A Novel Urinary Metabolite Signature for Diagnosing Major Depressive Disorder

Abstract

Major depressive disorder (MDD) is a prevalent and debilitating mental disorder. Yet, there are no objective biomarkers available to support diagnostic laboratory testing for this disease. Here, gas chromatography-mass spectrometry was applied to urine metabolic profiling of 126 MDD and 134 control subjects. Orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to identify the differential metabolites in MDD subjects relative to healthy controls. The OPLS-DA analysis of data from training samples (82 first-episode, drug-naïve MDD subjects and 82 well-matched healthy controls) showed that the depressed group was significantly distinguishable from the control group. Totally, 23 differential urinary metabolites responsible for the discrimination between the two groups were identified. Postanalysis, 6 of the 23 metabolites (sorbitol, uric acid, azelaic acid, quinolinic acid, hippuric acid, and tyrosine) were defined as candidate diagnostic biomarkers for MDD. Receiver operating characteristic analysis of combined levels of these six biomarkers yielded an area under the receiver operating characteristic curve (AUC) of 0.905 in distinguishing training samples; this simplified metabolite signature classified blinded test samples (44 MDD subjects and 52 healthy controls) with an AUC of 0.837. Furthermore, a composite panel by the addition of previously identified urine biomarker (N-methylnicotinamide) to this biomarker panel achieved a more satisfactory accuracy, yielding an AUC of 0.909 in the training samples and 0.917 in the test samples. Taken together, these results suggest this composite urinary metabolite signature should facilitate development of a urine-based diagnostic test for MDD.