Low Plasma Levels of Contactin-Associated Protein-Like 2 in Children with Autism Spectrum Disorder: Links to Neural Development

Laila Yosif Alayadhi,1,2 Dost Muhammad Halepoto,1 Abdulrahman Mohammed Alhowikan,1,2 Nadra Elyass Elamin,1 Aurangzeb Taj Halepota2 1Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Riyadh, Saudi Arabia; 2Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, 11461, Saudi ArabiaCorrespondence: Dost Muhammad Halepoto, Autism Research and Treatment Center (99), Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia, Tel +966 14699350, Fax +9661499349, Email [email protected]: Autism spectrum disorder (ASD) is a condition of atypical neurodevelopment and is characterized by social communication problems and repetitive patterns of behavior. Early diagnosis and intervention are decisive for managing symptoms and improving outcomes. Contactin-associated protein-like 2 (CNTNAP2) protein is implicated in neural development and plays a role in brain connectivity and synapse formation. Genetic research has shown a possible link between CNTNAP2 and ASD.Aim: We aimed to discover the blood plasma levels of CNTNAP2 in children with ASD and explore the potential association between CNTNAP2 concentrations and ASD severity.Methodology: This case-control study included children with ASD (n=40) and aged-matched healthy controls (n=40). Blood plasma levels of CNTNAP2 were measured using enzyme-linked immunosorbent assay (ELISA). The Children Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS) were used to assess the severity of the ASD. Spearman correlation coefficient (r) was used to correlate the variables.Results: Children with severe ASD had significantly lower CNTNAP2 levels (0.31 (0.14) ng/mL, p=0.003) compared to normal controls (0.47 (0.24) ng/mL). However, CNTNAP2 levels of children with mild autism (0.44(0.22), ng/mL, p=0.77) were not significantly different as compared to normal controls (0.47 (0.24) ng/mL). Furthermore, a significant difference was found between CNTNAP2 levels, by comparing the mild and severe groups based on the CARS (p= 0.05). Furthermore, no significant correlation between CNTNAP2 levels, and severity scores (CARS and SRS), was obtained. However, a significant correlation between CNTNAP2 and age was observed.Conclusion: The low CNTNAP2 plasma level in children with ASD indicated that it might be involved in the pathophysiology of ASD. Nevertheless, these results should be interpreted with care till more studies are achieved using a larger population to decide whether the reduction in CNTNAP2 plasma level is a mere outcome of ASD or it plays a pathogenic role in the disease.Keywords: autism spectrum disorder, contactin-associated protein-like 2, children autism rating scale, social responsiveness scale