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...

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Vydané v:Frontiers in pharmacology Ročník 12; s. 638882
Hlavní autori: Senner, Fanny, Kohshour, Mojtaba Oraki, Abdalla, Safa, Papiol, Sergi, Schulze, Thomas G.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Switzerland Frontiers Media S.A 25.03.2021
Predmet:
bipolar disorder
candidate-gene association studies
GWAS
linkage and segregation studies
lithium
pharmacogenetics
Pharmacology
lithium
side effect
bipolar disorder
GWAS
treatment response
candidate-gene association studies
linkage and segregation studies
pharmacogenetics
ISSN:1663-9812, 1663-9812
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Abstract 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.
AbstractList 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.
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.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.
Author Abdalla, Safa
Kohshour, Mojtaba Oraki
Senner, Fanny
Papiol, Sergi
Schulze, Thomas G.
AuthorAffiliation 5 Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY , United States
4 Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Khartoum , Sudan
1 Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich , Germany
2 Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich , Germany
3 Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz , Iran
AuthorAffiliation_xml – name: 3 Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz , Iran
– name: 1 Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich , Germany
– name: 5 Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY , United States
– name: 2 Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich , Germany
– name: 4 Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Khartoum , Sudan
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Copyright Copyright © 2021 Senner, Kohshour, Abdalla, Papiol and Schulze.
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Keywords lithium
side effect
bipolar disorder
GWAS
treatment response
candidate-gene association studies
linkage and segregation studies
pharmacogenetics
Language English
License Copyright © 2021 Senner, Kohshour, Abdalla, Papiol and Schulze.
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This article was submitted to Pharmacogenetics and Pharmacogenomics, a section of the journal Frontiers in Pharmacology
Reviewed by: Claudia Pisanu, University of Cagliari, Italy
These authors have contributed equally to this work
Edited by: Roos van Westrhenen, Parnassia Psychiatric Institute, Netherlands
Cheryl D. Cropp, Samford University, United States
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Snippet 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...
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SubjectTerms bipolar disorder
candidate-gene association studies
GWAS
linkage and segregation studies
lithium
pharmacogenetics
Pharmacology
Title The Genetics of Response to and Side Effects of Lithium Treatment in Bipolar Disorder: Future Research Perspectives
URI https://www.ncbi.nlm.nih.gov/pubmed/33867988
https://www.proquest.com/docview/2515071799
https://pubmed.ncbi.nlm.nih.gov/PMC8044839
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