Sex-specific urinary biomarkers for diagnosing bipolar disorder.

Jian-Jun Chen,Liang Fang,Peng He,Peng Xie,Yong-Tao Yang,Peng Zheng,Jing-Jing Zhou,De-Zhi Zhou,De-Yu Yang,Hua Huang,Li-Bo Zhao,Ioannis P Androulakis

doi:10.1371/journal.pone.0115221

Abstract

Sex-based differences are prominent in affective disorders, but there are no biomarkers available to support sex-specific, laboratory-based diagnostics for male and female bipolar disorder (BD) patients. Here, a NMR-based metabonomic approach was used to preliminarily identify sex-specific urinary metabolite biomarkers for diagnosing male and female BD patients. A male-specific biomarker panel consisting of four metabolites (α-hydroxybutyrate, choline, formate, and N-methylnicotinamide) effectively discriminated between male BD and healthy controls (HC) subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.942. A female-specific biomarkers panel consisting of four metabolites (α-hydroxybutyrate, oxalacetate, acetone, and N-methylnicotinamide) effectively discriminated between female BD and HC subjects, achieving an AUC of 0.909. The male-specific biomarker panel displayed low discriminatory power in the female group, and the female-specific biomarker panel displayed low discriminatory power in the male group. Moreover, several other metabolites showed different trends between male and female BD subjects. These findings suggest that male and female BD patients have distinct biomarker fingerprints and that these two sex-specific biomarker panels may serve as effective diagnostic tools in distinguishing male and female BD patients from their healthy counterparts. Our work may provide a window into the mechanisms underlying the pathoetiology of BD in both men and women.

Highlights

Bipolar disorder (BD), known as bipolar affective disorder, manic-depressive disorder, or manic depression, is a debilitating mental disorder that affects up to 1% of the general population [1] and is typically characterized by episodes of elevated mood known as mania alternating with episodes of depression
A total of eighty-six BD subjects and ninety-six healthy controls (HC) subjects were recruited into this work
There were no significant differences in the demographic variables of age and body mass index (BMI) between male BD and HC subjects as well as female BD and HC subjects

Summary

Introduction

Bipolar disorder (BD), known as bipolar affective disorder, manic-depressive disorder, or manic depression, is a debilitating mental disorder that affects up to 1% of the general population [1] and is typically characterized by episodes of elevated mood known as mania alternating with episodes of depression. Nuclear magnetic resonance spectroscopy (NMR), one of three major analytical platforms with proven utility in metabonomic applications, has proven to be a well-established strategy for identifying diseasespecific biomarkers because of its highly sensitive, high-throughput molecular screening capability [8]. Using this method, our group has identified a panel of potential metabolite biomarkers capable of discriminating major depressive disorder (MDD) subjects from healthy controls (HC) with both high sensitivity and specificity [9, 10]

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Discussion

Conclusion