Blood d-serine levels as a predictive biomarker for the rapid antidepressant effects of the NMDA receptor antagonist ketamine

This letter to the editor proposes blood d-serine levels as a predictive biomarker for the effects of ketamine.

Abstract

No Abstract is provided for this Letter to the Editor.

Author: Kenji Hashimoto

Summary

Ketamine is the most effective antidepressant drug for patients with treatment-resistant major depressive disorder or bipolar disorder. However, the biochemical pathways defining the differences between patients who respond to ketamine are currently unknown.

D-serine acts as an endogenous, obligatory co-agonist at the NMDA receptor, and the authors found that the levels of D-serine were significantly lower in ketamine responders than in ketamine non-responders. A significant correlation was found between baseline D-serine and the percentage change in Montgomery sberg Depression Rating Scale (MADRS) scores, 230 min after ketamine infusion. Additionally, the percentage of D-serine to total serine at baseline was higher in the responder group than in the non-responder group.

In a previous study, serum levels of D-serine were significantly lower in patients with schizophrenia than in healthy subjects, whereas serum levels of L-serine were significantly higher in patients with schizophrenia than in healthy subjects. The percentage of D-serine to total serine in patients with treatment-resistant MDD was higher than in healthy controls.

D-Serine is synthesized from L-serine by serine racemase, metabolized by D-amino acid oxidase, and also synthesized in astrocytes from 3-phosphoglycerate. All of these enzymes are capable of affecting NMDA receptor function.

Ketamine is a racemic mixture containing equal parts of R-andS-ketamine. Recent studies suggest that R-ketamine is more potent and longer-lasting antidepressant effects than the S-stereoisomer, and may be a safer antidepressant, relative to the S-stereoisomer.