The kynurenine pathway in bipolar disorder: a meta-analysis on the peripheral blood levels of tryptophan and related metabolites
The kynurenine pathway in bipolar disorder: a meta-analysis on the peripheral blood levels of tryptophan and related metabolites
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DOI：
10.1038/s41380-020-00913-1
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发表时间：
2020-10-19
影响因子：
11
通讯作者：
Carra, Giuseppe
中科院分区：
文献类型：
--
作者：
Bartoli, Francesco;Misiak, Blazej;Carra, Giuseppe
越来越多的证据表明，犬尿氨酸途径（KP）的失调发生在双相情感障碍（BD）。本系统综述和荟萃分析旨在评估双相障碍患者和健康对照者外周血KP代谢物水平的可能差异。我们在Medline、Embase和PsycInfo电子数据库中检索了索引至2020年2月的文章。我们纳入了所有比较成年双相障碍患者和健康对照者外周血中至少一种KP代谢物水平的观察性研究。随机效应荟萃分析产生合并标准化平均差异（SMDs）。使用他们的i(2)指数估计研究之间的异质性。进行meta回归和敏感性分析。16项研究符合纳入标准，纳入我们的研究。荟萃分析显示，与健康对照组相比，BD患者外周血色氨酸（SMD = -0.29）、犬尿氨酸（SMD = -0.28）、犬尿酸（SMD = -0.30）和黄嘌呤酸（SMD = -0.55）水平较低，犬尿酸/犬尿氨酸（SMD = -0.60）和犬尿酸/喹啉酸（SMD = -0.37）比值也较低。躁狂发作的个体色氨酸水平下降幅度最大（SMD = -0.51），而抑郁期的犬尿酸水平下降幅度更大（SMD = -0.70）。meta回归和敏感性分析证实了我们的结果。本荟萃分析的结果支持了BD中KP异常的假设。考虑到研究结果的部分不一致和估计效应大小的中小型，需要进一步的研究来评估可能的介质或混杂因素。
Growing evidence suggests that a dysregulation of the kynurenine pathway (KP) occurs in bipolar disorder (BD). This systematic review and meta-analysis aimed at assessing the possible differences in peripheral blood levels of KP metabolites between individuals with BD and healthy controls. We searched Medline, Embase, and PsycInfo electronic databases for articles indexed up to February 2020. We included any observational study comparing the peripheral blood levels of at least one KP metabolite between adults with BD and healthy controls. Random-effects meta-analyses were carried out generating pooled standardized mean differences (SMDs). Heterogeneity between studies was estimated using theI(2)index. Meta-regression and sensitivity analyses were conducted. Sixteen studies met inclusion criteria and were included in our study. Meta-analyses showed that individuals with BD have lower peripheral blood levels of tryptophan (SMD = -0.29), kynurenine (SMD = -0.28), kynurenic acid (SMD = -0.30), and xanthurenic acid (SMD = -0.55), along with lower kynurenic acid to kynurenine (SMD = -0.60) and kynurenic acid to quinolinic acid (SMD = -0.37) ratios, than healthy controls. Individuals with a manic episode showed the greatest reductions in tryptophan levels (SMD = -0.51), whereas kynurenic acid levels were more reduced among subjects in a depressive phase (SMD = -0.70). Meta-regression and sensitivity analyses confirmed our results. The findings of the present meta-analysis support the hypothesis of an abnormality of the KP in BD. Considering the partial inconsistency of the findings and the small-to-medium magnitude of the estimated effect sizes, additional research assessing possible mediators or confounders is needed.