Altered biological aging-related brain profile in adolescents with autism: A neuroimaging study based on DunedinPACNI

Individuals with Autism Spectrum Disorder (ASD) show increased rates of physical health conditions across major organ systems, some of which are commonly linked with aging, suggesting that body-wide biological profiles may be altered compared to neurotypical controls. Since brain structure associates with peripheral physiology and biomarkers of aging, it may inform understanding of broader biological differences and physical health risks in ASD. Here, we assessed this possibility using DunedinPACNI, a neuroimaging-based model that estimates the pace of longitudinal aging in peripheral organ systems from brain structural information, in 329 adolescents (8-18 years) from the Autism Centers of Excellence network, with replication in an independent age-matched sample of comparable size from the Autism Brain Imaging Data Exchange. Across both datasets and sensitivity analyses, autistic individuals showed significantly larger DunedinPACNI values than controls, consistent with brain structural features that align with patterns associated with a faster pace of biological aging in adults. Group differences were mainly driven by the volume of the 3 ^rd ventricle, cortical thickness of the left entorhinal cortex, grey matter volume of the right entorhinal cortex and grey-to-white matter ratio in the left temporal pole. No association between DunedinPACNI and core autistic traits was found. Our results provide novel evidence for a possible altered brain-body profile in ASD, motivating future studies combining neuroimaging with peripheral biomarkers to better understand the neurobiology of physical health conditions in autism.