Rightward brain structural asymmetry in young children with autism

Abstract

To understand the neural mechanism of autism spectrum disorder (ASD) and developmental delay/intellectual disability (DD/ID) that can be associated with ASD, it is important to investigate individuals at an early stage with brain, behavioural and also genetic measures, but such research is still lacking. Here, using the cross-sectional sMRI data of 1030 children under 8 years old, we employed developmental normative models to investigate the atypical development of gray matter volume (GMV) asymmetry in individuals with ASD without DD/ID, ASD with DD/ID and individuals with only DD/ID, and their associations with behavioral and clinical measures and transcription profiles. By extracting the individual deviations of patients from the typical controls with normative models, we found a commonly abnormal pattern of GMV asymmetry across all ASD children: more rightward laterality in the inferior parietal lobe and precentral gyrus, and higher individual variability in the temporal pole. Specifically, ASD with DD/ID children showed a severer and more extensive abnormal pattern in GMV asymmetry deviation values, which was linked with both ASD symptoms and verbal IQ. The abnormal pattern of ASD without DD/ID children showed higher and more extensive individual variability, which was linked with ASD symptoms only. DD/ID children showed no significant differences from healthy population in asymmetry. Lastly, the GMV laterality patterns of all patient groups were significantly associated with both shared and unique gene expression profiles. Our findings provide evidence for rightward GMV asymmetry of some cortical regions in young ASD children (1–7 years) in a large sample (1030 cases), show that these asymmetries are related to ASD symptoms, and identify genes that are significantly associated with these differences.