Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
Department of Pharmacy, University of Patras School of Health Sciences, Patras, Greece.
Drug Dev Res. 2020 May;81(3):268-273. doi: 10.1002/ddr.21612. Epub 2019 Nov 1.
Major depressive disorder (MDD) is a chronic, severe psychiatric illness with an incidence of 3% worldwide. MDD patients have a significantly impaired quality of life and reduced life expectancy compared to unaffected individuals, the latter being largely accounted for by an increased incidence of suicide and cardiovascular disorders. The premature mortality observed in MDD has been considered a signature of accelerated aging, a hypothesis supported by data showing altered functioning and morphology of several brain regions that are typically present in the aging population. Telomere shortening is a hallmark of cellular aging, and as such several studies explored the involvement of disrupted telomere dynamics in MDD, reporting contrasting findings. In the current study, we measured leukocyte telomere length (LTL) in a sample of 54 MDD patients and 47 non-psychiatric controls characterized for response to antidepressant treatment. After correcting for age, sex, and body mass index, we showed significantly reduced LTL in affected individuals compared to controls (beta = -.22, p = .02). There was no difference in LTL between treatment resistant or responsive MDD patients. Moreover, we observed no correlation between lifetime exposure to antidepressants and LTL. Our study showed that MDD patients have shorter telomeres compared to controls, supporting the hypothesis of accelerated aging in this disorder. However, LTL seemed not to be influenced by antidepressant treatment or to correlate with clinical response to these antidepressants. Further investigations in larger samples and possibly with longitudinal design are warranted to elucidate the role of altered telomere dynamics in MDD.
重度抑郁症（MDD）是一种慢性、严重的精神疾病，全球发病率为 3%。与未受影响的个体相比，MDD 患者的生活质量显著受损，预期寿命缩短，后者主要归因于自杀和心血管疾病发病率的增加。MDD 中观察到的过早死亡被认为是加速衰老的特征，这一假设得到了数据的支持，这些数据显示了几个大脑区域的功能和形态发生了改变，而这些区域在老年人群中很常见。端粒缩短是细胞衰老的标志，因此有几项研究探讨了端粒动力学紊乱在 MDD 中的参与情况，报告了相互矛盾的发现。在当前的研究中，我们测量了 54 名 MDD 患者和 47 名非精神科对照者的白细胞端粒长度（LTL），这些对照者的抗抑郁治疗反应特征。在校正年龄、性别和体重指数后，我们发现受影响的个体的 LTL 明显低于对照组（β=-.22，p=0.02）。在治疗抵抗或有反应的 MDD 患者中，LTL 没有差异。此外，我们观察到抗抑郁药暴露与 LTL 之间没有相关性。我们的研究表明，与对照组相比，MDD 患者的端粒较短，支持了这种疾病加速衰老的假设。然而，LTL 似乎不受抗抑郁治疗的影响，也与这些抗抑郁药的临床反应无关。需要进一步在更大的样本中进行研究，可能还需要进行纵向设计，以阐明端粒动力学改变在 MDD 中的作用。
