Major depressive disorder (MDD) is one of the most prevalent and debilitating psychiatric disorders, with a large number of patients not showing an effective therapeutic response to available treatments. Several biopsychosocial factors, such as stress in childhood and throughout life, and factors related to biological aging, may increase the susceptibility to MDD development. Included in critical biological processes related to aging and underlying biological mechanisms associated with MDD is the shortening of telomeres and changes in telomerase activity. This comprehensive review discusses studies that assessed the length of telomeres or telomerase activity and function in peripheral blood cells and brain tissues of MDD individuals. Also, results from in vitro protocols and animal models of stress and depressive-like behaviors were included. We also expand our discussion to include the role of telomere biology as it relates to other relevant biological mechanisms, such as the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, inflammation, genetics, and epigenetic changes. In the text and the discussion, conflicting results in the literature were observed, especially considering the size of telomeres in the central nervous system, on which there are different protocols with divergent results in the literature. Finally, the context of this review is considering cell signaling, transcription factors, and neurotransmission, which are involved in MDD and can be underlying to senescence, telomere shortening, and telomerase functions.

中文翻译：

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端粒：缩短和衰老在重度抑郁症中的作用及其治疗意义

重度抑郁症 (MDD) 是最普遍和使人衰弱的精神疾病之一，大量患者对现有治疗没有表现出有效的治疗反应。一些生物心理社会因素，例如童年和整个生命中的压力，以及与生物衰老相关的因素，可能会增加 MDD 发展的易感性。与衰老相关的关键生物学过程和与 MDD 相关的潜在生物学机制包括端粒的缩短和端粒酶活性的变化。这篇综合综述讨论了评估 MDD 个体外周血细胞和脑组织中端粒长度或端粒酶活性和功能的研究。此外，结果来自体外包括压力和抑郁样行为的协议和动物模型。我们还将讨论范围扩大到包括端粒生物学的作用，因为它与其他相关生物学机制有关，例如下丘脑-垂体-肾上腺 (HPA) 轴、氧化应激、炎症、遗传学和表观遗传变化。在文本和讨论中，观察到了文献中相互矛盾的结果，特别是考虑到中枢神经系统中端粒的大小，文献中存在不同的方案，结果不同。最后，本综述的背景是考虑细胞信号传导、转录因子和神经传递，它们与 MDD 相关并且可能是衰老、端粒缩短和端粒酶功能的基础。