兴奋-抑制失衡与孤独症谱系障碍:作用机制及治疗进展

Excitatory⁃inhibitory Imbalance and Autism Spectrum Disorder:Mechanism and Treatment Progress

孤独症谱系障碍(autism spectrum disorder,ASD)是世界上患病率增长最快的神经发育障碍,该病具有显著的遗传异质性,给临床治疗带来了巨大挑战。研究表明,中枢神经系统的兴奋-抑制(excitatory-inhibitory,E-I)失衡可能是ASD的重要发病机制之一,在多种ASD动物模型中进行神经环路E-I失衡调节,能够改善模型动物的孤独症样行为。相关临床试验将E-I失衡作为ASD的治疗靶点,恢复特定皮质区域原有的E-I平衡状态,能够对ASD患者起到一定的治疗作用。本文就E-I失衡在ASD中的作用机制及E-I失衡调节剂治疗ASD的研究进展作一综述,以期为ASD的临床诊疗提供新思路。

Autism spectrum disorder(ASD)is becoming one of the fastest growing neurodevelopmen⁃tal disorders around the world,yet its clinical treatment still faces challenge due to the heterogeneity in etiolo⁃gy and symptom phenotypes.It is believed that excitatory⁃inhibitory(E⁃I)imbalance in the central nervous system may play an important role in the pathogenic mechanisms of ASD.E⁃I imbalances in synaptic transmis⁃sion and neural circuits are frequently observed in different animal models of ASD,and the corresponding re⁃version normalizes the autism⁃like behaviors in these animals.Some E⁃I modulators have been tested for their therapeutic potential on ASD patients with encouraging results.This article expounds the mechanism of E⁃I imbalance in ASD and E⁃I imbalance regulators treatment progress,to provide new insights on the therapeutic targets for ASD.