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初诊未用药的双相情感障碍患者血浆中循环无细胞游离线粒体 DNA 增加:一项病例对照和 4 周随访研究。

Increased circulating cell-free mitochondrial DNA in plasma of first-diagnosed drug-naïve bipolar disorder patients: A case-control and 4-week follow-up study.

机构信息

National Clinical Research Center for Mental Disorders, Department of Psychiatry, China National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China.

Department of Psychiatry, Qingdao Mental Health Center, China.

出版信息

J Affect Disord. 2024 Jun 15;355:378-384. doi: 10.1016/j.jad.2024.03.113. Epub 2024 Mar 26.

Abstract

BACKGROUND

The study of clinical biological indicators in bipolar disorder (BD) is important. In recent years, basic experiments have associated the pathophysiological mechanism of BD is related to mitochondrial dysfunction, but few clinical studies have confirmed this finding.

OBJECT

The present study aimed to evaluate whether plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) levels, which can represent the degree of mitochondrial damage in vivo, are altered in patients with BD in early onset and during treatment compared with controls.

METHOD

A total of 75 first-diagnosed drug-naive patients with BD and 60 HCs were recruited and followed up for 1 month. The clinical symptoms were assessed using HAMD, HAMA, and YMRS, and ccf-mtDNA levels were measured by qPCR before and after drug treatment in BD.

RESULT

(1) The plasma ccf-mtDNA levels in first-diagnosed drug-naive patients with BD increased compared with those in HCs (p = 0.001). (2) Drug treatment for 1 month can decrease the expression of ccf-mtDNA in BD (p < 0.001). (3) No significant correlation was observed between the changes in ccf-mtDNA levels and the improvement of clinical symptoms in BD after drug treatment.

CONCLUSION

The plasma ccf-mtDNA level was increased in BD, and decreased after pharmacological treatment. These outcomes suggested that plasma ccf-mtDNA level is likely to be sensitive to the drug response in BD, and mitochondrial pathway is a potential target for further therapy.

摘要

背景

研究双相障碍(BD)的临床生物标志物很重要。近年来,基础实验将 BD 的病理生理机制与线粒体功能障碍相关联,但很少有临床研究证实这一发现。

目的

本研究旨在评估早期发病和治疗期间的 BD 患者血浆循环无细胞线粒体 DNA(ccf-mtDNA)水平是否发生变化,该水平可反映体内线粒体损伤程度。

方法

共纳入 75 例初诊未用药的 BD 患者和 60 名健康对照(HCs),并进行为期 1 个月的随访。采用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)和杨氏躁狂量表(YMRS)评估临床症状,采用 qPCR 检测 BD 患者药物治疗前后的 ccf-mtDNA 水平。

结果

(1)初诊未用药的 BD 患者血浆 ccf-mtDNA 水平高于 HCs(p=0.001)。(2)药物治疗 1 个月可降低 BD 患者的 ccf-mtDNA 表达(p<0.001)。(3)BD 患者药物治疗后 ccf-mtDNA 水平的变化与临床症状的改善无显著相关性。

结论

BD 患者血浆 ccf-mtDNA 水平升高,药物治疗后降低。这些结果表明,血浆 ccf-mtDNA 水平可能对 BD 的药物反应敏感,线粒体途径可能是进一步治疗的潜在靶点。

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