Gamma-aminobutyric acid and glutamate system dysregulation in a small population of Egyptian children with autism spectrum disorder.

Autism spectrum disorder (ASD) is associated with various symptoms, including repetitive behaviors, restricted interests, and deficits in proper communication. Earlier studies have linked these symptoms to abnormalities in the balance between excitatory (glutamatergic signaling) and inhibitory (GABAergic signaling) neurotransmission. The present study aimed to analyze the levels of different biomarkers in children with ASD compared to neurotypical (NT) controls. The study included 80 children, of whom 40 were cases (children with ASD) and 40 were age- and sex-matched NT controls. Serum levels of GABA, and GABA receptors, glutamate, zinc, potassium, and calcium were measured in both groups. ASD diagnosis was verified using the Childhood Autism Rating Scale (CARS) and Autism Diagnostic Interview-Revised (ADI-R). There was a significant decrease (P < 0.001) in the median serum levels of GABA (0.6) and GABA receptors (2.03) in children with ASD compared to controls. Additionally, a significant increase in median serum glutamate levels was observed in ASD children (102, P < 0.001) compared to controls. Children with ASD also showed a significant reduction (P < 0.001) in median levels of all studied blood minerals compared to controls, including potassium (3.8 vs. 4.6), calcium (9.0 vs. 9.7), and zinc (57.0 vs. 92.0). The roles of GABA and zinc as potential pathological biomarkers were investigated due to their highly significant inverse correlations with stereotypic and repetitive behaviors (ADI-R domain), with rho = -0.393 (P = 0.012) and rho = -0.488 (P = 0.001), respectively. Further analysis of pathways regulating these biomarkers may provide deeper insights into the etiology and pathophysiology of ASD, paving the way for potential therapeutic interventions.