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与精神分裂症患者对抗精神病药物治疗反应有效或无效相关的血浆脂质组变化。

Changes in the blood plasma lipidome associated with effective or poor response to atypical antipsychotic treatments in schizophrenia patients.

机构信息

Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

Gas Chromatography Laboratory, Chemistry Institute, University of Campinas(UNICAMP), Campinas, SP, Brazil.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jul 13;101:109945. doi: 10.1016/j.pnpbp.2020.109945. Epub 2020 Apr 15.

Abstract

Atypical antipsychotics are widely used to manage schizophrenia symptoms. However, these drugs can induce deleterious side effects, such as MetS, which are associated with an increased cardiovascular risk to patients. Lipids play a central role in this context, and changes in lipid metabolism have been implicated in schizophrenia's pathobiology. Furthermore, recent evidence suggests that lipidome changes may be related to antipsychotic treatment response. The aim of this study was to evaluate the lipidome changes in blood plasma samples of schizophrenia patients before and after 6 weeks of treatment with either risperidone, olanzapine, or quetiapine. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis showed changes in the levels of ceramides (Cer), glycerophosphatidic acids (PA), glycerophosphocholines (PC), phosphatidylethanolamines (PE), phosphatidylinositols (PI), glycerophosphoglycerols (PG), and phosphatidylserines (PS) for all treatments. However, the treatment with risperidone also affected diacylglycerides (DG), ceramide 1-phosphates (CerP), triglycerides (TG), sphingomyelins (SM), and ceramide phosphoinositols (PI-Cer). Moreover, specific lipid profiles were observed that could be used to distinguish poor and good responders to the different antipsychotics. As such, further work in this area may lead to lipid-based biomarkers that could be used to improve the clinical management of schizophrenia patients.

摘要

非典型抗精神病药物被广泛用于治疗精神分裂症症状。然而,这些药物会引起有害的副作用,如代谢综合征(MetS),这会增加患者的心血管风险。脂质在这方面起着核心作用,脂质代谢的变化与精神分裂症的病理生物学有关。此外,最近的证据表明,脂质组的变化可能与抗精神病药物治疗反应有关。本研究旨在评估精神分裂症患者在接受利培酮、奥氮平或喹硫平治疗 6 周前后血浆样本中的脂质组变化。液相色谱-串联质谱(LC-MS/MS)分析显示,所有治疗方法均改变了神经酰胺(Cer)、甘油磷酸酰基酸(PA)、甘油磷酸胆碱(PC)、磷脂酰乙醇胺(PE)、磷脂酰肌醇(PI)、甘油磷酸甘油(PG)和磷脂酰丝氨酸(PS)的水平。然而,利培酮治疗还影响了二酰基甘油(DG)、神经酰胺 1-磷酸(CerP)、甘油三酯(TG)、鞘磷脂(SM)和神经酰胺磷酸肌醇(PI-Cer)。此外,观察到了特定的脂质谱,可以用于区分对不同抗精神病药物的不良和良好反应者。因此,该领域的进一步研究可能会导致基于脂质的生物标志物,可用于改善精神分裂症患者的临床管理。

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