Health Care Management Papers

Document Type

Journal Article

Date of this Version

5-27-2006

Publication Source

Biological Psychiatry

Volume

61

Issue

2

Start Page

216

Last Page

222

DOI

10.1016/j.biopsych.2006.02.027

Abstract

Background: Bipolar disorder has been linked to alterations in the multifunctional enzyme glycogen synthase kinase-3β (GSK3β). The mood stabilizer lithium inhibits GSK3β in vitro and in mouse brain, and this is currently the strongest known potential therapeutic target of lithium. We tested whether lithium modified GSK3β in vivo or in vitro in peripheral blood mononuclear cells (PBMCs) from healthy control and bipolar disorder subjects.

Methods: The PBMCs were obtained from 23 healthy control subjects, 9 bipolar subjects currently treated with lithium, and 13 lithium-free bipolar subjects. Immunoblot analyses were used to measure the inhibited, serine9-phosphorylated GSK3β.

Results: The level of phospho-Ser9-GSK3β in PBMCs was regulated by agents that modified kinases and phosphatases acting on GSK3β and was increased by in vitro lithium treatment. More important, phospho-Ser9-GSK3β levels were eightfold higher in PBMCs from lithium-treated bipolar than healthy control subjects.

Conclusions: Signaling pathways regulating serine9-phosphorylation of GSK3β can be studied in human PBMCs. Both in vitro and in vivo therapeutic lithium treatment is associated with a large increase in phospho-Ser9-GSK3β in PBMCs. Therefore, the inhibitory serine9-phosphorylation of GSK3β in human PBMCs may provide a biochemical marker to evaluate the association between GSK3β inhibition and therapeutic responses to lithium treatment.

Copyright/Permission Statement

© 2006. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

Bipolar disorder, GSK3, lithium, PBMC

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Date Posted: 27 November 2017

This document has been peer reviewed.