Figure 1. Hitting ceramide for depression. Gulbins et al. have evidence that blocking the production of ceramide, a phospholipid signaling molecule, has antidepressive effects.

Ordinarily, the membrane-associated phospholipid sphingomyelin [a] is cleaved by sphingomyelin phosphodiesterase 1 acid lysosomal (SMPD1; ASM) [b] to yield ceramide [c]. Gulbins et al. showed that in cell culture and mice, accumulation of ceramide correlated with depressive behavior and reduced neuronal growth and survival [d].

The team also showed that two known antidepressants-fluoxetine and amitriptyline-lowered ceramide levels and decreased activity of SMPD1 compared with no treatment. Fendiline, a nonselective calcium channel blocker, also reduced SMPD1 activity and normalized depression-like behavior.