多维微环境失调视角下的孤独症谱系障碍研究：从致病网络到精准干预

Research on Autism Spectrum Disorder from the Perspective of Multidimensional Microenvironmental Dysregulation: From Pathogenic Networks to Precision Intervention

摘要: 孤独症谱系障碍(ASD)是一组以社交沟通障碍和重复刻板行为为核心特征的神经发育疾病，全球患病率已超过1%，美国CDC最新数据达1/31，成为重大公共卫生议题。ASD的病因学呈现高度异质性，传统还原论思路难以解释其复杂的发病机制。近年来，研究揭示ASD的发病是一个由遗传易感性、免疫失调、表观遗传修饰、突触可塑性异常、肠脑轴紊乱等多维因素动态交织构成的致病网络。本文系统整合ASD流行病学趋势、多维发病机制及诊疗技术创新，重点评述“微环境失调”这一整合性理论框架——该框架将免疫失衡、表观遗传调控、突触功能异常与肠脑轴交互纳入统一视角，强调早期生命阶段遗传风险与环境暴露的交叉对话如何通过神经–免疫–肠道信号回路持续影响神经发育。在诊疗层面，多模态脑影像标志物、基于机器学习的预测模型以及靶向“社会脑”环路的精准神经调控正推动ASD诊疗从经验化走向个体化。本文提出“微环境解析–亚型分层–靶向干预”三位一体的未来研究框架，为ASD的精准医学研究提供理论参考。

Abstract: Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions characterized by core features of social communication deficits and restricted repetitive behaviors. With a global prevalence exceeding 1% and the latest CDC estimate reaching 1 in 31 children in the United States, ASD has become a major public health concern. The etiology of ASD exhibits remarkable heterogeneity, and traditional reductionist approaches have proven insufficient to explain its complex pathogenesis. Recent research has revealed that ASD arises from a dynamic pathogenic network involving genetic susceptibility, immune dysregulation, epigenetic modifications, synaptic plasticity abnormalities, and gut-brain axis disturbances. This review systematically synthesizes epidemiological trends, multidimensional pathogenic mechanisms, and diagnostic and therapeutic innovations in ASD. Particular emphasis is placed on the “microenvironment dysregulation” framework—an integrative theoretical model that unifies immune imbalance, epigenetic regulation, synaptic dysfunction, and gut-brain interactions, emphasizing how the cross-talk between genetic risk and environmental exposures during early life shapes neurodevelopment through neural-immune-gut signaling circuits. On the diagnostic and therapeutic front, multimodal neuroimaging biomarkers, machine learning-based predictive models, and precision neuromodulation targeting the “social brain” circuitry are driving ASD toward individualized approaches. This review proposes a three-tiered future research framework—“microenvironment characterization—subtype stratification—targeted intervention”—to inform precision medicine research in ASD.