ArticleTranslational psychiatry2026
Brain age prediction in generalized anxiety disorder using a convolutional neural network.
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Article in Translational psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Brain Ageing in Social Anxiety Disorder: An ENIGMA-Anxiety Mega-Analysis Across 26 International Cohorts.medRxiv : the preprint server for health sciences · 2026Article
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Authors and funding
91 authors.
Corey RichierDepartment of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL, USA. coreyjr2@illinois.edu.ORCID http://orcid.org/0000-0001-9766-9146
André ZugmanEmotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-6126-7759
Anita HarrewijnEmotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.
Elise M CardinaleEmotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.
Parmis KhosraviEmotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.
Moji AghajaniLeiden University, Institute of Education & Child Studies, Section Forensic Family & Youth Care, Leiden, The Netherlands.ORCID http://orcid.org/0000-0003-2040-4881
Willem B BruinLeiden University, Institute of Education & Child Studies, Section Forensic Family & Youth Care, Leiden, The Netherlands.ORCID http://orcid.org/0000-0002-0672-8903
Kevin HilbertDepartment of Psychology, HMU Health and Medical University Erfurt, Erfurt, Germany.ORCID http://orcid.org/0000-0002-7986-4113
Narcis CardonerSant Pau Mental Health Research Group, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain.ORCID http://orcid.org/0000-0001-9633-0888
Daniel Porta-CasteràsSant Pau Mental Health Research Group, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain.ORCID http://orcid.org/0000-0002-3921-3607
Marta CanoSant Pau Mental Health Research Group, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain.ORCID http://orcid.org/0000-0003-0675-9483
Savannah GosnellMenninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
Ramiro SalasMenninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-1105-566X
Andrea P JackowskiLiNC, Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil.ORCID http://orcid.org/0000-0001-8842-5406
Pedro M PanLiNC, Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil.ORCID http://orcid.org/0000-0002-1943-6520
Giovanni A SalumSection on Negative Affect and Social Processes, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Karina S BlairCenter for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, NE, USA.
James R BlairChild and Adolescent Mental Health Center, Copenhagen University Hospital - Mental Health Services CPH, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-6377-2361
Mohammed R MiladDepartment of Psychiatry, NYU School of Medicine, New York University, New York, NY, USA.
Katie L BurkhouseDepartment of Psychology, Penn State University, University Park, PA, USA.
K Luan PhanDepartment of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA.
Heidi K SchroederDepartment of Psychiatry & Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA.
Jeffrey R StrawnDepartment of Psychiatry & Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA.
Katja Beesdo-BaumBehavioral Epidemiology, Institute of Clinical Psychology and Psychotherapy, TUD Dresden University of Technology, Dresden, Germany.
Neda JahanshadImaging 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 ThomopoulosImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.ORCID http://orcid.org/0000-0002-0046-4070
Jared A NielsenCenter for Brain Science & Department of Psychology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2717-193X
Jordan W SmollerDepartment of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Jair C SoaresCenter 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.ORCID http://orcid.org/0000-0002-5466-5628
Benson MwangiCenter 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.ORCID http://orcid.org/0000-0002-1717-4395
Mon-Ju WuCenter 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.ORCID http://orcid.org/0000-0002-0540-8027
Giovana B Zunta-SoaresCenter 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 AssafOlin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.ORCID http://orcid.org/0000-0001-5307-1986
Gretchen J DiefenbachDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Paolo BrambillaDepartment of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.ORCID http://orcid.org/0000-0002-4021-8456
Eleonora MaggioniDepartment of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.ORCID http://orcid.org/0000-0003-4331-4029
David HofmannInstitute of Medical Psychology and Systems Neuroscience, University of Muenster, Muenster, Germany.ORCID http://orcid.org/0000-0003-3494-634X
Thomas StraubeInstitute of Medical Psychology and Systems Neuroscience, University of Muenster, Muenster, Germany.
Carmen AndreescuDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-3767-5127
Rebecca B PriceDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-7590-4325
Gisele G ManfroAnxiety Disorder Program, Hospital de Clínicas de Porto Alegre, Department of Psychiatry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.ORCID http://orcid.org/0000-0002-0109-7591
Federica AgostaNeuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0003-3121-4979
Elisa CanuNeuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Camilla CividiniNeuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Massimo FilippiNeuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0002-5485-0479
Milutin KostićInstitute of Mental Health, University of Belgrade, Belgrade, Serbia.
Ana Munjiza JovanovicInstitute of Mental Health, University of Belgrade, Belgrade, Serbia.
Brenda BensonEmotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.
Gabrielle F FreitagEmotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.
Ellen LeibenluftEmotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8971-2087
Grace V RingleinEmotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.
Kathryn WerwathPsychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Hannah ZwiebelEmotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.
