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).
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).
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.