Association of Clinical Severity in Autism Spectrum Disorder with Biomolecules Involved in Lipid Metabolism,...

Autism spectrum disorder (ASD) is a heterogeneous neurological condition with an unclear etiology and pathogenesis. In recent years, studies have identified changes in lipid metabolism, inflammation, mitochondrial dysfunction, and mitophagy in patients with ASD. However, the specific interactions between these molecular signatures and their clinical applications in ASD remain largely unexplored. The aim of our study is to search for correlations between changes in gene and miRNA expression and the clinical characteristics of ASD. The investigation included a cohort of children with idiopathic ASD and healthy controls (HC). Diagnosis was established based on ADOS assessment (autism diagnostic observation schedule). Gene expression levels of sphingomyelin phosphodiesterases (SMPD1 and 5), ceramide synthases (CerS1 and 6), cyclooxygenase-2 (COX2), chitinase-3-like protein 1 (YKL40), and lysosome-associated membrane proteins 1 and 2 (LAMP1 and 2) were assessed using qPCR. The TaqMan assay was used for the quantification of miR-143-3p and miR-181a-5p. Our findings provide novel data on altered expression profiles of molecules related to lipid metabolism and LAMP1/2 in patients with ASD. We observed increased mRNA levels of CerS1, SMPD5, COX2, YKL40, LAMP1, and LAMP2 and decreased expression of miRNA-181a-5p in ASD patients compared to HC. Additionally, we identified a correlation between CerS1, CerS6, COX2, and miRNA-143-5p with ADOS scores. Multiple regression analysis revealed that 48.0% of the variance in the total ADOS score was explained by the combined effects of COX2, miRNA-143-3p, CerS1, CerS6 and age. These results provide new insights into the molecular alterations associated with ASD and may reinforce future studies aimed at clarifying their functional relevance.