Identification and validation of argininosuccinate synthase as a candidate urinary biomarker for major depressive disorder

Abstract

BackgroundMajor depressive disorder (MDD) is a debilitating psychiatric mood disorder. However, no objective laboratory-based test is yet available to aid in the diagnosis of this disorder. MethodsIn order to identify urinary protein biomarker candidates for MDD, the differential proteomic analysis of urine samples from first-episode drug-naïve MDD subjects and healthy controls (HC) was carried out by using two-dimensional gel electrophoresis separation followed by MALDI-TOF/TOF-MS/MS identification. Then, the differential expression levels of some candidate proteins were further validated by immunoblot analysis. ResultsThrough mass spectrometry and database searching, a total of 27 differential proteins were identified, primarily including enzymes, plasma proteins, serpins, and adhesion molecules. Five proteins were selected for subsequent validation by Western blotting. One arginine recycling enzyme – argininosuccinate synthase (ASS1) – was further confirmed to be significantly downregulated in the urine of 30 depressed subjects while remaining unchanged in the plasma. Importantly, receiver–operator curve analyses revealed that ASS1 displayed strong efficacy in distinguishing MDD subjects from HC. ConclusionThe present study provides a range of urinary protein biomarker candidates for MDD, and further demonstrates that ASS1 has a potential for clinical diagnosis of this disorder.