Blake, Kimberly, Hilbert, Kevin, Ipser, Jonathan, Han, Laura, Bas-Hoogendam, Janna Marie, Ahs, Fredrik, Bauer, Jochen, Beesdo-Baum, Katja, Bjorkstrand, Johannes, Blanco-Hinojo, Laura, Bohnleim, Joscha, Bulow, Robin, Cano, Marta, Cardoner, Narcis, Caseras, Xavier  ORCID: https://orcid.org/0000-0002-8490-6891, Dannlowski, Udo, Fredrikson, Mats, Goossens, Liesbet, Grade, Hans, Grotegerd, Dominik, Hahn, Tim, Hamm, Alfons, Heinig, Ingmar, Kindt, Martin, Kircher, Tilo, Klahn, Anna, Koelkebeck, Katja, Krug, Axel, Leechr, Elisabeth, Lotze, Martin, Margraf, Juergen, Muehlhan, Markus, Nenadic, Igor, Penate, Wenceslao, Pittig, Andre, Plag, Jens, Pujol, Jesus, Richter, Jan, Ribberbusch, Isabelle, Rivero, Francisco, Schafer, Axel, Schafer, Judith, Schiencle, Anne, Schrammen, Elisabeth, Schruers, Koen, Seidl, Esther, Stark, Rudolf, Straube, Benjamin, Straube, Thomas, Strohle, Andreas, Teutenberg, Lea, Thomopoulos, Sophia, Ventura-Bort, Carlos, Visser, Renee, Volzke, Henry, Wabnegger, Albert, Wendt, Julia, Wittchen, Hans-Ulrich, Wittfeld, Katharina, Yang, Yunbo, Zilverstand, Anna, Zwanzger, Peter, Schmaal, Lianne, Aghajani, Moji, Pine, Daniel, Thompson, Paul, Vander Wee, Nic, Stein, Dan, Lueken, Ulrike and Groenewold, Nynke
2026.
Brain aging in specific phobia: An ENIGMA-anxiety mega-analysis.
Human Brain Mapping
47
(10)
, e70595.
10.1002/hbm.70595
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Abstract
Specific phobia (SPH) is a prevalent anxiety disorder and may involve advanced biological aging. However, limited brain age research has been conducted in anxiety disorders. This mega-analysis investigated brain aging in SPH participants within the ENIGMA-Anxiety Working Group. 3D brain structural MRI scans from 17 international samples (600 SPH individuals, of whom 504 formally diagnosed and 96 questionnaire-based cases; 1134 controls; age range: 22–75 years) were processed with FreeSurfer. Brain age was estimated from 77 subcortical and cortical regions with a publicly available ENIGMA brain age model. The brain-predicted age difference (brain-PAD) was calculated as brain age minus chronological age. Linear mixed-effects models examined group differences in brain-PAD and moderation by age. No significant group difference in brain-PAD manifested (βdiagnosis [SE] = 0.37 years [0.43], p = 0.39). A negative diagnosis-by-age interaction was identified, which was most pronounced in formally diagnosed SPH (βdiagnosis-by-age = −0.08 [0.03], pFDR = 0.02). This interaction remained significant when excluding participants with anxiety comorbidities, depressive comorbidities, and medication use. Post hoc analyses revealed a group difference for formal SPH diagnosis in younger participants (22–35 years; βdiagnosis = 1.20 [0.60], p < 0.05, mixed-effects d [95% confidence interval] = 0.14 [0.00–0.28]), but not older participants (36–75 years; βdiagnosis = 0.07 [0.65], p = 0.91). Brain aging did not relate to SPH in the full sample. However, a diagnosis-by-age interaction was observed across analyses, and was strongest in formally diagnosed SPH. Post hoc analyses showed subtle advanced brain aging in young adults with formally diagnosed SPH. Taken together, these findings indicate the importance of clinical severity, impairment, and persistence, and may suggest a slightly earlier end to maturational processes or subtle decline of brain structure in SPH.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine Research Institutes & Centres > MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) |
| Publisher: | Wiley-Blackwell |
| ISSN: | 1065-9471 |
| Date of First Compliant Deposit: | 20 July 2026 |
| Date of Acceptance: | 20 June 2026 |
| Last Modified: | 20 Jul 2026 14:29 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/178224 |
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