Over several decades, we have become aware that among the seven serotonin receptor subtypes, some of them should be blocked, like 5-HT2AR and 5-HT7R, to reduce major depression, while others should be activated, like the postjunctional 5-HT1AR and 5-HT4R [10,11,13,37,38,39,50,51]. Here, HTR4 is linked to major depressive disorder.