抑郁症(major depressive disorder，MDD)是一类以心境抑郁、兴趣减退为主要临床表现的精神障碍疾病。其病因机制不清，具有高发病率、高复发率及高自杀率特点。当下主流的单胺类假说不能充分阐明其病理学特征，部分抑郁症患者对现有抗抑郁药治疗应答不佳。N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor，NMDAR)拮抗剂和γ-氨基丁酸A(γ-aminobutyric acid A，GABAA)受体正向变构调节剂具有潜在快速抗抑郁效果，可能是抑郁症发病的新机制和临床治疗的突破口。NMDAR具有双向调节作用，适当激活可促进树突发育、神经元生长和长时程增强，但过度刺激会引起毒性反应，导致突触萎缩和神经元死亡。此外，炎症反应可诱导NMDAR功能改变从而产生抑郁症状。目前临床上新型抗抑郁药物NMDAR拮抗剂氯胺酮可能通过促进脑源性神经营养因子(brain-derived neurotrophic factor，BDNF)释放增加、激活雷帕霉素靶蛋白复合物1(mammalian target of rapamycin complex 1，mTORC1)信号通路，进而促进蛋白质合成、增强突触可塑性，从而起到快速抗抑郁和延缓抑郁复发的作用，但由于MDD患者NMDAR基因变异性较大，其潜在功能多态性影响临床症状表现和药物敏感性。本文通过梳理分析国内外最新研究，综述NMDAR功能异常与抑郁症发病、抗抑郁治疗作用以及临床应用现状，以期为抑郁症患者精准治疗提供理论基础。“,”Major depressive disorder(MDD) is a kind of mental disorder with depression and decreased interest as the main clinical manifestations. The pathogenesis of MDD is unclear, and MDD is characterized by high incidence, high recurrence rate and high suicide rate. At present, the hypothesis of monomamine mechanism can not fully clarify its pathological characteristics, and a considerable number of patients with depression do not respond well to existing antidepressants. N-methyl-D-aspartate receptor (NMDAR) antagonist and γ-aminobutyric acid A(GABAA) receptor positive allosteric regulator have a potential rapid antidepressant effect, which may be a breakthrough in the pathogenesis and clinical treatment of depression. NMDAR has bidirectional regulation, when proper activation of NMDAR can promote dendrite development, neuronal growth and long-term potentiation, but overstimulation of NMDAR can cause toxic reaction, leading to synaptic atrophy and neuronal death. In addition, inflammation can induce changes in NMDAR function and lead to depressive symptoms. At present, ketamine, a new antidepressant NMDAR antagonist, may plays a role in rapid antidepressant and delayed recurrence of depression by increasing the release of BDNF, activating the signal pathway of mammalian target of rapamycin complex 1(mTORC1), and promoting protein synthesis and synaptic plasticity. Thus, ketamine has the effect of rapid antidepressant and delaying the recurrence of depression. However, due to the large variability of NMDAR gene in patients with MDD, its potential functional polymorphism affects clinical symptoms and drug sensitivity. Therefore, by analyzing the latest research at home and abroad, this review comprehensively summarizes the pathogenesis of NMDAR dysfunction, the pathogenesis of MDD, antidepressant treatment and clinical application status, in order to provide theoretical basis for clinical accurate treatment of MDD patients in the future.