Is glycogen synthase kinase-3 a central modulator in mood regulation

Xiaohua Li, Richard S. Jope

Research output: Contribution to journalReview articlepeer-review

221 Scopus citations


Little is known regarding the mechanisms underlying the complex etiology of mood disorders, represented mainly by major depressive disorder and bipolar disorder. The 1996 discovery that lithium inhibits glycogen synthase kinase-3 (GSK3) raised the possibility that impaired inhibition of GSK3 is associated with mood disorders. This is now supported by evidence from animal biochemical, pharmacological, molecular, and behavioral studies and from human post-mortem brain, peripheral tissue, and genetic studies that are reviewed here. Mood disorders may result in part from impairments in mechanisms controlling the activity of GSK3 or GSK3-regulated functions, and disruptions of these regulating systems at different signaling sites may contribute to the heterogeneity of mood disorders. This substantial evidence supports the conclusion that bolstering the inhibitory control of GSK3 is an important component of the therapeutic actions of drugs used to treat mood disorders and that GSK3 is a valid target for developing new therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)2143-2154
Number of pages12
Issue number11
StatePublished - Oct 2010
Externally publishedYes


  • glycogen synthase kinase-3
  • lithium
  • molecular and cellular neurobiology
  • mood disorders
  • neuropharmacology
  • signal transduction

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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