Higher proportion of inactive Gsk3β in platelets of elderly patients with bipolar disorder: an effect of treatment?

It has been postulated that mood stabilizers inhibit glycogen synthase kinase 3-beta (Gsk3β) activity, mainly through its phosphorylation on serine-9 (Ser9). However, in vivo studies addressing Gsk3β activity in patients with bipolar disorder are scarce. Here, we compare Gsk3β inactivation (as indicated by Ser9-phosphorylation) in platelets of elderly patients with bipolar disorder undergoing clinical treatment and healthy elderly adults not taking medication. Platelet samples were obtained from 37 elderly adults (bipolar disorder = 19, controls = 18). Relative changes in Gsk3β inactivation was estimated by comparing the ratios of phosphorylated Gsk3β to total Gsk3β (p-Gsk3β Ser9/Gsk3β) between the disease and control groups. Phosphorylated-Gsk3β (p < 0.001) and the p-Gsk3β Ser9/Gsk3β ratio (p = 0.006) were elevated in bipolar patients. In the bipolar disorder group, p-Gsk3β Ser9/Gsk3β was positively correlated with serum lithium levels (r = 0.478, p = 0.039). Gsk3β inactivation is higher in this group of elderly adults undergoing treatment for bipolar disorder. However, whether the treatment or the disease causes Gsk3β inactivation was confounded by the lack of an unmedicated, bipolar control group and the non-uniform treatment regimens of the bipolar disorder group. Thus, further studies should help distinguish whether Gsk3β inactivation is an effect of drug treatment or an intrinsic characteristic of bipolar disorder.