精神分裂症谱系障碍患者血液中犬尿氨酸通路的改变：一项荟萃分析。
Blood-based kynurenine pathway alterations in schizophrenia spectrum disorders: A meta-analysis.
机构信息
Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium; Scientific Initiative of Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Centre Duffel, Duffel, Belgium.
Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium; Scientific Initiative of Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Centre Duffel, Duffel, Belgium.
出版信息
Schizophr Res. 2020 Sep;223:43-52. doi: 10.1016/j.schres.2020.09.007. Epub 2020 Sep 25.
INTRODUCTION
The kynurenine pathway (KP) has been proposed as indirect link between systemic immune responses and clinical symptom development in schizophrenia spectrum disorders (SSD). Empirical evidence for such immune-related KP shifts in SSD has however resulted in divergent findings.
METHODS
We conducted a systematic literature search in PubMed. Thirty papers (total number of patients n = 1506; controls: n = 1432) reported on peripheral concentrations of KP metabolites in SSD patients versus controls. Six KP metabolites were included in a meta-analysis, with secondary analysis of covariate and subgroup effects of patients' symptomatic state, age and duration of illness.
RESULTS
Tryptophan (SMD: -0.30; p = .003) and Xanthurenic Acid (SMD: -0.80; p < .001) were significantly decreased in SSD compared to controls, while Quinolinic Acid (SMD: -0.40; p = .08) and Kynurenic Acid (SMD: -0.39; p = .04) were only significantly decreased in patients with acute or highly symptomatic illness. Finally, in relatively older patient cohorts Kynurenine (SMD: -0.31; p = .02) and Kynurenic Acid (SMD: -0.40; p = .002) were found to be decreased.
CONCLUSION
A partial downregulation of the KP is observed in SSD patients, in particular during acute symptomatic states and in older age, effects that were independent from each other. In contrast, younger and stable or remitted patients display limited to no KP metabolite abnormalities. The current meta-analysis illustrates the dynamic nature of KP abnormalities. It should be noted that all included studies investigated peripheral KP metabolites, which do not necessarily reflect central KP metabolite abnormalities in schizophrenic patients.
简介
色氨酸犬尿氨酸途径（KP）被认为是精神分裂症谱系障碍（SSD）中全身免疫反应与临床症状发展之间的间接联系。然而，SSD 中这种与免疫相关的 KP 变化的实证证据得出的结果却存在差异。
方法
我们在 PubMed 中进行了系统的文献检索。30 篇论文（患者总数 n=1506；对照组 n=1432）报告了 SSD 患者与对照组之间外周 KP 代谢物的浓度。对 6 种 KP 代谢物进行了荟萃分析，并对患者症状状态、年龄和疾病持续时间的协变量和亚组效应进行了二次分析。
结果
与对照组相比，色氨酸（SMD：-0.30；p=0.003）和黄尿酸（SMD：-0.80；p<0.001）在 SSD 中显著降低，而喹啉酸（SMD：-0.40；p=0.08）和犬尿酸（SMD：-0.39；p=0.04）仅在急性或高度症状性疾病的患者中显著降低。最后，在年龄较大的患者队列中，发现犬尿氨酸（SMD：-0.31；p=0.02）和犬尿酸（SMD：-0.40；p=0.002）降低。
结论
在 SSD 患者中观察到 KP 的部分下调，特别是在急性症状状态和老年时，这些效应彼此独立。相比之下，年轻且稳定或缓解的患者显示出有限的或没有 KP 代谢物异常。当前的荟萃分析说明了 KP 异常的动态性质。需要注意的是，所有纳入的研究都检测了外周 KP 代谢物，这些代谢物不一定反映出精神分裂症患者中枢 KP 代谢物的异常。
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