Although these authors indicate brain endothelial cells as the major cell to be impacted by blood-derived ceramide in MDD, such data suggests the potential importance of variations in astrocyte oxidant status and fluxes on neuronal activity and interarea neuronal patterning, as well as on endothelial function, including via the capacity of GSH to suppress nSMase2-induced ceramide. This evidence concerns the gene SMPD3 and major depressive disorder.