Exploring the genetics of lithium response in bipolar disorders

Herrera-Rivero M, Adli M, Akiyama K, Akula N, Amare AT, Ardau R, Arias B, Aubry JM, Backlund L, Bellivier F, Benabarre A, Bengesser S, Bhattacharjee AK, Biernacka JM, Birner A, Cearns M, Cervantes P, Chen HC, Chillotti C, Cichon S, Clark SR, Colom F, Cruceanu C, Czerski PM, Dalkner N, Degenhardt F, Del Zompo M, DePaulo JR, Etain B, Falkai P, Ferensztajn-Rochowiak E, Forstner AJ, Frank J, Frisén L, Frye MA, Fullerton JM, Gallo C, Gard S, Garnham JS, Goes FS, Grigoroiu-Serbanescu M, Grof P, Hashimoto R, Hasler R, Hauser J, Heilbronner U, Herms S, Hoffmann P, Hou L, Hsu YH, Jamain S, Jiménez E, Kahn JP, Kassem L, Kato T, Kelsoe J, Kittel-Schneider S, Kuo PH, Kusumi I, König B, Laje G, Landén M, Lavebratt C, Leboyer M, Leckband SG, Maj M, Manchia M, Marie-Claire C, Martinsson L, McCarthy MJ, McElroy SL, Millischer V, Mitjans M, Mondimore FM, Monteleone P, Nievergelt CM, Novák T, Nöthen MM, O’Donovan C, Ozaki N, Papiol S, Pfennig A, Pisanu C, Potash JB, Reif A, Reininghaus E, Richard-Lepouriel H, Roberts G, Rouleau GA, Rybakowski JK, Schalling M, Schofield PR, Schubert KO, Schulte EC, Schweizer BW, Severino G, Shekhtman T, Shilling PD, Shimoda K, Simhandl C, Slaney CM, Squassina A, Stamm T, Stopkova P, Streit F, Tekola-Ayele F, Thalamuthu A, Tortorella A, Turecki G, Veeh J, Vieta E, Viswanath B, Witt SH, Zandi PP, Alda M, Bauer M, McMahon FJ, Mitchell PB, Rietschel M, Schulze TG, Baune BT (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 12

Article Number: 20

Journal Issue: 1

DOI: 10.1186/s40345-024-00341-y

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.

Authors with CRIS profile

Involved external institutions

Hospital del Mar Spain (ES) Universitätsspital Basel Switzerland (CH) Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) Germany (DE) Universität Münster (ehem. Westfälische Wilhelms-Universität (WWU)) Germany (DE) Mayo Clinic United States (USA) (US) Dokkyo Medical University Japan (JP) Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG) Switzerland (CH) Klinikum der Universität München (LMU Klinikum) Germany (DE) Forschungszentrum Jülich / Research Centre Jülich (FZJ) Germany (DE) University of New South Wales (UNSW) Australia (AU) Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE) Johns Hopkins University (JHU) United States (USA) (US) Università degli Studi di Cagliari Italy (IT) Université Sorbonne Paris Cité France (FR) National Taiwan University Hospital (NTUH) / 國立台灣大學醫學院附設醫院 Taiwan (TW) Poznan University of Medical Sciences / Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu Poland (PL) Universidad Peruana Cayetano Heredia Peru (PE) Dalhousie University Canada (CA) Mood Disorders Ottawa Canada (CA) Universitätsklinikum Bonn Germany (DE) National Institute of Mental Health Information Resource Center United States (USA) (US) Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset Sweden (SE) Università degli Studi di Perugia Italy (IT) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Universitätsklinikum Würzburg Germany (DE) Douglas Mental Health University Institute Canada (CA) National Institute of Mental Health and Neuroscience (NIMHANS) India (IN) Juntendo University Japan (JP) National Taiwan University (NTU) Taiwan (TW) University of Adelaide Australia (AU) Charité - Universitätsmedizin Berlin Germany (DE) Paris-Est Créteil University / Université Paris-Est Créteil Val-de-Marne (UPEC) / Université Paris XII-Val-de-Marne / University Paris 12 Marne la Vallée France (FR) University of California, San Diego (UC San Diego, UCSD) United States (USA) (US) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) National Institute of Mental Health (NIMH) / Národní ústav duševního zdraví (NUDZ) Czech Republic (CZ) Université de Lorraine France (FR) VA San Diego Healthcare System United States (USA) (US) Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Spain (ES) University of Cincinnati United States (USA) (US) Karolinska Institute Sweden (SE) Università degli studi della Campania Luigi Vanvitelli Italy (IT) Università degli Studi di Salerno Italy (IT) Medizinische Universität Graz Austria (AT) Universitat de Barcelona (UB) / University of Barcelona Spain (ES) Centre Hospitalier Charles Perrens (CHCP) France (FR) McGill University Health Centre (MUHC) / Centre universitaire de santé McGill Canada (CA) Städtisches Klinikum Neunkirchen Germany (DE) US National Institutes of Health (NIH) United States (USA) (US) Harvard T.H. Chan School of Public Health United States (USA) (US) Montreal Neurological Institute and Hospital (MNI, The Neuro) Canada (CA) Nagoya University / 名古屋大学 Japan (JP) Sigmund-Freud-Privatuniversität Wien (SFU) / Sigmund Freud University Austria (AT)

How to cite

APA:

Herrera-Rivero, M., Adli, M., Akiyama, K., Akula, N., Amare, A.T., Ardau, R.,... Baune, B.T. (2024). Exploring the genetics of lithium response in bipolar disorders. International Journal of Bipolar Disorders, 12(1). https://doi.org/10.1186/s40345-024-00341-y

MLA:

Herrera-Rivero, Marisol, et al. "Exploring the genetics of lithium response in bipolar disorders." International Journal of Bipolar Disorders 12.1 (2024).

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