Structural brain alterations associated with brain age may link to social dysfunction in male adults with autism...

While atypical brain development in autism spectrum disorder (ASD) has been extensively characterized during childhood and adolescence, it remains unclear how these neurodevelopmental deviations persist into adulthood and affect brain aging. Existing studies relying on single morphometric measures have yielded inconsistent findings, underscoring the need for integrative, multiscale neuroimaging approaches.

Using data from the Autism Brain Imaging Data Exchange I (ABIDE-I) dataset, we investigated brain structural alterations in 90 adult males with ASD and 132 age-matched typically developing (TD) controls. All participants were right-handed and aged 18-55 years. Voxel-based morphometry (VBM) was employed to assess gray matter volume (GMV), and surface-based morphometry (SBM) was used to quantify cortical fractal dimension (FD). Global brain aging was evaluated using MRI-derived brain age estimation, from which the brain age gap (BAG) was calculated. Site-related effects were harmonized using the ComBat method. Group comparisons were performed for GMV, FD, and BAG using multiple linear regression, with age, full-scale IQ, and total intracranial volume included as covariates. Associations between neuroimaging metrics and Autism Diagnostic Observation Schedule (ADOS) scores were further examined.

Cross-sectional comparisons demonstrated that adults with ASD exhibited higher estimated BAG values relative to TD controls (F = 6.838, p = 0.01, partial η² = 0.031). ComBat-harmonized morphometric analyses revealed exploratory localized GMV and FD differences, including increased GMV and FD in the right precuneus and increased FD in the lingual gyrus and lateral orbitofrontal cortex. GMV in the right precuneus showed an exploratory positive correlation with ADOS social-domain scores (r = 0.214, q = 0.044).

Adults with ASD exhibited higher estimated BAG relative to TD controls in this cross-sectional sample. An exploratory association between right precuneus GMV and ADOS social-domain scores suggests a possible link between localized structural variation and social symptom severity, although this finding requires replication in longitudinal and clinically richer datasets given their sensitivity to the harmonization strategy.