Urinary metabonomic study on biochemical changes in chronic unpredictable mild stress model of depression.

Depression is a prevalent complex psychiatric disorder and its pathophysiological mechanism is not yet well understood. We investigated the metabolic profiling of urine samples from depression model rats to find potential disease biomarkers and research pathology of depression. An animal model of depression was produced by chronic unpredictable mild stress (CUMS). Metabolic profiling of the urine was performed by using ultra performance liquid chromatography coupled to mass spectrometry (UPLC-MS). Principal component analysis (PCA) was utilized to classify and reveal the differences between the model group and control group. Principal component analysis displayed a clear separation between CUMS-treated rats and control rats. CUMS-treated rats were characterized by the increase of kynurenic acid, xanthurenic acid, phenylalanine, N(2)-succinyl-l-ornithine, hippuric acid and phenylacetylglycine together with the decrease of tryptophan, indoxyl sulfate, indole-3-acetate, citrate, alpha-ketoglutarate and creatinine in urine. These biochemical changes are related to the disturbance in energy metabolism, amino acid metabolism and gut microflora. Metabonomic approach is helpful to further understanding the pathophysiology of depression and assisting in clinical diagnosis of depression. Copyright 2009 Elsevier B.V. All rights reserved.