Given the known roles of sphingomyelins at the plasma membrane and the correlations that we observed between sphingomyelins and the TSPAN5 and ERICH3 SNPs in our network analysis, we hypothesize a functional, as well as a statistical relationship between hydroxylated sphingomyelins (or their isomeric/isobaric relatives) and TSPAN5/ERICH3 mechanisms of pathophysiology in MDD. This evidence concerns the gene TSPAN5 and major depressive disorder.