Epigenetic aging in anxiety disorders: diagnostic subtype differences and associations with social functioning

Abstract

Background: Anxiety disorders, including subtypes such as social anxiety disorder (SAD), panic disorder (PD), and generalized anxiety disorder (GAD), are among the most common psychiatric disorders. They are characterized by excessive fear, anxiety, and behavioral disturbances, leading to significant impairments in social and occupational functioning. While both accelerated and suppressed epigenetic aging have been reported in various psychiatric disorders, findings in anxiety disorders remain limited. We investigated diagnostic subtype-specific patterns of epigenetic age acceleration in anxiety disorders and examined the influence of social functioning. Methods: DNA methylation (DNAm) was quantified in 266 healthy individuals and 30 individuals with anxiety disorders (11 SAD, 11 PD, and 8 GAD) using Illumina MethylationEPIC arrays. Epigenetic age acceleration was estimated using PCHannumG2013 as the primary clock, with sensitivity analyses conducted using four additional clocks. Social functioning was assessed with the Social Functioning Scale. Meta-analyses incorporating data from previous DNAm-based studies (423 healthy individuals and 278 individuals with anxiety disorders) were performed. Results: Compared with healthy individuals, individuals with anxiety disorders had suppressed epigenetic age acceleration, particularly in SAD, in our cohort. Lower social functioning, especially impaired independence-competence and reduced prosocial activities, was associated with suppressed epigenetic age acceleration. Meta-analyses revealed suppressed epigenetic aging in patients with SAD and a marginal increase in patients with PD. Sensitivity analyses revealed that the suppression in SAD was consistently detected across clock types, except for DunedinPACE. Conclusions: Our findings suggest possible diagnostic subtype-specific differences in epigenetic age acceleration in anxiety disorders, which may indicate a potential protective role of social avoidance in patients with SAD and the influence of inflammatory processes in patients with PD.