Intravenous injection of anti-ceramide antibodies to neutralize ceramide, ceramidase to consume ceramide, PLD to reconstitute endogenous phosphatidic acid, or phosphatidic acid itself rescued depressed mice and rapidly, i.e., within 24 h, normalized behavior and neuronal proliferation indicating the significance of this novel pathway for MDD. This evidence concerns the gene GPLD1 and major depressive disorder.