重性抑郁症发病过程中小胶质细胞生物学功能及稳态破坏的研究进展，这一成果由上海交通大学医学院方贻儒团队经过不懈努力而取得。相关论文于2026年1月19日发表在《神经科学通报》杂志上。

抑郁症是一个重大的全球公共卫生问题。抑郁症的反复发作及其不可预测的自杀风险构成了严峻的医学挑战，强调了对其潜在机制进行深入调查的迫切需要。虽然传统假设单胺类神经递质耗竭是重度抑郁症（MDD）的主要诱发因素，但这一理论并不能完全解释重度抑郁症的复杂性和临床变异性。难治性抑郁症（TRD）作为重度抑郁症的一个亚组，提供了令人信服的证据。免疫炎症假说受到越来越多的关注，越来越多的人关注小胶质细胞在这一框架中的关键作用。

小胶质细胞是中枢神经系统的常驻免疫细胞，在成年期通过自我更新来维持体内平衡。在正常生理条件下，它们对调节神经元存活、细胞凋亡和突触可塑性至关重要。在病理情况下，如创伤性损伤、感染、心理应激等，小胶质细胞接收刺激信号，迅速对事件做出反应。当小胶质细胞内稳态被破坏时，它们会过度激活，释放促炎细胞因子，激活相关信号通路，破坏神经递质代谢。这会引发神经炎症、氧化应激和线粒体功能障碍，从而阻碍神经发生，破坏神经回路，最终导致MDD的进展，甚至可能将其推进到TRD。

本文就小胶质细胞生物学与MDD之间的关系进行综述，全面分析小胶质细胞生物学特性、影响小胶质细胞功能的因素以及与MDD相关的潜在机制。综上所述，本文从小胶质细胞稳态失衡的角度对重度抑郁症的发病机制提供了一个新的视角，旨在为后续的机制研究奠定理论基础。此外，基于MDD中以小胶质细胞稳态失衡为主导的神经炎症机制，本文旨在为MDD甚至进展到TRD阶段提供两种新的有前景的治疗方法。

附：英文原文

Title: Research Progress on the Biological Function and Homeostatic Disruption of Microglia in the Pathogenesis of Major Depressive Disorder

Author: Kong, Shuqi, Huang, Zhuoyue, Fang, Yiru

Issue&Volume: 2026-01-19

Abstract: Depression is a major global public health issue. The recurrent episodes of depression and its unpredictable suicide risk have posed a critical medical challenge, highlighting the urgent need for an in-depth investigation into its underlying mechanisms. While the conventional hypothesis of monoamine neurotransmitter depletion is the primary cause of major depressive disorder (MDD), this theory does not entirely explain the complexity and clinical variability of MDD. The presence of treatment-resistant depression (TRD), as a subgroup of MDD, serves as compelling evidence. The immune-inflammation hypothesis has gained increasing attention, with a growing focus on the pivotal role of microglia in this framework. Microglia, the resident immune cells of the central nervous system, sustain homeostasis through self-renewal in adulthood. They are essential for regulating neuron survival, apoptosis, and synaptic plasticity under normal physiological conditions. Under pathological situations, such as traumatic injury, infection, and psychological stress, microglia receive stimulating signals to promptly respond to events. When microglia homeostasis is disrupted, they become over-activated, releasing pro-inflammatory cytokines, activating related signaling pathways, and disrupting neurotransmitter metabolism. This triggers neuroinflammation, oxidative stress, and mitochondrial dysfunction, which hinder neurogenesis, disrupt neural circuits, and ultimately contribute to MDD progression, or even potentially advance it to TRD. This review focuses on the relationship between the biology of microglia and MDD, providing a comprehensive analysis of microglial biological characteristics, factors affecting microglia function, and underlying mechanisms associated with MDD. In conclusion, this review provides a novel perspective on the pathogenesis of MDD from the angle of microglial homeostasis imbalance, aiming to lay a theoretical basis for subsequent investigation of the mechanism. In addition, based on the mechanism of neuroinflammation caused by microglial homeostasis imbalance in MDD, this review aims to offer two new promising therapeutic approaches for MDD and even its progression to the TRD stage.

DOI: 10.1007/s12264-025-01571-5

Source: https://link.springer.com/article/10.1007/s12264-025-01571-5