Journal article
White Matter Microstructure Alterations in Social Anxiety Disorder: A Mega-Analysis Across Twelve Cohorts in the ENIGMA-Anxiety Working Group
Biological psychiatry : cognitive neuroscience and neuroimaging, Vol.11(4), pp.438-449
04/01/2026
DOI: 10.1016/j.bpsc.2025.11.007
PMID: 41338325
Abstract
Studies investigating social anxiety disorder (SAD) have reported inconsistent alterations in white matter (WM) microstructure. The ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-Anxiety Working Group investigated differences in the microstructure of 25 WM tracts between individuals with SAD and healthy control (HC) participants in a mega-analysis.
We analyzed data from 487 individuals with SAD and 1604 HC participants (ages 8–65 years) from 12 cohorts worldwide. Analyses and quality control were performed using standardized ENIGMA diffusion tensor imaging protocols. We primarily examined fractional anisotropy (FA) as the main parameter of WM microstructure. Linear mixed-effects analyses were conducted to compare individuals with SAD with HC participants in the total sample. Next, adult (age >21) and adolescent (age ≤21) samples were analyzed separately. In sensitivity analyses, additional effects of sex, medication, symptom severity, and comorbid psychiatric disorders were investigated.
In the total sample, individuals with SAD showed lower FA in several tracts, including the corpus callosum and fornix, compared with HC participants. Widespread sex × diagnosis interactions were observed, mostly driven by lower FA in females with SAD. Adults with SAD showed lower FA in multiple tracts, while age × diagnosis interactions were observed in adolescents.
Using a mega-analytic approach, several differences in WM microstructure were found between individuals with SAD and HC participants, both in the full sample and in age group–specific sensitivity analyses. Some neurobiological changes in WM tracts in individuals with SAD may vary with age and sex, whereas others may relate to broader transdiagnostic neurobiological features underlying psychopathology. Further research should investigate these issues in more detail.
Details
- Title: Subtitle
- White Matter Microstructure Alterations in Social Anxiety Disorder: A Mega-Analysis Across Twelve Cohorts in the ENIGMA-Anxiety Working Group
- Creators
- Eline F. Roelofs - Leiden University Medical CenterNynke A. Groenewold - University of Cape TownKinga Farkas - Semmelweis UniversityAlyssa H. Zhu - University of Southern CaliforniaSi Gao - The University of Texas Health Science CenterTiana Borgers - University of MünsterUdo Dannlowski - University of MünsterKira Flinkenflügel - University of MünsterDominik Grotegerd - University of MünsterTim Hahn - University of MünsterAndreas Jansen - Philipps University of MarburgElisabeth J. Leehr - University of MünsterTilo T.J. Kircher - Philipps University of MarburgHannah Meinert - University of MünsterIgor Nenadić - Philipps University of MarburgFrederike Stein - Philipps University of MarburgBenjamin Straube - Philipps University of MarburgTamer Demiralp - Istanbul UniversityRaşit Tükel - Istanbul UniversityP. Michiel Westenberg - Leiden UniversityJochen Bauer - University of MünsterAnna Kraus - University of MünsterAlexander G.G. Doruyter - University of Cape TownChristine Lochner - Stellenbosch UniversityDavid Hofmann - University of MünsterThomas Straube - University of MünsterAndré Zugman - National Institute of Mental HealthMonica E. Calkins - NeuroDevelopment CenterRaquel E. Gur - University of PennsylvaniaRuben C. Gur - University of PennsylvaniaBart S. Larsen - University of MinnesotaTheodore D. Satterthwaite - University of PennsylvaniaTheresa M. Slump - University of MünsterRoman A. Vogler - University of MünsterSuzanne N. Avery - Vanderbilt University Medical CenterJennifer U. Blackford - Nebraska Medical CenterJacqueline A. Clauss - Massachusetts General HospitalSu Lui - Sichuan UniversitySophia I. Thomopoulos - University of Southern CaliforniaRobert R.J.M. Vermeiren - Leiden University Medical CenterNeda Jahanshad - University of Southern CaliforniaPeter V. Kochunov - University of HoustonPaul M. Thompson - University of Southern CaliforniaDaniel S. Pine - National Institute of Mental HealthDan J. Stein - University of Cape TownNic J.A. van der Wee - Leiden University Medical CenterJanna Marie Bas-Hoogendam - Leiden University
- Resource Type
- Journal article
- Publication Details
- Biological psychiatry : cognitive neuroscience and neuroimaging, Vol.11(4), pp.438-449
- DOI
- 10.1016/j.bpsc.2025.11.007
- PMID
- 41338325
- NLM abbreviation
- Biol Psychiatry Cogn Neurosci Neuroimaging
- ISSN
- 2451-9022
- eISSN
- 2451-9030
- Publisher
- Elsevier Inc
- Number of pages
- 12
- Language
- English
- Date published
- 04/01/2026
- Academic Unit
- Psychiatry
- Record Identifier
- 9985223620102771
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