Bipolar disorder (BD) has been previously associated with premature mortality and aging, including acceleration of epigenetic aging. Suicide attempts (SA) are greatly elevated in BD and are associated with decreased lifespan, biological aging, and poorer clinical outcomes. We investigated the relationship between GrimAge, an epigenetic clock trained on time-to-death and associated with mortality and lifespan, and SA in two independent cohorts of BD individuals (discovery cohort - controls (n = 50), BD individuals with (n = 77, BD/SA) and without (n = 67, BD/non-SA) lifetime history of SA; replication cohort - BD/SA (n = 48) and BD/non-SA (n = 47)). An acceleration index for the GrimAge clock (GrimAgeAccel) was computed from blood DNA methylation (DNAm) and compared between groups with multiple general linear models. Differences in epigenetic aging from the discovery cohort were validated in the independent replication cohort. In the discovery cohort, controls, BD/non-SA, and BD/SA significantly differed on GrimAgeAccel (F = 5.424, p = 0.005), with the highest GrimAgeAccel in BD/SA (p = 0.004, BD/SA vs. controls). Within the BD individuals, BD/non-SA and BD/SA differed on GrimAgeAccel in both cohorts (p = 0.008) after covariate adjustment. Finally, DNAm-based surrogates revealed possible involvement of plasminogen activator inhibitor 1, leptin, and smoking pack-years in driving accelerated epigenetic aging. These findings pair with existing evidence that not only BD, but also SA, may be associated with an accelerated biological aging and provide putative biological mechanisms for morbidity and premature mortality in this population.
This research output has an Altmetric Attention Score of 12. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 October 2023.
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