An update on the role of glutamate in the pathophysiology of depression

Objective: To review the literature on the involvement of glutamate (Glu), including its interactions with other neurochemical systems, in the pathophysiology of depression. Method: A MEDLINE search using the terms glutamate, depression and major depressive disorder, was performed. Results: Alterations in proteins involved in glutamatergic signalling are implicated in variations in behaviour in animal models of depression. Drugs acting at Glu receptors appear to have antidepressant-like effects in these models, and traditional antidepressant pharmacotherapies act on the glutamatergic system. Recent evidence from genetic studies and in vivo spectroscopy also correlate glutamatergic dysfunction with depression. Trials of N-methyl-d-aspartate receptor antagonists in humans have provided mixed results. Conclusion: A growing body of evidence indicates that the glutamatergic system is involved in the pathophysiology of depression, and may represent a target for intervention.