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Background:  Major depressive disorder (MDD) is a common disease which is complicated by metabolic disorder. Although MDD has been studied relatively intensively, its metabolism is yet to be elucidated.   Methods:  To profile the global pathophysiological processes of MDD patients, we used metabolomics to identify differential metabolites and applied a new database Metabolite set enrichment analysis (MSEA) to discover dysfunctions of metabolic pathways of this disease. Hydrophilic metabolomics were applied to identify metabolites by profiling the plasma from 55 MDD patients and 100 sex-, gender-, BMI-matched healthy controls. The metabolites were then analyzed in MSEA in an attempt to discover different metabolic pathways. To investigate dysregulated pathways, we further divided MDD patients into two cohorts: (1) MDD patients with anxiety symptoms and (2) MDD patients without anxiety symptoms.   Results:  Metabolites which were hit in those pathways correlated with depressive and anxiety symptoms. Altogether, 17 metabolic pathways were enriched in MDD patients, and 23 metabolites were hit in those pathways. Three metabolic pathways were enriched in MDD patients without anxiety, including glycine and serine metabolism, arginine and proline metabolism, and phenylalanine and tyrosine metabolism. In addition, L-glutamic acid was positively correlated with the severity of depression and retardation if hit in MDD patients without anxiety symptoms.   Conclusions:  Different kinds of metabolic pathophysiological processes were found in MDD patients. Disorder of glycine and serine metabolism was observed in both MDD patients with anxiety and those without.

Plasma Metabolomics Profiling of Metabolic Pathways Affected by Major Depressive Disorder