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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/225088
Exploring the genetics of lithium response in bipolar disorders.
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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.
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CICHON, Sven, CLARK, Scott r., COLOM, Francesc, CRUCEANU, Cristiana, CZERSKI, Piotr m., DALKNER, Nina, DEGENHARDT, Franziska, DEL ZOMPO, Maria, HERRERA-RIVERO, Marisol, ADLI, Mazda, AKIYAMA, Kazufumi, AKULA, Nirmala, AMARE, Azmeraw t., ARDAU, Raffaella, ARIAS SAMPÉRIZ, Bárbara, AUBRY, Jean‑michel, BACKLUND, Lena, BELLIVIER, Frank, BENABARRE HERNANDEZ, Antonio, BENGESSER, Susanne, BHATTACHARJEE, Abesh kumar, BIERNACKA, Joanna m., BIRNER, Armin, CEARNS, Micah, CERVANTES, Pablo, CHEN, Hsi‑chung, CHILLOTTI, Caterina, DePaulo JR, Etain B, Falkai P, Ferensztajn-Rochowiak E, Forstner AJ, FRANK, Josef, 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, JIMENEZ, Esther, 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 NIUBO, Marina, Mondimore FM, Monteleone P, Nievergelt CM, Novák T, Nöthen MM, O'Donovan C, Ozaki N, PAPIOL, Sergi, 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 PASCUAL, Eduard, Viswanath B, Witt SH, Zandi PP, Alda M, Bauer M, McMahon FJ, Mitchell PB, Rietschel M, Schulze TG, Baune BT. Exploring the genetics of lithium response in bipolar disorders.. _International Journal of Bipolar Disorders_. 2024. Vol. 12, núm. 1. [consulta: 3 de gener de 2026]. ISSN: 2194-7511. [Disponible a: https://hdl.handle.net/2445/225088]