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.

中文翻译：

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双相情感障碍患者和健康对照者的脑脊液氧化应激代谢产物：一项纵向病例对照研究。

躁郁症（BD）是一种精神障碍，其特征是情感发作反复发作，认知障碍，疾病进展和预期寿命缩短。在一些神经退行性疾病和BD中发现全身性氧化产生的核苷损伤增加。首先，这项自然主义的前瞻性，纵向随访病例对照研究调查了脑脊液（CSF）氧化应激标记物8-oxo-7,8-dihydroguanosine（8-oxoGuo）和8-oxo-7,8-dihydro- 2'-脱氧鸟苷（8-oxodG）分别与RNA和DNA损伤有关。在基线（T0），评估期间（T1）和新患者之后评估了BD患者（n = 86，女性为51％）和性别和年龄相匹配的健康对照个体（HC; n = 44，44％，女性）。情感发作（T2）（如果发生）以及一年后（T3）。使用超高效液相色谱-串联质谱分析脑脊液和尿液中的氧化应激标志物。在T0时，BD中的CSF-8-oxoGuo在统计学上显着高于HC（18％（p = 0.003），在T3时，CSF-8-oxoGuo显着高于HC）。在随访期间经历发作的患者，CSF-8-oxoGuo从T0到T3增加了15％（p = 0.042），从T2到T3增加了14％（p = 0.021）。在随访期间经历发作的患者，从T0到T2，CSF-8-oxodG升高了26％（p = 0.054），从T2到T3降低了19％（p = 0.041）。在一年的随访期间，CSF-8-oxoGuo在HC方面未显示出统计学上的显着变化。CSF和尿液8-oxoGuo水平呈中等程度相关。总之，CSF RNA损伤8-oxoGuo的氧化应激标记物显示BD的状态和性状依赖性以及HC的稳定性。