What are the levels and interactions of neuroligin-1, neuroligin-3, and inflammatory cytokines (IL-6, IL-8) in children diagnosed with autism spectrum disorder?

Abstract

Autism spectrum disorder (ASD) is characterized by deficits in social interaction, restricted interests, and repetitive behaviors. Several genes, including synaptic proteins and environmental risk factors, play a role in the etiology of autism. We aimed to evaluate the relationship between neuroligin-1 (NLGN-1) and neuroligin-3 (NLGN-3) levels, which are neuronal cell adhesion molecules (CAMs), and inflammatory cytokine (IL-6, IL-8) levels with disease severity and symptom clusters and with each other in children with ASD. Eighty children diagnosed with autism who met the inclusion criteria and sixty-five typically developing children matched for age and sex were included in the study. The children were evaluated psychiatrically through a semi-structured interview, DSM-5 criteria, the Childhood Autism Rating Scale (CARS), and the Social Communication Questionnaire (SCQ). IL-6, IL-8, NLGN-1, and NLGN-3 levels were analyzed in peripheral serum samples using human ELISA kits. IL-8 and NLGN-3 levels were higher in the autism group (p < 0.001, p < 0.001). IL-6 was positively related to CARS and SCQ total scores (p = 0.021, p = 0.040, respectively). IL-8, and NLGN-3 were positively associated with the all subtests of the SCQ and the SCQ total score (all p values <0.001). NLGN-1, NLGN-3, and inflammatory cytokine (IL-6, IL-8) levels were positively correlated (all p values <0.001). Neuroligins play a central role in the brain's ability to process information and maybe a key target in the pathogenesis of ASD. Further research is needed to determine whether, to what extent and how neuronal CAMs and immunity modulate each other and whether this contributes to ASD pathogenesis. Future studies should also be expanded to investigate the influence of variables such as oxidative stress, metalloproteases responsible for ectodomain shedding, or epigenetic regulation.