Our findings that inhibition of TREK-1 by antidepressants, activation by mood stabilizers, and modulation of TREK-1 expression extend the possibility that TREK-1 could be a potential target for treatment of not only depression but also bipolar disorder, while TREK-2 is likely to be involved in the regulation of major depression, since TREK-2 is modulated by only antidepressants and antipsychotics, but not mood stabilizers. Here, KCNK2 is linked to major depressive disorder.