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

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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.

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Abbreviations

SCH:

Schizophrenia

LC–MS:

Liquid chromatography coupled to mass spectrometry

MS/MS:

Tandem mass spectrometry

TOF:

Time of flight

QC:

Quality control

CE:

Cholesteryl ester

DG:

Diacylglycerol

TG:

Triacylglycerol

FA:

Fatty acid

LysoPC:

Lysophosphatidylcholine

LysoPE:

Lysophosphatidylethanolamine

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

p-PC:

Plasmenyl-PC

p-PE:

Plasmenyl-PE

PI:

Phosphatidylinositol

SM:

Sphingomyelin

GlcCer:

Glucosylceramide

Cer:

Ceramide

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Acknowledgements

Research reported in this publication was supported by the Fund for Fostering Young Scholars of Peking University Health Science Center (Grant No. BMU2018PY006), the Interdisciplinary Medicine Seed Fund of Peking University (Grant No. BMU2017MX006), the 111 Project (Grant B07001) and the Lam Chung Nin Foundation for Systems Biomedicine.

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Authors and Affiliations

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

    Lailai Yan, Dongfang Wang & Yaqiong Liu

  2. Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China

    Juntuo Zhou & Yuxin Yin

  3. AB Sciex Analytical Instrument Trading Co., Ltd, Beijing Office, Beijing, 100015, China

    Dandan Si

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

    Lailai Yan, Lijun Zhong & Yuxin Yin

  5. Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China

    Yuxin Yin

  6. Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center for Life Sciences, Beijing, 100191, China

    Yuxin Yin

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  1. Lailai Yan
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  2. Juntuo Zhou
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  3. Dongfang Wang
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  5. Yaqiong Liu
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Correspondence to Lijun Zhong or Yuxin Yin.

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The authors declare that they have no competing interests.

Ethics approval

This study was conducted in accordance with the guidelines of the Declaration of Helsinki and the Principles of Good Clinical Practice. The Ethical Review Board of the Peking University Health Science Center approved the study.

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Informed consent was obtained from all patients who were asked to donate blood.

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Lailai Yan and Juntuo Zhou are equal contributors.

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Yan, L., Zhou, J., Wang, D. et al. Unbiased lipidomic profiling reveals metabolomic changes during the onset and antipsychotics treatment of schizophrenia disease. Metabolomics 14, 80 (2018). https://doi.org/10.1007/s11306-018-1375-3

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