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The role of NMDA receptor in neurobiology and treatment of major depressive disorder: Evidence from translational research

Authors
Amidfar, MeysamWoelfer, MarieReus, Gislaine Z.Quevedo, JoaoWalter, MartinKim, Yong-Ku
Issue Date
30-8월-2019
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Keywords
NMDA receptor; Ketamine; Memantine; Synaptic plasticity; Major depressive disorder
Citation
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v.94
Indexed
SCIE
SCOPUS
Journal Title
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume
94
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/63464
DOI
10.1016/j.pnpbp.2019.109668
ISSN
0278-5846
Abstract
There is accumulating evidence demonstrating that dysfunction of glutamatergic neurotransmission, particularly via N-methyl-d-aspartate (NMDA) receptors, is involved in the pathophysiology of major depressive disorder (MDD). Several studies have revealed an altered expression of NMDA receptor subtypes and impaired NMDA receptor-mediated intracellular signaling pathways in brain circuits of patients with MDD. Clinical studies have demonstrated that NMDA receptor antagonists, particularly ketamine, have rapid antidepressant effects in treatment-resistant depression, however, neurobiological mechanisms are not completely understood. Growing body of evidence suggest that signal transduction pathways involved in synaptic plasticity play critical role in molecular mechanisms underlying rapidly acting antidepressant properties of ketamine and other NMDAR antagonists in MDD. Discovering the molecular mechanisms underlying the unique antidepressant actions of ketamine will facilitate the development of novel fast acting antidepressants which lack undesirable effects of ketamine. This review provides a critical examination of the NMDA receptor involvement in the neurobiology of MDD including analyses of alterations in NMDA receptor subtypes and their interactive signaling cascades revealed by postmortem studies. Furthermore, to elucidate mechanisms underlying rapid-acting antidepressant properties of NMDA receptor antagonists we discussed their effects on the neuroplasticity, mostly based on signaling systems involved in synaptic plasticity of mood-related neurocircuitries.
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