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Sex differences in the corpus callosum in preschool-aged children with autism spectrum disorder
Christine Wu Nordahl1, Ana-Maria Iosif2, Gregory S Young1
1The MIND Institute, University of California at Davis, School of Medicine, 2805 50th Street, Sacramento, CA 95817 USA ; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California at Davis, Sacramento, CA 95817 USA.
Insights
Autism spectrum disorder (ASD) shows sex differences in corpus callosum development in young children. Neuroanatomy alterations in males and females with ASD differ, impacting frontal cortex connections.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Autism Spectrum Disorder Research
Background:
- Corpus callosum abnormalities are noted in autism spectrum disorder (ASD), but studies in young children and sex differences are limited.
- Previous research has not fully explored sex-based variations in callosal organization and diffusion characteristics in ASD.
Purpose of the Study:
- To investigate sex differences in corpus callosum neuroanatomy and diffusion properties in preschool-aged children with ASD.
- To compare callosal organization using diffusion tensor imaging (DTI) tractography and midsagittal area analysis.
Main Methods:
- Acquired structural and diffusion-weighted MRI scans from 139 preschool-aged children with ASD and 82 typically developing (TD) controls.
- Evaluated callosal organization via DTI tractography defining cortical projection zones and midsagittal area analysis (Witelson subdivisions).
- Assessed diffusion measures (MD, AD, RD) and performed longitudinal analyses on a subset of participants.
Main Results:
- Sex differences emerged in callosal organization patterns; both ASD males and females showed smaller superior frontal cortex projection zones.
- Males with ASD had reduced orbitofrontal cortex projections, while females with ASD had smaller anterior frontal cortex projections.
- Females with ASD exhibited increased mean, axial, and radial diffusivity, unlike males with ASD. Both sexes with ASD showed reduced midsagittal area.
Conclusions:
- Preschool-aged children with ASD exhibit sex-specific patterns of corpus callosum neurodevelopmental alterations.
- These findings highlight the importance of considering sex as a biological variable in ASD research.
- Longitudinal data indicated no significant differences in growth rates or diffusion measure changes between 3 and 5 years.
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.
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