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Neuronal plasticity and fast antidepressant response

ABSTRACT: Neuronal plasticity has for a long time been considered important for the recovery from depression and for the antidepressant drug action, but how the drug action is translated to plasticity has remained unclear. Brain-derived neurotrophic factor (BDNF) and its receptor TRKB are critical r...

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Autor principal: Castrén, E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10417866/
http://dx.doi.org/10.1192/j.eurpsy.2023.68
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author Castrén, E.
author_facet Castrén, E.
author_sort Castrén, E.
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description ABSTRACT: Neuronal plasticity has for a long time been considered important for the recovery from depression and for the antidepressant drug action, but how the drug action is translated to plasticity has remained unclear. Brain-derived neurotrophic factor (BDNF) and its receptor TRKB are critical regulators of neuronal plasticity and have been implicated in the antidepressant action. We have recently found that many, if not all, different antidepressants, including serotonin selective SSRIs, tricyclic as well as fast-acting ketamine, directly bind to TRKB, thereby promoting TRKB translocation to synaptic membranes, which increases BDNF signaling. We have previously shown that antidepressant treatment induces a juvenile-like state of activity in the cortex that facilitates beneficial rewiring of abnormal networks. It is important to note that enhanced plasticity does not necessarily promote recovery, but may also be maladaptive if the environment is adverse. Our findings open a new framework for the antidepressant action and for treatment of depression: antidepressants directly bind to TRKB and allosterically promote BDNF signaling, thereby inducing a state of plasticity that allows re-wiring of abnormal networks for better functionality, when optimal supportive therapy is provided at the time of enhanced plasticity. DISCLOSURE OF INTEREST: E. Castrén Speakers bureau of: Janssen-Cilag
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spelling pubmed-104178662023-08-12 Neuronal plasticity and fast antidepressant response Castrén, E. Eur Psychiatry Abstract ABSTRACT: Neuronal plasticity has for a long time been considered important for the recovery from depression and for the antidepressant drug action, but how the drug action is translated to plasticity has remained unclear. Brain-derived neurotrophic factor (BDNF) and its receptor TRKB are critical regulators of neuronal plasticity and have been implicated in the antidepressant action. We have recently found that many, if not all, different antidepressants, including serotonin selective SSRIs, tricyclic as well as fast-acting ketamine, directly bind to TRKB, thereby promoting TRKB translocation to synaptic membranes, which increases BDNF signaling. We have previously shown that antidepressant treatment induces a juvenile-like state of activity in the cortex that facilitates beneficial rewiring of abnormal networks. It is important to note that enhanced plasticity does not necessarily promote recovery, but may also be maladaptive if the environment is adverse. Our findings open a new framework for the antidepressant action and for treatment of depression: antidepressants directly bind to TRKB and allosterically promote BDNF signaling, thereby inducing a state of plasticity that allows re-wiring of abnormal networks for better functionality, when optimal supportive therapy is provided at the time of enhanced plasticity. DISCLOSURE OF INTEREST: E. Castrén Speakers bureau of: Janssen-Cilag Cambridge University Press 2023-07-19 /pmc/articles/PMC10417866/ http://dx.doi.org/10.1192/j.eurpsy.2023.68 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Abstract
Castrén, E.
Neuronal plasticity and fast antidepressant response
title Neuronal plasticity and fast antidepressant response
title_full Neuronal plasticity and fast antidepressant response
title_fullStr Neuronal plasticity and fast antidepressant response
title_full_unstemmed Neuronal plasticity and fast antidepressant response
title_short Neuronal plasticity and fast antidepressant response
title_sort neuronal plasticity and fast antidepressant response
topic Abstract
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10417866/
http://dx.doi.org/10.1192/j.eurpsy.2023.68
work_keys_str_mv AT castrene neuronalplasticityandfastantidepressantresponse