Increased DNA and RNA damage by oxidation in patients with bipolar I disorder.

A S Jacoby,K Munkholm,H E Poulsen,L V Kessing,M Vinberg

doi:10.1038/tp.2016.141

A S Jacoby, K Munkholm + Show 3 more

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https://doi.org/10.1038/tp.2016.141

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Abstract

The mechanisms underlying bipolar disorder (BD) and the associated medical burden are unclear. Damage generated by oxidation of nucleosides may be implicated in BD pathophysiology; however, evidence from in vivo studies is limited and the extent of state-related alterations is unclear. This prospective study investigated for we believe the first time the damage generated by oxidation of DNA and RNA strictly in patients with type I BD in a manic or mixed state and subsequent episodes and remission compared with healthy control subjects. Urinary excretion of 8-oxo-deoxyguanosine (8-oxodG) and 8-oxo-guanosine (8-oxoGuo), valid markers of whole-body DNA and RNA damage by oxidation, respectively, was measured in 54 patients with BD I and in 35 healthy control subjects using a modified ultraperformance liquid chromatography and mass spectrometry assay. Repeated measurements were evaluated in various affective phases during a 6- to 12-month period and compared with repeated measurements in healthy control subjects. Independent of lifestyle and demographic variables, a 34% (P<0.0001) increase in RNA damage by oxidation across all affective states, including euthymia, was found in patients with BD I compared with healthy control subjects. Increases in DNA and RNA oxidation of 18% (P<0.0001) and 8% (P=0.02), respectively, were found in manic/hypomanic states compared with euthymia, and levels of 8-oxodG decreased 15% (P<0.0001) from a manic or mixed episode to remission. The results indicate a role for DNA and RNA damage by oxidation in BD pathophysiology and a potential for urinary 8-oxodG and 8-oxoGuo to function as biological markers of diagnosis, state and treatment response in BD.

Highlights

Bipolar disorder (BD) is associated with increased mortality[1] and 8–12 years decreased life expectancy.[2]
MATERIALS AND METHODS We conducted a multicenter, longitudinal, clinical study investigating damage generated by oxidation of nucleosides in patients with bipolar disorder (BD) I in an acute manic or mixed episode and during follow-up compared with repeated measures in healthy control individuals
This study investigated, for the first time, state-specific, intraindividual alterations in urinary markers of nucleoside damage generated by oxidation strictly in patients with BD I included in a manic or mixed episode compared with repeated measurements in healthy control subjects

Summary

Introduction

Bipolar disorder (BD) is associated with increased mortality[1] and 8–12 years decreased life expectancy.[2]. Oxidative damage to RNA was recently proposed as a novel disease mechanism contributing to medical diseases;[15] in vivo studies in BD are limited, with only one study investigating urinary levels,[16] which are considered more reliable than plasma levels.[15]

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Results

Conclusion