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The Role of Glutamate Underlying Treatment-resistant Depression

The monoamine hypothesis has significantly improved our understanding of mood disorders and their treatment by linking monoaminergic abnormalities to the pathophysiology of mood disorders. Even 50 years after the monoamine hypothesis was established, some patients do not respond to treatments for de...

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Autores principales: Kim, Jeongseop, Kim, Tae-Eun, Lee, Seung-Hwan, Koo, Ja Wook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean College of Neuropsychopharmacology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10335903/
https://www.ncbi.nlm.nih.gov/pubmed/37424412
http://dx.doi.org/10.9758/cpn.22.1034
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author Kim, Jeongseop
Kim, Tae-Eun
Lee, Seung-Hwan
Koo, Ja Wook
author_facet Kim, Jeongseop
Kim, Tae-Eun
Lee, Seung-Hwan
Koo, Ja Wook
author_sort Kim, Jeongseop
collection PubMed
description The monoamine hypothesis has significantly improved our understanding of mood disorders and their treatment by linking monoaminergic abnormalities to the pathophysiology of mood disorders. Even 50 years after the monoamine hypothesis was established, some patients do not respond to treatments for depression, including selective serotonin reuptake drugs. Accumulating evidence shows that patients with treatment-resistant depression (TRD) have severe abnormalities in the neuroplasticity and neurotrophic factor pathways, indicating that different treatment approaches may be necessary. Therefore, the glutamate hypothesis is gaining attention as a novel hypothesis that can overcome monoamine restrictions. Glutamate has been linked to structural and maladaptive morphological alterations in several brain areas associated with mood disorders. Recently, ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has shown efficacy in TRD treatment and has received the U.S. Food and Drug Administration approval, revitalizing psychiatry research. However, the mechanism by which ketamine improves TRD remains unclear. In this review, we re-examined the glutamate hypothesis, bringing the glutamate system onboard to join the modulation of the monoamine systems, emphasizing the most prominent ketamine antidepressant mechanisms, such as NMDAR inhibition and NMDAR disinhibition in GABAergic interneurons. Furthermore, we discuss the animal models used in preclinical studies and the sex differences in the effects of ketamine.
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spelling pubmed-103359032023-08-31 The Role of Glutamate Underlying Treatment-resistant Depression Kim, Jeongseop Kim, Tae-Eun Lee, Seung-Hwan Koo, Ja Wook Clin Psychopharmacol Neurosci Review The monoamine hypothesis has significantly improved our understanding of mood disorders and their treatment by linking monoaminergic abnormalities to the pathophysiology of mood disorders. Even 50 years after the monoamine hypothesis was established, some patients do not respond to treatments for depression, including selective serotonin reuptake drugs. Accumulating evidence shows that patients with treatment-resistant depression (TRD) have severe abnormalities in the neuroplasticity and neurotrophic factor pathways, indicating that different treatment approaches may be necessary. Therefore, the glutamate hypothesis is gaining attention as a novel hypothesis that can overcome monoamine restrictions. Glutamate has been linked to structural and maladaptive morphological alterations in several brain areas associated with mood disorders. Recently, ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has shown efficacy in TRD treatment and has received the U.S. Food and Drug Administration approval, revitalizing psychiatry research. However, the mechanism by which ketamine improves TRD remains unclear. In this review, we re-examined the glutamate hypothesis, bringing the glutamate system onboard to join the modulation of the monoamine systems, emphasizing the most prominent ketamine antidepressant mechanisms, such as NMDAR inhibition and NMDAR disinhibition in GABAergic interneurons. Furthermore, we discuss the animal models used in preclinical studies and the sex differences in the effects of ketamine. Korean College of Neuropsychopharmacology 2023-08-31 2023-08-31 /pmc/articles/PMC10335903/ /pubmed/37424412 http://dx.doi.org/10.9758/cpn.22.1034 Text en Copyright© 2023, Korean College of Neuropsychopharmacology https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Kim, Jeongseop
Kim, Tae-Eun
Lee, Seung-Hwan
Koo, Ja Wook
The Role of Glutamate Underlying Treatment-resistant Depression
title The Role of Glutamate Underlying Treatment-resistant Depression
title_full The Role of Glutamate Underlying Treatment-resistant Depression
title_fullStr The Role of Glutamate Underlying Treatment-resistant Depression
title_full_unstemmed The Role of Glutamate Underlying Treatment-resistant Depression
title_short The Role of Glutamate Underlying Treatment-resistant Depression
title_sort role of glutamate underlying treatment-resistant depression
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10335903/
https://www.ncbi.nlm.nih.gov/pubmed/37424412
http://dx.doi.org/10.9758/cpn.22.1034
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