It may be related to the problem that increases in extracellular serotonin levels induced by SSRIs, activates not only 5-HTR subtypes that reduce depression (such as postsynaptic 5-HT1AR and 5-HT4R) but also others that enhance depression (such as 5-HT1A auto-receptors and 5HT2A/C receptors) [3,5,6]. This evidence concerns the gene HTR4 and major depressive disorder.