Translational Psychiatry (Oct 2021)
Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group
- Anita Harrewijn,
- Elise M. Cardinale,
- Nynke A. Groenewold,
- Janna Marie Bas-Hoogendam,
- Moji Aghajani,
- Kevin Hilbert,
- Narcis Cardoner,
- Daniel Porta-Casteràs,
- 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. Thomopoulos,
- Randy Buckner,
- Jared A. Nielsen,
- Jordan W. Smoller,
- Jair C. Soares,
- Benson Mwangi,
- Mon-Ju Wu,
- Giovana B. 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 G. Manfro,
- Federica Agosta,
- Elisa Canu,
- Camilla Cividini,
- Massimo Filippi,
- Milutin Kostić,
- Ana Munjiza Jovanovic,
- Bianca A. V. Alberton,
- 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 Auwera,
- Katharina Wittfeld,
- Henry Völzke,
- Robin Bülow,
- Nicholas L. Balderston,
- Monique Ernst,
- Christian Grillon,
- Lilianne R. Mujica-Parodi,
- Helena van Nieuwenhuizen,
- 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. Kaczkurkin,
- Bart Larsen,
- Theodore D. Satterthwaite,
- 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 Wee,
- Anderson M. Winkler,
- Daniel S. Pine
Affiliations
- Anita Harrewijn
- Emotion and Development Branch, National Institute of Mental Health
- Elise M. Cardinale
- Emotion and Development Branch, National Institute of Mental Health
- Nynke A. Groenewold
- Department of Psychiatry & Neuroscience Institute, University of Cape Town
- Janna Marie Bas-Hoogendam
- Department of Psychiatry, Leiden University Medical Center
- Moji Aghajani
- Department of Psychiatry, Amsterdam UMC, location VUMC
- Kevin Hilbert
- Department of Psychology, Humboldt-Universität zu Berlin
- Narcis Cardoner
- Department of Mental Health, University Hospital Parc Taulí-I3PT
- Daniel Porta-Casteràs
- Department of Mental Health, University Hospital Parc Taulí-I3PT
- Savannah Gosnell
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine
- Ramiro Salas
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine
- Andrea P. Jackowski
- LiNC, Department of Psychiatry, Federal University of São Paulo
- Pedro M. Pan
- LiNC, Department of Psychiatry, Federal University of São Paulo
- Giovanni A. Salum
- Section on Negative Affect and Social Processes, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul
- Karina S. Blair
- Center for Neurobehavioral Research, Boys Town National Research Hospital
- James R. Blair
- Center for Neurobehavioral Research, Boys Town National Research Hospital
- Mira Z. Hammoud
- Department of Psychiatry, NYU School of Medicine, New York University
- Mohammed R. Milad
- Department of Psychiatry, NYU School of Medicine, New York University
- Katie L. Burkhouse
- Department of Psychiatry, University of Illinois at Chicago
- K. Luan Phan
- Department of Psychiatry and Behavioral Health, The Ohio State University
- Heidi K. Schroeder
- Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati
- Jeffrey R. Strawn
- Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati
- Katja Beesdo-Baum
- Behavioral Epidemiology, Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden
- Neda Jahanshad
- Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California
- Sophia I. Thomopoulos
- Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California
- Randy Buckner
- Center for Brain Science & Department of Psychology, Harvard University
- Jared A. Nielsen
- Center for Brain Science & Department of Psychology, Harvard University
- Jordan W. Smoller
- Department of Psychiatry, Massachusetts General Hospital
- Jair C. Soares
- Center Of Excellence On Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston
- Benson Mwangi
- Center Of Excellence On Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston
- Mon-Ju Wu
- Center Of Excellence On Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston
- Giovana B. Zunta-Soares
- Center Of Excellence On Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston
- Michal Assaf
- Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital
- Gretchen J. Diefenbach
- Department of Psychiatry, Yale School of Medicine
- Paolo Brambilla
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
- Eleonora Maggioni
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
- David Hofmann
- Institute of Medical Psychology and Systems Neuroscience, University of Muenster
- Thomas Straube
- Institute of Medical Psychology and Systems Neuroscience, University of Muenster
- Carmen Andreescu
- Department of Psychiatry, University of Pittsburgh
- Rachel Berta
- Department of Psychiatry, University of Pittsburgh
- Erica Tamburo
- Department of Psychiatry, University of Pittsburgh
- Rebecca B. Price
