Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland; Department of Psychiatry, St. Patrick's University Hospital, Trinity College Dublin, James Street, Dublin 8, Ireland.
Department of Psychiatry, St. Patrick's University Hospital, Trinity College Dublin, James Street, Dublin 8, Ireland.
Prog Neuropsychopharmacol Biol Psychiatry. 2023 Mar 8;121:110656. doi: 10.1016/j.pnpbp.2022.110656. Epub 2022 Oct 7.
Mitochondrial dysfunction may play a role in various psychiatric conditions. Mitochondrial DNA copy number (mtDNAcn), the ratio of mitochondrial DNA to nuclear DNA, represents an attractive marker of mitochondrial health that is easily measured from stored DNA samples, and has been shown to be altered in depression. In this study, we measured mtDNAcn in whole blood samples from medicated patients with depression (n = 100) compared to healthy controls (n = 89) and determined the relationship between mtDNAcn and depression severity and the therapeutic response to electroconvulsive therapy (ECT). We also explored the relationship between mtDNAcn and telomere length and inflammatory markers. Our results show that mtDNAcn was significantly elevated in blood from patients with depression when compared to control samples, and this result survived statistical adjustment for potential confounders (p = 0.002). mtDNAcn was significantly elevated in blood from subgroups of patients with non-psychotic or unipolar depression. There was no difference in mtDNAcn noted in subgroups of ECT remitters/non-remitters or responders/non-responders. Moreover, mtDNAcn was not associated with depression severity, telomere length, or circulating inflammatory marker concentrations. Overall, our results show that mtDNAcn is elevated in blood from patients with depression, though whether this translates to mitochondrial function is unknown. Further work is required to clarify the contribution of mitochondria and mtDNA to the pathophysiology of depression and the therapeutic response to antidepressant treatments.
线粒体功能障碍可能在各种精神疾病中起作用。线粒体 DNA 拷贝数 (mtDNAcn)，即线粒体 DNA 与核 DNA 的比值，是线粒体健康的一个有吸引力的标志物，它可以从储存的 DNA 样本中很容易地测量出来，并已被证明在抑郁症中发生改变。在这项研究中，我们测量了接受药物治疗的抑郁症患者（n=100）和健康对照组（n=89）全血样本中的 mtDNAcn，并确定了 mtDNAcn 与抑郁症严重程度和电惊厥治疗（ECT）的治疗反应之间的关系。我们还探索了 mtDNAcn 与端粒长度和炎症标志物之间的关系。我们的研究结果表明，与对照组样本相比，抑郁症患者的血液中 mtDNAcn 明显升高，且这一结果在对潜在混杂因素进行统计学调整后仍然成立（p=0.002）。mtDNAcn 在非精神病性或单相抑郁症患者的血液中明显升高。在 ECT 缓解者/非缓解者或反应者/非反应者亚组中，mtDNAcn 没有差异。此外，mtDNAcn 与抑郁症严重程度、端粒长度或循环炎症标志物浓度无关。总的来说，我们的研究结果表明，抑郁症患者的血液中 mtDNAcn 升高，尽管这是否转化为线粒体功能尚不清楚。需要进一步的工作来阐明线粒体和 mtDNA 对抑郁症病理生理学和抗抑郁治疗反应的贡献。
