title: Discovery and validation of plasma biomarkers for major depressive disorder classification based on liquid chromatography-mass spectrometry.
abstract: Major depressive disorder (MDD) is a debilitating mental disease with a pronounced impact on the quality of life of many people; however, it is still difficult to diagnose MDD accurately. In this study, a nontargeted metabolomics approach based on ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to find the differential metabolites in plasma samples from patients with MDD and healthy controls. Furthermore, a validation analysis focusing on the differential metabolites was performed in another batch of samples using a targeted approach based on the dynamic multiple reactions monitoring method. Levels of acyl carnitines, ether lipids, and tryptophan pronouncedly decreased, whereas LPCs, LPEs, and PEs markedly increased in MDD subjects as compared with the healthy controls. Disturbed pathways, mainly located in acyl carnitine metabolism, lipid metabolism, and tryptophan metabolism, were clearly brought to light in MDD subjects. The binary logistic regression result showed that carnitine C10:1, PE-O 36:5, LPE 18:1 sn-2, and tryptophan can be used as a combinational biomarker to distinguish not only moderate but also severe MDD from healthy control with good sensitivity and specificity. Our findings, on one hand, provide critical insight into the pathological mechanism of MDD and, on the other hand, supply a combinational biomarker to aid the diagnosis of MDD in clinical usage.
authors.affiliation: †Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: ‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China.|§Institute of Neuroscience, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zheng
authors.affiliation: †Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Zhao
authors.affiliation: ‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China.|§Institute of Neuroscience, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: †Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China.
authors.forename: Chunxiu
authors.initials: C
authors.lastname: Hu
authors.affiliation: †Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: †Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China.
authors.forename: Jieyu
authors.initials: J
authors.lastname: Zhao
authors.affiliation: ‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China.|§Institute of Neuroscience, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: ‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, China.|§Institute of Neuroscience, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
authors.affiliation: †Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China.
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003865:Major Depressive Disorder / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D016015:Logistic Models; D008244:Lysophosphatidylcholines / Q000097:blood; D008246:Lysophospholipids / Q000097:blood; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D010714:Phosphatidylethanolamines / Q000097:blood; D011788:Quality of Life; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014364:Tryptophan / Q000031:analogs & derivatives / Q000097:blood*
chemical_list: D015415:Biomarkers; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D010714:Phosphatidylethanolamines; C008301:lysophosphatidylethanolamine; C483858:phosphatidylethanolamine; D014364:Tryptophan; D002331:Carnitine
keywords: LC−MS; diagnosis biomarker; major depressive disorder; metabolomics