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The Genetics of Response to and Side Effects of Lithium Treatment in Bipolar Disorder: Future Research Perspectives
Although the mood stabilizer lithium is a first-line treatment in bipolar disorder, a substantial number of patients do not benefit from it and experience side effects. No clinical tool is available for predicting lithium response or the occurrence of side effects in everyday clinical practice. Mult...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044839/ https://www.ncbi.nlm.nih.gov/pubmed/33867988 http://dx.doi.org/10.3389/fphar.2021.638882 |
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author | Senner, Fanny Kohshour, Mojtaba Oraki Abdalla, Safa Papiol, Sergi Schulze, Thomas G. |
author_facet | Senner, Fanny Kohshour, Mojtaba Oraki Abdalla, Safa Papiol, Sergi Schulze, Thomas G. |
author_sort | Senner, Fanny |
collection | PubMed |
description | Although the mood stabilizer lithium is a first-line treatment in bipolar disorder, a substantial number of patients do not benefit from it and experience side effects. No clinical tool is available for predicting lithium response or the occurrence of side effects in everyday clinical practice. Multiple genetic research efforts have been performed in this field because lithium response and side effects are considered to be multifactorial endophenotypes. Available results from linkage and segregation, candidate-gene, and genome-wide association studies indicate a role of genetic factors in determining response and side effects. For example, candidate-gene studies often report GSK3β, brain-derived neurotrophic factor, and SLC6A4 as being involved in lithium response, and the latest genome-wide association study found a genome-wide significant association of treatment response with a locus on chromosome 21 coding for two long non-coding RNAs. Although research results are promising, they are limited mainly by a lack of replicability and, despite the collaboration of consortia, insufficient sample sizes. The need for larger sample sizes and “multi-omics” approaches is apparent, and such approaches are crucial for choosing the best treatment options for patients with bipolar disorder. In this article, we delineate the mechanisms of action of lithium and summarize the results of genetic research on lithium response and side effects. |
format | Online Article Text |
id | pubmed-8044839 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80448392021-04-15 The Genetics of Response to and Side Effects of Lithium Treatment in Bipolar Disorder: Future Research Perspectives Senner, Fanny Kohshour, Mojtaba Oraki Abdalla, Safa Papiol, Sergi Schulze, Thomas G. Front Pharmacol Pharmacology Although the mood stabilizer lithium is a first-line treatment in bipolar disorder, a substantial number of patients do not benefit from it and experience side effects. No clinical tool is available for predicting lithium response or the occurrence of side effects in everyday clinical practice. Multiple genetic research efforts have been performed in this field because lithium response and side effects are considered to be multifactorial endophenotypes. Available results from linkage and segregation, candidate-gene, and genome-wide association studies indicate a role of genetic factors in determining response and side effects. For example, candidate-gene studies often report GSK3β, brain-derived neurotrophic factor, and SLC6A4 as being involved in lithium response, and the latest genome-wide association study found a genome-wide significant association of treatment response with a locus on chromosome 21 coding for two long non-coding RNAs. Although research results are promising, they are limited mainly by a lack of replicability and, despite the collaboration of consortia, insufficient sample sizes. The need for larger sample sizes and “multi-omics” approaches is apparent, and such approaches are crucial for choosing the best treatment options for patients with bipolar disorder. In this article, we delineate the mechanisms of action of lithium and summarize the results of genetic research on lithium response and side effects. Frontiers Media S.A. 2021-03-25 /pmc/articles/PMC8044839/ /pubmed/33867988 http://dx.doi.org/10.3389/fphar.2021.638882 Text en Copyright © 2021 Senner, Kohshour, Abdalla, Papiol and Schulze. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Senner, Fanny Kohshour, Mojtaba Oraki Abdalla, Safa Papiol, Sergi Schulze, Thomas G. The Genetics of Response to and Side Effects of Lithium Treatment in Bipolar Disorder: Future Research Perspectives |
title | The Genetics of Response to and Side Effects of Lithium Treatment in Bipolar Disorder: Future Research Perspectives |
title_full | The Genetics of Response to and Side Effects of Lithium Treatment in Bipolar Disorder: Future Research Perspectives |
title_fullStr | The Genetics of Response to and Side Effects of Lithium Treatment in Bipolar Disorder: Future Research Perspectives |
title_full_unstemmed | The Genetics of Response to and Side Effects of Lithium Treatment in Bipolar Disorder: Future Research Perspectives |
title_short | The Genetics of Response to and Side Effects of Lithium Treatment in Bipolar Disorder: Future Research Perspectives |
title_sort | genetics of response to and side effects of lithium treatment in bipolar disorder: future research perspectives |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044839/ https://www.ncbi.nlm.nih.gov/pubmed/33867988 http://dx.doi.org/10.3389/fphar.2021.638882 |
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