Indeed, while one study showed that Cry1 or Cry2 single-KO and Cry1/2 double-KO mice showed increased anxiety states, but not depression-like behaviors (De Bundel et al., 2013), another study reported Cry1/2 double-KO displayed increased anhedonia compared to WT mice (Savalli et al., 2015a). This evidence concerns the gene CRY1 and major depressive disorder.