Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Copenhagen University Hospital Frederiksberg, Copenhagen, Denmark.
University of Copenhagen, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Transl Psychiatry. 2024 Feb 8;14(1):81. doi: 10.1038/s41398-024-02772-8.
Excessive oxidative stress-generated nucleoside damage seems to play a key role in bipolar disorder (BD) and may present a trait phenomenon associated with familial risk and is one of the putative mechanisms explaining accelerated atherosclerosis and premature cardiovascular diseases (CVD) in younger patients with BD. However, oxidative stress-generated nucleoside damage has not been studied in young BD patients and their unaffected relatives (UR). Therefore, we compared oxidative stress-generated damage to DNA and RNA in young patients newly diagnosed with BD, UR, and healthy control individuals (HC). Systemic oxidative stress-generated DNA and RNA damage levels were compared by analyzing urinary levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydroguanosine in participants aged 15-25 years, including 133 patients newly diagnosed with BD, 57 UR, and 83 HC. Compared with HC, damage to DNA was 21.8% higher in BD patients (B = 1.218, 95% CI = 1.111-1.335, p = <0.001) and 22.5% higher in UR (B = 1.225, 95% CI = 1.090-1.377, p = <0.002), while damage to RNA was 14.8% higher in BD patients (B = 1.148, 95% CI = 1.082-1.219, p = <0.001) and 14.0% higher in UR (B = 1.140, 95% CI = 1.055-1.230, p = < 0.001) in models adjusted for sex and age after correction for multiple comparison. Levels did not differ between patients with BD and UR. Our findings support higher oxidative stress-generated nucleoside damage being a trait phenomenon in BD associated with familial risk and highlight the importance of early diagnosis and treatment to prevent illness progression and development of premature CVD.
过量的氧化应激产生的核苷损伤似乎在双相情感障碍（BD）中起着关键作用，并且可能表现出与家族风险相关的特征现象，是解释年轻 BD 患者加速动脉粥样硬化和过早心血管疾病（CVD）的潜在机制之一。然而，氧化应激产生的核苷损伤在年轻的 BD 患者及其未受影响的亲属（UR）中尚未得到研究。因此，我们比较了新诊断为 BD、UR 和健康对照个体（HC）的年轻患者中氧化应激产生的 DNA 和 RNA 损伤。通过分析参与者尿液中 8-氧代-7,8-二氢-2'-脱氧鸟苷和 8-氧代-7,8-二氢鸟苷的水平，比较了系统氧化应激产生的 DNA 和 RNA 损伤水平，参与者年龄在 15-25 岁之间，包括 133 名新诊断为 BD 的患者、57 名 UR 和 83 名 HC。与 HC 相比，BD 患者的 DNA 损伤高 21.8%（B=1.218，95%CI=1.111-1.335，p<0.001），UR 的 DNA 损伤高 22.5%（B=1.225，95%CI=1.090-1.377，p<0.002），而 BD 患者的 RNA 损伤高 14.8%（B=1.148，95%CI=1.082-1.219，p<0.001），UR 的 RNA 损伤高 14.0%（B=1.140，95%CI=1.055-1.230，p<0.001），在调整性别和年龄后的模型中，经过多次比较校正后。BD 患者和 UR 之间的水平没有差异。我们的研究结果支持更高的氧化应激产生的核苷损伤是与家族风险相关的 BD 的特征现象，并强调早期诊断和治疗以预防疾病进展和过早 CVD 发展的重要性。
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