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Human induced pluripotent stem cells technology in treatment resistant depression: novel strategies and opportunities to unravel ketamine’s fast-acting antidepressant mechanisms
Approximately 30% of Major Depressive Disorder (MDD) patients develop treatment-resistant depression (TRD). Among the different causes that make TRD so challenging in both clinical and research contexts, major roles are played by the inadequate understanding of MDD pathophysiology and the limitation...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649879/ https://www.ncbi.nlm.nih.gov/pubmed/33224469 http://dx.doi.org/10.1177/2045125320968331 |
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author | Marcatili, Matteo Sala, Carlo Dakanalis, Antonios Colmegna, Fabrizia D’Agostino, Armando Gambini, Orsola Dell’Osso, Bernardo Benatti, Beatrice Conti, Luciano Clerici, Massimo |
author_facet | Marcatili, Matteo Sala, Carlo Dakanalis, Antonios Colmegna, Fabrizia D’Agostino, Armando Gambini, Orsola Dell’Osso, Bernardo Benatti, Beatrice Conti, Luciano Clerici, Massimo |
author_sort | Marcatili, Matteo |
collection | PubMed |
description | Approximately 30% of Major Depressive Disorder (MDD) patients develop treatment-resistant depression (TRD). Among the different causes that make TRD so challenging in both clinical and research contexts, major roles are played by the inadequate understanding of MDD pathophysiology and the limitations of current pharmacological treatments. Nevertheless, the field of psychiatry is facing exciting times. Combined with recent advances in genome editing techniques, human induced pluripotent stem cell (hiPSC) technology is offering novel and unique opportunities in both disease modelling and drug discovery. This technology has allowed innovative disease-relevant patient-specific in vitro models to be set up for many psychiatric disorders. Such models hold great potential in enhancing our understanding of MDD pathophysiology and overcoming many of the well-known practical limitations inherent to animal and post-mortem models. Moreover, the field is approaching the advent of (es)ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, claimed as one of the first and exemplary agents with rapid (in hours) antidepressant effects, even in TRD patients. Although ketamine seems poised to transform the treatment of depression, its exact mechanisms of action are still unclear but greatly demanded, as the resulting knowledge may provide a model to understand the mechanisms behind rapid-acting antidepressants, which may lead to the discovery of novel compounds for the treatment of depression. After reviewing insights into ketamine’s mechanisms of action (derived from preclinical animal studies) and depicting the current state of the art of hiPSC technology below, we will consider the implementation of an hiPSC technology-based TRD model for the study of ketamine’s fast acting antidepressant mechanisms of action. |
format | Online Article Text |
id | pubmed-7649879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-76498792020-11-19 Human induced pluripotent stem cells technology in treatment resistant depression: novel strategies and opportunities to unravel ketamine’s fast-acting antidepressant mechanisms Marcatili, Matteo Sala, Carlo Dakanalis, Antonios Colmegna, Fabrizia D’Agostino, Armando Gambini, Orsola Dell’Osso, Bernardo Benatti, Beatrice Conti, Luciano Clerici, Massimo Ther Adv Psychopharmacol Novel Strategies for the Treatment of Depression Approximately 30% of Major Depressive Disorder (MDD) patients develop treatment-resistant depression (TRD). Among the different causes that make TRD so challenging in both clinical and research contexts, major roles are played by the inadequate understanding of MDD pathophysiology and the limitations of current pharmacological treatments. Nevertheless, the field of psychiatry is facing exciting times. Combined with recent advances in genome editing techniques, human induced pluripotent stem cell (hiPSC) technology is offering novel and unique opportunities in both disease modelling and drug discovery. This technology has allowed innovative disease-relevant patient-specific in vitro models to be set up for many psychiatric disorders. Such models hold great potential in enhancing our understanding of MDD pathophysiology and overcoming many of the well-known practical limitations inherent to animal and post-mortem models. Moreover, the field is approaching the advent of (es)ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, claimed as one of the first and exemplary agents with rapid (in hours) antidepressant effects, even in TRD patients. Although ketamine seems poised to transform the treatment of depression, its exact mechanisms of action are still unclear but greatly demanded, as the resulting knowledge may provide a model to understand the mechanisms behind rapid-acting antidepressants, which may lead to the discovery of novel compounds for the treatment of depression. After reviewing insights into ketamine’s mechanisms of action (derived from preclinical animal studies) and depicting the current state of the art of hiPSC technology below, we will consider the implementation of an hiPSC technology-based TRD model for the study of ketamine’s fast acting antidepressant mechanisms of action. SAGE Publications 2020-11-02 /pmc/articles/PMC7649879/ /pubmed/33224469 http://dx.doi.org/10.1177/2045125320968331 Text en © The Author(s), 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Novel Strategies for the Treatment of Depression Marcatili, Matteo Sala, Carlo Dakanalis, Antonios Colmegna, Fabrizia D’Agostino, Armando Gambini, Orsola Dell’Osso, Bernardo Benatti, Beatrice Conti, Luciano Clerici, Massimo Human induced pluripotent stem cells technology in treatment resistant depression: novel strategies and opportunities to unravel ketamine’s fast-acting antidepressant mechanisms |
title | Human induced pluripotent stem cells technology in treatment resistant depression: novel strategies and opportunities to unravel ketamine’s fast-acting antidepressant mechanisms |
title_full | Human induced pluripotent stem cells technology in treatment resistant depression: novel strategies and opportunities to unravel ketamine’s fast-acting antidepressant mechanisms |
title_fullStr | Human induced pluripotent stem cells technology in treatment resistant depression: novel strategies and opportunities to unravel ketamine’s fast-acting antidepressant mechanisms |
title_full_unstemmed | Human induced pluripotent stem cells technology in treatment resistant depression: novel strategies and opportunities to unravel ketamine’s fast-acting antidepressant mechanisms |
title_short | Human induced pluripotent stem cells technology in treatment resistant depression: novel strategies and opportunities to unravel ketamine’s fast-acting antidepressant mechanisms |
title_sort | human induced pluripotent stem cells technology in treatment resistant depression: novel strategies and opportunities to unravel ketamine’s fast-acting antidepressant mechanisms |
topic | Novel Strategies for the Treatment of Depression |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649879/ https://www.ncbi.nlm.nih.gov/pubmed/33224469 http://dx.doi.org/10.1177/2045125320968331 |
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