title: Plasma-metabolite-biomarkers for the therapeutic response in depressed patients by the traditional Chinese medicine formula Xiaoyaosan: A (1)H NMR-based metabolomics approach.
abstract: BACKGROUND
  Depression is one of the most prevalent and serious mental disorders. Xiaoyaosan, a well-known Chinese prescription, has been widely used for the treatment of depression in China. Both clinical studies and animal experiments indicate that Xiaoyaosan has an obvious antidepressant activity. Additionally, a large number of candidate biomarkers have emerged that can be used for early disease detection and for monitoring ongoing treatment response to therapy because of their correlations with the characteristics of the disease. However, there have been few reports on biomarkers that measure the treatment response to the clinical use of Xiaoyaosan using a metabolomics approach. The current study is aimed at discovering biomarkers and biochemical pathways to facilitate the diagnosis of depression and the efficient evaluation of Xiaoyaosan using plasma metabolomics profiles based on (1)H NMR.
  
  
  METHODS
  Sixteen depressed patients diagnosed by standard methods (HAMD and CGI-SI) and sixteen healthy volunteers were recruited. (1)H NMR-based metabolomics techniques and multivariate statistical methods were used to analyze the plasma metabolites of the depressed patients before and after treatment and to compare them with healthy controls.
  
  
  RESULTS
  The plasma levels of trimethylamine oxide, glutamine and lactate in depressed patients increased significantly (p≤0.05) compared with healthy controls, whereas the levels of phenylalanine, valine, alanine, glycine, leucine, citrate, choline, lipids and glucose decreased significantly (p≤0.05). Additionally, alanine, choline, trimethylamine oxide, glutamine, lactate and glucose were returned to normal levels after Xiaoyaosan treatment. These statistically significant perturbations are involved in energy metabolism, amino acid metabolism and gut microbiota metabolism.
  
  
  CONCLUSIONS
  Additional experimentation with gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) is required to confirm our findings.
  
  
  CONCLUSIONS
  Application of these biomarkers in clinical practice may help to optimize the diagnosis of depression and to evaluate the efficacy of Xiaoyaosan. Metabolomics is promising as a biomarker discovery tool.
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China.
authors.forename: Cai-Chun
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Department of traditional Chinese medicine, First Hospital of Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Wu
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China.
authors.forename: Guang-Ming
authors.initials: GM
authors.lastname: Feng
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Gao
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China.
authors.forename: Yu-Zhi
authors.initials: YZ
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Beijing Charity Hospital of China Rehabilitation Research Center, Beijing 100068, PR China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Hou
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Qin
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China; Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, PR China. Electronic address: dugh@imm.ac.cn.
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Du
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China. Electronic address: jstian@sxu.edu.cn.
authors.forename: Jun-Sheng
authors.initials: JS
authors.lastname: Tian
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D002681:China; D003863:Depression / Q000097:blood / Q000188:drug therapy; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008516:Medicine, Chinese Traditional; D055432:Metabolomics; D008875:Middle Aged
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; C532268:xiaoyaosan
keywords: Biomarkers; Depressed patients; Metabolomics; Proton nuclear magnetic resonance ((1)H NMR).; Xiaoyaosan