N-methyl-D-aspartic receptor and major depressive disorder
10.3760/cma.j.cn371468-20200729-01604
- VernacularTitle:N-甲基-D-天冬氨酸受体与抑郁症
- Author:
Yunxia ZHU
;
Shuming ZHONG
;
Shunkai LAI
;
Yanbin JIA
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2021;30(3):284-288
- CountryChina
- Language:Chinese
-
Abstract:
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.