Department of Psychiatry, Eumsung-somang Hospital, Eumsung, Republic of Korea.
Department of Pharmacology, School of Medicine, Eulji University, 77, Gyeryong-ro 771 beon-gil, Jung-gu, Daejeon 34824, Republic of Korea.
Psychiatry Res. 2019 Dec;282:112616. doi: 10.1016/j.psychres.2019.112616. Epub 2019 Oct 14.
Mitochondrial dysfunction is implicated in the pathophysiology of major depressive disorder (MDD). This dysfunction can be indirectly assessed using the mitochondrial DNA (mtDNA) copy number. A total of 118 patients with MDD and 116 age- and sex-matched control subjects were recruited for this study, and mtDNA copy numbers were measured in peripheral blood cells. This study also examined the potential variables that might impact mtDNA copy number in MDD, including age and clinical features. Additionally, epigenetic control of mtDNA copy number was examined by assessing DNA methylation ratios in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) promoter in nuclear DNA and the displacement loop (D-loop) region of mtDNA. The present results showed that patients with MDD had a higher mtDNA copy number and a decreased DNA methylation status in the PGC1α promoter. mtDNA copy numbers were negatively associated with an age, psychomotor agitation, and somatic symptoms in MDD. These results suggest that the alterations in mitochondrial function and epigenetic change of PGC1α may be relevant to the pathophysiology of MDD.
线粒体功能障碍与重度抑郁症（MDD）的病理生理学有关。这种功能障碍可以使用线粒体 DNA（mtDNA）拷贝数间接评估。本研究共招募了 118 名 MDD 患者和 116 名年龄和性别匹配的对照者，测量外周血细胞中的 mtDNA 拷贝数。本研究还检查了可能影响 MDD 中 mtDNA 拷贝数的潜在变量，包括年龄和临床特征。此外，通过评估核 DNA 中过氧化物酶体增殖物激活受体γ共激活因子 1-α（PGC1α）启动子和 mtDNA 位移环（D-loop）区域中的 DNA 甲基化比率，检查了 mtDNA 拷贝数的表观遗传控制。本研究结果表明，MDD 患者的 mtDNA 拷贝数较高，PGC1α 启动子中的 DNA 甲基化状态降低。mtDNA 拷贝数与 MDD 中的年龄、精神运动激越和躯体症状呈负相关。这些结果表明，线粒体功能的改变和 PGC1α 的表观遗传变化可能与 MDD 的病理生理学有关。
