TY - JOUR

T1 - Glycogen synthase kinase-3β

T2 - Variation over time and the possible association with mood and cognition in healthy individuals

AU - Munkholm, Klaus

AU - Lenskjold, Toke

AU - Jacoby, Anne Sophie

AU - Miskowiak, Kamilla Woznica

AU - Vinberg, Maj

AU - Joaquim, Helena Giroud Passarelli

AU - Talib, Leda Leme

AU - Gattaz, Wagner Farid

AU - Kessing, Lars Vedel

PY - 2016

Y1 - 2016

N2 - Evidence indicates a role for glycogen synthase kinase-3β (GSK-3β) in the pathophysiology of mood disorders and in cognitive disturbances; however, the natural variation in GSK-3β activity over time is unknown. We aimed to investigate GSK-3β 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-3β and serine-9-phosphorylated GSK-3β in peripheral blood mononuclear cells were quantitated using enzyme immunometric assays. The activity of GSK-3β (serine-9-phosphorylated GSK-3β/total GSK-3β) was lower at baseline compared with follow-up. No significant mean change over time was observed in levels of total GSK-3β and serine-9-phosphorylated GSK-3β. Exploratory analysis revealed lower activity of GSK-3β in spring and summer compared with the fall season. No correlation was observed between GSK-3β activity and emotional lability, subjective mood fluctuations or cognitive function. The results suggest that intra- and interindividual variation in GSK-3β activity over time could contribute to the heterogeneity of findings in clinical studies. The stability of GSK-3β activity and the role of potential moderators of GSK-3β activity warrant further investigation. Clinical studies of GSK-3β should consider including repeated measures of both cases and healthy individuals.

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

KW - Biomarker

KW - Bipolar disorder

KW - Peripheral blood

U2 - 10.1159/000444489

DO - 10.1159/000444489

M3 - Journal article

C2 - 27003416

AN - SCOPUS:84961393803

VL - 73

SP - 108

EP - 115

JO - Neuropsychobiology

JF - Neuropsychobiology

SN - 0302-282X

IS - 2

ER -