Epigenetic GrimAge acceleration and cognitive impairment in bipolar disorder

Bipolar disorder (BD) has been previously associated with clinical signs of premature aging, in-cluding accelerated epigenetic aging in blood and brain, and a steeper age-related decline in cognitive function. However, the clinical drivers and cognitive correlates of epigenetic aging in BD are still unknown. We aimed to investigate the relationship between multiple measures of epigenetic aging acceleration with clinical, functioning, and cognitive outcomes in patients with BD and controls. Blood genome-wide DNA methylation levels were measured in BD patients (n = 153) and matched healthy controls (n = 50) with the Infinium MethylationEPIC Bead-Chip (Illumina). Epigenetic age estimates were calculated using an online tool, including the recently developed lifespan predictor GrimAge, and analyzed with generalized linear models European Neuropsychopharmacology (2022) controlling for demographic variables and blood cell proportions. BD was significantly associ-ated with greater GrimAge acceleration (AgeAccelGrim, 0= 0.197, p = 0.009), and significant group-dependent interactions were found between AgeAccelGrim and blood cell proportions (CD4+ T-lymphocytes, monocytes, granulocytes, and B-cells). Within patients, higher AgeAc-celGrim was associated with worse cognitive function in multiple domains (short-term affective memory ( 0=-0.078, p = 0.030), short-term non-affective memory ( 0=-0.088, p = 0.018), inhi-bition ( 0= 0.064, p = 0.046), and problem solving ( 0=-0.067, p = 0.034)), age of first diagnosis with any mood disorder ( 0=-0.076, p = 0.039) or BD ( 0=-0.102, p = 0.016), as well as with cur-rent non-smoking status ( 0=-0.392, p < 0.001). Overall, our findings support the contribution of epigenetic factors to the aging-related cognitive decline and premature mortality reported in BD patients, with an important driving effect of smoking in this population.(c) 2022 Elsevier B.V. and ECNP. All rights reserved.

Automated summary

The study found that patients with bipolar disorder show signs of accelerated epigenetic aging in their blood and brain, which is associated with cognitive decline and other clinical outcomes.