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.

自闭症谱系障碍背后的分子特征仍然很大程度上未知。本研究确定了轻度和重度特发性自闭症患者中 mTOR 和 MAPK 通路的差异表达。总共招募了 55 名受试者，其中 22 名是典型发育个体，33 名是年龄在 3 岁至 11 岁之间的自闭症谱系障碍患者。对每位患者进行详细的病史记录，包括体格检查、发育评估、心理健康史和自闭症诊断观察计划。在蛋白质水平上分析外周血中 mTOR 和 MAPK 信号通路的成分。然后根据患者的临床表型对患者进行分层，并分析分子谱与自闭症严重程度的关系。在这组患者中，我们发现 mTOR 和 MAPK 通路（突触发生和蛋白质合成的关键调节因子）活性增加。具体来说，rpS6、p-eIF4E、TSC1 和 p-MNK1 表达根据患者的临床诊断来区分患者，这表明蛋白质合成信号通路的组成部分可能构成自闭症谱系障碍临床严重程度的分子特征。