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

AI Summary

Latent profile analysis identified two epigenetic ageing subgroups in BD: accelerated (58%) and decelerated (42%).
Accelerated subgroup showed higher depressive symptoms, lower mtDNA copy number, and increased systemic inflammation; associations remained significant after multiple testing.
Subgroups did not differ by sociodemographic factors, BD course, psychiatric comorbidities, or current medication; accelerated group may suit personalised prevention and treatment.

Bipolar Disord. 2026 Aug;28(5):e70143. doi: 10.1111/bdi.70143.

ABSTRACT

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.

PMID:42400340 | DOI:10.1111/bdi.70143

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