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Brain Aging in Specific Phobia: An ENIGMA-Anxiety Mega-Analysis.
Kimberly V Blake1, Kevin Hilbert2, Jonathan C Ipser1
1Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Human Brain Mapping
|July 6, 2026
Summary
Specific phobia (SPH) shows no overall brain age difference. However, formally diagnosed SPH in young adults exhibits subtle advanced brain aging, suggesting earlier maturational processes or structural decline.
Area of Science:
- Neuroscience
- Psychiatry
- Radiology
Background:
- Specific phobia (SPH) is a common anxiety disorder.
- Biological aging, including brain aging, may be altered in SPH.
- Research on brain age in anxiety disorders is limited.
Purpose of the Study:
- To investigate brain aging in individuals with SPH using a large-scale mega-analysis.
- To determine if brain age differs between SPH patients and controls.
- To explore the relationship between brain age and chronological age in SPH.
Main Methods:
- A mega-analysis of 17 international samples including 600 SPH individuals and 1134 controls.
- 3D brain structural MRI scans processed using FreeSurfer.
- Brain age estimated using a publicly available ENIGMA brain age model, calculating brain-predicted age difference (brain-PAD).
- Linear mixed-effects models analyzed group differences and age interactions.
Main Results:
- No significant overall group difference in brain-PAD was found in the full sample.
- A significant diagnosis-by-age interaction was identified, particularly in formally diagnosed SPH.
- Post hoc analyses revealed subtle advanced brain aging in younger adults (22-35 years) with formally diagnosed SPH, but not in older adults.
Conclusions:
- Brain aging does not uniformly relate to SPH across all age groups.
- A diagnosis-by-age interaction suggests that brain aging patterns in SPH are age-dependent.
- Findings may indicate earlier maturational processes or subtle brain structure decline in young adults with SPH, highlighting the importance of clinical severity.
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