Disruption of mTOR and MAPK pathways correlates with severity in idiopathic autism

The molecular signature underlying autism spectrum disorder remains largely unknown. This study identifiesdifferential expression of mTOR and MAPK pathways in patients affected by mild and severe idiopathic autism. Atotal of 55 subjects were enrolled, of which 22 were typically developing individuals and 33 were patients agedbetween 3 and 11 years, with autism spectrum disorder. A detailed history, including physical examination,developmental evaluation, mental health history and autism diagnostic observation schedule were performed foreach patient. Components of the mTOR and MAPK signalling pathways were analysed from peripheral blood at theprotein level. Patients were then stratified according to their clinical phenotypes, and the molecular profiling wasanalysed in relation to the degree of autism severity. In this cohort of patients, we identified increased activity ofmTOR and the MAPK pathways, key regulators of synaptogenesis and protein synthesis. Specifically, rpS6, p-eIF4E,TSC1 and p-MNK1 expression discriminated patients according to their clinical diagnosis, suggesting thatcomponents of protein synthesis signalling pathways might constitute a molecular signature of clinical severity inautism spectrum disorder.