Brain Ageing in Social Anxiety Disorder: An ENIGMA-Anxiety Mega-Analysis Across 26 International Cohorts
Year: 2026
Type: preprint
Abstract: Social anxiety disorder (SAD) is among the most prevalent anxiety disorders, and it has been associated with signs of advanced biological ageing. Despite this, brain age research on anxiety disorders remains limited. This mega-analysis investigated brain ageing in adults with SAD within the ENIGMA-Anxiety Working Group. Structural MRI scans from 576 participants with SAD and 1 355 non-affected healthy controls (HCs) across 26 international samples were included. Brain age was estimated from 77 cortical and subcortical regions using a publicly available ENIGMA brain age model. The brain-predicted age difference (brain-PAD) was calculated as the difference between brain age and chronological age. Group and subgroup differences (comorbidity, medication) were assessed using linear mixed-effect models. In the full sample, there was no group difference in brain-PAD ( β diagnosis (SE)=0.70 (0.37) years, p =0.061). In a subgroup of participants with SAD with comorbid anxiety disorders (n=184 SAD, n=1 355 HCs), a brain-PAD of +2.39 (0.93) years (Cohen’s d =0.23, p FDR=0.003) was observed. This brain-PAD became smaller after exclusion of participants with comorbid agoraphobia and specific phobia, suggesting that these disorders may partly drive the advanced brain-PAD. In conclusion, this ENIGMA-Anxiety mega-analysis did not find evidence of advanced brain ageing in the full sample of adult participants with SAD relative to HCs. However, a sub-analysis suggested that SAD with co-occurring phobic disorders, or the phobic disorders themselves, are associated with neurostructural patterns typical of older brains. Future research could utilise transdiagnostic samples with information on age of onset and disorder duration to further clarify this relation.
Source: medRxiv
Authors: Kimberly V. Blake, Jonathan C. Ipser, Alyssa R. Amod, Tobias Kaufmann, Yair Bar-Haim, Jochen Bauer, Ali Bayram, Katja Beesdo-Baum, Laura Blanco-Hinojo, Tiana Borgers, Robin Bülow, Marta Cano, Narcís Cardoner, Christopher R. K. Ching, Soo-Hee Choi, Udo Dannlowski, Christopher G. Davey, Alexander G. G. Doruyter, Kira Flinkenflügel, Gregory A. Fonzo, Tomas Furmark, Dominik Grotegerd, Hans J. Grabe, Tim Hahn, Ben J. Harrison, Alexandre Heeren, Kevin Hilbert, Yoshiyuki Hirano, Joy Hirsch, David Hofmann, Yuko Isobe, Neda Jahanshad, Hamidreza Jamalabadi, Alec J. Jamieson, Andreas Jansen, Jaehyun Edmund Kim, Tilo Kircher, Hitomi Kitagawa, Anna Luisa Klahn, Saskia B. J. Koch, Axel Krug, Harald Kugel, Dasom Lee, Elisabeth J. Leehr, Christine Lochner, Ulrike Lueken, Amirhossein Manzouri, Kristoffer N. T. Månsson, Koji Matsumoto, Susanne Meinert, Alicia Menze, Markus Muehlhan, Benson Mwangi, Igor Nenadić, Ziphozihle Ntwatwa, Hyuntaek Oh, Spiro P. Pantazatos, Martin P. Paulus, Jutta Peterburs, Jesus Pujol, Karin Roelofs, Ramiro Salas, Franklin R. Schneier, Elisabeth Schrammen, Eiji Shimizu, Lisa Sindermann, Theresa M. Slump, Jair C. Soares, Benjamin Straube, Thomas Straube, Murray B. Stein, Ardesheer Talati, Florian Thomas-Odenthal, Sophia I. Thomopoulos, Raşit Tükel, Anna Tyborowska, Marie-José Van Tol, Dick J. Veltman, Roman A. Vogler, Inge Volman, Henry Völzke, P. Michiel Westenberg, Katharina Wittfeld, Mon-Ju Wu, Noga Yair, Tokiko Yoshida, Chen Zhang, Xi Zhu, Giovana B. Zunta-Soares, Peter Zwanzger, Daniel S. Pine, Moji Aghajani, Paul M. Thompson, Nic J. A. Van der Wee, Dan J. Stein, Janna Marie Bas-Hoogendam, Nynke A. Groenewold
Institutions: University of Cape Town, University of Oslo, Deutsches Zentrum für Psychische Gesundheit, University of Tübingen, Tel Aviv University, University of Münster, University Hospital Münster, Istanbul University, Technische Universität Dresden, Hospital Del Mar, Universitätsmedizin Greifswald, Universität Greifswald, Hospital de Sant Pau, Institut de Recerca Sant Pau, University of Southern California, Seoul National University, The University of Melbourne, Stellenbosch University, The University of Texas at Austin, Uppsala University, UCLouvain, HMU Health and Medical University Erfurt, Chiba University, Chiba University Hospital, The University of Osaka, Yale University, Philipps University of Marburg, University of Gothenburg, Radboud University Nijmegen, Donders