Lithium monotherapy is associated with global DNA hypomethylation

Mood Stabilizers and the Influence on Global Leukocyte DNA Methylation in Bipolar Disorder

Lena Backlund,b,d,e,*Ya Bin Wei,b,eLina Martinsson,a,bPhilippe A. Melas,a,eJia Jia Liu,b,e,fNinni Mu,b,eClaes-Göran Östenson,cTomas J. Ekström,a,eMartin Schalling,b,e and Catharina Lavebrattb,e


Little is known about the relationship between treatments for bipolar disorder (BD), their therapeutic responses and the DNA methylation status. We investigated whether global DNA methylation levels differ between healthy controls and bipolar patients under different treatments. Global DNA methylation was measured in leukocyte DNA from bipolar patients under lithium monotherapy (n = 29) or combination therapy (n = 32) and from healthy controls (n = 26). Lithium response was assessed using the Alda scale. Lithium in monotherapy was associated with hypomethylation (F = 4.63, p = 0.036). Lithium + valproate showed a hypermethylated pattern compared to lithium alone (F = 7.27, p = 0.011). Lithium response was not associated with DNA methylation levels. These data suggest that the choice of treatment in BD may lead to different levels of global DNA methylation. However, further research is needed to understand its clinical significance.

My take – In bipolar patients not on medications there could be a global DNA hypomethylation. Whether lithium results in global DNA hypomethylation, there is a pre-existing global DNA hypermethylation in bipolar disorder or both is not clear from this research.