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Updated: May 16, 2025

Using the Threat Probability Task to Assess Anxiety and Fear During Uncertain and Certain Threat
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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.

Medrxiv : the Preprint Server for Health Sciences
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Summary

Specific phobia (SPH) did not show overall differences in brain age. However, younger adults with diagnosed SPH exhibited subtle advanced brain aging, suggesting potential maturational differences.

Keywords:
Phobic disordersbrain agebrain morphometrymachine learningmega-analysisneuroimaging

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Radiology

Background:

  • Specific phobia (SPH) is a common anxiety disorder.
  • Biological aging, particularly brain aging, may be implicated in SPH.
  • Previous brain age research has focused on mood and psychotic disorders, leaving SPH understudied.

Purpose of the Study:

  • To investigate brain aging patterns in individuals with specific phobia (SPH) using a large-scale mega-analysis.
  • To examine differences in brain-predicted age difference (brain-PAD) between SPH patients and controls.
  • To explore the moderating role of age on brain aging in SPH.

Main Methods:

  • A mega-analysis of 3D structural MRI scans from 17 international samples, including 600 SPH individuals and 1,134 controls (ages 22-75).
  • Brain age estimation using the ENIGMA brain age model, calculating brain-PAD (brain age minus chronological age).
  • Linear mixed-effect models were employed to analyze group differences and age interactions.

Main Results:

  • No significant overall difference in brain-PAD was found between SPH and control groups.
  • A significant diagnosis-by-age interaction was observed, particularly in formally diagnosed SPH.
  • Post-hoc analyses revealed subtle advanced brain aging in younger adults (22-35 years) with formally diagnosed SPH.

Conclusions:

  • Brain aging is not globally altered in specific phobia (SPH) across all age groups.
  • A significant interaction between SPH diagnosis and age suggests age-specific effects on brain aging.
  • Findings indicate potential maturational differences or subtle brain structure changes in young adults with SPH.