Cerebrospinal fluid oxidative stress metabolites in patients with bipolar disorder and healthy controls: a longitudinal case-control study

Ulla Knorr,Steen Gregers Hasselbalch,Peter Roos,Julie Forman,Morten Akhøj,Maj Vinberg,Anja Hviid Simonsen,Thomas Kirkegaard,Ellen-Margrethe Christensen,Rie Lambæk Mikkelsen,Rasmus Nejst Jensen,Allan Weimann,Henrik Enghusen Poulsen,Trine Henriksen,Lars Vedel Kessing

doi:10.1038/s41398-019-0664-6

Ulla Knorr, Steen Gregers Hasselbalch + Show 13 more

Open Access

https://doi.org/10.1038/s41398-019-0664-6

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Abstract

Bipolar disorder (BD) is a mental disorder characterized by recurrent relapses of affective episodes, cognitive impairment, illness progression, and reduced life expectancy. Increased systemic oxidatively generated nucleoside damage have been found in some neurodegenerative disorders and in BD. As the first, this naturalistic prospective, longitudinal follow-up case-control study investigated cerebrospinal fluid (CSF) oxidative stress markers 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) that relate to RNA and DNA damage, respectively. Patients with BD (n = 86, 51% female) and gender-and-age-matched healthy control individuals (HC; n = 44, 44% female) were evaluated at baseline (T0), during (T1) and after a new affective episode (T2), if it occurred, and after a year (T3). Cerebrospinal and urine oxidative stress markers were analyzed using ultra-performance liquid chromatography–tandem mass spectrometry. CSF-8-oxoGuo was statistically significantly higher by 18% (p = 0.003) in BD versus HC at T0, and by 22% (p = 0) at T3. CSF-8-oxoGuo had increased by 15% (p = 0.042) from T0 to T3, and by 14% (p = 0.021) from T2 to T3 in patients, who experienced an episode during follow-up. CSF-8-oxodG had increased by 26% (p = 0.054) from T0 to T2 and decreased by 19% (p = 0.041) from T2 to T3 in patients, who experienced an episode during follow-up. CSF-8-oxoGuo did not show a statistically significant change in HC during the one-year follow-up. CSF and urine-8-oxoGuo levels correlated moderately. In conclusion, CSF oxidative stress marker of RNA damage 8-oxoGuo showed both state and trait dependence in BD and stability in HC. Central RNA damage may be a potential biomarker for BD.

Highlights

Bipolar disorder (BD) is a disabling mental illness with a prevalence of 1%, a high risk of recurrence of manic and depressive episodes, a lifelong elevated risk of suicide[1] and a heritability of 60–80%2
Patients were most frequently treated with lithium, lamotrigine, and quetiapine, but three patients did not get any psychotropic medication at inclusion
Patients with BD and healthy control individuals (HC) individuals were well matched according to age, gender and, body mass index (BMI) at baseline and there were no differences either at follow-up

Summary

Introduction

Bipolar disorder (BD) is a disabling mental illness with a prevalence of 1%, a high risk of recurrence of manic and depressive episodes, a lifelong elevated risk of suicide[1] and a heritability of 60–80%2. A vast body of literature evidence show clinical progression in BD with increasing risk of developing new mood episodes with every episode, progressive shortening of inter-episode intervals with each recurrence, and with increasing cognitive disabilities during the course of illness[1,3,4,5,6,7,8]. Elevated levels of peripheral markers of oxidative stress have been found in psychiatric disorders, diabetes, and neurodegenerative disorders[9,10,11].

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