Regulation of glycogen synthase kinase-3 during bipolar mania treatment

Authors

  • Xiaohong Li,

    1. Beijing Anding Hospital, Capital Medical University, Beijing, China
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  • Min Liu,

    1. Beijing Anding Hospital, Capital Medical University, Beijing, China
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  • Zhuoji Cai,

    1. Beijing Anding Hospital, Capital Medical University, Beijing, China
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  • Gang Wang,

    1. Beijing Anding Hospital, Capital Medical University, Beijing, China
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    • Xiaohua Li currently receives research funding from NIH, Ortho-McNeil-Janssen, and Otsuka. Xiaohong Li, Min Liu, Zhuoji Cai, and Gang Wang have no conflicts of interest to report.

  • Xiaohua Li

    1. Department of Psychiatry and Behavioral Neurobiology
    2. Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA
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    • Xiaohua Li currently receives research funding from NIH, Ortho-McNeil-Janssen, and Otsuka. Xiaohong Li, Min Liu, Zhuoji Cai, and Gang Wang have no conflicts of interest to report.


Corresponding author:
Dr. Xiaohua Li
Department of Psychiatry and BehavioralNeurobiology
University of Alabama at Birmingham
1720 Seventh Avenue South
Sparks Center 1001A
Birmingham, AL 35294-0017, USA
Fax: +1-205-934-2500
E-mail: xili@uab.edu

Abstract

Li X, Liu M, Cai Z, Wang G, Li X. Regulation of glycogen synthase kinase-3 during bipolar mania treatment.
Bipolar Disord 2010: 12: 741–752. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Bipolar disorder is a debilitating psychiatric illness presenting with recurrent mania and depression. The pathophysiology of bipolar disorder is poorly understood, and molecular targets in the treatment of bipolar disorder remain to be identified. Preclinical studies have suggested that glycogen synthase kinase-3 (GSK3) is a potential therapeutic target in bipolar disorder, but evidence of abnormal GSK3 in human bipolar disorder and its response to treatment is still lacking.

Methods:  This study was conducted in acutely ill type I bipolar disorder subjects who were hospitalized for a manic episode. The protein level and the inhibitory serine phosphorylation of GSK3 in peripheral blood mononuclear cells of bipolar manic and healthy control subjects were compared, and the response of GSK3 to antimanic treatment was evaluated.

Results:  The levels of GSK3α and GSK3β in this group of bipolar manic subjects were higher than healthy controls. Symptom improvement during an eight-week antimanic treatment with lithium, valproate, and atypical antipsychotics was accompanied by a significant increase in the inhibitory serine phosphorylation of GSK3, but not the total level of GSK3, whereas concomitant electroconvulsive therapy treatment during a manic episode appeared to dampen the response of GSK3 to pharmacological treatment.

Conclusions:  Results of this study suggest that GSK3 can be modified during the treatment of bipolar mania. This finding in human bipolar disorder is in agreement with preclinical data suggesting that inhibition of GSK3 by increasing serine phosphorylation is a response of GSK3 to psychotropics used in bipolar disorder, supporting the notion that GSK3 is a promising molecular target in the pharmacological treatment of bipolar disorder.

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