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

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.

SUBMITTER: Knorr U

PROVIDER: S-EPMC6882849 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Knorr Ulla U Simonsen Anja Hviid AH Roos Peter P Weimann Allan A Henriksen Trine T Christensen Ellen-Margrethe EM Vinberg Maj M Mikkelsen Rie Lambæk RL Kirkegaard Thomas T Jensen Rasmus Nejst RN Akhøj Morten M Forman Julie J Poulsen Henrik Enghusen HE Hasselbalch Steen Gregers SG Kessing Lars Vedel LV

Translational psychiatry 20191128 1

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-d ...[more]

PMID: 31780642

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Project description:IntroductionAnalyses of cerebrospinal fluid (CSF) metabolites in large, healthy samples have been limited and potential demographic moderators of brain metabolism are largely unknown.ObjectiveOur objective in this study was to examine sex and race differences in 33 CSF metabolites within a sample of 129 healthy individuals (37 African American women, 29 white women, 38 African American men, and 25 white men).MethodsCSF metabolites were measured with a targeted electrochemistry-based metabolomics platform. Sex and race differences were quantified with both univariate and multivariate analyses. Type I error was controlled for by using a Bonferroni adjustment (0.05/33 = .0015).ResultsMultivariate Canonical Variate Analysis (CVA) of the 33 metabolites showed correct classification of sex at an average rate of 80.6% and correct classification of race at an average rate of 88.4%. Univariate analyses revealed that men had significantly higher concentrations of cysteine (p < 0.0001), uric acid (p < 0.0001), and N-acetylserotonin (p = 0.049), while women had significantly higher concentrations of 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.001). African American participants had significantly higher concentrations of 3-hydroxykynurenine (p = 0.018), while white participants had significantly higher concentrations of kynurenine (p < 0.0001), indoleacetic acid (p < 0.0001), xanthine (p = 0.001), alpha-tocopherol (p = 0.007), cysteine (p = 0.029), melatonin (p = 0.036), and 7-methylxanthine (p = 0.037). After the Bonferroni adjustment, the effects for cysteine, uric acid, and 5-HIAA were still significant from the analysis of sex differences and kynurenine and indoleacetic acid were still significant from the analysis of race differences.ConclusionSeveral of the metabolites assayed in this study have been associated with mental health disorders and neurological diseases. Our data provide some novel information regarding normal variations by sex and race in CSF metabolite levels within the tryptophan, tyrosine and purine pathways, which may help to enhance our understanding of mechanisms underlying sex and race differences and potentially prove useful in the future treatment of disease.

Dataset Information

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

Publications

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

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