Cerebral Cortex Morphometry and Relaxometry in Male Children With Fragile X Syndrome and Autism

PURPOSE: An estimated 30%-50% of male individuals with fragile X syndrome (FXS) meet criteria for autism spectrum disorder (ASD), indicating phenotypic overlap but potentially distinct neurobiology. Here, we aimed to characterize shared and divergent cortical features between FXS and ASD. METHOD: High-resolution, motion-corrected quantitative MRI was used to compare cortical morphometry and relaxometry in 61 male participants (9-18 years) with FXS or ASD. To increase power, ASD participants were pooled from multiple MPnRAGE studies and harmonized across protocols using ComBat. Cortical thickness and R1 (longitudinal relaxation rate; proxy for myelination) were computed across the cerebral cortex. FINDING: Relative to ASD, FXS exhibited greater cortical thickness predominantly in early sensory cortices implicated in low-level visual and auditory processing spanning occipital, parietal, and temporal regions. No significant group differences in R1 were found. CONCLUSION: Thicker cortex in FXS within primary and early associative sensory areas suggests divergent early sensory processing mechanisms between FXS and ASD. Characterizing different neuroanatomical features between the two disorders provides a grounding to develop more disorder-specific interventions despite similar behavioral difficulties. Future work should test developmental trajectories, include females and comorbidities, and link imaging markers to individual sensory/clinical profiles to inform and improve personalized therapies and interventions.