The Cingulate Structures in Autism Spectrum Disorder: Exploring Its Implication on Social Awareness and the Role of CNTNAP2

Abstract

Backgrounds Although evidence suggests that the activity of the anterior cingulate cortex involves social cognition, there are inconsistent results regarding the aberrant cingulate gray matter (GM) and scanty evidence about altered cortical thickness and white matter (WM) of cingulate in individuals with autism spectrum disorder (ASD). Evidence supports the association between the autism risk gene CNTNAP2 variants and altered brain connectivity. This study investigated the cingulate substructure and its association with social awareness deficits and the CNTNAP2 variants in individuals with ASD. Methods We assessed 122 individuals with ASD and 118 typically-developing controls (TDC) with MRI and clinical evaluation. The GM, WM volumes and cortical thickness of the cingulate gyrus were compared between ASD and TDC based on fine parcellation. Five SNPs of the CNTNAP2 linking to ASD and brain structural abnormality were genotyped. Results ASD individuals showed thinner cortical thickness in bilateral cingulate subregions than TDC but no significant group differences in GM and WM volumes. The WM volume of the right anterior cingulate gyrus was correlated with social awareness deficits in ASD. Two CNTNAP2 variants demonstrated the main effects on the WM volumes of the right middle cingulate gyrus and the cortical thickness of the right posterior ventral cingulate gyrus. Besides, the CNTNAP2 variants interacted with ASD status and age on the cortical thickness of the left anterior middle cingulate cortex.Limitations The CNTNAP2 variants selected in this study were based on the current literature that repeatedly revealed genetic associations with ASD and brain structures. Future studies may consider fine mapping or sequencing of this gene. Besides, we measured social awareness deficits by caregiver-report questionnaire. Although the observation from caregivers may reflect social function in daily life, a social cognition task may better provide a standardized measurement.Conclusions Our findings suggest that aberrant cingulate structure in ASD may be associated with the severity of autistic symptoms and genetic variants of the CNTNAP2. These novel findings need validation. Trial registration: ClinicalTrials.gov number, NCT01582256