BACKGROUND In the last decade, there has been growing evidence that an interaction exists between inflammation and the kynurenine pathway in schizophrenia. Additionally, many authors found microglial activation in cases of schizophrenia due to inflammatory mechanisms related mostly to an increase of pro-inflammatory cytokines. In order to gain new insights into the pathophysiology of schizophrenia, it is important to incorporate the latest published evidence concerning inflammatory mechanisms and kynurenine metabolism. This systematic review aims to collect reliable recent findings within the last decade supporting such a theory. METHODS A structured search of electronic databases was conducted for publications between 2008 and 2018 to identify eligible studies investigating patients with schizophrenia/psychosis and the relationship between inflammation and kynurenine pathway. Applicable studies were systematically scored using the NIH Quality Assessment Tools. Two researchers independently extracted data on diagnosis (psychosis/schizophrenia), inflammation, and kynurenine/tryptophan metabolites. RESULTS Ten eligible articles were identified where seven studies assessed blood samples and three assessed cerebrospinal fluid in schizophrenic patients. Of these articles: Four investigated the relationship between immunoglobulins and the kynurenine pathway and found correlations between IgA-mediated responses and levels of tryptophan metabolites (i.e., kynurenine pathway).Five examined the correlation between cytokines and kynurenine metabolites where three showed a relationship between elevated IL-6, TNF-α concentrations, and the kynurenine pathway.Only one study discovered correlations between IL-8 and the kynurenine pathway.Two studies showed correlations with lower concentrations of IL-4 and the kynurenine pathway.Moreover, this systematic review did not find a significant correlation between CRP (n = 1 study), IFN-γ (n = 3 studies), and the kynurenine pathway in schizophrenia. INTERPRETATION These results emphasize how different inflammatory markers can unbalance the tryptophan/kynurenine pathway in schizophrenia. Several tryptophan/kynurenine pathway metabolites are produced which can, in turn, underlie different psychotic and cognitive symptoms via neurotransmission modulation. However, due to heterogeneity and the shortage of eligible articles, they do not robustly converge to the same findings. Hence, we recommend further studies with larger sample sizes to elucidate the possible interactions between the various markers, their blood vs. CSF ratios, and their correlation with schizophrenia symptoms.

中文翻译：

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炎症对精神分裂症犬尿氨酸途径的影响-系统评价。

背景技术在过去的十年中，越来越多的证据表明炎症和精神分裂症中的犬尿氨酸途径之间存在相互作用。此外，许多作者发现精神分裂症患者的小胶质细胞活化是由于炎症机制引起的，而炎症机制主要与促炎细胞因子的增加有关。为了获得对精神分裂症的病理生理学的新见解，重要的是纳入有关炎症机制和犬尿氨酸代谢的最新公开证据。本系统综述旨在收集支持该理论的最近十年内可靠的最新发现。方法对电子数据库进行结构化搜索，以寻找2008年至2018年之间的出版物，以鉴定符合条件的研究，以调查精神分裂症/精神病患者以及炎症与犬尿氨酸途径之间的关系。使用NIH质量评估工具对适用的研究进行系统评分。两名研究人员独立提取了有关诊断（精神病/精神分裂症），炎症和犬尿氨酸/色氨酸代谢物的数据。结果确定了十篇合格的文章，其中七项研究评估了精神分裂症患者的血样和三篇评估了脑脊液。这些文章中：四篇研究了免疫球蛋白与犬尿氨酸途径之间的关系，并发现了IgA介导的反应与色氨酸代谢产物水平（犬尿氨酸途径）之间的相关性。有五项研究了细胞因子与犬尿氨酸代谢产物之间的相关性，其中三项显示IL-6，TNF-α浓度升高与犬尿氨酸途径之间的关系;只有一项研究发现了IL-8与犬尿氨酸途径之间的相关性;两项研究表明与较低的IL-8，犬尿氨酸途径相关IL-4的浓度和犬尿氨酸途径。此外，本系统评价未发现精神分裂症的CRP（n = 1研究），IFN-γ（n = 3研究）与犬尿氨酸途径之间存在显着相关性。解释这些结果强调了不同的炎症标记物如何使精神分裂症中的色氨酸/犬尿氨酸途径失衡。产生了几种色氨酸/犬尿氨酸途径代谢物，这些代谢物又可以通过神经传递调节而成为不同的精神病和认知症状的基础。然而，由于异质性和合格文章的短缺，它们无法可靠地收敛到相同的发现。因此，我们建议进行更大样本量的进一步研究，以阐明各种标志物之间的可能相互作用，其血液与脑脊液比率以及它们与精神分裂症症状的相关性。