Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group.
Journal: Translational psychiatry
Volume: 11
Issue: 1
Year of Publication: 2021
Affiliated Institutions:
Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA. anita.harrewijn@nih.gov.
Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.
Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Department of Psychiatry, Amsterdam UMC, location VUMC, Amsterdam, The Netherlands.
Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Mental Health, University Hospital Parc Taulí-IPT, Barcelona, Spain.
Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
LiNC, Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil.
Section on Negative Affect and Social Processes, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, NE, USA.
Department of Psychiatry, NYU School of Medicine, New York University, New York, NY, USA.
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.
Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA.
Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA.
Behavioral Epidemiology, Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Center for Brain Science & Department of Psychology, Harvard University, Cambridge, MA, USA.
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
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, Houston, TX, USA.
Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Institute of Medical Psychology and Systems Neuroscience, University of Muenster, Muenster, Germany.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Anxiety Disorder Program, Hospital de Clínicas de Porto Alegre, Department of Psychiatry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Institute of Mental Health, University of Belgrade, Belgrade, Serbia.
Graduate Program in Electrical and Computer Engineering, Universidade Tecnológica Federal do Paraná, Curitiba, Puerto Rico, Brazil.
Department of Psychiatry and Human Behavior, Brown University Warren Alpert Medical School, Providence, RI, USA.
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
Center for Neuromodulation in Depression and Stress, University of Pennsylvania, Philadelphia, PA, USA.
Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, Bethesda, MD, USA.
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
Department of Physics, Stony Brook University, Stony Brook, NY, USA.
Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
Centre for Neuroimaging Science, Kings College London, London, UK.
School of Psychology, University of Sussex, Brighton, UK.
Department of Psychology, Sapienza University of Rome, Rome, Italy.
Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Department of Psychiatry and Behavioral Sciences, The University of Texas at Austin Dell Medical School, Austin, TX, USA.
Laureate Institute for Brain Research, Tulsa, OK, USA.
Department of Psychiatry, School of Medicine and Herbert Wertheim School of Public Health, University of California, San Diego, La Jolla, CA, USA.
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Department of Psychiatry, Washington University, St. Louis, MO, USA.
South African Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Abstract summary
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.
Authors & Co-authors:
Harrewijn Anita A
Cardinale Elise M EM
Groenewold Nynke A NA
Bas-Hoogendam Janna Marie JM
Aghajani Moji M
Hilbert Kevin K
Cardoner Narcis N
Porta-Casteràs Daniel D
Gosnell Savannah S
Salas Ramiro R
Jackowski Andrea P AP
Pan Pedro M PM
Salum Giovanni A GA
Blair Karina S KS
Blair James R JR
Hammoud Mira Z MZ
Milad Mohammed R MR
Burkhouse Katie L KL
Phan K Luan KL
Schroeder Heidi K HK
Strawn Jeffrey R JR
Beesdo-Baum Katja K
Jahanshad Neda N
Thomopoulos Sophia I SI
Buckner Randy R
Nielsen Jared A JA
Smoller Jordan W JW
Soares Jair C JC
Mwangi Benson B
Wu Mon-Ju MJ
Zunta-Soares Giovana B GB
Assaf Michal M
Diefenbach Gretchen J GJ
Brambilla Paolo P
Maggioni Eleonora E
Hofmann David D
Straube Thomas T
Andreescu Carmen C
Berta Rachel R
Tamburo Erica E
Price Rebecca B RB
Manfro Gisele G GG
Agosta Federica F
Canu Elisa E
Cividini Camilla C
Filippi Massimo M
Kostić Milutin M
Munjiza Jovanovic Ana A
Alberton Bianca A V BAV
Benson Brenda B
Freitag Gabrielle F GF
Filippi Courtney A CA
Gold Andrea L AL
Leibenluft Ellen E
Ringlein Grace V GV
Werwath Kathryn E KE
Zwiebel Hannah H
Zugman André A
Grabe Hans J HJ
Van der Auwera Sandra S
Wittfeld Katharina K
Völzke Henry H
Bülow Robin R
Balderston Nicholas L NL
Ernst Monique M
Grillon Christian C
Mujica-Parodi Lilianne R LR
van Nieuwenhuizen Helena H
Critchley Hugo D HD
Makovac Elena E
Mancini Matteo M
Meeten Frances F
Ottaviani Cristina C
Ball Tali M TM
Fonzo Gregory A GA
Paulus Martin P MP
Stein Murray B MB
Gur Raquel E RE
Gur Ruben C RC
Kaczkurkin Antonia N AN
Larsen Bart B
Satterthwaite Theodore D TD
Harper Jennifer J
Myers Michael M
Perino Michael T MT
Sylvester Chad M CM
Yu Qiongru Q
Lueken Ulrike U
Veltman Dick J DJ
Thompson Paul M PM
Stein Dan J DJ
Van der Wee Nic J A NJA
Winkler Anderson M AM
Pine Daniel S DS
Study Outcome
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