Rengasamy Manivel, Marsland Anna, Spada Meredith, Hsiung Kimberly, Kovats Tessa, Price Rebecca B
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
J Affect Disord Rep. 2021 Dec;6. doi: 10.1016/j.jadr.2021.100177. Epub 2021 Jun 19.
Cytokines are an important part of the immune system. Certain cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), have well-described associations with depression. Various mechanisms exist that may explain bidirectional effects of cytokines on depression and vice versa. No recent reviews to our knowledge have comprehensively characterized both these mechanisms and the interaction of these mechanisms using evidence from the molecular level to the clinical level. The goal of this review is to both evaluate the present knowledge base and identify knowledge gaps to help guide future research.
We conducted an extensive bibliographic search across multiple databases, using both general (e.g. "cytokine") and topic-specific (e.g. "kynurenine") keywords.
We describe the most recent evidence outlining these mechanisms, including the role of the hypothalamic pituitary axis, the kynurenine pathway, and neural circuitry. For relevant topics, we outline the pathways by which cytokine activation may lead to depressive symptoms, and how depressive symptomology may lead to elevations in cytokines. We also identify key areas for future research, including the need for longitudinal clinical studies to examine causality in pertinent mechanisms and modulating factors in the cytokine-depression interaction.
Given the numerous potential mechanisms associating cytokines and depressions, this review paper solely focuses on the most commonly described mechanisms at a basic level.
Bidirectional evidence exists for several mechanisms in the relationship between cytokines and depression. However, more work is required to further elucidate the role of these mechanisms in specific clinical populations.
细胞因子是免疫系统的重要组成部分。某些细胞因子，如白细胞介素-6（IL-6）和肿瘤坏死因子α（TNFα），与抑郁症有着明确的关联。存在多种机制可以解释细胞因子与抑郁症之间的双向作用，反之亦然。据我们所知，最近没有综述全面描述这些机制以及从分子水平到临床水平这些机制的相互作用。本综述的目的是评估当前的知识库并识别知识空白，以帮助指导未来的研究。
我们使用通用关键词（如“细胞因子”）和特定主题关键词（如“犬尿氨酸”）在多个数据库中进行了广泛的文献检索。
我们描述了概述这些机制的最新证据，包括下丘脑-垂体轴、犬尿氨酸途径和神经回路的作用。对于相关主题，我们概述了细胞因子激活可能导致抑郁症状的途径，以及抑郁症状如何导致细胞因子升高。我们还确定了未来研究的关键领域，包括需要进行纵向临床研究以检验相关机制中的因果关系以及细胞因子-抑郁症相互作用中的调节因素。
鉴于细胞因子与抑郁症之间存在众多潜在机制，本综述仅关注基础层面最常描述的机制。
细胞因子与抑郁症之间的关系存在多种机制的双向证据。然而，需要更多工作来进一步阐明这些机制在特定临床人群中的作用。
