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

Abstract

Background: Major 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.

Methods: In 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.

Results: Through 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.

Conclusion: The 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.

Keywords: Argininosuccinate synthase; Biomarker; Diagnostic; Major depressive disorder; Proteomics; Urinary; Urine.