Brain-derived neurotrophic factor serum levels following ketamine and esketamine intervention for treatment-resistant depression: secondary analysis from a randomized trial.

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Abstract

Evidence suggests that ketamine's influence on brain-derived neurotrophic factor (BDNF) might be involved in its mechanism of rapid antidepressant action. We aimed to evaluate the differential impact of ketamine and esketamine on serum BDNF levels and its association with response patterns in treatment-resistant depression (TRD).

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Most cited references 46

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Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report

A Rush, Madhukar Trivedi, Stephen R Wisniewski … (2006)

This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

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NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses

Anita Autry, Megumi Adachi, Elena Nosyreva … (2011)

Clinical studies consistently demonstrate that a single sub-psychomimetic dose of ketamine, an ionotropic glutamatergic n-methyl-d-aspartate receptor (NMDAR) antagonist, produces fast-acting antidepressant responses in patients suffering from major depressive disorder (MDD), although the underlying mechanism is unclear 1-3 . Depressed patients report alleviation of MDD symptoms within two hours of a single low-dose intravenous infusion of ketamine with effects lasting up to two weeks 1-3 , unlike traditional antidepressants (i.e. serotonin reuptake inhibitors), which take weeks to reach efficacy. This delay is a major drawback to current MDD therapies, leaving a need for faster acting antidepressants particularly for suicide-risk patients 3 . Ketamine's ability to produce rapidly acting, long-lasting antidepressant responses in depressed patients provides a unique opportunity to investigate underlying cellular mechanisms. We show that ketamine and other NMDAR antagonists produce fast-acting behavioural antidepressant-like effects in mouse models that depend on rapid synthesis of brain-derived neurotrophic factor (BDNF). We find that ketamine-mediated NMDAR blockade at rest deactivates eukaryotic elongation factor 2 (eEF2) kinase (also called CaMKIII) resulting in reduced eEF2 phosphorylation and desuppression of BDNF translation. Furthermore, we find inhibitors of eEF2 kinase induce fast-acting behavioural antidepressant-like effects. Our findings suggest that protein synthesis regulation by spontaneous neurotransmission may serve as a viable therapeutic target for fast-acting antidepressant development.

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Antidepressant effects of ketamine in depressed patients

Robert M. Berman, Angela Cappiello, Amit Anand … (2000)

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Author and article information

Journal

Journal ID (iso-abbrev): Trends Psychiatry Psychother

Title: Trends in psychiatry and psychotherapy

Publisher: EDITORA SCIENTIFIC

ISSN (Electronic): 2238-0019

ISSN (Print): 2237-6089

Publication date (Electronic): Oct 06 2021

Affiliations

[1 ] Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil. Laboratório de Neuropsicofarmacologia, Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

[2 ] Laboratório de Neuropsicofarmacologia, Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil. Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil. Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

[3 ] Laboratório de Neuropsicofarmacologia, Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil. Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

[4 ] Laboratório de Pesquisas Clínicas, Instituto Gonçalo Moniz, Fiocruz, Salvador, Bahia, Brazil. Serviço de Imunologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

[5 ] Laboratório Interdisciplinar de Neurociências Clínicas, Universidade Federal de São Paulo, São Paulo, Brazil.

[6 ] Laboratório de Neuropsicofarmacologia, Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

[7 ] Laboratório de Neuropsicofarmacologia, Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil. Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

[8 ] Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.

[9 ] Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.

[10 ] Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil. Laboratório de Neuropsicofarmacologia, Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil. Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil. Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

Article

DOI: 10.47626/2237-6089-2021-0298

PubMed ID: 34904800

SO-VID: 2bf24247-dabf-4a0f-be0a-240ed1405c11

History

Keywords: BDNF,NMDA antagonists,biochemical markers,major depressive disorder,neurotrophins

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Keywords: BDNF, NMDA antagonists, biochemical markers, major depressive disorder, neurotrophins

Brain-derived neurotrophic factor serum levels following ketamine and esketamine intervention for treatment-resistant depression: secondary analysis from a randomized trial.

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Most cited references 46

Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report

NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses

Antidepressant effects of ketamine in depressed patients

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