Structural brain differences associated with panic disorder: an ENIGMA-Anxiety Working Group mega-analysis of 4924 individuals worldwide
Molecular Psychiatry, vol. 31, pp. 2402–2417
Abstract
Neuroanatomical findings on panic disorder (PD) are typically difficult to replicate, with inconsistent effects. These concerns prompted a paradigm shift towards large-scale collaborations, focused on harmonized data extraction and processing for robust examination of PD brain correlates. Hence, leveraging the largest-ever multi-site neuroimaging database on PD (Age: 10–66 years; global sites: 28), compiled by the ENIGMA-Anxiety Working Group, we report on cortical and subcortical differences in individuals with PD (N = 1146) versus healthy controls (HC: N = 3778). The analyses revealed lower thickness and smaller cortical surface area within fronto-temporo-parietal regions in PD (Cohen’s ds: −0.08–0.13), along with lower thalamic and caudate volumes (Cohen’s ds: −0.07–0.12). Diagnosis-by-age2 interactions (Cohen’s ds: 0.07–0.12) revealed lower thickness in individuals with PD compared to HC in certain regions during adulthood (25–55 years), with relative absence of such differences during youth (<25 years) or late adulthood (>55 years). Finally, patient subgroup analyses showed that early disease onset (≤21 years) in PD was associated with larger lateral ventricles (Cohen’s ds: 0.31–0.38), whilst no medication, comorbidity, or severity effects were found. These findings lend support to neurocircuitry models of PD, which postulate differences within fronto-striato-limbic circuits and temporo-parietal regions. Moreover, findings highlight the potential importance of abnormal development and aging in neuroanatomical differences related to PD. Given its unprecedented scale, the current study is an important milestone towards identifying the structural brain correlates of PD.
Authors 80
-
The University of Melbourne · Amsterdam Neuroscience · Orygen · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Neuroscience, Amsterdam, Netherlands. l.han@amsterdamumc.nl
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam, Netherlands. l.han@amsterdamumc.nl
Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia. l.han@amsterdamumc.nl
Orygen, Parkville, VIC, Australia. l.han@amsterdamumc.nl
-
Leiden University · Amsterdam UMC Location University of Amsterdam · Amsterdam Neuroscience · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Neuroscience, Amsterdam, Netherlands
Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Amsterdam, Netherlands
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam, Netherlands
Institute of Education & Child Studies, Leiden University, Leiden, Netherlands
-
Janna Marie Bas‐Hoogendam Aachen Department of Psychiatry, Leiden University Medical Center Developmental and Educational Psychology Institute of Psychology, Leiden University Leiden Institute for Brain and Cognition
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
Developmental & Educational Psychology, Institute of Psychology, Leiden University, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands
-
Affiliation as printed
Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa
-
Humboldt-Universität zu Berlin · HMU Health and Medical University Erfurt
Affiliation as printed
Department of Psychology, HMU Health and Medical University Erfurt, Erfurt, Germany
Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
-
National Institutes of Health · The University of Texas Rio Grande Valley · National Institute of Mental Health
Affiliation as printed
Department of Human Genetics, University of Texas Rio Grande Valley, Brownsville, Texas, USA
National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
-
National Institutes of Health · National Institute of Mental Health
Affiliation as printed
National Institutes of Health, National Institute of Mental Health, Section on Development and Affective Neuroscience, Bethesda, USA
-
Affiliation as printed
Department of Psychiatry, Yokohama City University School of Medicine, Yokohama, Japan
-
Adelphi University · University of Pennsylvania
Affiliation as printed
Adelphi University, Garden City, NY, USA
University of Pennsylvania, Philadelphia, PA, USA
-
Affiliation as printed
Psychiatry & Clinical Psychobiology, Division of Neuroscience, IRCSS Ospedale San Raffaele, Milan, Italy
-
University of Copenhagen · Mental Health Services · Copenhagen University Hospital
Affiliation as printed
Child and Adolescent Mental Health Centre, Mental Health Services, Copenhagen University Hospital - Mental Health services CPH, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
-
Affiliation as printed
Clinical Psychology and Translational Psychotherapy, University of Münster, Münster, Germany
Institute for Translational Psychiatry, University of Münster, Münster, Germany
-
University of Milan · Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Affiliation as printed
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
-
Affiliation as printed
Institute for Translational Psychiatry, University of Münster, Münster, Germany
-
Harvard University · Massachusetts General Hospital · Athinoula A. Martinos Center for Biomedical Imaging
Affiliation as printed
Department of Psychiatry and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA
Department of Psychology and Center for Brain Science, Harvard University, Cambridge, MA, USA
-
Universitätsmedizin Greifswald · Universität Greifswald
Affiliation as printed
Institute for diagnostic radiology and neuroradiology, University Medicine Greifswald, 17475, Greifswald, Germany
-
Affiliation as printed
Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
-
Natalia Chechko Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Faculty of Medicine
Jülich Aachen Research Alliance · Max Planck Institute of Psychiatry · RWTH Aachen University
Affiliation as printed
Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
Institute of Neuroscience and Medicine: JARA-Institute Brain Structure Function Relationship (INM 10), Jülich, Germany
Max Planck Institute of Psychiatry, Munich, Germany
-
Affiliation as printed
Institute for Translational Psychiatry, University of Münster, Münster, Germany
-
Affiliation as printed
Institute for Translational Psychiatry, University of Münster, Münster, Germany
-
University of Freiburg · University Medical Center Freiburg
Affiliation as printed
Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
-
Deutsches Zentrum für Psychische Gesundheit · University of Tübingen
Affiliation as printed
Department of Psychiatry and Psychotherapy, Tuebingen Center for Mental Health, University of Tuebingen, 72076, Tuebingen, Germany
German Center for Mental Health (DZPG), partner site Tuebingen, Tübingen, Germany
LEAD Graduate School & Research Network, University of Tuebingen, 72072, Tuebingen, Germany
-
University of Würzburg · Max Planck Institute of Psychiatry
Affiliation as printed
Department of Psychiatry, University of Wuerzburg, Wuerzburg, Germany
Max Planck Institute of Psychiatry, Munich, Germany
-
The University of Texas at Austin
Affiliation as printed
Center for Psychedelic Research and Therapy, Department of Psychiatry and Behavioral Sciences, The University of Texas at Austin Dell Medical School, Austin, US
-
University of Bonn · Philipps University of Marburg · Forschungszentrum Jülich · University Hospital Bonn
Affiliation as printed
Centre for Human Genetics, University of Marburg, Marburg, Germany
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, Germany
-
Universitätsmedizin Greifswald · Universität Greifswald
Affiliation as printed
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
-
Affiliation as printed
Institute for Translational Psychiatry, University of Münster, Münster, Germany
-
Children's Hospital of Philadelphia · University of Pennsylvania
Affiliation as printed
Department of Psychiatry, Neurodevelopment & Psychosis Section, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA
Lifespan Brain Institute (LiBI) at Penn & CHOP, Philadelphia, PA, USA
University of Pennsylvania, Philadelphia, PA, USA
-
Children's Hospital of Philadelphia · University of Pennsylvania
Affiliation as printed
Department of Psychiatry, Neurodevelopment & Psychosis Section, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA
Lifespan Brain Institute (LiBI) at Penn & CHOP, Philadelphia, PA, USA
University of Pennsylvania, Philadelphia, PA, USA
-
Warneford Hospital · University of Oxford
Affiliation as printed
Department of Psychiatry, University of Oxford, Oxford, UK
Oxford Health NHS Trust, Warneford Hospital, Oxford, UK
-
Affiliation as printed
University of Münster, Münster, Germany
-
Amsterdam Neuroscience · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Neuroscience, Compulsivity Impulsivity & Attention program, Amsterdam, The Netherlands
Amsterdam UMC, Department of Psychiatry, Department of Anatomy & Neurosciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
-
University of Southern California
Affiliation as printed
Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
-
Philipps University of Marburg
Affiliation as printed
Department of Psychiatry, University of Marburg, Marburg, Germany
-
Affiliation as printed
Department of General Psychiatry, University of Tuebingen, Tuebingen, Germany
-
Amsterdam Neuroscience · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands
Amsterdam UMC, Department of Psychiatry, Department of Anatomy & Neurosciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
-
Humboldt-Universität zu Berlin
Affiliation as printed
Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
-
CHA University Bundang Medical Center · CHA University
Affiliation as printed
Department of Psychiatry, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
-
Affiliation as printed
Institute for Translational Psychiatry, University of Münster, Münster, Germany
-
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico · Fondazione Politecnico di Milano · Politecnico di Milano
Affiliation as printed
Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy
Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
-
University of Rochester Medicine · University of Rochester
Affiliation as printed
The Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
-
Affiliation as printed
Institute for Translational Neuroscience, University of Münster, Münster, Germany
Institute for Translational Psychiatry, University of Münster, Münster, Germany
-
Affiliation as printed
Institute for Translational Psychiatry, University of Münster, Münster, Germany
-
Albert Einstein College of Medicine
Affiliation as printed
Albert Einstein College of Medicine, New York City, NY, USA
-
The University of Texas Health Science Center at Houston
Affiliation as printed
Center of Excellence on Mood Disorders, Louis A. Faillace, Houston, MD, USA
Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA
-
Brigham Young University · Harvard University
Affiliation as printed
Center for Brain Science & Department of Psychology, Harvard University, Cambridge, MA, 02138, USA
Department of Psychology & Neuroscience Center, Brigham Young University, Provo, UT 84602, USA
-
Affiliation as printed
University of Münster, Münster, Germany
-
