Epigenetic Age Accelerations and the Clinical Presentation of Bipolar Disorders: A Latent Profile Analysis in the FACE ‐ BD Sample

BACKGROUND: Epigenetic age accelerations have been associated with the clinical expression of BD; however, with few available studies. METHOD: We calculated Horvath, Hannum, EN, GrimAge, and PhenoAge epigenetic ages in a sample of 139 individuals with BD. We used a latent profile analysis to identify subgroups of individuals based on their profile of epigenetic age accelerations. We compared these profiles for socio-demographic characteristics, course of BD, associated psychiatric conditions, current medication use, telomere length, mitochondrial DNA copy number (mtDNAcn), markers of metabolic syndrome, and of systemic inflammation. RESULTS: The latent profile analysis identified two subgroups, one with accelerated and one with decelerated epigenetic aging (respectively 58% and 42%). Subgroups did not differ for socio-demographic characteristics, course of BD, associated psychiatric conditions, nor current medication use. The accelerated aging subgroup was characterized by higher depressive symptoms (p < 0.001), lower mtDNAcn (p < 0.001), higher levels of systemic inflammation (platelet/neutrophil ratio, neutrophil/lymphocyte ratio, systemic inflammation index, p < 0.001) that remained significant after correction for multiple testing. Some associations with anxiety symptoms, social functioning, blood pressure, and waist circumference did not remain significant after correction for multiple testing. CONCLUSIONS: Most individuals with BD were characterized by an accelerated epigenetic age profile. This study suggests a link between epigenetic age acceleration, systemic inflammation, and mtDNAcn. This subgroup might represent a target for personalized prevention and treatment.