Rightward brain structural asymmetry in young children with autism

Abstract To understand the neural mechanisms of autism spectrum disorder (ASD) and developmental delay/intellectual disability (DD/ID) that can be associated with ASD, it is important to include brain, behavioural and also genetic measures and to investigate individuals at an early age, but such research is still lacking. Here, using structural MRI 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 behavioural and clinical measures and transcription profiles. By computing the individual deviations from typical controls, we found increased right- vs left laterality in ASD children in the inferior parietal cortex and precentral cortex, and also higher variability in temporal pole asymmetry. In addition, ASD with DD/ID children had some cortical regions (e.g. the isthmus cingulate) with leftward asymmetry; ASD without DD/ID children had some cortical regions (e.g. the parahippocampal gyrus) with higher variability in asymmetry; and children with DD/ID without ASD showed no significant differences in asymmetry. The GMV laterality of ASD without DD/ID children was associated with ASD symptoms, whereas the laterality of ASD with DD/ID children was associated with both ASD symptoms and verbal IQ. Last, the GMV laterality of all three groups was significantly associated with shared and unique gene expression profiles. Our findings provide evidence for rightward GMV asymmetry of some cortical regions in young 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.