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Is Poor Lithium Response in Individuals with Bipolar Disorder Associated with Increased Degradation of Tryptophan along the Kynurenine Pathway? Results of an Exploratory Study
Bipolar disorder is associated with an inflammation-triggered elevated catabolism of tryptophan to the kynurenine pathway, which impacts psychiatric symptoms and outcomes. The data indicate that lithium exerts anti-inflammatory effects by inhibiting indoleamine-2,3-dioxygenase (IDO)-1 activity. This...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103936/ https://www.ncbi.nlm.nih.gov/pubmed/35566641 http://dx.doi.org/10.3390/jcm11092517 |
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author | Fellendorf, Frederike T. Manchia, Mirko Squassina, Alessio Pisanu, Claudia Dall’Acqua, Stefano Sut, Stefania Nasini, Sofia Congiu, Donatella Reininghaus, Eva Z. Garzilli, Mario Guiso, Beatrice Suprani, Federico Paribello, Pasquale Pulcinelli, Vittoria Iaselli, Maria Novella Pinna, Ilaria Somaini, Giulia Arru, Laura Corrias, Carolina Pinna, Federica Carpiniello, Bernardo Comai, Stefano |
author_facet | Fellendorf, Frederike T. Manchia, Mirko Squassina, Alessio Pisanu, Claudia Dall’Acqua, Stefano Sut, Stefania Nasini, Sofia Congiu, Donatella Reininghaus, Eva Z. Garzilli, Mario Guiso, Beatrice Suprani, Federico Paribello, Pasquale Pulcinelli, Vittoria Iaselli, Maria Novella Pinna, Ilaria Somaini, Giulia Arru, Laura Corrias, Carolina Pinna, Federica Carpiniello, Bernardo Comai, Stefano |
author_sort | Fellendorf, Frederike T. |
collection | PubMed |
description | Bipolar disorder is associated with an inflammation-triggered elevated catabolism of tryptophan to the kynurenine pathway, which impacts psychiatric symptoms and outcomes. The data indicate that lithium exerts anti-inflammatory effects by inhibiting indoleamine-2,3-dioxygenase (IDO)-1 activity. This exploratory study aimed to investigate the tryptophan catabolism in individuals with bipolar disorder (n = 48) compared to healthy controls (n = 48), and the associations with the response to mood stabilizers such as lithium, valproate, or lamotrigine rated with the Retrospective Assessment of the Lithium Response Phenotype Scale (or the Alda scale). The results demonstrate an association of a poorer response to lithium with higher levels of kynurenine, kynurenine/tryptophan ratio as a proxy for IDO-1 activity, as well as quinolinic acid, which, overall, indicates a pro-inflammatory state with a higher degradation of tryptophan towards the neurotoxic branch. The treatment response to valproate and lamotrigine was not associated with the levels of the tryptophan metabolites. These findings support the anti-inflammatory properties of lithium. Furthermore, since quinolinic acid has neurotoxic features via the glutamatergic pathway, they also strengthen the assumption that the clinical drug response might be associated with biochemical processes. The relationship between the lithium response and the measurements of the tryptophan to the kynurenine pathway is of clinical relevance and may potentially bring advantages towards a personalized medicine approach to bipolar disorder that allows for the selection of the most effective mood-stabilizing drug. |
format | Online Article Text |
id | pubmed-9103936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91039362022-05-14 Is Poor Lithium Response in Individuals with Bipolar Disorder Associated with Increased Degradation of Tryptophan along the Kynurenine Pathway? Results of an Exploratory Study Fellendorf, Frederike T. Manchia, Mirko Squassina, Alessio Pisanu, Claudia Dall’Acqua, Stefano Sut, Stefania Nasini, Sofia Congiu, Donatella Reininghaus, Eva Z. Garzilli, Mario Guiso, Beatrice Suprani, Federico Paribello, Pasquale Pulcinelli, Vittoria Iaselli, Maria Novella Pinna, Ilaria Somaini, Giulia Arru, Laura Corrias, Carolina Pinna, Federica Carpiniello, Bernardo Comai, Stefano J Clin Med Article Bipolar disorder is associated with an inflammation-triggered elevated catabolism of tryptophan to the kynurenine pathway, which impacts psychiatric symptoms and outcomes. The data indicate that lithium exerts anti-inflammatory effects by inhibiting indoleamine-2,3-dioxygenase (IDO)-1 activity. This exploratory study aimed to investigate the tryptophan catabolism in individuals with bipolar disorder (n = 48) compared to healthy controls (n = 48), and the associations with the response to mood stabilizers such as lithium, valproate, or lamotrigine rated with the Retrospective Assessment of the Lithium Response Phenotype Scale (or the Alda scale). The results demonstrate an association of a poorer response to lithium with higher levels of kynurenine, kynurenine/tryptophan ratio as a proxy for IDO-1 activity, as well as quinolinic acid, which, overall, indicates a pro-inflammatory state with a higher degradation of tryptophan towards the neurotoxic branch. The treatment response to valproate and lamotrigine was not associated with the levels of the tryptophan metabolites. These findings support the anti-inflammatory properties of lithium. Furthermore, since quinolinic acid has neurotoxic features via the glutamatergic pathway, they also strengthen the assumption that the clinical drug response might be associated with biochemical processes. The relationship between the lithium response and the measurements of the tryptophan to the kynurenine pathway is of clinical relevance and may potentially bring advantages towards a personalized medicine approach to bipolar disorder that allows for the selection of the most effective mood-stabilizing drug. MDPI 2022-04-29 /pmc/articles/PMC9103936/ /pubmed/35566641 http://dx.doi.org/10.3390/jcm11092517 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fellendorf, Frederike T. Manchia, Mirko Squassina, Alessio Pisanu, Claudia Dall’Acqua, Stefano Sut, Stefania Nasini, Sofia Congiu, Donatella Reininghaus, Eva Z. Garzilli, Mario Guiso, Beatrice Suprani, Federico Paribello, Pasquale Pulcinelli, Vittoria Iaselli, Maria Novella Pinna, Ilaria Somaini, Giulia Arru, Laura Corrias, Carolina Pinna, Federica Carpiniello, Bernardo Comai, Stefano Is Poor Lithium Response in Individuals with Bipolar Disorder Associated with Increased Degradation of Tryptophan along the Kynurenine Pathway? Results of an Exploratory Study |
title | Is Poor Lithium Response in Individuals with Bipolar Disorder Associated with Increased Degradation of Tryptophan along the Kynurenine Pathway? Results of an Exploratory Study |
title_full | Is Poor Lithium Response in Individuals with Bipolar Disorder Associated with Increased Degradation of Tryptophan along the Kynurenine Pathway? Results of an Exploratory Study |
title_fullStr | Is Poor Lithium Response in Individuals with Bipolar Disorder Associated with Increased Degradation of Tryptophan along the Kynurenine Pathway? Results of an Exploratory Study |
title_full_unstemmed | Is Poor Lithium Response in Individuals with Bipolar Disorder Associated with Increased Degradation of Tryptophan along the Kynurenine Pathway? Results of an Exploratory Study |
title_short | Is Poor Lithium Response in Individuals with Bipolar Disorder Associated with Increased Degradation of Tryptophan along the Kynurenine Pathway? Results of an Exploratory Study |
title_sort | is poor lithium response in individuals with bipolar disorder associated with increased degradation of tryptophan along the kynurenine pathway? results of an exploratory study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103936/ https://www.ncbi.nlm.nih.gov/pubmed/35566641 http://dx.doi.org/10.3390/jcm11092517 |
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