Exploring the genetics of lithium response in bipolar disorders

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• dc.contributor.author Herrera-Rivero, Marisol
• dc.contributor.author Colom, Francesc
• dc.contributor.author Baune, Bernhard T.
• dc.date.accessioned 2025-06-03T06:11:37Z
• dc.date.available 2025-06-03T06:11:37Z
• dc.date.issued 2024
• dc.description.abstract Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
• dc.format.mimetype application/pdf
• dc.identifier.citation Herrera-Rivero M, Adli M, Akiyama K, Akula N, Amare AT, Ardau R, et al. Exploring the genetics of lithium response in bipolar disorders. Int J Bipolar Disord. 2024 Jun 12;12(1):20. DOI: 10.1186/s40345-024-00341-y
• dc.identifier.doi http://dx.doi.org/10.1186/s40345-024-00341-y
• dc.identifier.issn 2194-7511
• dc.identifier.uri http://hdl.handle.net/10230/70596
• dc.language.iso eng
• dc.publisher Springer
• dc.relation.ispartof Int J Bipolar Disord. 2024 Jun 12;12(1):20
• dc.rights © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Bipolar disorder
• dc.subject.keyword Comorbidity
• dc.subject.keyword Genetics
• dc.subject.keyword Lithium treatment
• dc.subject.keyword Psychiatric symptoms
• dc.title Exploring the genetics of lithium response in bipolar disorders
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion