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

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.

Involved external institutions

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

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. , 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." 12.1 (2024).

BibTeX: Download