The interplay between functional connectivity of medial and lateral visual networks, behavioral measures, and oxytocin receptor gene polymorphism (rs2254298) in autism.

Oxytocin influences various social cognitive functions and is linked to the development of autism. The rs2254298 polymorphism in the oxytocin receptor (OXTR) gene is associated with autism susceptibility and differences in social functioning. However, research exploring the effects of rs2254298 on functional brain connectivity and neuropsychological performance in individuals with autism remains limited. This study included 105 individuals with a clinical diagnosis of autism, confirmed by the Autism Diagnostic Interview-Revised, and 105 typically developing controls (TDC). Both groups underwent resting-state functional MRI (fMRI) and neuropsychological assessments, including the Conners’ Continuous Performance Test (CCPT) for attention and the Autism Spectrum Quotient (AQ) for evaluating autistic symptoms severity. We utilized independent component analysis and dual regression to analyze functional connectivity. Approximately 50.5% of autistic participants and 45.7% of TDCs were carriers of the risk allele of rs2254298 (A allele). Functional connectivity analysis showed that A carriers within the autism group exhibited hypoconnectivity in the medial visual network, especially in the right insular cortex, and hyperconnectivity in the lateral visual network, particularly in the right pre/postcentral gyrus. These connectivity patterns were associated with attention challenges and greater severity of autistic symptoms, notably on the socialness and patterns subscales of the AQ. Our findings demonstrate significant differences in brain connectivity linked to the rs2254298 polymorphism in individuals with autism. By integrating genetics, neuroimaging, and neuropsychological performance with clinical measures, these findings highlight the role of OXTR in the pathogenesis of autism, particularly in visual processing.