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无偏脂质组学分析揭示了精神分裂症发病和抗精神病药物治疗期间的代谢组学变化。

Unbiased lipidomic profiling reveals metabolomic changes during the onset and antipsychotics treatment of schizophrenia disease.

机构信息

Department of Laboratorial Science and Technology, Vaccine Research Center, School of Public Health, Peking University, Beijing, 100191, China.

Medical and Health Analytical Center, Peking University Health Science Center, Beijing, 100191, China.

出版信息

Metabolomics. 2018 Jun 1;14(6):80. doi: 10.1007/s11306-018-1375-3.

Abstract

INTRODUCTION

Schizophrenia (SCH) is one of the most common psychiatric disorders, which involves impairments in motivation and cognition. The pathological mechanisms underlying SCH are still unknown, and no effective therapies can prevent or treat perfectly the cognitive impairments and deficit symptoms caused by SCH.

OBJECTIVES

We aimed to find the lipid expression change in plasma that underlie SCH onset and antipsychotics treatment.

METHODS

We performed a data independent acquisition-based untargeted lipidomic approach on a quadrupole-time of flight liquid chromatography coupled to mass spectrometry platform. The plasma lipidomic profiles of SCH patients (n = 20) pre- and post-antipsychotics treatment were acquired as well as healthy controls (n = 29). Grouped or paired t-test were used to analyze the data.

RESULTS

Over 1000 features were detected by our lipidomic analysis, of which 445 lipids belonging to 17 lipid species were reliably identified by tandem mass spectrometry. After statistical analysis, 47 lipids belonging to 9 lipid species were found to be dysregulated between naive SCH patients and healthy controls, and 50 lipids belonging to 9 lipid species were found to be dysregulated after antipsychotics treatment. These findings include several new SCH-relevant lipid species such as sphingomyelin, acylcarnitine and ceramide. Four types of lipid expression regulative patterns can be concluded from the above mentioned findings, revealing information about mechanism, side-effect and potential target of antipsychotics.

CONCLUSIONS

The work presented here have revealed several new lipid species which are significantly dysregulated in SCH disease development or antipsychotics treatment. These lipids provide new evidence for the pathological studies of SCH and new antipsychotics development, or can be considered as potentially candidate biomarkers for further validation.

摘要

简介

精神分裂症(SCH)是最常见的精神疾病之一,涉及动机和认知障碍。SCH 背后的病理机制尚不清楚,也没有有效的治疗方法可以完全预防或治疗 SCH 引起的认知障碍和缺陷症状。

目的

我们旨在寻找导致 SCH 发病和抗精神病药物治疗的血浆中脂质表达变化。

方法

我们在四极飞行时间液相色谱-质谱联用平台上采用基于数据非依赖性采集的非靶向脂质组学方法。我们获得了 SCH 患者(n=20)在抗精神病药物治疗前后以及健康对照者(n=29)的血浆脂质组学图谱。采用分组或配对 t 检验分析数据。

结果

通过我们的脂质组学分析检测到超过 1000 个特征,其中通过串联质谱可靠鉴定的 445 种脂质属于 17 种脂质。经过统计分析,在未经治疗的 SCH 患者和健康对照者之间,发现有 47 种脂质属于 9 种脂质发生了失调,在抗精神病药物治疗后,发现有 50 种脂质属于 9 种脂质发生了失调。这些发现包括几种新的与 SCH 相关的脂质种类,如神经鞘磷脂、酰基肉碱和神经酰胺。从上述发现中可以总结出四种类型的脂质表达调节模式,揭示了抗精神病药物的作用机制、副作用和潜在靶点的信息。

结论

本研究揭示了几种在 SCH 疾病发展或抗精神病药物治疗中明显失调的新脂质种类。这些脂质为 SCH 的病理研究和新的抗精神病药物开发提供了新的证据,或者可以被认为是进一步验证的潜在候选生物标志物。

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