孤独症谱系障碍发病机制的研究进展

Research progress in mechanisms underlying autism spectrum disorders

孤独症谱系障碍(ASD)是由三个核心行为领域的损伤定义的一组复杂的神经精神病症:社交互动、言语和非言语交流、以及受限制的兴趣/重复行为。广泛的遗传学研究已经鉴定了许多孤独症的易感基因,并增加了对从头变异和遗传拷贝数变异的贡献的理解。笔者将最近的基因发现置于发育和大脑回路环境中,并从遗传、分子、细胞和神经多个回路领域对孤独症神经病理学进行基本理解。回顾利用小鼠动物模型以探求ASD脑机制的文献,以期从了解大脑发育背景下揭示个体风险基因可能如何运作以及和患者症状的关联。明确研究与大脑神经环路相关的机制可能从理论上指导对孤独症的面向特定神经回路的个性化治疗的方案,从而产生更好的干预疾病进程和良性的行为转化的结果。

The autism spectrum disorders(ASDs)are a complex group of neuropsychiatric conditions defined by impairment in three core behavioral domains:social interaction,verbal and non-verbal communication,and restricted interests/repetitive behaviors. Extensive genetic studies have led to the identification of many autism susceptibility genes,and increased understanding on the contribution of de novo and inherited copy number variation. Here,we seek to place recent genetic findings within a developmental and brain circuit context,and approach the basic understanding of autism neuropathology from multiple genetic,molecular,cellular and neural circuit domains. The authors reviewed literatures that interrogates brain mechanisms of ASDs utilizing animal models,primarily in mice. Understanding genetic data within a brain development context will shed light on how individual risk genes operate to determine patient symptomatology,which will inform circuit specific behavioral interventions leading to better intervention and disease outcomes.