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


Journal

Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664

Informations de publication

Date de publication:
01 10 2021
Historique:
received: 27 08 2021
accepted: 14 09 2021
revised: 02 09 2021
entrez: 2 10 2021
pubmed: 3 10 2021
medline: 12 10 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 34599145
doi: 10.1038/s41398-021-01622-1
pii: 10.1038/s41398-021-01622-1
pmc: PMC8486763
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

502

Subventions

Organisme : NIMH NIH HHS
ID : R01 MH065413
Pays : United States
Organisme : NIDA NIH HHS
ID : U24 DA041147
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041120
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : K23MH114023
Organisme : Intramural NIH HHS
ID : ZIA MH002782
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH100019
Pays : United States
Organisme : NIMH NIH HHS
ID : K23 MH086686
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041025
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041106
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041148
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101497
Pays : United States
Organisme : NIMH NIH HHS
ID : K23 MH100259
Pays : United States
Organisme : CSRD VA
ID : I01 CX000994
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : K23MH109983
Organisme : NIDA NIH HHS
ID : U01 DA041093
Pays : United States
Organisme : NIMH NIH HHS
ID : K23 MH109983
Pays : United States
Organisme : NIDA NIH HHS
ID : U24 DA041123
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : K23MH100259
Organisme : NIDA NIH HHS
ID : U01 DA041134
Pays : United States
Organisme : NIMH NIH HHS
ID : K23 MH114023
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH116147
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041022
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : K99MH117274
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : K23 MH 086686
Organisme : NIDA NIH HHS
ID : U01 DA041156
Pays : United States
Organisme : NIBIB NIH HHS
ID : U54 EB020403
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH117601
Pays : United States
Organisme : NIMH NIH HHS
ID : K24 MH064122
Pays : United States
Organisme : NICHD NIH HHS
ID : K99 HD105002
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH014654
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041089
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH108509
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG058854
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01MH11760
Organisme : NIDA NIH HHS
ID : U01 DA041117
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA MH002798
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01MH101497
Organisme : NIDA NIH HHS
ID : U01 DA041028
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041048
Pays : United States
Organisme : NIMH NIH HHS
ID : K99 MH117274
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01 MH 108509
Organisme : NIDA NIH HHS
ID : U01 DA041174
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101486
Pays : United States

Informations de copyright

© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

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Auteurs

Anita Harrewijn (A)

Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA. anita.harrewijn@nih.gov.

Elise M Cardinale (EM)

Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.

Nynke A Groenewold (NA)

Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

Janna Marie Bas-Hoogendam (JM)

Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Department of Developmental and Educational Psychology, Institute of Psychology, Leiden University, Leiden, The Netherlands.
Leiden Institute for Brain and Cognition, Leiden, The Netherlands.

Moji Aghajani (M)

Department of Psychiatry, Amsterdam UMC, location VUMC, Amsterdam, The Netherlands.
Department of Research & Innovation, GGZ InGeest, Amsterdam, The Netherlands.

Kevin Hilbert (K)

Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.

Narcis Cardoner (N)

Department of Mental Health, University Hospital Parc Taulí-I3PT, Barcelona, Spain.
Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid, Spain.

Daniel Porta-Casteràs (D)

Department of Mental Health, University Hospital Parc Taulí-I3PT, Barcelona, Spain.
Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid, Spain.

Savannah Gosnell (S)

Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.

Ramiro Salas (R)

Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.

Andrea P Jackowski (AP)

LiNC, Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil.

Pedro M Pan (PM)

LiNC, Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil.

Giovanni A Salum (GA)

Section on Negative Affect and Social Processes, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Karina S Blair (KS)

Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, NE, USA.

James R Blair (JR)

Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, NE, USA.

Mira Z Hammoud (MZ)

Department of Psychiatry, NYU School of Medicine, New York University, New York, NY, USA.

Mohammed R Milad (MR)

Department of Psychiatry, NYU School of Medicine, New York University, New York, NY, USA.

Katie L Burkhouse (KL)

Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.

K Luan Phan (KL)

Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA.

Heidi K Schroeder (HK)

Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA.

Jeffrey R Strawn (JR)

Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA.

Katja Beesdo-Baum (K)

Behavioral Epidemiology, Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany.

Neda Jahanshad (N)

Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.

Sophia I Thomopoulos (SI)

Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.

Randy Buckner (R)

Center for Brain Science & Department of Psychology, Harvard University, Cambridge, MA, USA.
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.

Jared A Nielsen (JA)

Center for Brain Science & Department of Psychology, Harvard University, Cambridge, MA, USA.
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Psychology Department & Neuroscience Center, Brigham Young University, Provo, USA.

Jordan W Smoller (JW)

Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.

Jair C Soares (JC)

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.

Benson Mwangi (B)

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.

