Metabonomics Analysis Of Feces From Major Depressive Disorder

Background:Major depressive disorders(MDD) are among the most prevalent lifetime psychiatric disorders. MDD has high probability of incidence, recurrence and curative ratio. Currently, it is still of great difficulty to diagnose and treat this disease. Previously, several hypotheses had been presented to explain MDD’s etiology, including the of Nor epinephrine(NE), 5-hydroxytryptamine(5-HT),Dopamine(DA) and acetylcholine( Ach). However, none of the mentionedtheory has been widely accepted. Moreover, the diagnosis of MDD still depends on the subjective identification of symptom clusters. As the clinical symptoms of MDD are highly heterogeneous, a considerable error rate occurs, companying the diagnostic modality. In the view of these facts, identification of the candidate biomarkers of MDD facilitates to not only reveals the physiopathologic mechanism, but also develop the diagnostic of MDD.Metabonomics enpowers synchronous quantitative measurement of numerous low molecular weight molecules, for this reason metabonomics has been widely used in the researche of psychiatric disorders within a particular sample such as cerebrospinal fluid,bloodandurine. Our former metabonomic researche paid attention to characterizing metabolic alterations in depressed animal models, revealing the maladjustment of the peripheral and central metabolism were involved in the onset of depression. Given animal model cannot entirely reveal the heterogeneity of clinical, it is absolutely necessary to perform the metabolic analysis of the feces from the patients.Purpose1. NMR based metabonomic method was used to compare the feces profiling of patients and healthy controls. This step was aimed to identify the metabolic differences in major depression disorder patients relative to healthy controls.2. We aimed to uncover the molecular basis of MDD, by comprehensively analyzing the function of feces sample.Method1. Samples: The feces samples were used to identify the candidate biomarkers.Feces: After overnight fasting, morning feces samples were collected, including 71 first-episode MDD subjects and 82 healthy controls.2. Acquisition of the feces samples spectra: NMR based metabonomics platform.3. Data analysis: Multivariate statistics approaches were used to visualize the discrimination between the patients and healthy controls and identify the metabolic differences in the depressed patients relative to healthy controls.Results:1. The feces metabonomics research of depressionNMR-based a metabonomic method was used to compare metabolic profiling of feces sampled from major depression disorder patients and healthy controls. The score plots of OPLS-DA model showed that the depressed patients were statistically distinguishable from healthy controls. As compared to healthy controls, MDD subjects were characterized by higher levels of Acetoacetate, Aspartate, Creatine, Dimethylglycine, Ethanolamine, Glutamate, Glutamine, Glyceroyl phosphocholine, Glycine, Lactate, Lysine, Malonate, Methylamine, myo-Inositol, Taurine, Threonine, Trimethylamine;along with lower levels of Acetate, Adenine, Butyrate,. Functional analysis of these differences suggested that depression was mainly involved in disturbances of lipid metabolism, small molecule biochemistryand amino acid metabolism.ConclusionUsing the metabonomics analysis of feces acquired from the major depression disorder patients and healthy controls, we finally successfully identified a panel of differential metabolites of depression infeces. By analyzing the underlying molecular function of these differential metabolites, we discovered valuable clues for uncovering the underlying mechanisms of depression.