Histidine Metabolic Pathway Contributes to Clozapine-Induced Sialorrhea Based on Nontargeted Metabolomics.

IF 2.3 4区心理学 Q3 NEUROSCIENCES Neuropsychobiology Pub Date : 2023-01-01 Epub Date: 2023-08-28 DOI:10.1159/000528807

Kun Zhang, Shengwei Wu, Youtian Wang, Yufang Zhou, Jianxiong Guo, Aixiang Xiao, Junrong Ye, Baofeng Wu, Shuyun Li, Fujian Zhu, Zezhi Li, Lin Yu

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Abstract

Introduction: Clozapine-induced sialorrhea (CIS) is one of the most common side effects of clozapine use, while the mechanism remains unclear.

Methods: A total of 51 schizophrenia patients taking clozapine were selected. Among them, 32 had sialorrhea, and 19 had no sialorrhea. Saliva metabolites were identified using ultra-high-performance liquid chromatography-MS/MS (UHPLC-MS/MS), and the differences in saliva metabolites in each group were analyzed through qualitatively searching HMDB, KEGG, and self-built databases, combined with multivariate statistics. After further evaluation by receiver-operating characteristic curve (ROC) analysis, the screened differential metabolites were enriched and topologically analyzed.

Results: The biomarkers potentially related to CIS included 37 differential metabolites involving 17 metabolic pathways, mainly histidine metabolism (p < 0.05, impact = 0.50), pyrimidine metabolism (p < 0.05, impact = 0.08), and β-alanine metabolism (p < 0.05, impact = 0.06).

Conclusion: Our study indicates that histidine metabolic pathway may contribute to the mechanism of CIS.

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基于非靶向代谢组学的组氨酸代谢途径对氯氮平诱导的唾液漏的作用。

引言：氯氮平引起的唾液溢（CIS）是氯氮平使用最常见的副作用之一，但其机制尚不清楚。方法：选择51例服用氯氮平的精神分裂症患者。其中32例有唾液溢液，19例无唾液溢液。使用超高效液相色谱MS/MS（UHPLC-MS/MS）鉴定唾液代谢产物，并通过定性搜索HMDB、KEGG和自建数据库，结合多元统计分析各组唾液代谢产物的差异。通过受试者工作特性曲线（ROC）分析进一步评估后，对筛选出的差异代谢产物进行富集和拓扑分析。结果：与CIS潜在相关的生物标志物包括37种不同的代谢产物，涉及17种代谢途径，主要是组氨酸代谢（p<0.05，impact=0.50）、嘧啶代谢（p>0.05，impact=0.08）和β-丙氨酸代谢（p<0.05、impact=0.06）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropsychobiology 医学-精神病学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： The biological approach to mental disorders continues to yield innovative findings of clinical importance, particularly if methodologies are combined. This journal collects high quality empirical studies from various experimental and clinical approaches in the fields of Biological Psychiatry, Biological Psychology and Neuropsychology. It features original, clinical and basic research in the fields of neurophysiology and functional imaging, neuropharmacology and neurochemistry, neuroendocrinology and neuroimmunology, genetics and their relationships with normal psychology and psychopathology. In addition, the reader will find studies on animal models of mental disorders and therapeutic interventions, and pharmacoelectroencephalographic studies. Regular reviews report new methodologic approaches, and selected case reports provide hints for future research. ''Neuropsychobiology'' is a complete record of strategies and methodologies employed to study the biological basis of mental functions including their interactions with psychological and social factors.