SMPD1 and major depressive disorder: Abnormalities in ASM bioactivity result in disturbed sphingomyelin degradation and ceramide generation, leading to extreme accumulation of sphingomyelin but deficient ceramide production.1, 13 Aberrant ASM-dominated sphingomyelin-ceramide signaling is associated with numbers of human nervous disorders including Alzheimer disease, Parkinson disease, schizophrenia,and depression.13 In particular, ASM deficiency contributes to lipid storage disorders, i.e., Niemann–Pick disease.11, 14