Hans J GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Sandra Van der AuweraDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-1757-7768
Katharina WittfeldDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0003-4383-5043
Henry VölzkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Robin BülowInstitute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0003-1884-5784
Nicholas L BalderstonCenter for Neuromodulation in Depression and Stress, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8565-1544
Monique ErnstSection on Neurobiology of Fear and Anxiety, National Institute of Mental Health, Bethesda, MD, USA.
Lilianne R Mujica-ParodiDepartment of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
Helena van NieuwenhuizenDepartment of Physics, Stony Brook University, Stony Brook, NY, USA.
Hugo D CritchleyDepartment of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.ORCID http://orcid.org/0000-0002-2445-9284
Elena MakovacDepartment of Psychology, Brunel University London, Uxbridge, UK.
Matteo Mancini"Enrico Fermi" Research Center, Rome, Italy.
Frances MeetenDepartment of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID http://orcid.org/0000-0002-0648-0194
Cristina OttavianiDepartment of Psychology, Sapienza University of Rome, Rome, Italy.ORCID http://orcid.org/0000-0002-5240-4387
Gregory A FonzoDepartment of Psychiatry and Behavioral Sciences, The University of Texas at Austin Dell Medical School, Austin, TX, USA.ORCID http://orcid.org/0000-0002-0213-1034
Martin P PaulusLaureate Institute for Brain Research, Tulsa, OK, USA.ORCID http://orcid.org/0000-0002-0825-3606
Murray B SteinDepartment of Psychiatry, School of Medicine and Herbert Wertheim School of Public Health, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9564-2871
Raquel E GurDepartment of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Ruben C GurDepartment of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-4082-8502
Antonia N KaczkurkinDepartment of Psychology, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-0943-3094
Bart LarsenDepartment of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-7896-4342
Theodore D SatterthwaiteDepartment of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Jennifer HarperDepartment of Psychiatry, Washington University, St. Louis, MO, USA.
Michael T PerinoDepartment of Psychiatry, Washington University, St. Louis, MO, USA.
Chad M SylvesterDepartment of Psychiatry, Washington University, St. Louis, MO, USA.
Qiongru YuDepartment of Psychiatry, Washington University, St. Louis, MO, USA.
Patrick McClureMachine Learning Core, National Institute of Mental Health, Bethesda, MD, USA.
Francisco PereiraMachine Learning Core, National Institute of Mental Health, Bethesda, MD, USA.
Ulrike LuekenDepartment of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0003-1564-4012
Dick J VeltmanDepartment of Psychiatry, Amsterdam UMC, location VUMC, Amsterdam, The Netherlands.
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.ORCID http://orcid.org/0000-0002-4720-8867
Nynke A GroenewoldDepartment of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.ORCID http://orcid.org/0000-0002-0865-8427
Janna Marie Bas-HoogendamDepartment of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0001-8982-1670
Dan J SteinDepartment of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.ORCID http://orcid.org/0000-0001-7218-7810
Nic J A Van der WeeDepartment of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Anderson M WinklerEmotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.
Daniel S PineEmotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.
Chelsea K SawyersEmotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-9704-6555
Funding
fMRI Studies Of Pediatric Mood And Anxiety DisordersZIAMH002781 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI PINE, DANIEL · 2009 to 2025
$41.5MIntramural NIH HHS ZIA MH002781
Abstract
Higher predicted brain age difference has been associated with several psychiatric disorders. Generalized anxiety disorder (GAD) is associated with markers of accelerated aging. In this study, we determined brain predicted age difference (PAD) in individuals with GAD and healthy controls (HC) as well as group differences in PAD variability using voxel-wise structural MRI. The training dataset included 3511 controls, and the testing dataset included 1595 individuals with GAD and 4552 HC from the ENIGMA-Anxiety GAD Working Group. A convolutional neural network model using four input modalities per subject and a model ensemble approach was used to predict brain age. The PAD was then calculated by subtracting chronological age from the predicted age. Model performance was consistent with other image-based brain age prediction models with similar accuracy across the training set (mean absolute error (MAE) = 2.95 years) and HC in the testing set (MAE = 2.94). We found no evidence of accelerated brain aging in individuals with GAD compared to individuals without GAD, though we did find evidence for greater variation in PAD for individuals with GAD (Levene's test: W = 442.98, p < 0.001) and evidence for greater variability in PAD of those with GAD over 25 years of age. In several exploratory analyses, we found that symptom severity related significantly to PAD, even after controlling for medication and comorbid diagnoses, echoing previous brain age research. These findings underscore the need for consideration of heterogeneity and dimensionality of psychopathology when examining brain age predicted differences.
Indexed as
AgingAnxiety DisordersBrainGeneralized Anxiety DisorderAdultCase-Control StudiesConvolutional Neural NetworksFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedYoung Adult
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