| Title: |
Exploring the genetics of lithium response in bipolar disorders |
| Authors: |
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; Mitchell, Philip; Thalamuthu, Anbu |
| Source: |
urn:ISSN:2194-7511 ; International Journal of Bipolar Disorders, 12, 1, 20 |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2024 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
3214 Pharmacology and Pharmaceutical Sciences; 32 Biomedical and Clinical Sciences; 3202 Clinical Sciences; Genetics; Brain Disorders; Bipolar Disorder; Clinical Research; Cardiovascular; Depression; Hypertension; Mental Health; Mental Illness; Behavioral and Social Science; Serious Mental Illness; Suicide; 2.1 Biological and endogenous factors; 6.1 Pharmaceuticals; 2.3 Psychological; social and economic factors; 4.1 Discovery and preclinical testing of markers and technologies; 3 Good Health and Well Being; Comorbidity; Lithium treatment; Psychiatric symptoms; anzsrc-for: 3214 Pharmacology and Pharmaceutical Sciences; anzsrc-for: 32 Biomedical and Clinical Sciences; anzsrc-for: 3202 Clinical Sciences; anzsrc-for: 1103 Clinical Sciences; anzsrc-for: 4203 Health services and systems |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://hdl.handle.net/1959.4/102610 |
| DOI: |
10.1186/s40345-024-00341-y |
| Availability: |
https://hdl.handle.net/1959.4/102610; https://unsworks.unsw.edu.au/bitstreams/00741d36-2535-4730-8717-13b3b69e7f15/download; https://doi.org/10.1186/s40345-024-00341-y |
| Rights: |
open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ ; free_to_read |
| Accession Number: |
edsbas.35ACC5DB |
| Database: |
BASE |