Differential diagnosis of unipolar versus bipolar depression by GSK3 levels in peripheral blood: a pilot experimental study

BackgroundThe differential diagnosis of patients presenting for the first time with a depressive episode into unipolar disorder versus bipolar disorder is crucial to establish the correct pharmacological therapy (antidepressants vs mood stabilizers), but no biological markers are currently available. Several lines of evidence indicate an involvement of Glycogen Synthase Kinase-3 (GSK3) in the pathophysiology of depression. However, previous reports about GSK3 in peripheral blood were incomplete or inconsistent, so a specific marker is not yet available. The aim was to search for consistent differences in GSK3 alpha and GSK3 beta or of their phosphorylated forms in samples of peripheral blood from patients with unipolar and bipolar depression.MethodsMononucleate peripheral blood cells (PBMCs) of samples from patients presenting with a depressive episode were analyzed with the western blot technique.ResultsThe total amount of GSK3 beta in PBMCs was significantly lower in patients with bipolar disorder than in patients with unipolar depression. The sensitivity based on GSK3 beta was 85%. GSK3 alpha was not significantly different but allowed a correct detection of 57% of BD patients. The combination in series of GSK3 beta and GSK3 alpha yields a sensitivity of about 100%, but with 26.7% false negatives.ConclusionsOur results suggest that PBMC GSK3 beta could be a candidate biomarker for the differential diagnosis of bipolar disorder versus unipolar depression. This finding may help in implementing the still limited panel of peripheral biomarkers for differential diagnosis between unipolar and bipolar disorder in patients presenting with a depressive episode.