Université de Paris, INSERM UMR-S 1144, Optimisation Thérapeutique en Neuropsychopharmacologie, OTeN, F-75006, Paris, France.
Département de Psychiatrie et de Médecine Addictologique, Hôpitaux Lariboisière-Fernand Widal, GHU APHP.Nord - Université de Paris, Paris, F-75010, France.
Transl Psychiatry. 2022 Apr 1;12(1):135. doi: 10.1038/s41398-022-01891-4.
The 10-15-years decrease in life expectancy observed in individuals with bipolar disorder (BD) has been linked to the concept of accelerated cellular aging. Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) have been proposed as markers of cellular aging and comparisons between individuals with BD and healthy controls (HC) sometimes led to conflicting results. Previous studies had moderate sample sizes and studies combining these two markers into a single analysis are scarce. Using quantitative polymerase chain reaction, we measured both TL and mtDNAcn in DNA (peripheral blood) in a sample of 130 individuals with BD and 78 HC. Regression analyses, receiver operating characteristic (ROC), and clustering analyses were performed. We observed significantly lower TL and mtDNAcn in individuals with BD as compared to HC (respective decrease of 26.5 and 35.8%). ROC analyses showed that TL and mtDNAcn highly discriminated groups (AUC = 0.904 for TL and AUC = 0.931 for mtDNAcn). In the whole population, clustering analyses identified a group of young individuals (age around 36 years), with accelerated cellular aging (both shorter TL and lower mtDNAcn), which consisted mostly of individuals with BD (85.5%). The subgroup of patients with young age but accelerated aging was not characterized by specific clinical variables related to the course of BD or childhood maltreatment. However, patients in this subgroup were more frequently treated with anticonvulsants. Further characterization of this subgroup is required to better understand the molecular mechanisms and the risk factors of accelerated cellular aging in BD.
在双相情感障碍 (BD) 患者中观察到的预期寿命减少 10-15 年与细胞加速衰老的概念有关。端粒长度 (TL) 和线粒体 DNA 拷贝数 (mtDNAcn) 已被提议作为细胞衰老的标志物，BD 患者与健康对照 (HC) 之间的比较有时会得出相互矛盾的结果。以前的研究样本量适中，将这两种标志物结合到单一分析中的研究很少。我们使用定量聚合酶链反应，测量了 130 名 BD 患者和 78 名 HC 患者外周血 DNA 中的 TL 和 mtDNAcn。进行了回归分析、接受者操作特征 (ROC) 和聚类分析。与 HC 相比，我们观察到 BD 患者的 TL 和 mtDNAcn 明显较低（分别降低 26.5%和 35.8%）。ROC 分析表明 TL 和 mtDNAcn 可高度区分组（TL 的 AUC=0.904，mtDNAcn 的 AUC=0.931）。在整个人群中，聚类分析确定了一组年轻个体（年龄约为 36 岁），存在细胞加速衰老（TL 较短且 mtDNAcn 较低），其中大多数为 BD 患者（85.5%）。年龄较小但加速衰老的患者亚组的特征不是与 BD 病程或儿童期虐待相关的特定临床变量。然而，该亚组中的患者更频繁地接受抗惊厥药物治疗。需要进一步表征这个亚组，以更好地了解 BD 中加速细胞衰老的分子机制和危险因素。
