The hippocampal SIK2-CRTC1 system is implicated in both the development of depression and the effectiveness of antidepressants like paroxetine and fluoxetine.
Recent research suggests that paroxetine, a selective serotonin reuptake inhibitor, may also influence this SIK2-CRTC1 pathway beyond its effects on serotonin.
Experimental results show that paroxetine's antidepressant effects in mice are linked to its ability to prevent chronic stress impacts on SIK2 and CRTC1, while knocking down CRTC1 negates these beneficial effects.