Abstract
There is high mortality among patients with bipolar disorder (BD). Studies have reported accelerated biological aging in patients with BD. Recently, Horvath and Hannum et al. independently developed DNA methylation (DNAm) profiles as “epigenetic clocks,” which are the most accurate biological age estimate. This led to the development of two accomplished measures of epigenetic age acceleration (EAA) using blood samples, namely, intrinsic and extrinsic EAA (IEAA and EEAA, respectively). IEAA, which is based on Horvath’s clock, is independent of blood cell counts and indicates cell-intrinsic aging. On the other hand, EEAA, which is based on Hannum’s clock, is associated with age-dependent changes in blood cell counts and indicates immune system aging. Further, Lu et al. developed the “GrimAge” clock, which can strongly predict the mortality risk, and DNAm-based telomere length (DNAmTL). We used a DNAm dataset from whole blood samples obtained from 30 patients with BD and 30 healthy controls. We investigated Horvath EAA, IEAA, Hannum EAA, EEAA, Grim EAA, DNAmTL, and DNAm-based blood cell composition. Compared with controls, there was a decrease in Horvath EAA and IEAA in patients with BD. Further, there was a significant decrease in Horvath EAA and IEAA in patients with BD taking medication combinations of mood stabilizers (including lithium carbonate, sodium valproate, and carbamazepine) than in those taking no medication/monotherapy. This study provides novel evidence indicating decelerated epigenetic aging associated with mood stabilizers in patients with BD.
Highlights
Bipolar disorder (BD) is a recurrent chronic mental disorder characterized by periods of depressive and manic states that affects ~1% of the general population[1]
There was a significant correlation between chronological age and Horvath Age (r = 0.907, p < 0.001), Hannum Age (r = 0.918, p < 0.001), GrimAge (r = 0.866, p < 0.001), and DNAm-based telomere length (DNAmTL) (r = −0.714, p < 0.001) (Figs. 1 and 2)
The strong linear relationships between each DNA methylation (DNAm) age/DNAmTL and chronological age indicated a valid high accuracy of the epigenetic estimator used in this study
Summary
Bipolar disorder (BD) is a recurrent chronic mental disorder characterized by periods of depressive and manic states that affects ~1% of the general population[1]. A high mortality rate has been observed in patients with BD, resulting from both natural causes (such as cardiovascular and cerebrovascular diseases) and unnatural causes (such as suicide and accident)[2]. The accelerated aging hypothesis of BD has been proposed to explain these. Several studies have shown accelerated telomere shortening in patients with BD5–10; other studies have observed no significant difference compared with controls[11,12]. Others have demonstrated longer TL in patients with BD, resulting from the potential effects of lithium carbonate (Li), which is a firstline mood stabilizer[13,14]. Aging research has progressed substantially in recent decades. One review concluded that epigenetic clocks were the most promising models among six potential
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