Abstract

Major depressive disorder (MDD) is a common mental disorder that can cause substantial impairments in quality of life. Clinical treatment is usually built on a trial-and-error method, which lasts ~12 weeks to evaluate whether the treatment is efficient, thereby leading to some inefficient treatment measures. Therefore, we intended to identify early candidate urine biomarkers to predict efficient treatment response in MDD patients. In this study, urine samples were collected twice from 19 respondent and 10 non-respondent MDD patients receiving 0-, 2-, and 12-week treatments with escitalopram. Differential urinary proteins were subsequently analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Our two pilot tests suggested that the urine proteome reflects changes associated with major depressive disorder at the early stage of treatment measures. On week 2, 20 differential proteins were identified in the response group compared with week 0, with 14 of these proteins being associated with the mechanisms of MDD. In the non-response group, 60 differential proteins were identified at week 2, with 28 of these proteins being associated with the mechanisms of MDD. In addition, differential urinary proteins at week 2 between the response and non-response groups can be clearly distinguished by using orthogonal projection on latent structure-discriminant analysis (OPLS-DA). Our small pilot tests indicated that the urine proteome can reflect early effects of escitalopram therapy between the response and non-response groups since at week 2, which may provide potential early candidate urine biomarkers to predict efficient treatment measures in MDD patients.

Highlights

  • Major depressive disorder (MDD) is a severe and debilitating psychiatric disorder characterized by depressed mood, anhedonia, and altered cognitive function [1]

  • The urine proteome changes of escitalopram treatment at 2 weeks’ and 12 weeks’ time points were identified using liquid chromatography coupled with tandem mass spectrometry (LC-Mass spectrometry (MS)/MS)

  • A significant number of identified differential proteins and enriched pathways were found to be associated with MDD or related pathways, which support the correlation between the urinary proteome changes and treatment response of MDD patients

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Summary

Introduction

Major depressive disorder (MDD) is a severe and debilitating psychiatric disorder characterized by depressed mood, anhedonia, and altered cognitive function [1]. MDD was recently ranked as the single largest contributor to global disability according to the World Health Organization (WHO) for its significant social and financial burden [2]. The pathogenesis has not been clearly elucidated because depression is highly heterogeneous and involves complex interactions between genetic factors and multiple molecular pathways. Even positive treatment effects may be very slow to appear and each level of treatment requires 12 weeks. The problem of treatment-resistant depression has led to the continued search for effective measurements for antidepressant treatments. Treatment response biomarkers are urgently needed to eliminate multiple treatment steps and provide effective treatment options

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