Biological aging analysis based on DNA methylation status for social anxiety disorder.

Aim: 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.

Methods: 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.

Results: 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.

Conclusions: 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.