Alterations in the transcript level of the Contactin Associated Protein 2 gene could conceivably influence verbal Theory of Mind and predict autism spectrum disorder incidence

Abstract

Abstract Objective: Social interaction and communication impairments in autism spectrum disorder (ASD) are supposed to be related to impairments in Theory of Mind (ToM), which is the ability to attribute mental states to oneself and other social agents. Language and ToM are intertwined cognitive components, and higher-order manifestations of the ToM cannot be achieved in the absence of specific language competencies. The gene Contactin Associated Protein 2 (CNTNAP2) is associated with language/verbal skills as well as changes in social cognition. As of yet, no study has assessed the association of CNTNAP2 expression with ASD and ToM. This study aimed at assessing CNTNAP2 expression alterations in ASD individuals and to model ASD and ToM leveraging cognitive and genetic measures. Method: 43 children and adolescents with high-function autism between the ages of 8 and 18 years old, as well as 44 matched age and sex typically developed (TD) individuals participated in the study. SYBR green Real-time PCR was used to determine CNTNAP2 expression evaluation. To measure verbal and non-verbal ToM, Happe's Strange Stories test and Moving Shapes paradigms were employed. The social responsiveness scale (SRS-2) was also used to assess social functioning. The statistical analysis was performed using a 95% confidence interval. Results: Compared to TD group, we found a significant downregulation of CNTNAP2 expression in ASD subjects. Moreover, correlation tests and linear regression indicated that there is no significant correlation between cognitive variables and expression of CNTNAP2 in the ASD group. However, the expression of CNTNAP2 in TD was significantly correlated with verbal ToM variables, but not with non-verbal ToM. Finally, the general linear model suggested that non-verbal ToM parameters and CNTNAP2expression could predict ASD, and verbal ToM may serve as a moderator variable for CNTNAP2 expression. Conclusion: Briefly, we found that CNTNAP2was downregulated in ASD samples compared to TD individuals. Also, our results suggest a molecular-cognitive model for ASD. Further studies should be conducted to determine whether the findings of this study are reliable.