抑郁症(depression)是一种常见的精神障碍,其发病机制主要涉及神经递质合成代谢、小胶质细胞激活、下丘脑-垂体-肾上腺轴失调、炎症小体激活、微生物组改变以及大脑再生可塑性等学说。现有的一线抗抑郁药物如选择性5-羟色胺再摄取抑制剂、5-羟色胺和去甲肾上腺素再摄取抑制剂仍存在起效慢、有效率低、个体差异显著等局限性。近年来,随着对抑郁症、免疫研究的深入以及分子生物学的不断发展,越来越多的证据提示免疫炎症通路与抑郁症之间存在联系。犬尿氨酸通路(kynurenine pathway)是色氨酸代谢的最主要途径,其代谢产物在神经、免疫和炎症调节中发挥重要作用,尤其在免疫调节中具有复杂的双重效应。构建外周-中枢免疫网络全景视角并深入探讨色氨酸-犬尿氨酸代谢通路在抑郁症发病中的作用机制,对于进一步完善抑郁症发病的病理生理机制及药物研发具有重要意义。

Depression is a prevalent mental disorder characterized by a multifaceted pathogenesis involving theories such as neurotransmitter dysregulation, microglial activation, hypothalamicpituitary-adrenal (HPA) axis dysregulation, inflammasome activation, microbiome alterations, and impaired neuroplasticity. Current first-line antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), exhibit limitations such as delayed onset, low efficacy rates, and significant interindividual variability. In recent years, driven by advances in molecular biology and immunopsychiatry research, growing evidence has indicated an interplay between immune-inflammatory pathways and depression. The kynurenine pathway, a predominant route for tryptophan metabolism, generates metabolites that play significant roles in neural, immune, and inflammatory regulation, particularly exhibiting complex dual effects in immune modulation. It is essential to construct a comprehensive view of the peripheral-central immune network and delve into the mechanistic role of the tryptophankynurenine metabolic pathway within this network in the pathogenesis of depression, thus further advancing our knowledge of the pathophysiological mechanisms of depression and facilitating drug development.