Centre for Cognitive Neuroimaging, University of Bonn, University Hospital Bonn, Seoul National University Hospital, South African Medical Research Council, Humboldt-Universität zu Berlin, Karolinska Institutet, MSH Medical School Hamburg – University of Applied Sciences and Medical University, The University of Texas Health Science Center at Houston, Baylor College of Medicine, Menninger Clinic, Mount Sinai Hospital, Columbia University Irving Medical Center, New York State Psychiatric Institute, Columbia University, Icahn School of Medicine at Mount Sinai, Laureate Institute for Brain Research, Michael E. DeBakey VA Medical Center, University of California San Diego, University Medical Center Groningen, University of Groningen, Amsterdam UMC Location University of Amsterdam, Amsterdam University Medical Centers, Leiden University, The University of Texas at Arlington, Inn-Salzach-Klinikum, Ludwig-Maximilians-Universität München, National Institute of Mental Health, Leiden University Medical Center
Language: English
Subfield: Experimental and Cognitive Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: green
Funders: Japan Agency for Medical Research and Development, South African Medical Research Council, Deutsche Forschungsgemeinschaft, Cain Foundation, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Harry Crossley Foundation, University of Cape Town, Ernest Oppenheimer Memorial Trust, Medical Delta, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, Japan Society for the Promotion of Science, Agencia Estatal de Investigación, National Institute of Mental Health, National Institute of Biomedical Imaging and Bioengineering, European Social Fund
Awards: G1438067556, G165739213, G179444772, G2258400832, G2275668389, G238323396, G246808151, G2511155013, G2546134456, G2786142078, G2831939486, G3138944228, 社交不安症における体内炎症と脳機能・構造を考慮した治療選択への応用, 機械学習を用いた児童青年期の強迫症患者における認知行動療法の効果予測因子の同定, G3369844642, G3434867832, G346361644, G3480869486, G3762292575, Prediction of therapeutic effect of cognitive behavioral therapy for anxiety and obsessive-compulsive disorder, G3954542742, G398641320, Using MRI to Identify Predictors of Treatment Response to Cognitive Behavioral Therapy in Social Anxiety Disorder, Functional brain network analysis and biomarker development of risk factors for anxiety and obsessive-compulsive disorder, Development of therapeutic biomarkers for anxiety and obsessive-compulsive disorders by analysis of brain function and morphological networks, The effects of trauma-focused psychotherapy on reward circuitry function and information encoding, G4448254891, Searching for Endophenotypes of Bipolar Disorder, G4701589155, High Capacity, High Performance Storage System for Neuroscience, TRR 58: Furcht, Angst, Angsterkrankungen, G4874941962, A brain-based model of anxiety sensitivity in panic disorder, Development of a very early risk assessment method for depression and anxiety using functional and morphological brain imaging, G5885064267, Identification of Distinct Multimodal Biotypes of PTSD Using Data Driven Approach: A Multisite Big Data Study, ENIGMA Center for Worldwide Medicine, Imaging & Genomics, G6125999700, Development of the Foundation for an Innovative Stepped Approach to Accelerate the Social Implementation of Cognitive Therapy for Social Anxiety Disorder, G648958512, Identifying brain networks to predict treatment resistance and post-surgical outcome: An ENIGMA-Epilepsy initiative, G656100070, G6714403342, G6733821374, G7046466684, G705501481, G7084143925, Born to be shy? An international mega-analysis on the neurobiological link between inhibited temperament and social anxiety disorder, G7254884373, G7341669135, 古代説話における諸寺縁起の研究, G7746733964, Neural predictors of treatment response in youth depression, G8045000093, NeuroLabNL: Small Projects for NWA routes 21/22, G8087705, G850340926, G8600254050, G896427803, G9000004373, G9000020913, G9000064341, G9000135962, G9000168745, G9000210308, G9000310036, Large-scale fine mapping of brain morphometry in bipolar disorder and major depression, Global Deep Learning Initiative to Understand Outcomes in Major Depression, CentileBrain: A Normative Modeling Framework for Brain Health and Disease, fMRI Studies of Risk for Mood and Anxiety Disorders in Children
OpenAlex ID: W7167469765
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