Accelerated epigenetic aging in males with mood disorders accompanied by insomnia

Mood disorders (MDs), including major depressive disorders and bipolar disorders, are linked to premature mortality and accelerated aging. Epigenetic age (EA) is a reliable aging biomarker that can effectively capture biological aging. Prior research has indicated the presence of epigenetic age acceleration in individuals with MDs, yet the connection between epigenetic aging and clinical symptoms remains elusive. we assessed genome-wide DNA methylation in blood samples from 251 MDs patients and 181 healthy controls, using four epigenetic clocks and DNAm-based telomere length (DNAmTL) to calculate EA and epigenetic age acceleration (EAA: AgeAccelHorvath, AgeAccelHannum, AgeAccelPheno, AgeAccelGrim) and the age-adjusted estimate of DNAmTL (DNAmTLadjAge). We explored the potential association between EAA and the five symptom factors of Hamilton Depression Scale (HAMD-17), and performed subgroup analyses based on the severity of symptom. While no significant difference in EAA and DNAmTLadjAge was found between MDs patients and healthy controls overall, male MDs patients exhibited accelerated aging compared to female patients. Interestingly, we observed a strong correlation between AgeAccelGrim and insomnia symptoms in male MDs patients (r = 0.32, p = 0.0043). Specifically, male MDs patients with severe insomnia showed significantly higher AgeAccelGrim (p = 0.000147, Cohen's d = 0.9163) and elevated levels of DNAm GDF15, DNAm Leptin, and DNAm TIMP-1. These findings indicate the potential role of insomnia in the accelerated aging process of MDs patients, contributing to the understanding of the relationship between MDs and premature aging, and inform accurate patient stratification and targeted therapeutic intervention.