCCS Fondazione Ca'Granda – Ospedale Maggiore Policlinico - Milano (Author)
  • David Hofmann - , University of Münster (Author)
  • Thomas Straube - , University of Münster (Author)
  • Carmen Andreescu - , University of Pittsburgh (Author)
  • Rachel Berta - , University of Pittsburgh (Author)
  • Erica Tamburo - , University of Pittsburgh (Author)
  • Rebecca B. Price - , University of Pittsburgh (Author)
  • Gisele G. Manfro - , Universidade Federal do Rio Grande do Sul (Author)
  • Federica Agosta - , Vita-Salute San Raffaele University (Author)
  • Elisa Canu - , Vita-Salute San Raffaele University (Author)
  • Camilla Cividini - , Vita-Salute San Raffaele University (Author)
  • Massimo Filippi - , Vita-Salute San Raffaele University (Author)
  • Milutin Kostić - , University of Belgrade (Author)
  • Ana Munjiza Jovanovic - , University of Belgrade (Author)
  • Bianca A.V. Alberton - , Universidade Tecnológica Federal do Paraná (Author)
  • Brenda Benson - , National Institute of Mental Health (NIMH) (Author)
  • Gabrielle F. Freitag - , National Institute of Mental Health (NIMH) (Author)
  • Courtney A. Filippi - , National Institute of Mental Health (NIMH) (Author)
  • Andrea L. Gold - , Brown University (Author)
  • Ellen Leibenluft - , National Institute of Mental Health (NIMH) (Author)
  • Grace V. Ringlein - , National Institute of Mental Health (NIMH) (Author)
  • Kathryn E. Werwath - , National Institute of Mental Health (NIMH) (Author)
  • Hannah Zwiebel - , National Institute of Mental Health (NIMH) (Author)
  • André Zugman - , National Institute of Mental Health (NIMH) (Author)
  • Hans J. Grabe - , University of Greifswald (Author)
  • Sandra van der Auwera - , University of Greifswald (Author)
  • Katharina Wittfeld - , University of Greifswald (Author)
  • Henry Völzke - , University of Greifswald (Author)
  • Robin Bülow - , University of Greifswald (Author)
  • Nicholas L. Balderston - , University of Pennsylvania (Author)
  • Monique Ernst - , National Institute of Mental Health (NIMH) (Author)
  • Christian Grillon - , National Institute of Mental Health (NIMH) (Author)
  • Lilianne R. Mujica-Parodi - , Stony Brook University (Author)
  • Helena van Nieuwenhuizen - , Stony Brook University (Author)
  • Hugo D. Critchley - , University of Sussex (Author)
  • Elena Makovac - , King's College London (KCL) (Author)
  • Matteo Mancini - , Brighton and Sussex Medical School (Author)
  • Frances Meeten - , University of Sussex (Author)
  • Cristina Ottaviani - , IRCCS Fondazione Santa Lucia - Roma (Author)
  • Tali M. Ball - , Stanford Medicine (Author)
  • Gregory A. Fonzo - , University of Texas at Austin (Author)
  • Martin P. Paulus - , Laureate Institute for Brain Research (Author)
  • Murray B. Stein - , University of California San Diego Health (Author)
  • Raquel E Gur - , University of Pennsylvania (Author)
  • Ruben C Gur - , University of Pennsylvania (Author)
  • Antonia N. Kaczkurkin - , University of Pennsylvania (Author)
  • Bart Larsen - , University of Pennsylvania (Author)
  • Theodore D. Satterthwaite - , University of Pennsylvania (Author)
  • Jennifer Harper - , Washington University St. Louis (Author)
  • Michael Myers - , Washington University St. Louis (Author)
  • Michael T Perino - , Washington University St. Louis (Author)
  • Chad M. Sylvester - , Washington University St. Louis (Author)
  • Qiongru Yu - , Washington University St. Louis (Author)
  • Ulrike Lueken - , Humboldt University of Berlin (Author)
  • Dick J. Veltman - , University of Amsterdam, Amsterdam University Medical Centers (UMC) (Author)
  • Paul M Thompson - , University of Southern California (Author)
  • Dan J. Stein - , University of Cape Town (Author)
  • Nic J. A. van der Wee - , Leiden University Medical Centre (LUMC) (Author)
  • Anderson M. Winkler - , National Institute of Mental Health (NIMH) (Author)
  • Daniel S. Pine - , National Institute of Mental Health (NIMH) (Author)

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.

Details

Original languageEnglish
Article number502
JournalTranslational psychiatry
Volume11
Issue number1
Publication statusPublished - 1 Oct 2021
Peer-reviewedYes

External IDs

PubMed 34599145
ORCID /0000-0002-9687-5527/work/142235279