Department of Clinical Sciences Lund, Psychiatry, Faculty of Medicine, Lund University, Lund, Sweden.
Office for Psychiatry and Habilitation, Psychiatric Clinic Lund, Region Skåne, Sweden.
PLoS One. 2021 Nov 4;16(11):e0259591. doi: 10.1371/journal.pone.0259591. eCollection 2021.
Plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) is an immunogenic molecule and a novel biomarker of psychiatric disorders. Some previous studies reported increased levels of ccf-mtDNA in unmedicated depression and recent suicide attempters, while other studies found unchanged or decreased ccf-mtDNA levels in depression. Inconsistent findings across studies may be explained by small sample sizes and between-study variations in somatic and psychiatric co-morbidity or medication status.
We measured plasma ccf-mtDNA in a cohort of 281 patients with depressive disorders and 49 healthy controls. Ninety-three percent of all patients were treated with one or several psychotropic medications. Thirty-six percent had a personality disorder, 13% bipolar disorder. All analyses involving ccf-mtDNA were a priori adjusted for age and sex.
Mean levels in ccf-mtDNA were significantly different between patients with a current depressive episode (n = 236), remitted depressive episode (n = 45) and healthy controls (n = 49) (f = 8.3, p<0.001). Post-hoc tests revealed that both patients with current (p<0.001) and remitted (p = 0.002) depression had lower ccf-mtDNA compared to controls. Within the depressed group there was a positive correlation between ccf-mtDNA and "inflammatory depression symptoms" (r = 0.15, p = 0.02). We also found that treatment with mood stabilizers lamotrigine, valproic acid or lithium was associated with lower ccf-mtDNA (f = 8.1, p = 0.005).
Decreased plasma ccf-mtDNA in difficult-to-treat depression may be partly explained by concurrent psychotropic medications and co-morbidity. Our findings suggest that ccf-mtDNA may be differentially regulated in different subtypes of depression, and this hypothesis should be pursued in future studies.
血浆循环无细胞线粒体 DNA（ccf-mtDNA）是一种免疫原性分子，也是精神疾病的新型生物标志物。一些先前的研究报告称，未经治疗的抑郁症和最近自杀未遂者的 ccf-mtDNA 水平升高，而其他研究则发现抑郁症患者的 ccf-mtDNA 水平不变或降低。研究之间的不一致结果可能是由于样本量小，以及躯体和精神合并症或用药情况的研究间差异所致。
我们测量了 281 例抑郁症患者和 49 例健康对照者的血浆 ccf-mtDNA。所有患者中有 93%接受了一种或多种精神药物治疗。36%的患者有人格障碍，13%的患者有双相障碍。所有涉及 ccf-mtDNA 的分析均预先调整了年龄和性别。
当前发作的抑郁症患者（n=236）、缓解期的抑郁症患者（n=45）和健康对照组（n=49）之间的 ccf-mtDNA 平均水平差异有统计学意义（f=8.3，p<0.001）。事后检验显示，当前发作（p<0.001）和缓解期（p=0.002）的抑郁症患者的 ccf-mtDNA 均低于对照组。在抑郁组中，ccf-mtDNA 与“炎症性抑郁症状”呈正相关（r=0.15，p=0.02）。我们还发现，心境稳定剂拉莫三嗪、丙戊酸或锂的治疗与 ccf-mtDNA 降低有关（f=8.1，p=0.005）。
治疗困难的抑郁症患者的血浆 ccf-mtDNA 降低可能部分是由同时使用精神药物和合并症引起的。我们的研究结果表明，ccf-mtDNA 可能在不同类型的抑郁症中有不同的调节方式，这一假说应在未来的研究中进一步探讨。