Columbia University Irving Medical Center · New York State Psychiatric Institute · Columbia University
Affiliation as printed
Department of Psychiatry, Columbia University Medical Center, New York, NY, USA
New York State Psychiatric Institute, New York, NY, USA
-
University of California San Diego · Laureate Institute for Brain Research · University of Tulsa
Affiliation as printed
Department of Psychiatry and School of Public Health, University of California San Diego, La Jolla, CA, 92093, US
Laureate Institute for Brain Research, Tulsa, OK, USA
University of Tulsa, Tulsa, OK, USA
-
Amsterdam Neuroscience · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Neuroscience, Amsterdam, Netherlands
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam, Netherlands
-
Affiliation as printed
IRCCS Scientific Institute San Raffaele Hospital, Milan, Italy
-
Warneford Hospital · University of Oxford
Affiliation as printed
Department of Psychiatry, University of Oxford, Oxford, UK
Oxford Health NHS Trust, Warneford Hospital, Oxford, UK
-
Philipps University of Marburg
Affiliation as printed
Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
-
University of Rochester Medicine · University of Rochester
Affiliation as printed
The Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
-
Max Planck Institute of Psychiatry
Affiliation as printed
Max Planck Institute of Psychiatry, Munich, Germany
-
Children's Hospital of Philadelphia · University of Pennsylvania
Affiliation as printed
Penn Lifespan Informatics and Neuroimaging Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
Penn-CHOP Lifespan Brain Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
-
The University of Melbourne · Orygen
Affiliation as printed
Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia
Orygen, Parkville, VIC, Australia
-
Affiliation as printed
Institute for Translational Psychiatry, University of Münster, Münster, Germany
-
The University of Texas Health Science Center at Houston
Affiliation as printed
Center of Excellence on Mood Disorders, Louis A. Faillace, Houston, MD, USA
Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA
-
Affiliation as printed
Department of Psychiatry, Weill Cornell Medicine, New York, NY, USA
-
University of California San Diego
Affiliation as printed
Department of Psychiatry and School of Public Health, University of California San Diego, La Jolla, CA, 92093, US
-
Philipps University of Marburg
Affiliation as printed
Center for Mind, Brain and Behavior (CMBB), University of Marburg, Marburg, Germany
Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany
-
Affiliation as printed
Institute of Medical Psychology and Systems Neuroscience, University of Münster, Münster, Germany
-
University of Rochester Medicine · University of Rochester
Affiliation as printed
The Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
University of Rochester, Center for Visual Sciences, Rochester, NY, USA
-
Massachusetts General Hospital
Affiliation as printed
Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA, USA
Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
-
Columbia University Irving Medical Center · New York State Psychiatric Institute · Columbia University
Affiliation as printed
Department of Psychiatry, Columbia University Medical Center, New York, NY, USA
New York State Psychiatric Institute, New York, NY, USA
-
University of Southern California
Affiliation as printed
Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
-
University of Rochester Medicine · University of Rochester
Affiliation as printed
The Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
-
Universitätsmedizin Greifswald · Universität Greifswald
Affiliation as printed
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
-
Universitätsmedizin Greifswald · Universität Greifswald
Affiliation as printed
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
-
The University of Texas Health Science Center at Houston
Affiliation as printed
Center of Excellence on Mood Disorders, Louis A. Faillace, Houston, MD, USA
Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA
-
Affiliation as printed
Department of Experimental Psychopathology, Institute of Psychology, University of Hildesheim, Hildesheim, Germany
-
The University of Texas Health Science Center at Houston
Affiliation as printed
Center of Excellence on Mood Disorders, Louis A. Faillace, Houston, MD, USA
Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA
-
Humboldt-Universität zu Berlin
Affiliation as printed
Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
-
University of Southern California
Affiliation as printed
Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
-
National Institutes of Health · National Institute of Mental Health
Affiliation as printed
National Institutes of Health, National Institute of Mental Health, Section on Development and Affective Neuroscience, Bethesda, USA
-
South African Medical Research Council · University of Cape Town
Affiliation as printed
SAMRC Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa
-
Nic JA van der Wee Aachen Department of Psychiatry, Leiden University Medical Center Leiden Institute for Brain and Cognition
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands
-
Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam, Netherlands
-
Leiden University · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam, Netherlands. m.aghajani@fsw.leidenuniv.nl
Institute of Education & Child Studies, Leiden University, Leiden, Netherlands. m.aghajani@fsw.leidenuniv.nl
Cited by 1 stored of 1
1 result
No patents citing this paper on Lens.org (checked 2026-10-06).