Epigenetic signatures of accelerated aging and immune dysregulation in youth with social anxiety disorder

Abstract

Social anxiety disorder (SAD) is a prevalent psychiatric condition with significant psychological and socioeconomic consequences. While its psychological characteristics are well-documented, the underlying molecular mechanisms remain poorly understood, particularly in younger populations. This study investigates the epigenetic basis of SAD by identifying differential DNA methylation sites, pathway enrichment patterns, and tissue-specific expression profiles. Genome-wide methylation analysis revealed nominally significant CpG sites associated with SAD, mapping to genes involved in neurotransmitter release, synaptic function, and immune regulation. Tissue enrichment analysis demonstrated that these genes are preferentially modulated in brain regions critical for emotional and social processing, including the frontal cortex and anterior cingulate cortex. Additionally, individuals with young SAD exhibited significant differences in epigenetic age acceleration and immune cell composition, particularly in natural killer cell counts. Finally, colocalization analysis identified genetic variants that overlap with methylation quantitative trait loci, highlighting potential regulatory relationships between genetic risk factors and epigenetic modifications in SAD. These findings provide new insights into the molecular architecture of SAD in youth, offering potential biomarkers and mechanistic targets for future research and therapeutic development.