Abstract
Autism spectrum disorder (ASD) as a neurodevelopmental disorder is characterized by impairments in social interaction, communication, and restricted, repetitive behavior. Several and reproducible studies have suggested that oxidative stress may represent one of the primary etiological mechanism of ASD that can be targeted for therapeutic intervention. In the present study, multiple regression and combined receiver operating characteristic (ROC) analysis were used to search for a relationship between impaired energy and oxidative metabolic pathways in the etiology of ASD and to find the linear combination that maximizes the partial area under a ROC curve for a pre-identified set of markers related to energy metabolism and oxidative stress. Thirty children with ASD and 30 age and gender matched controls were enrolled in the study. Using either spectrophotometric or ELISA-colorimetric assay, levels of lipid peroxides, vitamin E, vitamin C, glutathione (GSH)/glutathione disulfide (GSSG) together with the enzymatic activity of catalase, plasma glutathione peroxidase (GPx), and blood superoxide dismutase (SOD), were measured in peripheral blood samples, as biomarkers related to oxidative stress. Creatine kinase, ectonucleotidases (ADPase and ATPase) Na+/K+ (ATPase), lactate, inorganic phosphate, and levels of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) together with adenylate energy charge, were also measured as markers of impaired energy metabolism. Statistical analysis using ROC curves, multiple and logistic regression were performed. A remarkable increase in the area under the curve for most of the combined markers, representing both energy impaired metabolism or oxidative stress, was observed by using combined ROC analyses. Moreover, higher specificity and sensitivity of the combined markers were also reported. The present study indicated that the measurement of the predictive value of selected biomarkers related to energy metabolism and oxidative stress in children with ASD using ROC analysis should lead to the better identification of the etiological mechanism of ASD associated with metabolism and diet. Agents with activity against the impaired metabolic pathway associated with ASD including the metabolic defects and involved enzymes hold a promise as a novel therapy for ASD.