Review articleCeramides and depression: A systematic review

- Aberrant sphingolipid metabolism is commonly present in depression.
- Ceramides have been implicated in depression due to pro-apoptotic characteristics.
- Ceramides C18:0 and C20:0 are most strongly linked to depression in humans.
- Pharmacologic reduction of certain ceramide species should be explored as treatment.

BackgroundMajor depressive disorder is a significant contributor to global disability and mortality. The mechanisms of depression are vast and not fully understood, and as a result current treatment of depression is suboptimal. Aberrant sphingolipid metabolism has been observed in some cases of depression, specifically alterations in ceramide concentrations. The role of ceramides and other sphingolipids in depression is a novel concept. This review summarizes and evaluates the current state of evidence for a role of ceramides in depression pathophysiology and the potential for novel depression pharmacotherapies targeting ceramide metabolism.MethodsMedline, Embase, and PsycINFO databases were searched through October 2016 for English-language studies using combinations of the search terms: ceramide, depression, sphingolipid, and depressive symptoms.ResultsOf the 489 articles screened, 14 were included in the qualitative synthesis of this review article. Pre-clinical and clinical evidence suggest that ceramide species may contribute to depression pathophysiology. In human studies, ceramides C18:0 and C20:0 are the species most strongly linked to depression. Evidence for altered ceramide metabolism in depression is present, but data for a causal role of ceramides in depression are lacking.LimitationsThis review was limited by potential reporting bias. Furthermore, a lack of specificity of which ceramides were altered in depression was common.ConclusionsPharmacotherapy targeting ceramide metabolism may be a novel treatment option for depression. A number of pharmacological targets exists for ceramide reduction and a number of currently approved medications inhibit ceramide production. More evidence, pre-clinical and clinical, is warranted to determine the extent and consistency of the role of ceramides in depression.