A Holistic View of Gene Signalling Pathways, Potential Related Biomarkers, and Suggested Combined Modulation in Children with Autistic Spectrum Disorder

Autistic spectrum disorders (ASD) are the most common neurodevelopmental pathology, with a global trend of increasing prevalence. The biomarker-based diagnosis and signaling pathways based modulation could improve both clinical symptoms and long-term outcomes. In the review, the role of viruses in causing prenatal CNS damage and the development of autism is discussed. The distinct CNS involvement of the most common pathogens such as Rubella, CMV, HSV, Influenza and Covid-19 virus elucidated. The specific importance of a retinoid metabolism disorder in the brain in prenatal rubella virus infection and of low levels of IgF-1 as a neurotrophic factor in Covid-19 infection has been demonstrated. The role of ferroptosis and changes in ferritin and transferrin levels in the development of ASD-like symptoms have been shown. Altered serotonin signaling could related to early prenatal factors and result in negative ASD symptoms. Hypermethylation of the oxytocin receptor gene in ASD patients results in impaired oxytocin metabolism, discoordination between nucleus basalis and ventral pallidum, and impaired visual attention and motivated behavior. The role of NMDA receptors and SHANK scaffolding proteins in ASD cognitive signs demonstrated. Clinically relevant biomarkers and a combined modulation approach were proposed based on the analysed information.