Abstract
BACKGROUND: Children with autism spectrum disorder (ASD) and developmental delay (DD; ASD + DD) have more severe clinical symptoms than those with ASD without DD (ASD-only). However, little is known about the underlying neuroimaging mechanisms. The aim of this study was to explore the volumetric difference between patients with ASD + DD and ASD-only and investigate the relationship between brain alterations and clinical manifestations. MATERIALS AND METHODS: A total of 184 children with ASD aged 2-6 years were included in this study, who were divided into two groups according to their cognitive development: ASD + DD and ASD-only. Clinical symptoms and language development were assessed using the Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), and the Putonghua Communicative Development Inventory. Of the 184 children, 60 age-matched males (30 ASD + DD and 30 ASD-only patients) with high-resolution structural neuroimaging scans were included for further voxel-based morphometry analysis to examine the relationship between clinical symptoms and gray matter volumes. RESULTS: The ASD + DD group had higher CARS and ADOS scores, lower gesture scores, and poorer performance in "responding to joint attention" (RJA) and "initiating joint attention" than the ASD-only group. Larger gray matter volumes in the temporal poles of the right and left middle temporal gyri were associated with the co-occurrence of DD in patients with ASD. Moreover, temporopolar volumes were correlated with CARS and ADOS scores, gesture scores, and RJA ability. Pre-language development significantly mediated the relationship between temporopolar volumes and both CARS and ADOS scores; RJA ability, but not gesture development, contributed to this mediating effect. CONCLUSION: In this study, we found that temporopolar volumes were enlarged in patients with ASD who had comorbid DD, and these patients showed an association between symptom severity and language ability during the pre-language stage. Offering early interventions focused on RJA and the temporal pole may help improve clinical symptoms.