Sex differences in the corpus callosum in preschool-aged children with autism spectrum disorder

Abstract

Background: Abnormalities in the corpus callosum have been reported in individuals with autism spectrum disorder (ASD), but few studies have evaluated young children. Sex differences in callosal organization and diffusion characteristics have also not been evaluated fully in ASD. Methods: Structural and diffusion-weighted images were acquired in 139 preschool-aged children with ASD (112 males/27 females) and 82 typically developing (TD) controls (53 males/29 females). Longitudinal scanning at two additional annual time points was carried out in a subset of these participants. Callosal organization was evaluated using two approaches: 1) diffusion tensor imaging (DTI) tractography to define subregions based on cortical projection zones and 2) as a comparison to previous studies, midsagittal area analysis using Witelson subdivisions. Diffusion measures of callosal fibers were also evaluated. Results: Analyses of cortical projection zone subregions revealed sex differences in the patterns of altered callosal organization. Relative to their sex-specific TD counterparts, both males and females with ASD had smaller regions dedicated to fibers projecting to superior frontal cortex, but patterns differed in callosal subregions projecting to other parts of frontal cortex. While males with ASD had a smaller callosal region dedicated to the orbitofrontal cortex, females with ASD had a smaller callosal region dedicated to the anterior frontal cortex. There were also sex differences in diffusion properties of callosal fibers. While no alterations were observed in males with ASD relative to TD males, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were all increased in females with ASD relative to TD females. Analyses of Witelson subdivisions revealed a decrease in midsagittal area of the corpus callosum in both males and females with ASD but no regional differences in specific subdivisions. Longitudinal analyses revealed no diagnostic or sex differences in the growth rate or change in diffusion measures of the corpus callosum from 3 to 5 years of age. Conclusions: There are sex differences in the pattern of altered corpus callosum neuroanatomy in preschool-aged children with ASD.