Kynurenine pathway (KP) metabolites are believed to be a link between inflammation and depression through effects on brain glutamate receptors. However, neither the relationship between plasma and cerebrospinal fluid (CSF) KP metabolites nor their association with inflammatory mediators is well-established in depression. Moreover, the clinical profile associated with combined activation of plasma inflammatory and kynurenine pathways is unknown. Accordingly, plasma and CSF-KP metabolites and inflammatory markers along with depressive symptoms and antidepressant treatment response were measured in 72 unmedicated depressed patients. Following bivariate analyses, component factors representing immune and kynurenine variables in the plasma and CSF were extracted and were used to examine directionality of associations in a path model. In addition, patients were clustered using individual markers that most accounted for the association between plasma immune and KP systems. Path analysis revealed a directional association extending from plasma inflammatory markers to plasma kynurenines, to CSF kynurenines. Among immune markers, plasma tumor necrosis factor (TNF) was robustly associated with plasma kynurenine (KYN) and KYN/tryptophan (TRP), which was in turn significantly associated with CSF KYN, kynurenic acid, and quinolinic acid. Clustering of patients based on plasma TNF and KYN/TRP yielded subgroups of high (N = 17) and low (N = 55) TNF-KYN/TRP groups. High TNF-KYN/TRP subjects exhibited greater depression severity, anhedonia, and treatment nonresponse. In conclusion, plasma-KP metabolites may mediate an inflammation-associated depressive symptom profile via CNS KP metabolites that can serve as a target for intervention at the level of inflammation, peripheral KYN metabolism, KYN transport to the brain, or effects of KP metabolites on glutamate receptors.

中文翻译：

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周围和中央犬尿氨酸途径代谢物与抑郁症炎症之间的关联。

Kynurenine途径（KP）代谢产物被认为是通过影响大脑谷氨酸受体而在炎症和抑郁之间建立联系。然而，在抑郁症中，血浆和脑脊液（CSF）KP代谢产物之间的关系及其与炎性介质的关联均未得到很好的确立。而且，与血浆炎性和犬尿氨酸途径的联合激活相关的临床概况是未知的。因此，在72名未接受药物治疗的抑郁症患者中，测定了血浆和CSF-KP代谢产物和炎性标志物以及抑郁症状和抗抑郁治疗反应。经过双变量分析，提取了代表血浆和CSF中免疫和犬尿氨酸变量的组成因子，并用于检验路径模型中关联的方向性。此外，使用单个标记物对患者进行分组，这些标记物最能说明血浆免疫和KP系统之间的关联。路径分析揭示了从血浆炎症标记物到血浆犬尿氨酸到CSF犬尿氨酸的方向性关联。在免疫标记中，血浆肿瘤坏死因子（TNF）与血浆犬尿氨酸（KYN）和KYN /色氨酸（TRP）密切相关，而后者与CSF KYN，犬尿酸和喹啉酸显着相关。根据血浆TNF和KYN / TRP对患者进行聚类，分为高（N = 17）和低（N = 55）TNF-KYN / TRP组。高TNF-KYN / TRP受试者表现出更高的抑郁症严重程度，快感缺失和治疗无反应。结论，