- Department of Psychiatry, University of Pittsburgh
- Gisele G. Manfro
- Anxiety Disorder Program, Hospital de Clínicas de Porto Alegre, Department of Psychiatry, Federal University of Rio Grande do Sul
- Federica Agosta
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute
- Elisa Canu
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute
- Camilla Cividini
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute
- Massimo Filippi
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute
- Milutin Kostić
- Institute of Mental Health, University of Belgrade
- Ana Munjiza Jovanovic
- Institute of Mental Health, University of Belgrade
- Bianca A. V. Alberton
- Graduate Program in Electrical and Computer Engineering, Universidade Tecnológica Federal do Paraná
- Brenda Benson
- Emotion and Development Branch, National Institute of Mental Health
- Gabrielle F. Freitag
- Emotion and Development Branch, National Institute of Mental Health
- Courtney A. Filippi
- Emotion and Development Branch, National Institute of Mental Health
- Andrea L. Gold
- Department of Psychiatry and Human Behavior, Brown University Warren Alpert Medical School
- Ellen Leibenluft
- Emotion and Development Branch, National Institute of Mental Health
- Grace V. Ringlein
- Emotion and Development Branch, National Institute of Mental Health
- Kathryn E. Werwath
- Emotion and Development Branch, National Institute of Mental Health
- Hannah Zwiebel
- Emotion and Development Branch, National Institute of Mental Health
- André Zugman
- Emotion and Development Branch, National Institute of Mental Health
- Hans J. Grabe
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald
- Sandra Van der Auwera
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald
- Katharina Wittfeld
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald
- Henry Völzke
- Institute for Community Medicine, University Medicine Greifswald
- Robin Bülow
- Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald
- Nicholas L. Balderston
- Center for Neuromodulation in Depression and Stress, University of Pennsylvania
- Monique Ernst
- Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health
- Christian Grillon
- Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health
- Lilianne R. Mujica-Parodi
- Department of Biomedical Engineering, Stony Brook University
- Helena van Nieuwenhuizen
- Department of Physics, Stony Brook University
- Hugo D. Critchley
- Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex
- Elena Makovac
- Centre for Neuroimaging Science, Kings College London
- Matteo Mancini
- Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex
- Frances Meeten
- School of Psychology, University of Sussex
- Cristina Ottaviani
- Department of Psychology, Sapienza University of Rome
- Tali M. Ball
- Psychiatry and Behavioral Sciences, Stanford University School of Medicine
- Gregory A. Fonzo
- Department of Psychiatry and Behavioral Sciences, The University of Texas at Austin Dell Medical School
- Martin P. Paulus
- Laureate Institute for Brain Research
- Murray B. Stein
- Department of Psychiatry, School of Medicine and Herbert Wertheim School of Public Health, University of California, San Diego
- Raquel E. Gur
- Department of Psychiatry, University of Pennsylvania
- Ruben C. Gur
- Department of Psychiatry, University of Pennsylvania
- Antonia N. Kaczkurkin
- Department of Psychiatry, University of Pennsylvania
- Bart Larsen
- Department of Psychiatry, University of Pennsylvania
- Theodore D. Satterthwaite
- Department of Psychiatry, University of Pennsylvania
- Jennifer Harper
- Department of Psychiatry, Washington University
- Michael Myers
- Department of Psychiatry, Washington University
- Michael T. Perino
- Department of Psychiatry, Washington University
- Chad M. Sylvester
- Department of Psychiatry, Washington University
- Qiongru Yu
- Department of Psychiatry, Washington University
- Ulrike Lueken
- Department of Psychology, Humboldt-Universität zu Berlin
- Dick J. Veltman
- Department of Psychiatry, Amsterdam UMC, location VUMC
- Paul M. Thompson
- Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California
- Dan J. Stein
- South African Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town
- Nic J. A. Van der Wee
- Department of Psychiatry, Leiden University Medical Center
- Anderson M. Winkler
- Emotion and Development Branch, National Institute of Mental Health
- Daniel S. Pine
- Emotion and Development Branch, National Institute of Mental Health
- DOI
- https://doi.org/10.1038/s41398-021-01622-1
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 15
Abstract
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.
