Hong Yanggang
The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Eur Arch Psychiatry Clin Neurosci. 2025 Aug 1. doi: 10.1007/s00406-025-02069-x.
Aging is a complex process influenced by genetic, environmental, and psychiatric factors. Recent evidence suggests that epigenetic age acceleration (EAA), a biomarker of biological aging, may be linked to psychiatric disorders, yet the causal direction remains unclear. This study employed a bidirectional two-sample Mendelian randomization (MR) analysis to explore the causal relationships between EAA (IEAA, HannumAA, GrimAA, PhenoAA) and ten psychiatric disorders. Genome-wide association study (GWAS) summary statistics from large European ancestry cohorts were used, and sensitivity analyses were conducted to ensure robustness. Forward MR analysis demonstrated that PhenoAge acceleration (PhenoAA) significantly increased the risk of attention-deficit hyperactivity disorder (ADHD) (OR = 1.043, P = 0.004), suggesting that cumulative biological aging may contribute to neurodevelopmental vulnerabilities. Conversely, Hannum age acceleration (HannumAA) was associated with a protective effect against obsessive-compulsive disorder (OCD) (OR = 0.904, P = 0.004). Reverse MR analysis revealed that autism spectrum disorder (ASD) was linked to a decrease in intrinsic epigenetic age acceleration (IEAA) (OR = 0.811, P = 0.027), while major depressive disorder (MDD) significantly increased both HannumAA (OR = 1.318, P = 0.005) and IEAA (OR = 1.226, P = 0.049). These findings suggest that psychiatric conditions may both influence and be influenced by biological aging processes. This study reveals a bidirectional link between psychiatric disorders and biological aging, showing that early-life mental health conditions may accelerate epigenetic aging and increase age-related disease risk. As psychiatric disorders are recognized as aging risk factors, these findings highlight the need for research on aging-targeted interventions in psychiatric populations.
衰老 是一个受遗传、环境和精神因素影响的复杂过程。最近的证据表明，表观遗传年龄加速（EAA）作为生物衰老的一个生物标志物，可能与精神障碍有关，但其因果关系仍不明确。本研究采用双向两样本孟德尔随机化（MR）分析，以探讨EAA（内在表观遗传年龄加速（IEAA）、汉纳姆表观遗传年龄加速（HannumAA）、格里姆表观遗传年龄加速（GrimAA）、表型年龄加速（PhenoAA））与十种精神障碍之间的因果关系。使用了来自欧洲裔大型队列的全基因组关联研究（GWAS）汇总统计数据，并进行了敏感性分析以确保结果的稳健性。正向MR分析表明，表型年龄加速（PhenoAA）显著增加了注意力缺陷多动障碍（ADHD）的风险（OR = 1.043，P = 0.004），这表明累积的生物衰老可能导致神经发育易损性。相反，汉纳姆表观遗传年龄加速（HannumAA）与强迫症（OCD）的保护作用相关（OR = 0.904，P = 0.004）。反向MR分析显示，自闭症谱系障碍（ASD）与内在表观遗传年龄加速（IEAA）降低有关（OR = 0.811，P = 0.027），而重度抑郁症（MDD）显著增加了汉纳姆表观遗传年龄加速（HannumAA）（OR = 1.318，P = 0.005）和内在表观遗传年龄加速（IEAA）（OR = 1.226，P = 0.049）。这些发现表明，精神状况可能既影响生物衰老过程，又受到生物衰老过程的影响。本研究揭示了精神障碍与生物衰老之间的双向联系，表明早期心理健康状况可能加速表观遗传衰老并增加与年龄相关的疾病风险。由于精神障碍被认为是衰老的风险因素，这些发现凸显了针对精神疾病人群进行衰老靶向干预研究的必要性。
