Two follow-up studies from the same laboratory then showed that the antidepressant effects of imipramine depend on CRTC1 in the medial prefrontal cortex (Wang et al., 2020), and that ARN-3236, a selective inhibitor of SIK2, induced significant antidepressant-like effects in both the CSDS and CUMS models of depression by acting on the hippocampal CRTC1-CREB-BDNF pathway (Liu et al., 2020). Here, SIK2 is linked to major depressive disorder.