title: Identification and validation of argininosuccinate synthase as a candidate urinary biomarker for major depressive disorder.
abstract: BACKGROUND
  Major depressive disorder (MDD) is a debilitating psychiatric mood disorder. However, no objective laboratory-based test is yet available to aid in the diagnosis of this disorder.
  
  
  METHODS
  In order to identify urinary protein biomarker candidates for MDD, the differential proteomic analysis of urine samples from first-episode drug-naïve MDD subjects and healthy controls (HC) was carried out by using two-dimensional gel electrophoresis separation followed by MALDI-TOF/TOF-MS/MS identification. Then, the differential expression levels of some candidate proteins were further validated by immunoblot analysis.
  
  
  RESULTS
  Through mass spectrometry and database searching, a total of 27 differential proteins were identified, primarily including enzymes, plasma proteins, serpins, and adhesion molecules. Five proteins were selected for subsequent validation by Western blotting. One arginine recycling enzyme - argininosuccinate synthase (ASS1) - was further confirmed to be significantly downregulated in the urine of 30 depressed subjects while remaining unchanged in the plasma. Importantly, receiver-operator curve analyses revealed that ASS1 displayed strong efficacy in distinguishing MDD subjects from HC.
  
  
  CONCLUSIONS
  The present study provides a range of urinary protein biomarker candidates for MDD, and further demonstrates that ASS1 has a potential for clinical diagnosis of this disorder.
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Department of Clinical Laboratory, The Fifth People's Hospital of Chongqing, Chongqing 400062, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400062, China.
authors.forename: Yong-Tao
authors.initials: YT
authors.lastname: Yang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Cheng-Long
authors.initials: CL
authors.lastname: Rao
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Shun-Jie
authors.initials: SJ
authors.lastname: Bai
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liao
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zi-Hong
authors.initials: ZH
authors.lastname: Liang
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: De-Yu
authors.initials: DY
authors.lastname: Yang
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: xiepeng@cqmu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001124:Argininosuccinate Synthase / Q000378:metabolism / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D015153:Blotting, Western; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000201:enzymology / Q000652:urine*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001124:Argininosuccinate Synthase
keywords: Argininosuccinate synthase; Biomarker; Diagnostic; Major depressive disorder; Proteomics; Urinary; Urine