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Open access Sep 2026

222. 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. Aims & Objectives We investigated diagnostic subtype-specific patterns of epigenetic age acceleration in anxiety disorders and examined the influence of social functioning. Method 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. Discussion & 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.

K. Ohi, D. Fujikane, Y. Oida et al. · 0 citations
Open access Aug 2026

Longitudinal change in resting-state functional brain connectivity associated with secondary sexual characteristics between ages 11 and 13 years.

Pubertal maturation drives brain development, yet longitudinal evidence linking it to resting-state functional connectivity (rs-FC) in early adolescence remains limited, and adolescent mental-health trajectories differ by sex, motivating sex-specific analyses. In a general-population cohort (255 adolescents scanned at Time 1; 68 girls and 70 boys with analysable two-wave data), we examined longitudinal change in rs-FC between ages ~11.5 and ~13.6 years, separately by sex. Whole-brain analyses were applied without predefined regions of interest, using principal component analysis (PCA) as a data-driven screen and network-based statistics (NBS) to localize subnetworks associated with pubertal stage (Tanner stage). Among girls, Tanner breast stage at Time 2 was significantly associated with the fingerprint stability (within-individual similarity) of whole-brain rs-FC. NBS identified a subnetwork positively associated with Tanner breast stage, linking the thalamus to visual, auditory, and motor areas and the prefrontal operculum to frontoparietal association areas, with the PCA screen converging on thalamic involvement. No comparable associations were observed in boys. These findings suggest that the level of pubertal maturation is associated with the longitudinal stability of large-scale brain networks in girls.

Susumu Morita, K. Kasai, Masahiro Kiyota et al. · 0 citations

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