NPAS2 and major depressive disorder: However, in populations meeting the DSM-IV criteria for MDD or BD with a winter seasonnality, two studies report that the development of SAD is associated with variants of circadian and melatoninergic genes, suggesting associations with an amino acid substitution in NPAS2 (471 Leu/Ser)24, as well as with a combination of variations in 3 circadian genes PER2, ARNTL (Bmal1), and NPAS225.