The 10–15-years decrease in life expectancy observed in individuals with bipolar disorder (BD) has been linked to the concept of accelerated cellular aging. Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) have been proposed as markers of cellular aging and comparisons between individuals with BD and healthy controls (HC) sometimes led to conflicting results. Previous studies had moderate sample sizes and studies combining these two markers into a single analysis are scarce. Using quantitative polymerase chain reaction, we measured both TL and mtDNAcn in DNA (peripheral blood) in a sample of 130 individuals with BD and 78 HC. Regression analyses, receiver operating characteristic (ROC), and clustering analyses were performed. We observed significantly lower TL and mtDNAcn in individuals with BD as compared to HC (respective decrease of 26.5 and 35.8%). ROC analyses showed that TL and mtDNAcn highly discriminated groups (AUC = 0.904 for TL and AUC = 0.931 for mtDNAcn). In the whole population, clustering analyses identified a group of young individuals (age around 36 years), with accelerated cellular aging (both shorter TL and lower mtDNAcn), which consisted mostly of individuals with BD (85.5%). The subgroup of patients with young age but accelerated aging was not characterized by specific clinical variables related to the course of BD or childhood maltreatment. However, patients in this subgroup were more frequently treated with anticonvulsants. Further characterization of this subgroup is required to better understand the molecular mechanisms and the risk factors of accelerated cellular aging in BD.

Background Life expectancy is significantly decreased in bipolar disorder (BD). This is associated with accelerated cellular aging which can be estimated by telomere length (TL). However, specific determinants of shorter TL in BD are under-explored. This study examines whether circadian misalignment (i.e. mismatch between preferred and actual phase of circadian activity rhythms) is associated with shorter TL in BD. Methods Euthymic individuals with BD (n = 101) undertook 21 consecutive days of actigraphy recording and completed the Composite Scale of Morningness (CSM) to assess phase preference for activities (chronotype). Polymerase chain reaction was used to measure TL in blood. Cluster analysis identified circadian aligned/misaligned subgroups as defined by preferred (CSM score) and actual phases of activity (actigraphically determined onset of active and inactive periods). We tested for any associations between TL and clusters, with adjustments for between-cluster differences in socio-demographic and illness factors. Results We identified three clusters: an "Aligned Morning" cluster (n = 31) with preferred and actual timing of activity in the morning, an "Aligned Evening" cluster (n = 37) with preferred and actual timing of activity in the evening and a "Misaligned" cluster (n = 32) with an evening chronotype, but an earlier objective onset of active periods. After adjustment for confounders, we found that TL was significantly associated with circadian misalignment and older age. Conclusions Circadian misalignment may partly explain shorter TL in BD and could contribute to accelerated aging in these individuals.

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