表观遗传钟识别了与抑郁症严重程度和认知缺陷相关的有害表观遗传衰老
Chao Liufu1, Tao Pang1, Haohao Zheng1
1Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.
Aging and disease
|September 3, 2025
概括
大型抑郁症与表观遗传衰老有关,影响认知功能. 这种加快的衰老与症状严重程度相关,可能是MDD患者认知缺陷的基础.
科学领域:
- 神经科学
- 遗传学
- 精神病学
背景情况:
- 大型抑郁症是一种普遍的精神疾病,对健康有重大影响.
- 认知障碍是MDD的一个常见症状,
- 通过DNA甲基化测量表观遗传衰老, 作为生物衰老的关键生物标志物.
研究的目的:
- 研究MDD,表观遗传衰老和认知功能之间的关系.
- 使用表观遗传时钟评估MDD患者的年龄加速.
- 探索表观遗传衰老标志物与MDD认知表现之间的相关性.
主要方法:
- 使用DNA甲基化数据来计算表观遗传时钟的年龄加速 (DamAge,Zhang).
- 在发现队列 (39名MDD患者,40名对照组) 中进行分析,并在独立队列 (359名MDD患者,68名对照组) 中进行验证.
- 在重要的CpG位点进行了全表观基因组关联研究 (EWAS) 和丰富分析.
主要成果:
- 患有MDD的患者的年龄加速显著增加 (DamAge) 和死亡风险增加 (Zhang时钟).
- DamAge的加速与抑郁症状的严重程度有正相关.
- 确定了1472个与DamAge加速相关的显著CpG位点,涉及细胞骨,信号和炎症通路.
- 认知评估显示了多个表观遗传时钟的情感识别与年龄加速之间的相关性.
结论:
- 加快表观遗传衰老是MDD的一个重要特征.
- 表观遗传衰老可能导致MDD的认知障碍.
- 表观遗传时钟提供了MDD背后的生物学机制及其认知后果的见解.
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