Recent findings of potential implications of glycogen synthase kinase-3β (GSK-3β) dysfunction in psychiatric disorders like depression, have increased focus for development of GSK-3β inhibitors with possible anti-depressant activity.
The gene depletion or pharmacological inhibition of GSK-3β reproduces some of the behavioral effects of lithium including reduction of depression- and manic-like behaviors in rodents, which attested the intracellular GSK- 3β inhibition as one of the critical steps in mediating behavioral effect of mood-stabilizers.
As a part of the serotoninergic dysfunction implicated in neurobiology of depression, evidence has focused on serotonin (5-HT) receptors downstream signaling intermediates including glycogen synthase kinase-3β (GSK-3β), cAMP response element binding protein (CREB) and brain derived neurotrophic factor (BDNF).
In mood disorder patients, the level of mania (in both acute and stabilized periods) and depression in stabilized periods was positively associated with GSK3Brs12630592 T only in FXR1 rs496250 A-allele carriers (Bonferroni-corrected interaction p=0.024, 0.052 and 0.017 respectively).