Noguchi Nobuhiko, Shirai Toshiyuki, Suda Akira, Hattori Saki, Miyauchi Masatoshi, Okazaki Satoshi, Fujita Junichi, Asami Takeshi, Otsuka Ikuo, Hishimoto Akitoyo
Department of Psychiatry, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
Neuropsychopharmacol Rep. 2024 Dec;44(4):774-783. doi: 10.1002/npr2.12487. Epub 2024 Oct 15.
Social anxiety disorder (SAD) is a common disorder characterized by excessive fear of scrutiny and embarrassment, leading to severe distress and avoidance behaviors or dysfunctions. SAD and other relevant diseases have been reported to be associated with a higher risk of aging-related diseases, such as Alzheimer's disease, Parkinson's disease, and diabetes mellitus. Recently, epigenetic clock analysis, which measures biological aging based on comprehensive DNA methylation (DNAm) status, has been widely conducted. We conducted epigenetic clock analyses in patients with SAD and controls, examining various epigenetic age acceleration and DNAm-based predictive values of aging-related proteins (GrimAge components and GrimAge2 components), including leptin level.
We used the publicly available DNAm dataset, GSE164056, which consists of 66 patients with SAD and 77 controls of Caucasian descent aged between 18 and 50 years. We conducted regression analyses investigating the association between SAD and various indices of epigenetic aging, using age and sex as covariates.
None of the epigenetic clocks showed significant differences in age acceleration. Of the DNAm-based predictive values of aging-related proteins, leptin level in GrimAge components (q = 0.0123) and GrimAge2 components (q = 0.0123) were significantly lower in patients with SAD than in controls.
The results of this study suggested that leptin may be involved in SAD pathogenesis as an aging-related protein. Therefore, further studies with different designs are required.
社交焦虑障碍（SAD）是一种常见疾病，其特征为过度害怕被审视和尴尬，导致严重痛苦以及回避行为或功能障碍。据报道，SAD及其他相关疾病与患阿尔茨海默病、帕金森病和糖尿病等与衰老相关疾病的较高风险有关。最近，基于综合DNA甲基化（DNAm）状态来测量生物衰老的表观遗传时钟分析已被广泛开展。我们对SAD患者和对照组进行了表观遗传时钟分析，检测了各种表观遗传年龄加速情况以及基于DNAm的衰老相关蛋白（GrimAge成分和GrimAge2成分）的预测值，包括瘦素水平。
我们使用了公开可用的DNAm数据集GSE164056，该数据集由66例SAD患者和77例年龄在18至50岁之间的白种人对照组组成。我们进行了回归分析，以年龄和性别作为协变量，研究SAD与各种表观遗传衰老指标之间的关联。
没有一个表观遗传时钟在年龄加速方面显示出显著差异。在基于DNAm的衰老相关蛋白预测值中，SAD患者的GrimAge成分（q = 0.0123）和GrimAge2成分（q = 0.0123）中的瘦素水平显著低于对照组。
本研究结果表明，瘦素作为一种与衰老相关的蛋白可能参与了SAD的发病机制。因此，需要采用不同设计进行进一步研究。
