The results show that genetic deficiency of neutral sphingomyelinase 2 protected mice from glucocorticocsterone- or chronic unpredictable stress-induced inhibition of PLD activity and reduction of phosphatidic acid levels in the hippocampus (Fig. 7A and B), consistent with the findings that deficiency of neutral sphingomyelinase 2 protects from signs of MDD in mice (see Fig. 4A and B). Here, SMPD3 is linked to major depressive disorder.