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抑郁症的炎症机制及诊疗新策略

苏文君¹, 曹志永^1,2, 蒋春雷^1,*

¹二军医大学心理与精神卫生学系应激医学研究室，上海 200433；²全军精神医学中心，中国人民解放军第102医院，常州 213003

摘要

抑郁症是一类重要的精神心理疾病，其因高患病率、高致残性和高疾病负担等特征成为困扰全球的严重健康问题。一般认为，抑郁症的病因是多方面的，与性别差异、慢性应激、饮食行为方式及药物、酒精的滥用等有关。目前关于该疾病的具体病理生理机制仍未明确，研究者提出了诸如单胺能神经递质紊乱、下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal, HPA)轴功能紊乱、神经营养因子以及细胞因子等学说。基于最新研究证据以及临床工作中传统抗抑郁药效果不佳的客观事实，细胞因子学说近年来备受关注。现阶段关于细胞因子在抑郁症发病中的作用与机制研究主要集中在促炎细胞因子，尤其是肿瘤坏死因子-α (tumor necrosis factor-α, TNF-α)、白细胞介素-1β (interleukin-1β, IL-1β)以及白细胞介素-6 (interleukin-6, IL-6)等。随着国内外研究的深入开展，越来越多新分子、新机制被不断揭示。本文从炎症反应的角度对抑郁症发生和发展的病理生理机制进行综述，针对目前临床抗抑郁治疗的低应答率现状，提出新的诊疗策略，即抑郁症患者入院时检测炎症反应水平，对高炎患者联合使用抗炎治疗，旨在解决由于高炎状态导致应答率不理想的难治性抑郁症。

关键词： 炎症; 细胞因子 ; 抑郁症 ; 肿瘤坏死因子-α ; 白细胞介素-1β ; 白细胞介素-6

分类号：R395.1；R74

Inflammatory mechanism of depression and its new strategy for diagnosis and treatment

SU Wen-Jun¹, CAO Zhi-Yong^1,2, JIANG Chun-Lei^1,*

¹Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, The Second Military Medical University, Shanghai 200433, China；²Psychiatry Center of PLA, the 102nd Hospital of PLA, Changzhou 213003, China

Abstract

 Depression is a major class of mental illness; owing to its high prevalence, high disability rate and heavy disease burden, it has become a stern and formidable global health problem. It is generally believed that the etiology of depression is multifactorial, which is related to gender differences, chronic stress, dietary behavior and drug abuse. At present, the exact pathophysiological mechanism of depression still remains unclear, but researchers across the globe put forward various hypotheses to interpret the possible access to this disease, including monoamine neurotransmitter disturbance, hypothalamic-pituitary-adrenal (HPA) axis dysfunction, lack of neurotrophic factors and excessive pro-inflammatory cytokines. Based on the latest research evidence and the objective fact that traditional antidepressants may be ineffective in some particular patients, the “cytokine theory” tends to attract more and more attention recently. To date, researches on the role of cytokines in the pathogenesis of depression mainly focus on pro-inflammatory cytokines, especially categories including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). With the proceeding of researches from all over the world, a variety of novel molecules and mechanisms were postulated. This paper summarized a large amount of in vitro and in vivo research evidence, in order to review the current progress of the researches on pathophysiology of depression from the perspective of pro-inflammatory cytokines. Since the response rate of antidepressant therapy during present medical practice is unsatisfying, we suggest a new feasible diagnosis and treatment strategy, that is to distinguish the inflammatory status of patients with depression and take anti-inflammatory treatment into consideration. Totally, this novel strategy aims at modulating the conventional clinical protocol for treatment-resistant depressive patients and overcoming the limitation of insufficient antidepressant response possibly resulted from inflammation.

Key words: Inflammation; cytokine ; depression ; tumor necrosis factor-α ; interleukin-1β ; interleukin-6

收稿日期：2017-04-17　　录用日期：2017-09-11

通讯作者：蒋春雷　　E-mail: cljiang@vip.163.com

DOI: 10.13294/j.aps.2017.0063

引用本文：

苏文君, 曹志永, 蒋春雷. 抑郁症的炎症机制及诊疗新策略[J]. 生理学报 2017; 69 (5): 715-722.

SU Wen-Jun, CAO Zhi-Yong, JIANG Chun-Lei. Inflammatory mechanism of depression and its new strategy for diagnosis and treatment. Acta Physiol Sin 2017; 69 (5): 715-722 (in Chinese with English abstract).