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Ceramides and depression: A systematic review.

Adam Dinoff1, Nathan Herrmann2, Krista L Lanctôt3

  • 1Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Journal of Affective Disorders
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Altered ceramide metabolism may play a role in depression. Further research is needed to explore ceramides as a novel therapeutic target for major depressive disorder.

Keywords:
CeramideDepressionSphingolipid

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Major depressive disorder (MDD) is a leading cause of global disability.
  • Current MDD treatments are often suboptimal due to incomplete understanding of its mechanisms.
  • Aberrant sphingolipid metabolism, particularly ceramide concentrations, is implicated in some depression cases.

Purpose of the Study:

  • To review and evaluate the evidence for ceramides in depression pathophysiology.
  • To explore the potential of targeting ceramide metabolism for novel depression pharmacotherapies.

Main Methods:

  • A systematic literature search of Medline, Embase, and PsycINFO databases was conducted.
  • Studies were selected based on keywords: ceramide, depression, sphingolipid, and depressive symptoms.
  • 14 English-language articles were included in the qualitative synthesis.

Main Results:

  • Pre-clinical and clinical evidence suggest ceramide species contribute to depression pathophysiology.
  • Ceramides C18:0 and C20:0 show the strongest association with depression in human studies.
  • While altered ceramide metabolism is evident, causal data in depression remain limited.

Conclusions:

  • Pharmacotherapy targeting ceramide metabolism presents a novel treatment avenue for depression.
  • Several pharmacological targets exist for ceramide reduction, with some approved medications inhibiting its production.
  • Further pre-clinical and clinical evidence is necessary to confirm the role and consistency of ceramides in depression.