Alterations in the transcript level of the CNTNAP2 gene could conceivably influence verbal Theory of Mind and estimate autism likelihood

Abstract Social cognition impairments in autism are supposed to be related to impairments in Theory of Mind (ToM), which is the ability to attribute mental states to oneself and others. Language and ToM are intertwined components, and higher-order ToM manifestations cannot be achieved without language competencies. CNTNAP2 gene is associated with language and social cognition skills. Heretofore, no study has assessed the association of CNTNAP2expression with ASD and ToM. This study aimed at assessing CNTNAP2expression alteration in autistics and modeling autism leveraging cognitive and genetic measures. 43 children and adolescents with autism and 44 typically developed (TD) peers participated in the study. Real-time PCR was used to measure CNTNAP2 expression alteration. To assess verbal and non-verbal ToM and social functioning, Happe's Strange Stories test, Frith-Happe' animations, and social responsiveness scale were employed. Compared to TD group, we found a significant CNTNAP2 downregulation in autistic individuals. Moreover, the CNTNAP2 expression in TD group was significantly correlated with verbal ToM. Finally, the cognitive model suggested that non-verbal ToM parameters and CNTNAP2 expression could predict autism likelihood, and verbal ToM abilities moderate CNTNAP2 expression. Briefly, we found downregulation of CNTNAP2 in autistic individuals. Also, our results suggest a molecular-cognitive model for autism.