Combining ROC Curves to Improve Diagnostic Values for Vitamin D3 and Chloride Co-Transporters in Connection to Epilepsy and Sleep Problems, Comorbidities in Autism Spectrum Disorders

Background: Autism spectrum disorders (ASDs) comprise a neurodevelopmental disease marked by impaired social communication and repetitive activities. An imbalance between excitatory and inhibitory neurotransmitters, such as glutamate and GABA, may play a significant function in ASDs. The neurophysiological process behind epilepsy is abnormal neuronal excitatory firing in particular brain regions brought on by a lack of GABAergic inhibition. The study of GABAergic dysfunction could explain the substantial comorbidity with epilepsy or increased susceptibility to seizures observed in people with autism. Objective: This study analyzes molecular indicators directly and indirectly related to GABAergic inhibitory signaling in individuals with autism and healthy controls, with the purpose of uncovering probable diagnoses. Methods: The study included 46 male autistic participants and 26 age- and gender-matched healthy controls. Plasma levels of two chloride co-transporters (KCC2, NKCC1), and vitamin D3 were evaluated using ELISA. Results: Autistic individuals showed a significant drop in all three examined variables when compared to healthy controls. Statistical methods such as correlation, combined receiver operating characteristic (ROC) curve analysis, and multiple regression modeling were used to assess the diagnostic value and interrelationships of these biomarkers. A significant increase in the area under the curve was seen using the combined ROC curve analysis. The combined variables also exhibited significantly higher sensitivity and specificity as an index of high predictiveness values. Measurement of plasma levels of vitamin D status and chloride co-transporters (KCC2, NKCC1) in children with ASD may help to better understand how sleep disturbances and epilepsy as comorbidities of ASD linked to vitamin D deficiency and peculiar inhibitory/excitatory effects of GABA.