Epigenetic Age Accelerations and the Clinical Presentation of Bipolar Disorders: A Latent Profile Analysis in the...

Epigenetic age accelerations have been associated with the clinical expression of BD; however, with few available studies.

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.

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.

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.