title: Divergent Urinary Metabolic Phenotypes between Major Depressive Disorder and Bipolar Disorder Identified by a Combined GC-MS and NMR Spectroscopic Metabonomic Approach.
abstract: Bipolar disorder (BD) is a complex debilitating mental disorder that is often misdiagnosed as major depressive disorder (MDD). Therefore, a large percentage of BD subjects are incorrectly treated with antidepressants in clinical practice. To address this challenge, objective laboratory-based tests are needed to discriminate BD from MDD patients. Here, a combined gas chromatography-mass spectrometry (GC-MS)-based and nuclear magnetic resonance (NMR) spectroscopic-based metabonomic approach was performed to profile urine samples from 76 MDD and 43 BD subjects (training set) to identify the differential metabolites. Samples from 126 healthy controls were included as metabolic controls. A candidate biomarker panel was identified by further analyzing these differential metabolites. A testing set of, 50 MDD and 28 BD subjects was then used to independently validate the diagnostic efficacy of the identified panel using an area under the receiver operating characteristic curve (AUC). A total of 20 differential metabolites responsible for the discrimination between MDD and BD subjects were identified. A panel consisting of six candidate urinary metabolite biomarkers (propionate, formate, (R*,S*)2,3-dihydroxybutanoic acid, 2,4-dihydroxypyrimidine, phenylalanine, and β-alanine) was identified. This panel could distinguish BD from MDD subjects with an AUC of 0.913 and 0.896 in the training and testing sets, respectively. These results reveal divergent urinary metabolic phenotypes between MDD and BD. The identified urinary biomarkers can aid in the future development of an objective laboratory-based diagnostic test for distinguishing BD from MDD patients.
authors.affiliation: †Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: †Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China.
authors.forename: Chan-Juan
authors.initials: CJ
authors.lastname: Zhou
authors.affiliation: ‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: ‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Fu
authors.affiliation: ‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zheng
authors.affiliation: †Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China.
authors.forename: De-Yu
authors.initials: DY
authors.lastname: Yang
authors.affiliation: ‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: ‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Mu
authors.affiliation: ‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: You-Dong
authors.initials: YD
authors.lastname: Wei
authors.affiliation: ‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhou
authors.affiliation: ‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.affiliation: †Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China.|‡Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D001714:Bipolar Disorder / Q000175:diagnosis / Q000378:metabolism / Q000652:urine*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000378:metabolism / Q000652:urine*; D003937:Diagnosis, Differential; D005260:Female; D005561:Formates / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D006885:Hydroxybutyrates / Q000652:urine; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D010649:Phenylalanine / Q000652:urine; D011422:Propionates / Q000652:urine; D011743:Pyrimidines / Q000652:urine; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult; D015091:beta-Alanine / Q000652:urine
chemical_list: C000593183:2,4-dihydroxypyrimidine; D015415:Biomarkers; D005561:Formates; D006885:Hydroxybutyrates; D011422:Propionates; D011743:Pyrimidines; C030544:formic acid; D015091:beta-Alanine; C041038:3,4-dihydroxybutanoic acid; D010649:Phenylalanine
keywords: BD; GC−MS; MDD; NMR; biomarker; bipolar disorder; gas chromatography−mass spectrometry; major depressive disorder; metabonomic; nuclear magnetic resonance