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

Transl Psychiatry. 2019 Jan 31;9(1):50. doi: 10.1038/s41398-018-0335-z.


The molecular signature underlying autism spectrum disorder remains largely unknown. This study identifies differential expression of mTOR and MAPK pathways in patients affected by mild and severe idiopathic autism. A total of 55 subjects were enrolled, of which 22 were typically developing individuals and 33 were patients aged between 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 for each patient. Components of the mTOR and MAPK signalling pathways were analysed from peripheral blood at the protein level. Patients were then stratified according to their clinical phenotypes, and the molecular profiling was analysed in relation to the degree of autism severity. In this cohort of patients, we identified increased activity of mTOR 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 that components of protein synthesis signalling pathways might constitute a molecular signature of clinical severity in autism spectrum disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autism Spectrum Disorder / genetics*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • MAP Kinase Signaling System / genetics*
  • Male
  • Neurogenesis / genetics*
  • Nucleocytoplasmic Transport Proteins / genetics
  • Protein Serine-Threonine Kinases / genetics
  • Ribosomal Protein S6 Kinases, 90-kDa / genetics
  • TOR Serine-Threonine Kinases / genetics*
  • Tuberous Sclerosis Complex 1 Protein / genetics


  • EIF4ENIF1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Nucleocytoplasmic Transport Proteins
  • TSC1 protein, human
  • Tuberous Sclerosis Complex 1 Protein
  • MKNK1 protein, human
  • MTOR protein, human
  • Protein Serine-Threonine Kinases
  • RPS6KA1 protein, human
  • Ribosomal Protein S6 Kinases, 90-kDa
  • TOR Serine-Threonine Kinases