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

Meysam Amidfar, Marie Woelfer, Gislaine Z. Réus, João Quevedo, Martin Walter, Yong Ku Kim

    Research output: Contribution to journalReview articlepeer-review

    57 Citations (Scopus)

    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.

    Original languageEnglish
    Article number109668
    JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
    Volume94
    DOIs
    Publication statusPublished - 2019 Aug 30

    Bibliographical note

    Funding Information:
    Translational Psychiatry Laboratory (Brazil) is funded by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) , Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) , Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC) , Instituto Cérebro e Mente and University of Southern Santa Catarina (UNESC) .

    Funding Information:
    Center of Excellence on Mood Disorders (USA) is funded by the Pat Rutherford Jr. Chair in Psychiatry, John S. Dunn Foundation and Anne and Don Fizer Foundation Endowment for Depression Research.

    Funding Information:
    Translational Psychiatry Program (USA) is funded by the Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth). Center of Excellence on Mood Disorders (USA) is funded by the Pat Rutherford Jr. Chair in Psychiatry, John S. Dunn Foundation and Anne and Don Fizer Foundation Endowment for Depression Research. Translational Psychiatry Laboratory (Brazil) is funded by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC), Instituto Cérebro e Mente and University of Southern Santa Catarina (UNESC). JQ is a 1A CNPq Research Fellow.

    Funding Information:
    Translational Psychiatry Program (USA) is funded by the Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth) .

    Publisher Copyright:
    © 2019 Elsevier Inc.

    Keywords

    • Ketamine
    • Major depressive disorder
    • Memantine
    • NMDA receptor
    • Synaptic plasticity

    ASJC Scopus subject areas

    • Pharmacology
    • Biological Psychiatry

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