The response to SSRIs is abolished in a subset of Tph2 KO mice (Angoa-Perez et al., 2014), thus showing that the antidepressant effects of SSRIs indeed partially depend on an intact 5-HT system, but central 5-HT deficiency is not a prerequisite in the onset of depression-like behaviors, at least in mice. This evidence concerns the gene TPH2 and major depressive disorder.