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在单相和双相抑郁症的当前发作期间和缓解后,8-氧代-2'-脱氧鸟苷和 8-氧鸟嘌呤 DNA 糖基化酶 1 的水平发生变化。

Alterations in levels of 8-Oxo-2'-deoxyguanosine and 8-Oxoguanine DNA glycosylase 1 during a current episode and after remission in unipolar and bipolar depression.

机构信息

Department of Psychiatry, Izmir University of Economics, Faculty of Medicine, Department of Psychiatry, Balçova, 35340, Izmir, Turkey.

Department of Neurosciences, Dokuz Eylul University, Health Sciences Institute, Izmir, Turkey.

出版信息

Psychoneuroendocrinology. 2020 Apr;114:104600. doi: 10.1016/j.psyneuen.2020.104600. Epub 2020 Feb 7.

Abstract

INTRODUCTION

Previous studies showed significant increases in DNA base damage markers and significant alterations in base excision repair enzymes in patients with unipolar and bipolar depression. We aimed to investigate changes in urine 8-Oxo-2'-deoxyguanosine (8-oxo-dG) and gene expression levels of 8-Oxoguanine DNA glycosylase 1 (OGG1) during a current depressive episode and after remission in bipolar and unipolar disorders.

METHODS

Twenty-four acutely depressed bipolar (BD), 33 unipolar depression (UD) patients and 61 healthy controls were included in the study. Clinical evaluations, blood and urine sampling were completed at baseline and at remission after eight weeks. The urine 8-oxo-dG levels were assessed by liquid chromatography tandem mass spectrometry and adjusted for urine creatinine levels. The gene expression levels of OGG1 were determined from cDNA extracted from blood samples, using real time-polymerase chain reaction.

RESULTS

At baseline, patients presented significantly higher levels of 8-oxo-dG (p = 0.008), and lower gene expression of OGG1 (p = 0.024) compared to controls. Levels of either 8-oxo-dG or OGG1 expression did not differ between BD and UD. In patients who remitted by the 8th week (n = 30), 8-oxo-dG decreased significantly (p = 0.001), and gene expression levels of OGG1 increased by 2.95 times compared to baseline levels (p = 0.001). All comparisons were adjusted for age, sex, smoking status and body mass index.

CONCLUSION

Our results suggest that patients with bipolar and unipolar mood disorders present increased 8-oxo-dG and decreased gene expression levels of OGG1 in current depressive episodes, and that these changes might be reversed by the resolution of depressive symptoms. The causal relationship between DNA damage and repair requires further exploration.

摘要

简介

先前的研究表明,单相和双相抑郁症患者的 DNA 碱基损伤标志物显著增加,碱基切除修复酶显著改变。我们旨在研究在双相和单相障碍的当前抑郁发作期间和缓解后,尿液 8-氧-2'-脱氧鸟苷(8-oxo-dG)和 8-氧鸟嘌呤 DNA 糖基化酶 1(OGG1)的基因表达水平的变化。

方法

本研究纳入了 24 例急性抑郁的双相障碍(BD)患者、33 例单相抑郁(UD)患者和 61 例健康对照者。在基线时和 8 周缓解后进行临床评估、血液和尿液采样。通过液相色谱串联质谱法评估尿液 8-oxo-dG 水平,并根据尿液肌酐水平进行调整。使用实时聚合酶链反应从血液样本中提取的 cDNA 测定 OGG1 的基因表达水平。

结果

基线时,与对照组相比,患者的 8-oxo-dG 水平显著升高(p = 0.008),OGG1 的基因表达水平显著降低(p = 0.024)。BD 和 UD 患者之间的 8-oxo-dG 或 OGG1 表达水平无差异。在第 8 周缓解的患者(n = 30)中,8-oxo-dG 显著降低(p = 0.001),OGG1 的基因表达水平比基线水平增加了 2.95 倍(p = 0.001)。所有比较均调整了年龄、性别、吸烟状况和体重指数。

结论

我们的结果表明,单相和双相心境障碍患者在当前抑郁发作时表现出增加的 8-oxo-dG 和减少的 OGG1 基因表达水平,并且这些变化可能在抑郁症状缓解后逆转。DNA 损伤与修复之间的因果关系需要进一步探讨。

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