Mon-Ju Wu (MJ)

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.

Giovana B Zunta-Soares (GB)

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.

Michal Assaf (M)

Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.

Gretchen J Diefenbach (GJ)

Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Anxiety Disorders Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.

Paolo Brambilla (P)

Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Eleonora Maggioni (E)

Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

David Hofmann (D)

Institute of Medical Psychology and Systems Neuroscience, University of Muenster, Muenster, Germany.

Thomas Straube (T)

Institute of Medical Psychology and Systems Neuroscience, University of Muenster, Muenster, Germany.

Carmen Andreescu (C)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Rachel Berta (R)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Erica Tamburo (E)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

Rebecca B Price (RB)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Department Psychology, University of Pittsburgh, Pittsburgh, PA, USA.

Gisele G Manfro (GG)

Anxiety Disorder Program, Hospital de Clínicas de Porto Alegre, Department of Psychiatry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Federica Agosta (F)

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.

Elisa Canu (E)

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Camilla Cividini (C)

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.

Massimo Filippi (M)

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurophysiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Milutin Kostić (M)

Institute of Mental Health, University of Belgrade, Belgrade, Serbia.
Department of Psychiatry, School of Medicine, University of Belgrade, Belgrade, Serbia.

Ana Munjiza Jovanovic (A)

Institute of Mental Health, University of Belgrade, Belgrade, Serbia.

Bianca A V Alberton (BAV)

Graduate Program in Electrical and Computer Engineering, Universidade Tecnológica Federal do Paraná, Curitiba, Puerto Rico, Brazil.

Brenda Benson (B)

Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.

Gabrielle F Freitag (GF)

Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.

Courtney A Filippi (CA)

Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.

Andrea L Gold (AL)

Department of Psychiatry and Human Behavior, Brown University Warren Alpert Medical School, Providence, RI, USA.

Ellen Leibenluft (E)

Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.

Grace V Ringlein (GV)

Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.

Kathryn E Werwath (KE)

Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.

Hannah Zwiebel (H)

Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.

André Zugman (A)

Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.

Hans J Grabe (HJ)

Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany.

Sandra Van der Auwera (S)

Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany.

Katharina Wittfeld (K)

Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany.

Henry Völzke (H)

Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.

Robin Bülow (R)

Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.

Nicholas L Balderston (NL)

Center for Neuromodulation in Depression and Stress, University of Pennsylvania, Philadelphia, PA, USA.

Monique Ernst (M)

Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, Bethesda, MD, USA.

Christian Grillon (C)

Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, Bethesda, MD, USA.

Lilianne R Mujica-Parodi (LR)

Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.

Helena van Nieuwenhuizen (H)

Department of Physics, Stony Brook University, Stony Brook, NY, USA.

Hugo D Critchley (HD)

Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.

Elena Makovac (E)

Centre for Neuroimaging Science, Kings College London, London, UK.

Matteo Mancini (M)

Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.

Frances Meeten (F)

School of Psychology, University of Sussex, Brighton, UK.

Cristina Ottaviani (C)

Department of Psychology, Sapienza University of Rome, Rome, Italy.
IRCCS Santa Lucia Foundation, Rome, Italy.

Tali M Ball (TM)

Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.

Gregory A Fonzo (GA)

Department of Psychiatry and Behavioral Sciences, The University of Texas at Austin Dell Medical School, Austin, TX, USA.

Martin P Paulus (MP)

Laureate Institute for Brain Research, Tulsa, OK, USA.

Murray B Stein (MB)

Department of Psychiatry, School of Medicine and Herbert Wertheim School of Public Health, University of California, San Diego, La Jolla, CA, USA.

Raquel E Gur (RE)

Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.

Ruben C Gur (RC)

Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.

Antonia N Kaczkurkin (AN)

Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.

Bart Larsen (B)

Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.

Theodore D Satterthwaite (TD)

Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.

Jennifer Harper (J)

Department of Psychiatry, Washington University, St. Louis, MO, USA.

Michael Myers (M)

Department of Psychiatry, Washington University, St. Louis, MO, USA.

Michael T Perino (MT)

Department of Psychiatry, Washington University, St. Louis, MO, USA.

Chad M Sylvester (CM)

Department of Psychiatry, Washington University, St. Louis, MO, USA.

Qiongru Yu (Q)

Department of Psychiatry, Washington University, St. Louis, MO, USA.

Ulrike Lueken (U)

Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.

Dick J Veltman (DJ)

Department of Psychiatry, Amsterdam UMC, location VUMC, Amsterdam, The Netherlands.

Paul M Thompson (PM)

Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.

Dan J Stein (DJ)

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.

Nic J A Van der Wee (NJA)

Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Leiden Institute for Brain and Cognition, Leiden, The Netherlands.

Anderson M Winkler (AM)

Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.

Daniel S Pine (DS)

Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.

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