Glycogen Synthase Kinase-3 beta: Variation over Time and the Possible Association with Mood and Cognition in Healthy Individuals

Abstract

Evidence indicates a role for glycogen synthase kinase-3 beta (GSK-3 beta) in the pathophysiology of mood disorders and in cognitive disturbances; however, the natural variation in GSK-3 beta activity over time is unknown. We aimed to investigate GSK-3 beta activity over time and its possible correlation with emotional lability, subjective mood fluctuations and cognitive function in healthy individuals. Thirty-seven healthy subjects were evaluated with neuropsychological tests and blood samples at baseline and 12-week follow-up. Total GSK-3 beta and serine-9-phosphorylated GSK-3 beta in peripheral blood mononuclear cells were quantitated using enzyme immunometric assays. The activity of GSK-3 beta (serine-9-phosphorylated GSK-3 beta/total GSK-3 beta) was lower at baseline compared with follow-up. No significant mean change over time was observed in levels of total GSK-3 beta and serine-9-phosphorylated GSK-3 beta. Exploratory analysis revealed lower activity of GSK-3 beta in spring and summer compared with the fall season. No correlation was observed between GSK-3 beta activity and emotional lability, subjective mood fluctuations or cognitive function. The results suggest that intra- and interindividual variation in GSK-3 beta activity over time could contribute to the heterogeneity of findings in clinical studies. The stability of GSK-3 beta activity and the role of potential moderators of GSK-3 beta activity warrant further investigation. Clinical studies of GSK-3 beta should consider including repeated measures of both cases and healthy individuals. (C) 2016 S. Karger AG, Basel