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精神分裂症患者外周色氨酸-犬尿氨酸代谢通路中代谢物水平与临床症状的关系

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背景 精神分裂症是一种常见的重性精神障碍,其发病机制复杂,目前关于精神分裂症外周血清和尿液犬尿氨酸(KYN)代谢物相关性的研究有限.目的 分析精神分裂症患者外周血清和尿液色氨酸(TRP)-KYN代谢物与白细胞介素-6(IL-6)的浓度以及血清与尿液KYN代谢物的相关性以及代谢物水平与临床症状的相关性,以期为探索精神分裂症的潜在生物标志物提供参考.方法 纳入2021年12月—2022年12月在杭州市第七人民医院住院治疗或门诊就诊的、符合《精神障碍诊断与统计手册(第5版)》(DSM-5)精神分裂症诊断标准的38例患者为研究对象,同期在杭州市社区招募健康对照组共26例.采用阳性和阴性症状量表(PANSS)评定患者的精神病性症状,采用超高效液相色谱串联三重四极杆质谱技术检测所有受试者血清和尿液TRP、KYN、犬尿喹啉酸(KYNA)、喹啉酸(QUIN)、吡啶甲酸(PIC)、黄尿酸和5-羟色胺(5-HT)水平,采用酶联免疫分析检测血清和尿液IL-6水平.采用Pearson相关分析考查精神分裂症患者血清与尿液TRP-KYN代谢物之间的相关性以及代谢物水平与临床症状的相关性.结果 精神分裂症患者血清IL-6水平高于健康对照组,差异有统计学意义(U=798.500,P<0.01).精神分裂症患者尿液PIC水平低于健康对照组,差异有统计学意义(U=253.000,P=0.013).精神分裂症患者血清KYN水平与尿液QUIN/KYNA、QUIN/PIC均呈正相关(r=0.562、0.438,P均<0.05).精神分裂症患者血清5-HT/KYN与PANSS总评分和阴性症状分量表评分均呈正相关(r=0.458、0.455,P均<0.01).结论 精神分裂症患者血清TRP-KYN代谢物水平与尿液中神经毒性代谢物比值有关,并与阴性症状严重程度呈正相关.
Relationship between metabolites of peripheral tryptophan-kynurenine metabolic pathway and clinical symptoms in patients with schizophrenia
Background Schizophrenia is a common severe mental disorder with complex pathogenesis.There are few studies on the correlation between kynurenine metabolites in peripheral serum and urine in schizophrenia.Objective To investigate the concentration of tryptophan-kynurenine metabolites and interleukin-6(IL-6)in serum and urine in patients with schizophrenia,and their correlation with clinical symptoms,so as to explore potential biological characteristics related to schizophrenia.Methods A total of 38 patients with schizophrenia who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5),and were hospitalized or attended outpatient clinic at Hangzhou Seventh People's Hospital from December 2021 to December 2022 were included in the study.Additionally,26 healthy individuals were concurrently recruited from the community of Hangzhou to serve as a control group.All participants were requested to complete the Positive and Negative Symptom Scale(PANSS).The levels of tryptophan(TRP),kynurenine(KYN),kynurenic acid(KYNA),quinolinic acid(QUIN),picolinic acid(PIC),xanthurenate and 5-hydroxytryptamine(5-HT)in both serum and urine were measured using ultra-high-performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry.Serum and urine IL-6 were measured using enzyme-linked immunosorbent assay.Pearson correlation analysis was conducted to examine the correlation between serum and urinary KYN metabolites,as well as the correlation between metabolite levels and clinical symptoms in the patient group.Results Patients with schizophrenia had significantly higher level of IL-6 in serum(U=798.500,P<0.01)and lower level of PIC in urine(U=253.000,P=0.013)compared with the control group.Additionally,level of serum KYN was positively correlated with QUIN/KYNA ratio and QUIN/PIC ratio(r=0.562,0.438,P<0.05)in patients with schizophrenia.5-HT/KYN ratio in serum was positively correlated with PANSS total score and negative symptom subscale score(r=0.458,0.455,P<0.01)in patients with schizophrenia.Conclusion Serum TRP-KYN pathway metabolite levels in patients with schizophrenia were associated with neurotoxic metabolite ratios in urine and the severity of negative symptoms.

SchizophreniaSerumUrineTryptophanKynurenineMetabolitesClinical symptoms

吴月、徐艳、黄鑫、王大可、黄晨韵、梁素改

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浙江大学医学院附属精神卫生中心,杭州市第七人民医院,浙江 杭州 310013

精神分裂症 血清 尿液 色氨酸 犬尿氨酸 代谢物 临床症状

浙江省医药卫生科技计划项目

2022KY990

2024

四川精神卫生
绵阳市精神卫生中心

四川精神卫生

CSTPCD
影响因子:0.565
ISSN:1007-3256
年,卷(期):2024.37(1)
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