Plasma-metabolite-biomarkers for the therapeutic response in depressed patients by the traditional Chinese medicine formula Xiaoyaosan: A 1H NMR-based metabolomics approach

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.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.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.Additional experimentation with gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) is required to confirm our findings.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.